Recent developments in ureteral stent: Substrate material, coating polymer and technology, therapeutic function.

The ureteral stent is an effective treatment for clinical ureteral stricture following urological surgery, and the functional coating of the stent could effectively inhibit bacterial colonization and other complications. The present review provides an analysis and description of the materials used in ureteral stents and their coatings. Emphasis is placed on the technological advancements of functional coatings, taking into consideration the characteristics of these materials and the properties of their active substances. Furthermore, recent advances in enhancing the therapeutic efficacy of functional coatings are also reviewed. It is anticipated that this article will serve as a valuable reference providing insights for future research development on new drug-loaded ureteral stents.

Correlation Analysis of the Therapy Adherence to Long-Acting Inhalers Among Patients with Stable COPD.

Purpose: Long-acting inhalers are the mainstay maintenance therapy for stable chronic obstructive pulmonary disease (COPD) management. The aim of this study was to assess adherence to inhalers among adults with COPD in China and to develop strategies to improve adherence for the next step. Patients and Methods: A cross-sectional study was conducted among 246 adult patients with COPD using long-acting inhalers to explore different demographic characteristics, disease characteristics and medication regimens. Adherence to inhalers was assessed using the Medication Adherence Report Scale (MARS). Results: Among the 246 patients included in the present study, 93 (37.80%) had good adherence, while 153 (62.20%) had poor adherence. From the comparison of patients with good and poor adherence, we found that the course of disease and education background had a significant effect on adherence (p < 0.05). Among the LAMA therapy group, inhaled tiotropium bromide spray (Ingelheim am Rhein, Germany) with active release technology had better adherence than inhaled tiotropium bromide powder (Ingelheim am Rhein, Germany) (p < 0.05). Moreover, COPD patients with good adherence had better pulmonary function and fewer moderate or severe exacerbations in the past year (p < 0.05). Conclusion: The factors affecting the use of inhalers in patients with stable COPD are complicated. Medical staff should select appropriate inhalers according to the patient's disease status and duration and provide medication education to improve adherence.

Integrative analysis of m3C associated genes reveals METTL2A as a potential oncogene in breast Cancer.

RNA methylation modifications, especially m6A mRNA modification, are known to be extensively involved in tumor development. However, the relationship between N3-methylcytidine (m3C) related genes and tumorigenesis has rarely been studied. In this research, we found that m3C-related genes were expressed at different levels and affected patients' prognosis across multiple cancer types from The Cancer Genome Atlas and multi-omics levels. Importantly, methyltransferase-like proteins 2A (METTL2A) had a high amplification frequency (~ 7%) in patients with breast invasive carcinoma (BRCA), and its overexpression was an independent predictor of poor overall survival. Enrichment analysis of associated genes revealed that METTL2A may activate DNA synthesis and cell proliferation pathways in BRCA cells. Through drug sensitivity analysis, Trifluridine, PD407824, and Taselisib were shown to be effective drugs for METTL2A-positive BRCA patients. Overall, our research conducts a holistic view of the expression level and prognostic signature of m3C-related genes with multiple malignancies. Importantly, METTL2A has been intensely explored as a potential oncogene in BRCA, to aid the development of potential drug agents for precision therapy in breast cancer patients.

LINC00152 induced by TGF-ß promotes metastasis via HuR in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the main causes of cancer-related mortality, with a strong tendency to metastasize early. Transforming growth factor-ß (TGF-ß) signaling is a powerful regulator to promote metastasis of LUAD. Here, we screened long non-coding RNAs (lncRNAs) responsive to TGF-ß and highly expressed in LUAD cells, and finally obtained our master molecular LINC00152. We proved that the TGF-ß promoted transcription of LINC00152 through the classical TGF-ß/SMAD3 signaling pathway and maintained its stability through the RNA-binding protein HuR. Moreover, LINC00152 increased ZEB1, SNAI1 and SNAI2 expression via increasing the interactions of HuR and these transcription factors, ultimately promoting epithelial-mesenchymal transition of LUAD cell and enhancing LUAD metastasis in vivo. These data provided evidence that LINC00152 induced by TGF-ß promotes metastasis depending HuR in lung adenocarcinoma. Designing targeting LINC00152 and HuR inhibitors may therefore be an effective therapeutic strategy for LUAD treatment.

Comprehensive Analysis of Ferroptosis- and Immune-Related Signatures to Improve the Prognosis and Diagnosis of Kidney Renal Clear Cell Carcinoma.

