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: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.

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: 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

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.

Objective We aimed to investigate whether sex hormone levels including total testosterone, estradiol, estradiol/total testosterone, and dehydroepiandrosterone ( DHEA ) were associated with macrovascular complications among Shanghai community-dwelling diabetic men. Methods Relying on the Environmental Pollutant Exposure and Metabolic Diseases in Shanghai (METAL) study (ChiCTR1800017573, www.chictr.org.cn), 2147 male diabetic participants were recruited from 10 communities. Carotid plaques and common carotid artery ( CCA) diameters were detected by carotid ultrasound. Cardiovascular disease ( CVD) was defined as a self-reported diagnosis of CVD, including coronary heart disease, myocardial infarction, or stroke. Results ( 1) The prevalence of CVD in this study was 36. 0％, and patients with CVD had higher rates of hypertension and dyslipidemia than those without CVD. ( 2) After controlling for multiple factors, serum DHEA levels were negatively correlated with the prevalence of CVD while estradiol levels were positively correlated with both the prevalences of CVD and carotid plaque, estradiol/total testosterone ratio was also positively correlated with the prevalence of CVD. ( 3) In subgroup with unilateral/bilateral CCA plaque, and after controlling for multiple factors, total serum testosterone was negatively associated with the mean CCA diameter. Conclusion The incidence of macrovascular complications was lower in male diabetic patients with higher serum total testosterone and DHEA levels and lower estradiol levels, suggesting that sex hormone levels may be a window for the diagnosis and treatment of diabetic macrovascular complications.

Objective: To investigate the effects of basic fibroblast growth factor (bFGF) on healing of Mycobacterium tuberculosis infective wound in New Zealand rabbit after debridement. Methods: Thirty-two New Zealand rabbits (3 to 4 months old, no matter male or female) were intradermally injected with 0.1 mL of complete Freund′s adjuvant on the buttocks. Six weeks later, each rabbit was injected with 0.5 mL 5×10⁷ colony forming unit/mL Bacillus Calmette-Guerin on both sides of the back to reproduce the model of Mycobacterium tuberculosis infective wound in New Zealand rabbit. After successful modeling, the 32 rabbits were divided into growth factor (GF) group, antituberculosis drug (AD) group, combined treatment (CT) group, and blank control (BC) group according to the random number table, with 8 rabbits in each group. After a complete debridement, the wounds of rabbits in group GF were treated with recombinant bovine bFGF gel (300 IU/cm^2, about 0.45 g for each wound), the wounds of rabbits in group AD were covered with gauze which was impregnated with 6 mL isoniazid injection and 0.15 g rifampicin powder-injection, the wounds of rabbits in group CT were covered with gauze which was impregnated with isoniazid injection and rifampicin powder-injection after being treated with recombinant bovine bFGF gel as before, the wounds of rabbits in group BC were covered with sterile gauze, with dressing change of once every two days until the wounds were completely healed. Immediately after surgery and on post surgery day (PSD) 7, 14, 21, and 28, the wounds of rabbits in each group were observed with naked eyes and photos. On PSD 7, 14, 21, and 28, the wound healing rate was calculated and the complete healing time of wound was recorded. On PSD 7, 14, 21, and 28, the tissue samples of wound edge were collected for histomorphological observation with hematoxylin and eosin staining and Masson staining. On PSD 21, the number of microvessels was counted with immunohistochemical method. On PSD 7, 14, 21, and 28, the content of hydroxyproline in wound edge was determined by enzyme-linked immunosorbent assay. The numbers of samples of above-mentioned experiments were all 8. Data were processed with analysis of variance for repeated measurement, analysis of variance of factorial design, one-way analysis of variance, least significant difference test and Bonferroni correction. Results: (1) The rabbits in four groups all survived to the end of experiment. Immediately after surgery, edema was observed in basal wounds of rabbits in the four groups. On PSD 7, the wounds of rabbits in the 4 groups were contracted with scabs and less edema. The wounds of rabbits in groups GF and CT became redder. On PSD 14, the wounds of rabbits in the 4 groups contracted obviously. There were no obvious exudates in wounds of rabbits in groups AD and CT, while 1 wound of rabbit in group GF and 2 wounds of rabbits in group BC became red and swelling with purulent exudates. On PSD 21, wounds of rabbits in groups GF and CT were basically healed, while 2 wounds of rabbits in group BC healed slowly with purulent secretion. On PSD 28, wounds of rabbits in the 4 groups were basically healed, while 2 wounds of rabbits in group BC hardly healed with redness and swelling. (2) From PSD 7 to 28, the wound healing rates of rabbits in groups GF, AD, and CT were significantly higher than those in group BC (P<0.05). On PSD 14 and 21, the wound healing rates of rabbits in groups GF and CT were significantly higher than those in group AD (P<0.05). From PSD 7 to 28, the wound healing rates of rabbits in group GF were close to those in group CT (P>0.05). (3) The complete healing time of wounds of rabbits in groups GF, AD, and CT was significantly shorter than that in group BC (P<0.05). The complete healing time of wounds of rabbits in groups GF and CT was significantly shorter than that in group AD (P<0.05). The complete healing time of wounds of rabbits in group GF was close to that in group CT (P>0.05). (4) On PSD 7, a large number of inflammatory cells infiltration were observed in wound tissue of rabbits in the 4 groups and a few epithelial cells were observed in wound tissue of rabbits in groups GF, AD, and CT. On PSD 14, more epithelial cells were observed in wound tissue of rabbits in groups GF and CT, and an obvious reduction of inflammatory cells infiltration was observed in wound tissue of rabbits in groups AD and CT. On PSD 21, there was a complete wound tissue structure and distinctive nuance of dyeing in wound tissue of rabbits in groups GF and CT while thinner new epithelium in wound tissue of rabbits in groups AD and BC, and inflammatory cell infiltration was observed in wound tissue of rabbits in group BC. On PSD 28, there was a complete wound tissue structure in wound tissue of rabbits in the 4 groups, the new epithelium in wound tissue of rabbits in groups GF, AD, and CT was thicker than that in group BC. (5) On PSD 7 and 14, the quantity of collagen fibers in wound tissue of rabbits in groups GF and CT was larger than that in the other two groups. On PSD 21, a large quantity of fibroblasts and well reorganized collagen fibers were observed in wound tissue of rabbits in groups GF and CT, a moderate quantity of fibroblasts and collagen fibers in a random arrangement were observed in wound tissue of rabbits in group AD, and a little quantity of fibroblasts and collagen fibers were observed in wound tissue of rabbits in group BC. On PSD 28, the quantity of collagen fibers in wound tissue of rabbits in the 4 groups was close to that of normal skin tissue, and the collagen fibers performed more well reorganized in wound tissue of rabbits in groups GF and CT. (6) On PSD 21, the numbers of microvessels per 200-time visual field in wound edge of rabbits in groups GF (31.6±1.2), AD (27.5±1.3), and CT (32.8±1.6) were significantly higher than the number in group BC (22.3±1.7, P<0.05). The numbers of microvessels in wound edge of rabbits in groups GF and CT were significantly higher than the number in group AD (P<0.05). The number of microvessels in wound edge of rabbits in group GF was close to that in group CT (P>0.05). (7) On PSD 7 and 28, there were no statistically significant differences in content of hydroxyproline in wound edge of rabbits in the 4 groups (F=0.916, 1.752, P>0.05). On PSD 14 and 21, the content of hydroxyproline in wound edge of rabbits in groups GF, AD, and CT was significantly higher than that in group BC (P<0.05). The content of hydroxyproline in the wound edge of rabbits in groups GF and CT was significantly higher than that in group AD (P<0.05). The content of hydroxyproline in the wound edge of rabbits in group GF was close to that in group CT (P>0.05). Conclusions bFGF can be used solely or combined with AD to promote Mycobacterium tuberculosis infective wound healing in New Zealand rabbit after complete debridement of wound, which is better than single use of AD.

