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 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 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.

Objective:To explore the clinical manifestations and imaging features of nocardia infection (NI) after lung transplantation and boost the diagnosis and treatment of NI.Methods:From January 2018 to December 2019, basic profiles, clinical manifestations, laboratory examinations, imaging features and treatment outcomes of 5 lung transplant recipients with a diagnosis of NF were retrospectively analyzed and summarized with the relevant literatures. There were 4 males and 1 female with a median age of 66(26-69) years. 3 patients were single-lung transplantation, 2 patients were bilateral-lung transplantation. The median time from an initial diagnosis of NI to lung transplant surgery was 6(5-19) months. Common symptoms included fever, cough with yellow phlegm and shortness of breath. Laboratory findings showed lymphopenia, significantly high C-reactive protein levels, a slight elevation of procalcitonin, hypoproteinemia and anemia. The major manifestations of high-resolution computed tomography (CT) included multiple nodules, consolidation, cavitation and pleural effusion.Results:Five strains of N. farcinica were identified from bloodstream infection ( n=2) and pulmonary infection ( n=3). After with a combined therapy of two sensitive agents, all patients improved and were discharged from hospital. During follow-ups, one patient died and the remainders were cured. Conclusions:Nocardia infection occurs in lung transplant recipients mostly within 1 year post-operation. There are non-specific symptoms and imaging features of multiple nodules and consolidation. Combination therapy of sensitive agents is indicated for lung transplant recipients with NI.

Objective:To explore the incidence, clinical characteristics and prognosis of invasive pulmonary fungal infection(IPFI)in recipients of lung transplantation(LT)in southern China.Methods:From January 2003 to August 2019, retrospective analysis was performed for 300 recipients of lung transplantation at three hospitals in southern China. There were 254 males and 46 females with an average age of (54.98±14.2)years. Clinical data were collected from medical records, including symptoms and signs, imaging studies, bronchoscopy examination, pathogen separation and culture from deep sputum and bronchoalveolar lavage fluid(BALF), fungal-related laboratory tests and tissue pathology.Results:Among 300 cases, 93(31.0%)had at least one episode of IPFI. The most common pathogen was aspergillosis(60.2%), followed by candida(15 cases, 16.1%)and Pneumocystis jeroveci (13 cases, 14.0%). Kaplan Meier analysis indicated that all-cause mortality was significantly higher in IPFI group than that in non-IPFI(nIPFI)group with one-year mortality of 45.2% vs. 26.7% in IPFI and nIPFI groups respectively( P<0.05). Conclusions:IPFI is prevalent after LT in southern China. And aspergillosis is the most common pathogen and Candida comes the next. The median occurring time for aspergillosis is 6 months after LT. Candida infection occurs earlier at airway anastomosis. A higher incidence of invasive fungal disease(IFD)associated with a lower survival indicates that IPFI has a substantial mortality among recipients after LT. Prophylactic agents should be optimized based upon an epidemiologically likely pathogen.

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.