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*

OBJECTIVE: A prospective randomized controlled study was conducted to investigate the early postoperative analgesic effectiveness of using liposomal bupivacaine (LB) for local infiltration anesthesia (LIA) in unicompartmental knee arthroplasty (UKA). METHODS: Between January 2024 and July 2024, a total of 80 patients with knee osteoarthritis (KOA) who met the selection criteria were enrolled in the study. Patients were randomly assigned to either the LB group or the "cocktail" group in a 1∶1 ratio using a random number table, with 40 patients in each group. Baseline characteristics, including gender, age, body mass index, operated side, Kellgren-Lawrence grade, and preoperative American Society of Anesthesiologists (ASA) classification, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee joint range of motion, showed no significant difference between the two groups ( P>0.05). Both groups received LIA and comprehensive pain management. The surgical duration, incision length, pain-related indicators [resting and activity visual analogue scale (VAS) scores, total dosage of oral morphine, WOMAC scores], knee joint range of motion, first ambulation time after operation, length of hospital stay, and postoperative adverse events. RESULTS: There was no significant difference between the two groups in surgical duration, incision length, first ambulation time after operation, length of hospital stay, total dosage of oral morphine, and pre-discharge satisfaction with surgery and WOMAC scores ( P>0.05). At 4, 12, and 24 hours after operation, the resting and activity VAS scores in the "cocktail" group were lower than those in the LB group; at 60 and 72 hours postoperatively, the resting VAS scores in the LB group were lower than those in the "cocktail" group, with the activity VAS scores also being lower at 60 hours; all showing significant differences ( P<0.05). There was no significant difference in the above indicators between the two groups at other time points ( P>0.05). On the second postoperative day, the sleep scores of the LB group were significantly higher than those of the "cocktail" group ( P<0.05), while there was no significant difference in sleep scores on the day of surgery and the first postoperative day ( P>0.05). Additionally, the incidence of complications showed no significant difference between the two groups ( P>0.05). CONCLUSION The use of LB for LIA in UKA can provide prolonged postoperative pain relief; however, it does not demonstrate a significant advantage over the "cocktail" method in terms of short-term analgesic effects or reducing opioid consumption and early functional recovery after UKA. Nevertheless, LB may help reduce postoperative sleep disturbances, making it a recommended option for UKA patients with cardiovascular diseases and insomnia or other mental health issues.
Aged ; Female ; Humans ; Male ; Middle Aged ; Anesthesia, Local/methods* ; Anesthetics, Local/administration & dosage* ; Arthroplasty, Replacement, Knee/methods* ; Bupivacaine/administration & dosage* ; Liposomes ; Osteoarthritis, Knee/surgery* ; Pain Measurement ; Pain, Postoperative/prevention & control* ; Prospective Studies ; Treatment Outcome

Transcriptomics technology has shown remarkable application effects in multiple disease fields, but its application in severe burns, especially in the field of burn sepsis, is still superficial. The use of transcriptomics and big data methods to solve the long-standing challenges of severe burns, especially in the field of burn sepsis, has great prospects and significance. This article comprehensively discusses the application value, current status, and future prospects of transcriptomics in the study of severe burns, especially burn sepsis, in order to provide new ideas for the treatment of severe burns.