Background: Almost 40% of patients with kidney renal clear cell carcinoma (KIRC) with advanced cancers eventually develop to metastases, and their 5-year survival rates are approximately 10%. Aberrant DNA methylations are significantly associated with the development of KIRC. The aim of our present study was to identify suitable ferroptosis- and immune-related (FI) biomarkers correlated with aberrant methylations to improve the prognosis and diagnosis of KIRC. Methods: ChAMP and DESeq2 in R (3.6.2) were used to screen the differentially expressed methylation probes and differentially expressed genes, respectively. Univariate and multivariate Cox regression were used to identify the overall survival (OS)-related biomarkers. Results: We finally identified five FI biomarkers (CCR4, CMTM3, IFITM1, MX2, and NR3C2) that were independently correlated with the OS of KIRC. The area under the curve value of the receiver operating characteristic value of prognosis model was 0.74, 0.68, and 0.72 in the training, validation, and entire cohorts, respectively. The sensitivity and specificity of the diagnosis model were 0.8698 and 0.9722, respectively. In addition, the prognosis model was also significantly correlated with several immune cells and factors. Conclusion: Our present study suggested that these five FI-DEGs (CCR4, CMTM3, IFITM1, MX2, and NR3C2) could be used as prognosis and diagnosis biomarkers for patients with KIRC, but further cross-validation clinical studies are still needed to confirm them.

MiR-129-5p/TRIP13 affects malignant phenotypes of colorectal cancer cells.

OBJECTIVE: Aberrant miR-129-5p expression is a key modulator of cancer development. But how the miRNA affects colorectal cancer (CRC) remains unclear. This study was designed to illustrate the underlying mechanism of miR-129-5p in CRC. METHODS: MiR-129-5p expression at cellular level was assayed by qRT-PCR. Its role in CRC cell phenotypes was studied by cell function experiments. The binding relationship between miR-129-5p and TRIP13 was analyzed and verified by target changed to bioinformatics prediction and dual-luciferase detection. Furthermore, the functional mechanism based on miR-129-5p and TRIP13 in CRC was studied through rescue experiments. RESULTS: CRC cell lines presented prominently lower miR-129-5p levels than the normal colon epithelial cell line. The forced miR-129-5p level suppressed CRC cell growth. TRIP13 was proved to be a target of miR-129-5p in CRC cells, and miR-129-5p overexpression reduced TRIP13 expression. TRIP13 knockdown resulted in cell cycle arrest. Additionally, TRIP13 overexpression restored the impacts of miR-129-5p overexpression on cell malignant phenotypes and cell cycle. CONCLUSION: MiR-129-5p down-regulated TRIP13 expression, thereby restraining the malignant progression of CRC cells. The findings may offer a new target for molecular therapy of CRC.

Comprehensive analysis of PTEN-related ceRNA network revealing the key pathways WDFY3-AS2 - miR-21-5p/miR-221-3p/miR-222-3p - TIMP3 as potential biomarker in tumorigenesis and prognosis of kidney renal clear cell carcinoma.

Kidney renal clear cell carcinoma (KIRC) is one of the most common malignancies, and there is still a lack of effective biomarkers for early detection and prognostic prediction. In here, we compared the characteristics of RNA sequencing data sets of KIRC samples based on the tumor suppressor gene phosphatase and tensin homolog (PTEN). The 1016 long noncoding RNAs, 48 microRNAs (miRNAs), and 2104 messenger RNAs associated with PTEN were identified and these genes were differentially expressed between tumor and paracancerous tissues. The most relevant pathway was found to be WDFY3-AS2 - miR-21-5p/miR-221-3p/miR-222-3p - TIMP3 according to the rules of competing endogenous RNA (ceRNA) regulation. WDFY3-AS2 and TIMP3 expression were positively correlated and reduced in KIRC samples, while miR-21-5p, miR-221-3p, and miR-222-3p were relatively highly expressed. The relatively low expression of WDFY3-AS2 and TIMP3 in KIRC were associated with poor prognosis in KIRC patients, while higher expression of miR-21-5p, miR-221-3p, and miR-222-3p predicted reduced survival (p < 0.05). Univariate and multivariate Cox regression analysis showed that lower expression of WDFY3-AS2 and TIMP3 was significantly related to tumor grade, tumor size, lymph node metastasis, distant metastasis, and TNM stage. The expression of TIMP3 in KIRC tissues was also verified by immunohistochemistry, and the results were consistent with our analytical data. In summary, this study constructed a new model with clinical predictive value and identified the WDFY3-AS2/TIMP3 pathway that was closely associated with the prognosis of KIRC, which could serve as a promising biomarker for the diagnosis and treatment of KIRC.

