BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective: To evaluate the diagnostic value and application of 24 h multichannel intraluminal impedance-pH (24 h MII-pH) monitoring in children with gastroesophageal reflux disease (GERD). Methods: This is a cross-sectional study. From January 2013 to December, 2020, 417 patients who received 24 h MII-pH monitoring in Department of Gastroenterology of Children's Hospital Capital Institute of Pediatrics were included. According to results, these children were divided into the GERD and non-GERD groups. Furthermore, the 132 children with GERD who had gastroscopy were divided into the reflux esophagitis (RE) and non-erosive reflux disease (NE) groups to investigate the differences in their refluxes. Non-parametric Mann-Whitney U test or indepentent sample t test was used for comparisons between the groups. Results: Among the 417 children, 232 were males and 185 females, aged (7.3±3.9) years. The course of disease was 0.5 (0.1, 2.0) years. The main clinical symptoms included acid reflux (128 cases), vomiting (173 cases), abdominal pain (101 cases), and cough (76 cases). The 24 h MII-pH monitoring were positive in 243 children (58.3%, 243/417), which was higher than that by 24 h esophageal pH monitoring (43.6%, 182/417). The 24 h MII-pH monitoring results demonstrated significant differences in the episodes of acid reflux, weakly acidic reflux, non-acidic reflux, liquid reflux and mixed reflux between GERD and non-GERD groups (10 (4, 19) vs. 4 (1, 9) times/24 h, 14 (6, 32) vs. 7 (3, 13) times/24 h, 0 (0, 0) vs. 0 (0, 0) times/24 h, 19 (10, 34) vs. 8 (3, 14) times/24 h, and 6 (2, 12) vs. 3 (1, 5) times/24 h, Z=-6.96, -7.25, -5.62, -8.75, and -6.48, all P<0.05, respectively). Besides, the results also showed significant differences in Boix-Ochoa score, episodes of long reflux, course of long reflux, and episodes of weakly acidic reflux between the RE and NE groups (51.2 (21.4, 153.2) vs. 20.7 (12.1, 34.7), 5 (2, 10) vs. 1 (0, 4) times/24 h, 19 (7, 87) vs. 8 (3, 22) min, and 5 (2, 15) vs. 15 (6, 33) times/24 h, Z=-3.44, -3.41, -2.65, and -2.27, all P<0.05, respectively). Conclusion: 24 h MII-pH monitoring not only improves the detection rate of GERD in children, but also provides a possibility to early etiological diagnosis.
Female ; Male ; Humans ; Child ; Cross-Sectional Studies ; Electric Impedance ; Gastroesophageal Reflux/diagnosis* ; Esophageal pH Monitoring ; Hydrogen-Ion Concentration

OBJECTIVE: To explore the clinical characteristics and genetic findings of patients with infantile intrahepatic cholestasis. METHODS: The clinical data were collected in children who were admitted to the Department of Gastroenterology in Children's Hospital, Capital Institute of Pediatrics from June 2017 to June 2019 and were suspected of inherited metabolic diseases. Next generation sequencing based on target gene panel was used for gene analysis in these children. Sanger sequencing technology was used to verify the genes of the members in this family. RESULTS: Forty patients were enrolled. Pathogenic gene variants were identified in 13 patients (32%), including CONCLUSIONS The etiology of infantile intrahepatic cholestasis is complex. Next generation sequencing is helpful in the diagnosis of infantile intrahepatic cholestasis.
Alagille Syndrome/genetics* ; Child ; Cholestasis, Intrahepatic/genetics* ; Citrullinemia ; Genetic Testing ; High-Throughput Nucleotide Sequencing ; Humans ; Mitochondrial Membrane Transport Proteins ; Mutation

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

Animals ; Apoptosis ; Brain/metabolism* ; Male ; Phosphatidylinositol 3-Kinases/metabolism* ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage/drug therapy* ; Thyroxine/pharmacology*

OBJECTIVE: To analyze the causes of vascular injury occurred in oblique lateral interbody fusion for treating lumbar degenerative diseases, and put forward preventive measures. METHODS: There were 235 patients analyzed from October 2014 to May 2017 in five hospitals, who were treated with oblique lateral interbody fusion with or without posterior pedicle screw fixation. There were 79 males and 156 females with an average age of (61.9±13.5) years old (ranged from 32 to 83 years). There were 7 cases of vascular injury, including 4 cases of segmental vessel injury, 1 case of left common iliac artery injury, 1 case of left common iliac veininjury and 1 case of ovarian vein injury. RESULTS: The follow up time ranged from 6 to 36 months, averagely (15.6±7.5) months. There was no pedicle screw loosen or fracture. The low back pain VAS decreased from preoperative 6.7±2.3 to 1.4±0.8 at the latest follow-up, which was statistically difference( CONCLUSION Oblique lateral interbody fusion technique provides a new method for minimally invasive fusion of lumbar internal fixation. However, it has a risk of vascular injury. In order to effectively prevent the occurrence of vascular injury, the operative indications and careful and meticulous operation should be strictly grasped.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Lumbar Vertebrae/surgery* ; Lumbosacral Region ; Male ; Middle Aged ; Pedicle Screws ; Retrospective Studies ; Spinal Fusion/adverse effects* ; Treatment Outcome ; Vascular System Injuries/surgery*