Objective To construct a Luciferace reporter vector containing the 3'untranslated region (3'UTR) of NFAT5 and measure the correlation between NFAT5 and miR-155.Methods The miR-155 targeting NFAT5 3'UTR was predicted by Target Scan,Mir Base and Pic Tar.NFAT5 and mutant NFAT5 sequence(NFAT5-mu) were then designed and synthesized,and they were cloned into pMIR-REPORTTM Luciferace reporter vector.Human embryonic kidney-293AD (HEK-293AD) cells of the 4th passage were divided into 4 groups according to the random number table.cells in plasimd +miR-155 mimics groups were transfected with pMIR-NFAT5 recombinant plasimid,pRL-Tk plasmid and miR-155 mimics;cells in plasimd + miR-155 mutated groups were transfected with pMIR-NFAT5-mu recombinant plasimid,pRL-Tk plasmid and miR-155 mimics;cells in plasimd + miR-155 control groups were transfected with pMIR-NFAT5 recombinant plasimid,pRL-Tk plasmid and miR-155 Negative control;cells in plasimd +miR-155 inhibitor were transfected with pMIR-NFAT5 recombinant plasimid,pRL-Tk plasmid and miR-155 inhibitor;and were respectively transfected into together by liposome.After culture for 24 h,the luciferase activity was detected by dual luciferase reporter assay system.Results TargetScan,Miranda and PicTar shared the results that NFAT5 has the complementary binding sites with 3'UTR of miR-155.And luciferase reporter vectorwas constructed.Therefore the result of sequencing and double digesting of recombined plasmid were completely correct.Dual-luciferase reporter assay showed that miR-155 possesses a target effect on 3'UTR of NFAT5.Compared to the pMIR-NFAT5 + miR-control group,the luciferase activity of the pMIR-NFAT5 + miR-1 5 5 mimics group was decreased,with statistically significant difference(P＜0.01),while there was no significant difference at other time points(P＞0.05).Conclusion The pMIR-NFAT5 recombinant plasmid and pMIR-NFAT5 recombinant mutated plasmid were confirmed with successful construction.and it was found that miR-155 can target NFAT5 mRNA 3'-UTR.The results provide the experiment data for further disclosing the mechanism of inhalation injury on the level of gene expression.