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 explore the clinical features of the patients with prolactinoma and changes of pituitary function before and after surgery.Methods The clinical data of 72 patients with prolactinoma admit-ted and operatively treated in the neurosurgery department of the Second Hospital of Lanzhou University from June 2018 to January 2023 were analyzed retrospectively and their clinical characteristics and change character-istics of pituitary function before and after surgery were summarized.Results (1) Most of the patients with prolactinoma included in this study were macroadenomas,and its clinical manifestations were mainly tumor compression symptoms such as headache and vision diminution;(2) there was a statistically significant differ-ence in tumor invasiveness between the patients with preoperative PRL≥200.000 ng/mL and those with pre-operative PRL<200.000 ng/mL (P<0.05).(3) The PRL level of prolactinoma after surgical treatment in the patients with prolactinoma was significantly decreased compared to preoperative level,and the difference was statistically significant (P<0.05).(4) Among 72 patients,44 patients already had hypopituitarism before surgery,the pituitary function in 2 cases returned to normal,15 cases of hypopituitarism were newly increased and there were 57 cases of postoperative hypopituitarism.Preoperative hypopituitarism was positively correla-ted with postoperative hypopituitarism (r=0.433,P<0.05).By the logistic multifactorial regression analy-sis,the tumor maximal diameter was a risk factor for hypopituitarism occurrence before and after surgery (P<0.05),and the tumor invasiveness was a risk factor for postoperative hypopituitarism (P<0.05),where-as the BMI and PRL level,age,gender,and whether or not pituitary apoplexy occurring had no relationship with hypopituitarism (P>0.05).(5) The gonadal axis was the most common hypofunction in uniaxial sys-tem,and gonadal+thyroid axis was the most common biaxial involvement.Conclusion The surgical treat-ment in the patients with prolactinoma is effective for relieving tumor mass occupation and improving hyperp-rolactinemia.The pituitary function should be fully evaluated before and after surgery.For the patients with hypopituitarism occurrence,the hormone replacement therapy should be given in time,and at the same time the hormonal changes should be closely monitored.

Objective To explore the clinical values of voxel-based morphometry(VBM)analysis in magnetic resonance imaging(MRI)for detecting secondary damage to the distant thalamus and substantia nigra in patients with cerebral infarction.Methods A total of nineteen patients with first-time unilateral middle cerebral artery(MCA)ischemic stroke were prospectively recruited.Three-dimensional whole-brain MRI scans were performed at 1 week,1 month,and 3 months after onset.VBM analysis was used to analyze changes in the thalamus and substantia nigra volumes.Results VBM analysis revealed that compared to ipsilateral thalamic volume at 1 week after onset,ipsilateral thalamic volume was significantly reduced at 1 month or 3 months after onset(reduced by 637 mm3 and 1488 mm3,respectively;P<0.01),with the atrophy primarily located in the dorsomedial nucleus of the thalamus.Similarly,compared to ipsilateral substantia nigra volume at 1 week after onset,the ipsilateral substantia nigra volume was significantly reduced at 1 month or 3 months after onset(reduced by 64 mm3 and 76 mm3,respectively;P<0.05).Conclusions VBM technology can be used to evaluate the ipsilateral thalamic and substantia nigra volume reduction in patients with cerebral infarction in the MCA supply area at 1-3 months after stroke,and to detect secondary damage.

Objective To construct a regulatory network of competing endogenous RNA(ceRNA)with prognostic value for bladder urothelial carcinoma(BLCA),and analyze the relationship between key messenger RNA(mRNA)and immune function.Methods The UCSC Xena database was used to download mRNA expression data from 404 BLCA patients and 28 normal individuals and key mRNAs were screened by differential analysis.ENCORI database was utilized to search microRNAs(miRNAs)that bind to key mRNAs and all long non-coding RNAs(LncRNAs)that bind to miRNAs.The expression data of miRNA and LncRNA were downloaded from TCGA database,co-expression analysis was performed to identify key mRNA with all miRNAs and miRNA with all LncRNAs,and thus key miRNAs and LncRNAs were screened out.Survival analysis was conducted based on the differences in expression levels of these key mRNAs,miRNAs,and LncRNAs between tumor patients and normal individuals,and finally a ceRNA regulatory network was constructed.The correlation between key mRNAs and immune cells,immune checkpoints(CD274,PDCD1 and CTLA4),and immune cell marker genes(IG)was analyzed using the TIMER 2.0 database.Results A total of 22 key mRNAs were screened,with the most significant difference being proline 3-hydroxylase 4(P3H4).The expression of P3H4 in patients with BLCA was high,and survival time was shorter in patients with high expression.A sum of 33 miRNAs and 14 LncRNAs were screened using the key mRNAs as the central link.Through co-expression analysis and survival analysis,hsa-miR-151a-3p and MIR100 HG were identified as the key miRNA and key LncRNA with prognostic value.The differences in the above analysis results were statistically significant(all P＜0.05).Based on these findings,a ceRNA regulatory network consisting of 1 mRNA,1 miRNA,and 1 LncRNA was constructed.Immunoassay firstly revealed a significant positive correlation between double positive T cells and P3H4 expression in the tumor microenvironment of BLCA.Moreover,there were 3 types of immune cells(tumor-associated neutrophils,and tumor-associated macrophages,dendritic cells),3 immune checkpoints(CD274,PDCD1,CTLA4),and 15 IGs with significant correlation with P3H4.These differences were statistically significant(all P＜0.01).Conclusion This study could help to reveal the progression mechanism of BLCA.The constructed ceRNA network and immune analysis can offer new insights into potential biological targets and immunotherapy directions for the diagnosis,treatment,and prediction of BLCA patients.