Objective To prepare isophenylcyclopentylamine hydrochloride capsules and evaluate its quality. Methods The suitable excipients were selected by the drug-excipient compatibility test,and after the formulation and preparation process design and screening,the micromeritic property and hygroscopicity of contents of capsules as well as the basic performance and stability of is-ophenylcyclopentylamine hydrochloride capsules were evaluate. Results The selected formulation was composed of isophenylcyclo-pentylamine hydrochloride 10 mg,anhydrous dibasic calcium phosphate 128.7 mg,mannitol 128.7 mg and aerosil 2.7 mg.The angle of repose of intermediate powders was(30.71±1.09)°,aerated and packed bulk densities were(0.76±0.01)and(0.90±0.02)g/ml re-spectively,Hausner value was 1.19±0.01,Carr′s index was(15.86±1.05)%,indicating good flowability and filling property as well as relatively low humidity.The contents,uniformity of contents and dissolution of capsules fulfilled the requirements.The quality of ca-pusles kept well in the 6-month accelerated and long-term stability test.Conclusion The formulation is simple and reasonable,and the preparation process showed a good reproducibility,which might be suitable for industrialization.

Alzheimer disease (AD) is one of the most common types of dementia.Serotonin (5-HT) plays an important role in the pathogenesis of AD,causing alterations in patients' cognitive abilities,as well as learning and memory capabilities,by regulating the cholinergic and glutamatergic neurotransmission through the signal transduction pathway.Patients suffer from emotional disorders including depression and apathy and clinical manifestations such as unrestrained diet,which are all related to the signaling function of 5-HT receptors.Strengthening the 5-HT receptor-mediated transduction pathway and increasing the concentration of synaptic 5-HT have been used as a novel therapy for delaying the progression of AD.This articles reviews the AD therapies targeting 5-HT transduction pathway.

BACKGROUNDUrine output (UO) is an essential criterion of the Kidney Disease Improving Global Outcomes (KDIGO) definition and classification system for acute kidney injury (AKI), of which the diagnostic value has not been extensively studied. We aimed to determine whether AKI based on KDIGO UO criteria (KDIGOUO) could improve the diagnostic and prognostic accuracy, compared with KDIGO serum creatinine criteria (KDIGOSCr).

METHODSWe conducted a secondary analysis of the database of a previous study conducted by China Critical Care Clinical Trial Group (CCCCTG), which was a 2-month prospective cohort study (July 1, 2009 to August 31, 2009) involving 3063 patients in 22 tertiary Intensive Care Units in Mainland of China. AKI was diagnosed and classified separately based on KDIGOUOand KDIGOSCr. Hospital mortality of patients with more severe AKI classification based on KDIGOUOwas compared with other patients by univariate and multivariate regression analyses.

RESULTSThe prevalence of AKI increased from 52.4% based on KDIGOSCrto 55.4% based on KDIGOSCrcombined with KDIGOUO. KDIGOUOalso resulted in an upgrade of AKI classification in 7.3% of patients, representing those with more severe AKI classification based on KDIGOUO. Compared with non-AKI patients or those with maximum AKI classification by KDIGOSCr, those with maximum AKI classification by KDIGOUOhad a significantly higher hospital mortality of 58.4% (odds ratio [OR]: 7.580, 95% confidence interval [CI]: 4.141-13.873, P< 0.001). In a multivariate logistic regression analysis, AKI based on KDIGOUO (OR: 2.891, 95% CI: 1.964-4.254, P< 0.001), but not based on KDIGOSCr (OR: 1.322, 95% CI: 0.902-1.939, P = 0.152), was an independent risk factor for hospital mortality.

CONCLUSIONUO was a criterion with additional value beyond creatinine criterion for AKI diagnosis and classification, which can help identify a group of patients with high risk of death.

Acute Disease ; mortality ; Aged ; Creatinine ; blood ; Critical Illness ; mortality ; Female ; Hospital Mortality ; Humans ; Kaplan-Meier Estimate ; Kidney Diseases ; blood ; mortality ; pathology ; urine ; Logistic Models ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; Risk Factors