MicroRNA-let-7 Targets HMGA2 to Regulate the Proliferation, Migration, and Invasion of Colon Cancer Cell HCT116.

OBJECTIVE: To investigate the effect of microRNA-let-7 (miR-let-7) on the proliferation, migration, and invasion of colon cancer cell HCT116 in vitro and its regulatory mechanism on downstream HMGA2. METHODS: It was planned to synthesize miR-let-7 overexpression (mimics) and interference expression (inhibitor) and transiently transfect colon cancer cell HCT116, detect the expression levels of miR-let-7 and HMGA2 in the cells after transfection and the targeted regulation effect of miR-let-7 on HMGA2, then detect the effect of upregulation/downregulation of miR-let-7 on HMGA2, and detect the proliferation, migration, and invasion of HCT116 cells. RESULTS: The expression of miR-let-7 was downregulated, and the expression of HMGA2 was upregulated in HCT116. The expression of miR-let-7 increased significantly after HCT116 was transfected with miR-let-7 mimics. The expression of miR-let-7 decreased significantly after HCT116 was transfected with miR-let-7 inhibitor. The bioinformatics websites predicted that miR-let-7 has a binding site with HMGA2, and the dual-luciferase reporter gene experiment detected that miR-let-7 has a targeting relationship with HMGA2. The expression of HMGA2 decreased after HCT116 was transfected with miR-let-7 mimics; the expression of HMGA2 increased after HCT116 was transfected with miR-let-7 inhibitor. After upregulating miR-let-7, the proliferation, migration, and invasion ability of HCT116 was weakened. After miR-let-7 was inhibited, the proliferation, migration, and invasion ability of HCT116 was enhanced. CONCLUSION: Abnormal expression of miR-let-7 is an important factor affecting the proliferation, migration, and invasion of HCT116 cells, and it can promote or inhibit the biological behavior of cancer cells by targeting the expression of HMGA2. This study provides ideas for the drug development of new gene targets.

[Research on the classification criteria of femoral intertrochanteric fractures based on irreducibility or not].

OBJECTIVE: To formulate the classification criteria of femoral intertrochanteric fractures based on irreducibility or not in order to predict the difficulty of fracture recovery. METHODS: A clinical data of 244 patients with closed femoral intertrochanteric fractures admitted between January 2017 and March 2020 was retrospectively analyzed. There were 116 males and 128 females with an average age of 77.9 years (range, 45-100 years). The cause of injury included falling in 190 cases, traffic accident in 36 cases, smashing in 13 cases, and falling from height in 5 cases. The time from injury to operation was 1-14 days (mean, 3.6 days). According toAO/Orthopaedic Trauma Association (AO/OTA) classification, the fractures were classified as type 31-A1 in 38 cases, type 31-A2 in 160 cases, and type 31-A3 in 46 cases. According to whether the recovery difficulty occurred after intraoperative closed traction reset, the patients were divided into reducible-group and irreducible-group; combined with the literature and preoperative imaging data of two groups, the classification criteria of femoral intertrochanteric fractures was formulated based on the irreducibility or not. The 244 fractures were classified by the doctors who did not attend the operation according to the classification criteria, predicted the difficulty of fracture reduction, and compared with the actual intraoperative reduction situation. RESULTS: The 244 patients were divided into reducible-group ( n=164, 67.21%) and irreducible-group ( n=80, 32.79%) according to the intraoperative difficulty of reduction. Comparing the imaging data and characteristics of the two groups, and formulating the classification criteria of femoral intertrochanteric fractures based on irreducibility or not, the fractures were mainly divided into two categories of irreducibility and reducibility. The fractures of irreducibility category was divided into typesⅠ-Ⅴ, among which type Ⅲ was divided into subtypes 1-4; the fractures of reducibility category was divided into typesⅠand Ⅱ. Compared with the actual intraoperative evaluation results, the total accuracy rate of the doctors who did not attend the operation was 81.15% (198/244) based on the classification criteria of femoral intertrochanteric fractures. The accuracy rate of irreducibility category was 65.74% (71/108), and the reducibility category was 93.38% (127/136). All patients were followed up 13-25 months, with an average of 17.6 months. All fractures healed except 2 cases died of infection. CONCLUSION: The classification criteria of femoral intertrochanteric fractures based on irreducibility or not can accurately predict the reducible cases preoperatively, and most of the irreducible cases can be correctly predicted in a wider way. But the classification criteria still need to be further improved and supplemented.