Objective:To investigate the concern about pollen broadcasting in Chinese population from multiple dimensions and to understand the information about allergic rhinitis (AR) in China by analyzing related factors.Methods:From March 1 to September 30, 2022, a large-scale multi-center cross-sectional survey was conducted based on the Questionnaire Star platform in 21 Chinese hospitals. A total of 7 056 subjects from 7 regions in China: Northeast, North, East, Central, South, Southwest, and Northwest China were included. Basic characteristics (including social demographic characteristics and disease characteristics of AR patients), concern about pollen broadcasting, the willingness of pollen-induced AR (PiAR) patients to receive pollen broadcasting, and the treatment satisfaction rate of AR patients were collected. The chi-square test, multivariate linear regression model, and Logistic regression analysis were used to analyze the concern about pollen broadcasting in the Chinese population and related factors from multiple dimensions.Results:Among 7 056 subjects, 23.02% were concerned about pollen broadcasting. Among 3 176 self-reported AR and 1 019 PiAR patients, 25.60% and 39.16% were concerned about pollen broadcasting, respectively, which was higher than that of non-AR or non-PiAR subjects ( χ2 value was 21.74 and 175.11, respectively, both P<0.001). Among AR patients, the proportion of spring and autumn allergen-positive patients concerned about pollen broadcasting was higher than that in perennial allergen-positive patients ( χ2 value was 20.90 and 19.51, respectively, both P<0.001). The proportion of AR patients with asthma, sinusitis, allergic conjunctivitis, and cardiovascular and cerebrovascular diseases was higher than those without complications ( χ2 value was 50.83, 21.97, 56.78, 7.62, respectively, all P<0.05). The proportion of AR patients in North China who could find pollen broadcasting locally was 31.01%, significantly higher than those in other regions (all P<0.05). Multivariate linear regression model analysis showed that among PiAR patients, those with higher per capita household income and higher AR disease cognition levels had been concerned about pollen broadcasting in the past, and those complicated with allergic conjunctivitis had stronger intention to receive pollen broadcasting (B value was 0.24, 0.13, 0.66, 0.47, respectively, all P<0.05). The higher the disease cognition level of PiAR patients, the stronger their willingness to actively participate in treatment ( R2=0.72, P<0.001). Only 18.89% of AR patients felt satisfied with the treatment effect. Logistic regression analysis showed that in AR patients, the treatment satisfaction rate was significantly higher among those concerned about pollen broadcasting compared to those who were not ( OR=1.83, P<0.001). Conclusions:Currently, the dissemination of pollen broadcasting in China is hindered by various factors such as disease cognition level. The treatment satisfaction among AR patients remains unsatisfactory.

Background and aims:Inflammatory factors play significant roles in the development and occurrence of hepatocellular carcinoma(HCC).However,the tumor-protective functions of growth differentiation factors(GDFs)in HCC are yet to be clarified.In this study,we aimed to evaluate the expression levels of 10 GDFs in tumor and paratumor tissues from patients with HCC and perform in vitro and in vivo ex-periments to elucidate the role of GDF7 in regulating the proliferation and metastasis of HCC.Methods:The gene expression of 10 GDFs was compared between HCC and paratumors using The Cancer Genome Atlas dataset and patient-derived tissues.A tumor microarray containing 108 HCC tissue samples was used to explore the prognostic value of GDF7 expression.Loss-of-function experiments were also performed in vitro and in vivo to investigate the role of GDF7 in HCC.Results:The mRNA and protein levels of GDF7 were significantly lower in HCC tumors than in para-tumors(P＜0.001).Kaplan-Meier analysis showed that decreased GDF7 expression in HCC was asso-ciated with worse overall survival(5-year rate:61.8％vs.27.5％,P＜0.001)and increased recurrence risk(P＜0.001).Multivariate Cox regression analysis demonstrated that low GDF7 expression,the presence of microvascular invasion,and elevated alpha-fetoprotein(AFP)levels were independent risk factors for tumor recurrence and poor survival.Downregulation of GDF7 also increased the tumor growth in HCC cells and in an HCC xenograft model.GDF7 knockdown promoted migration and invasion via epithelial-mesenchymal transition.Meanwhile,a negative correlation between JunB proto-oncogene(JUNB)and GDF7 was observed in HCC tissues.Modulating JUNB levels altered GDF7 protein expression.Conclusions:GDF7 is a potential biomarker for predicting superior outcomes in patients with HCC.GDF7 amplification is a potential therapeutic option for HCC.