Objective:To investigate the work stress and its influencing factors among hospice care physicians and nurses in medical institutions in Shanghai.Methods:It was a cross-sectional study. The study was carried out between December 2021 and January 2022. By use of multistage random sampling, 256 hospice care physicians and nurses were selected from community healthcare centers, secondary and tertiary hospitals in Shanghai to attend a WeChat-based survey using a self-designed questionnaire. The chi-square test was used to compare the differences in prevalence of work stress and stressors among all subjects with different characteristics. Binary logistic regression analysis was used to explore the major determinants associated with work stress. And the sources of work stress and the expepectd decompression countermeasures were investigated.Results:A total of 256 valid questionnaires were collected with a recovery rate of 100.0%. The median of work stress score was 7.5 (6.0, 9.0). Logistic regression analysis showed that those aged>40 years old and working for ≥5 years in hospice care service had higher level of work stress ( OR=3.78, 2.04; P=0.007, 0.039), and those with monthly income>10 000 RMB Yuan had lower level of work stress ( OR=0.34, P=0.005). The top three stressors were the death of patients (88.3%, 226/256), low income (78.1%, 200/256), difficulty in promotion (67.2%, 172/256). The top three way that doctors and nurses desired to reduce work stress were to increase income (88.3%, 226/256) and optimize performance appraisal target (78.1%, 200/256) and promotion mechanism (66.0%, 169/256). Conclusions:In general, the work stress among hospice care physicians and nurses is at a high level in Shanghai and the stressors are widely distributed. Age, monthly salary and years of working in hospice care unit are independent factors of work stress. Improving salary, optimizing performance appraisal target and promotion mechanism are the most desired strategies to reduce work stress among hospice care physicians and nurses.

Objective:To survey the status quo of hospice care service in community health service centers in Shanghai.Methods:A questionnaire survey was conducted to investigate the situation of hospice care services from January 2021 to December 2021 in 16 community health service centers selected by stratified sampling from 16 districts in Shanghai.Results:Among 16 community health service centers, 13 provided inpatient hospice care services, 16 provide home hospice care and 14 provided outpatient hospice care services; and totally 1 935 (77.93%), 158 (6.36%) and 390 (15.71%) patients received palliative care, respectively. In centers providing inpatient hospice care service, the average bed number was 12 (10, 20); the annual number of patients was 58 (29, 137); the average length of hospital stay was (29.55±11.18) days; and the bed occupancy rate was (55.51±30.02)%, which in urban districts was significantly higher than that in rural districts ((74.76±19.33)% vs.(39.00±28.32)%; t=2.61, P=0.024). The number of patients receiving home hospice care in each center was 10 (3, 19) and the average duration of home service was (66.97±29.41) days. The proportion of physician fee of inpatient hospice care and that of home hospice care were (8.61±5.27)% and (6.25±3.11)%, respectively. While the proportion of medication expenses of inpatient hospice care and that of home hospice care were (35.60±16.13)% and(49.58±9.16)%, respectively. The outpatient hospice service were opened 2.0 (1.0, 4.0) days a week in 14 centers and 95 (58, 199) patients received services. Inpatient services were mainly provided for the patients with non-malignant chronic diseases (53.23%, 1 030/1 935), while home hospice care (89.87%, 142/158) and outpatient hospice care (83.85%, 327/390) mainly provided service for malignant patients. Conclusion:There is still room for improvement about the hospice care services delivered by community health service centers in Shanghai:discrepancy of utilization of hospice care services between urban districts and rural districts, low utilization of home and outpatient hospice care services, unreasonable cost composition in inpatient and home hospice care services.