Systematic Investigation of DNA Methylation Associated With Platinum Chemotherapy Resistance Across 13 Cancer Types.

Background: Platinum resistance poses a significant problem for oncology clinicians. As a result, the role of epigenetics and DNA methylation in platinum-based chemoresistance has gained increasing attention from researchers in recent years. A systematic investigation of aberrant methylation patterns related to platinum resistance across various cancer types is urgently needed. Methods: We analyzed the platinum chemotherapy response-related methylation patterns from different perspectives of 618 patients across 13 cancer types and integrated transcriptional and clinical data. Spearman's test was used to evaluate the correlation between methylation and gene expression. Cox analysis, the Kaplan-Meier method, and log-rank tests were performed to identify potential risk biomarkers based on differentially methylated positions (DMPs) and compare survival based on DMP values. Support vector machines and receiver operating characteristic curves were used to identify the platinum-response predictive DMPs. Results: A total of 3,703 DMPs (p value < 0.001 and absolute delta beta >0.10) were identified, and the DMP numbers of each cancer type varied. A total of 39.83% of DMPs were hypermethylated and 60.17% were hypomethylated in platinum-resistant patients. Among them, 405 DMPs (Benjamini and Hochberg adjusted p value < 0.05) were found to be associated with prognosis in tumor patients treated with platinum-based regimens, and 664 DMPs displayed the potential to predict platinum chemotherapy response. In addition, we defined six DNA DMPs consisting of four gene members (mesothelin, protein kinase cAMP-dependent type II regulatory subunit beta, msh homeobox 1, and par-6 family cell polarity regulator alpha) that may have favorable prognostic and predictive values for platinum chemotherapy. Conclusion: The methylation-transcription axis exists and participates in the complex biological mechanism of platinum resistance in various cancers. Six DMPs and four associated genes may have the potential to serve as promising epigenetic biomarkers for platinum-based chemotherapy and guide clinical selection of optimal treatment.

[Oncolytic adenovirus expressing CCL19 enhances immunity against gastric cancer in mice].

Objective To explore whether oncolytic adenovirus expressing CCL19 can inhibit the growth of gastric cancer cells and activate anti-tumor immune response. Methods Mouse CCL19 gene was inserted into the E3 region of oncolytic adenovirus Ad5 to obtain engineered oncolytic adenovirus Ad5-CCL19. The expression of CCL19 in Ad5-CCL19-infected mouse MFC cells was detected by Western blotting. The effects of Ad5-CCL19 on the proliferation of MFC cells, MGC803 cells and BGC823 cells were tested by MTT assay. The anti-tumor activity of Ad5-CCL19 in vivo was examined by MFC cell subcutaneous transplantation tumor model. Immunofluorescence histochemical staining was used to detect CD4 and CD8 expression in tumor tissue. The secretion levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in tumor infiltrating T cells were detected by flow cytometry. Results Ad5-CCL19 could effectively infect MFC cells to secrete CCL19. Also, Ad5-CCL19 could induce significant dose-dependent cytotoxicity against target cells in vitro. The experiment in vivo showed that Ad5-CCL19 had stronger inhibitory effects on MFC cell tumor than Ad5 in the mice, and it could effectively enhance the infiltration of CD4+ T cells and CD8+ T cells and increase the secretion of IFN-γ and TNF-α in tumor tissues. Conclusion Ad5-CCL19 can significantly infect MFC gastric cancer cells to inhibit their growth and improve the anti-tumor immune activity of the tumor site.

School physician in primary and secondary schools in Yichang of Hubei Province during 2019-2020 / 中国学校卫生

Objective@#To understand school physician in primary and secondary schools in Yichang City, Hubei Province from 2019 to 2020, and to provide a reference for strengthening the school physician team in primary and secondary schools.@*Methods@#149 and 102 primary and secondary schools from 6 municipal districts in Yichang City, Hubei Province, were randomly selected in November 2019 and November 2020, respectively, and were administered by questionnaire survey.@*Results@#The proportion of school physicians increased from 39.6% in 2019 to 65.7% in 2020. In the past two years, the equipment rate of school physician in both central and fringe urban areas increased, especially the fringe urban areas, number of school physician increased from 38 to 96. A total of 93 and 141 school physicians were selected to pariticipate in questionaire survey in 2019 and 2020 respectively. The survey showed that more than 90% of school physicians in primary and secondary schools in Yichang received training, and 74.5% had college education level. However, most of them lack professional qualification and medical background.@*Conclusion@#School physician of primary and secondary of Yichang is well development over the past two years, and the proportion substantially increased. However, there is still room for improvement in the quantity and quality of school physicians, and professional qualification needs to be improved. More attention should be paid to the marginal urban areas to achieve a balance between quantity and quality.