In order to explore the mechanism by which Rehmannia extract enhances ovarian follicle development,reduces ovarian aging,and improves the production performance of chickens,35-week-old black skin and red crest chickens were randomly divided into a blank control group and groups supplemented with 0.1％,0.2％and 0.4％Rehmannia extract for feeding experiments.Changes of histological structure and molecular regulation for improving the reproductive perform-ance of black skin and red crest chicken were explored here by detecting the reproductive hormones and the corresponding receptors in ovary and quantifying the cell proliferation and apoptotic lesion.Based on the PI3K/AKT/mTOR and AMPK signaling pathways,mechanisms of Rehmannia ex-tract on promoting ovarian follicle development and alleviating ovarian aging were further studied to enrich the reproductive regulation theory of native breed chickens and improve their reproduc-tive performance.The results indicated that 0.4％Rehmannia extract could improve the levels of LH,E2 and P4 in serum,elevate the relative expression levels of FSHR,ERβ and PCNA mRNA in ovarian tissues,increase the content of PCNA protein,and decrease the number of apoptosis cells and the level of apoptosis protein Cleaved-Caspase-3.By enhancing the secretion of norepinephrine and activating the a2A-AR and the downstream PI3K/AKT/mTOR signaling pathway in ovary,the Rehmannia extract could effectively relieve the decline of ovarian function and maintain stable and efficient ovarian functions,which was independent of AMPK signaling pathway.Therefore,0.4％Rehmannia extract is conducive to enhancing the reproductive function via regulating PI3K/AKT/mTOR signaling pathway.

In order to explore the mechanism by which Rehmannia extract enhances ovarian follicle development,reduces ovarian aging,and improves the production performance of chickens,35-week-old black skin and red crest chickens were randomly divided into a blank control group and groups supplemented with 0.1％,0.2％and 0.4％Rehmannia extract for feeding experiments.Changes of histological structure and molecular regulation for improving the reproductive perform-ance of black skin and red crest chicken were explored here by detecting the reproductive hormones and the corresponding receptors in ovary and quantifying the cell proliferation and apoptotic lesion.Based on the PI3K/AKT/mTOR and AMPK signaling pathways,mechanisms of Rehmannia ex-tract on promoting ovarian follicle development and alleviating ovarian aging were further studied to enrich the reproductive regulation theory of native breed chickens and improve their reproduc-tive performance.The results indicated that 0.4％Rehmannia extract could improve the levels of LH,E2 and P4 in serum,elevate the relative expression levels of FSHR,ERβ and PCNA mRNA in ovarian tissues,increase the content of PCNA protein,and decrease the number of apoptosis cells and the level of apoptosis protein Cleaved-Caspase-3.By enhancing the secretion of norepinephrine and activating the a2A-AR and the downstream PI3K/AKT/mTOR signaling pathway in ovary,the Rehmannia extract could effectively relieve the decline of ovarian function and maintain stable and efficient ovarian functions,which was independent of AMPK signaling pathway.Therefore,0.4％Rehmannia extract is conducive to enhancing the reproductive function via regulating PI3K/AKT/mTOR signaling pathway.

Objective:To observe the efficacy and safety of the M receptor antagonist Bencycloquidium bromide nasal spray in treatment of seasonal allergic rhinitis with runny nose as the main symptom. Methods:From August 2021 to September 2021, 134 patients with seasonal allergic rhinitis were enrolled in the otolaryngology Outpatient Department of Peking University Third Hospital, First Affiliated Hospital of Harbin Medical University and China-Japanese Friendship Hospital of Jilin University, including 71 males and 63 females, with a median age of 38 years. TNSS score and visual analogue scale（VAS） of total nasal symptoms were observed during 2 weeks of treatment with Bencycloquidium bromide nasal spray. Results:TNSS score decreased from （8.89±3.31） on day 0 to （3.71±2.51） on day 14（P<0.001）, VAS score of nasal symptoms decreased from （24.86±7.40） on day 0 to （6.84±5.94） on day 14（P<0.001）, VAS score of rhinorrhoea decreased from （6.88±2.06） on day 0 to （1.91±1.81） on day 14（P<0.001）. Rhinoconjunctivitis quality of life questionnaire（RQLQ） score decreased from （94.63±33.35） on day 0 to （44.95±32.28） on day 14（P<0.001）. The incidence of adverse reaction was low and no serious adverse events occurred during the whole experiment. Conclusion:Bencycloquidium bromide nasal spray has significant efficacy and good safety in the treatment of seasonal allergic rhinitis.
Male ; Female ; Humans ; Adult ; Rhinitis, Allergic, Seasonal/drug therapy* ; Nasal Sprays ; Quality of Life ; Administration, Intranasal ; Rhinorrhea ; Double-Blind Method ; Treatment Outcome ; Rhinitis, Allergic/drug therapy*