BACKGROUND: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex. METHODS: The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases. RESULTS: WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group. CONCLUSIONS This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
Animals ; Mice ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Liver Neoplasms/genetics*

Objective:To investigate the status quo of pain management for cancer patients in hospice care wards of community health service centers.Methods:The electronic medical records of 373 cancer patients admitted in hospice wards of Kangjian Community Health Center of Xuhui District and Jinshanwei Town Community Health Center of Jinshan District from January 2015 to July 2021 were collected. The characteristics of cancer pain, the use of analgesic drugs, the effects of analgesic drugs and its influencing factors were analyzed.Results:The incidence of cancer pain in 373 patients was 93.0% (347/373), and the proportion of moderate to severe cancer pain was 55.6% (193/347). Analgesics were used in 304 patients, among whom 233 (76.6%) patients used oral analgesics, 297 (97.7%) used on time, 97.6%(285/292) used sustained-release opioids, and 94 (30.9%) used combinedly. Breakout pain occurred in 100 cases (32.9%), all of which was controlled with immediate-release morphine. Cancer pain was not relieved in 132 cases (43.42%), and multivariate logistic regression analysis showed that the pain degree on admission (moderate: OR=3.69, 95 %CI:2.09-6.49; severe: OR=5.52, 95 %CI:2.43-12.53), the presence of burst pain ( OR=3.28, 95 %CI:1.77-6.06), the type of analgesics used (non-steroidal+weak opioids: OR=0.39, 95 %CI:0.20-0.76; nonsteroidal+strong opioids: OR=0.20, 95 %CI:0.08-0.51) and the adverse reactions ( OR=1.92, 95 %CI:1.03-3.60) were the influencing factors of pain relief in cancer pain patients (all P<0.05). Conclusion:The pain of cancer patients admitted to community palliative care wards cannot be ignored. Although most cancer pain patients use analgesic drugs in a standard way, there are still a high proportion of patients whose pain is not controlled. Various factors affect the effect of analgesic treatment.

Acute cellular rejection (ACR) is a common complication after lung transplantation, which is mainly caused by the immune response of T lymphocytes recognizing the major histocompatibility complex on the cellular surface of grafts. It is currently considered as the main pattern of acute rejection. ACR is not only a direct cause of death of recipients, but also a high-risk factor for chronic rejection after lung transplantation. Nevertheless, it is a challenging task to deliver the diagnosis and treatment of ACR following lung transplantation. In this article, new progresses on the risk factors, pathogenesis, diagnosis and treatment of ACR in lung transplant recipients were summarized, aiming to improve the diagnostic and treatment efficiency of ACR and prolong the survival of recipients.

Objective To analyze the risk factors and clinical prognosis of acute kidney injury (AKI) early after lung transplantation. Methods Clinical data of 155 recipients undergoing lung transplantation or combined heart-lung transplantation were retrospectively analyzed, and they were divided into the AKI group (n=104) and non-AKI group (n=51) according to the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline. The incidence of AKI early after lung transplantation was summarized. The main indexes of recipients were collected. The risk factors of the occurrence of AKI early after lung transplantation were subjected to univariate and multivariate analysis. The clinical prognosis of lung transplant recipients was evaluated and the survival curve was delineated. Results The incidence of AKI early after lung transplantation was 67.1%(104/155), including 47 recipients with stage 1 AKI, 34 recipients with stage2 AKI and 23 recipients with stage 3 AKI, respectively. Sixteen recipients required continuous renal replacement therapy (CRRT) early after lung transplantation. Preoperative complication with diabetes mellitus, preoperative complication with pulmonary hypertension, intraoperative mean arterial pressure (MAP) < 60 mmHg, intraoperative massive blood transfusion, and treatment with excessive therapeutic concentration of tacrolimus (Tac) within postoperative 1 week were the independent risk factors for the occurrence of AKI early after lung transplantation. Up to the end of follow-up, 66 recipients (42.6%) died, including 50 recipients in the AKI group and 16 recipients in the non-AKI group. The cumulative survival rate in the AKI group was significantly lower than that in the non-AKI group (40% vs. 66%, P < 0.05). With the increase of AKI severity, the cumulative survival rate of lung transplant recipients was decreased. Conclusions AKI develops early after lung transplantation with high incidence and poor clinical prognosis. Preoperative complication with diabetes mellitus and pulmonary hypertension, intraoperative MAP < 60 mmHg and massive blood transfusion, and treatment with excessive therapeutic concentration of Tac within postoperative 1 week are the independent risk factors for the occurrence of AKI early after lung transplantation.