Objective:To evaluate the early efficacy and safety of transnasal endoscopic decompression in the annulus of zinn (AZ) region for refractory dysthyroid optic neuropathy (DON) and to preliminarily analyze the correlated factors of postoperative visual function outcome.Methods:From July 2021 to January 2023, 35 patients (56 eyes) with DON who received AZ area decompression in Peking University Third Hospital were included retrospectively, including 9 males (13 eyes) and 26 females (43 eyes), aging (52.2±12.0) years. Among them, 35 eyes underwent two-wall (medial and inferior) orbital decompression using an endonasal endoscopic approach, while 21 eyes received three-wall (medial, lateral, and inferior) orbital decompression through a combined approach. Key parameters such as best corrected visual acuity (BCVA), visual field (MD value), eyeball prominence, intraocular pressure, and complications were recorded. Postoperative data were collected one month after surgery. The statistical analysis was performed using paired t-test and Spearman correlation analysis. Results:Significant outcomes were observed post surgery in BCVA, visual field, intraocular pressure and proptosis ( t value was 8.37, 6.17, 4.50, and 9.20, respectively, all P<0.001). The reduction in proptosis was statistically significant between the 2-wall and 3-wall orbital decompression groups ( t=-2.82, P=0.007). Changes in BCVA, visual field, and intraocular pressure before and after surgery was greater in the 3-wall orbital decompression group compared to 2-wall orbital decompression group, although the difference was not statistically significant (all P>0.05). Change in postoperative visual acuity and visual field was significantly positively correlated with preoperative visual acuity and preoperative visual field (all P<0.001). Similarly, change in intraocular pressure and proptosis was positively correlated with preoperative intraocular pressure and preoperative protrusion (all P<0.001). Preoperative diplopia was reported in seven patients (20.0%), and two new cases (5.7%) were noted post-operation, which resolved within 3 months after surgery. Conclusions:Endoscopic endonasal decompression of the AZ area is a safe and effective surgical treatment for DON, with notable improvements in BCVA. Furthermore, three-orbital wall decompression seems to yield better outcomes in terms of eye retraction.

This study aimed to uncover underlying mechanisms and promising intervention targets of heart failure (HF)-related stroke. HF-related dataset GSE42955 and stroke-related dataset GSE58294 were obtained from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was conducted to identify key modules and hub genes. Gene Ontology (GO) and pathway enrichment analyses were performed on genes in the key modules. Genes in HF-and stroke-related key modules were intersected to obtain common genes for HF-related stroke, which were further intersected with hub genes of stroke-related key modules to obtain key genes in HF-related stroke. Key genes were functionally annotated through GO in the Reactome and Cytoscape databases. Finally, key genes were validated in these two datasets and other datasets. HF-and stroke-related datasets each identified two key modules. Functional enrichment analysis indicated that protein ubiquitination, Wnt signaling, and exosomes were involved in both HF-and stroke-related key modules. Additionally, ten hub genes were identified in stroke-related key modules and 155 genes were identified as common genes in HF-related stroke. OTU deubiquitinase with linear linkage specificity (OTULIN) and nuclear factor interleukin 3-regulated (NFIL3) were determined to be the key genes in HF-related stroke. Through functional annotation, OTULIN was involved in protein ubiquitination and Wnt signaling, and NFIL3 was involved in DNA binding and transcription. Importantly, OTULIN and NFIL3 were also validated to be differentially expressed in all HF and stroke groups. Protein ubiquitination, Wnt signaling, and exosomes were involved in HF-related stroke. OTULIN and NFIL3 may play a key role in HF-related stroke through regulating these processes, and thus serve as promising intervention targets.