Lymphopenia predicted illness severity and recovery in patients with COVID-19: A single-center, retrospective study.

The outbreak of SARS-CoV-2 began in December 2019 and rapidly became a pandemic. The present study investigated the significance of lymphopenia on disease severity. A total of 115 patients with confirmed COVID-19 from a tertiary hospital in Changsha, China, were enrolled. Clinical, laboratory, treatment and outcome data were gathered and compared between patients with and without lymphopenia. The median age was 42 years (1-75). Fifty-four patients (47.0%) of the 115 patients had lymphopenia on admission. More patients in the lymphopenia group had hypertension (30.8% vs. 10.0%, P = 0.006) and coronary heart disease (3.6% vs. 0%, P = 0.029) than in the nonlymphopenia group, and more patients with leukopenia (48.1% vs 14.8%, P<0.001) and eosinopenia (92.6% vs 54.1%, P<0.001) were observed. Lymphopenia was also correlated with severity grades of pneumonia (P<0.001) and C-reactive protein (CRP) level (P = 0.0014). Lymphopenia was associated with a prolonged duration of hospitalization (17.0 days vs. 14.0 days, P = 0.002). Lymphocyte recovery appeared the earliest, prior to CRP and chest radiographs, in severe cases, which suggests its predictive value for disease improvement. Our results demonstrated the clinical significance of lymphopenia for predicting the severity of and recovery from COVID-19, which emphasizes the need to dynamically monitor lymphocyte count.

Sinomenine hydrochloride attenuates the proliferation, migration, invasiveness, angiogenesis and epithelial-mesenchymal transition of clear-cell renal cell carcinoma cells via targeting Smad in vitro.

New strategies for the treatment of clear-cell renal cell carcinoma (ccRCC) are urgently needed. Recently, accumulating evidence has demonstrated that sinomenine hydrochloride (SH), extracted from the plant sinomenium acutum, has potent anti-cancer activity in multiple human malignant solid tumors. However, the underlying molecular mechanism by which SH treatment exerts its antagonizing tumorigenic effects has not been clearly elucidated. In this study, we showed that SH treatment exerted profound effects on cell growth in ccRCC in a dose- and time-dependent manner in vitro. Furthermore, treatment with SH significantly suppressed the migration, invasiveness and angiogenesis of ccRCC cells in vitro. Mechanistically, we revealed that SH treatment blocked epithelial-mesenchymal transition (EMT) through the downregulation of the expression of the transcription factors Snail1 and Twist in ccRCC cells. Additionally, the depletion of p-Smad2 and p-Smad3 was required for SH treatment to inhibit EMT effectively. Taken together, these findings indicate an anti-cancer role for SH in ccRCC cells and reveal a potential molecular mechanism by which Smad / EMT axis functions in ccRCC, as its hyperactivation has been associated with cell proliferation, migration, invasiveness and angiogenesis in this cancer type. These observations suggest that SH can act as an efficacious adjuvant chemotherapeutic candidate that targets the Smad/EMT axis in patients with ccRCC.

Dup-697, a specific COX-2 inhibitor, suppresses growth and induces apoptosis on K562 leukemia cells by cell-cycle arrest and caspase-8 activation.

This investigation was designed to assess the effect of DuP-697 on growth and apoptosis in a human chronic myeloid leukemia (CML) cell line (K562 cells) and primary CML cells from CML patient bone marrow. DuP-697 significantly suppressed K562 cells and primary CML cells growth and induced apoptosis in a concentration-dependent manner and the growth-inhibiting effect was independent on Philadelphia chromosome. The IC50 of DuP-697 at 36 h was 31.7 muM. It arrested G1-S phase transmit on cell cycle and its apoptosis activity was partially abrogated by pretreating K562 cells with Z-IETD-fmk, a specific inhibitor of caspase-8. This study suggested that Dup-697 suppresses growth and induces apoptosis on K562 leukemia cells by cell-cycle arrest and caspase-8 activation.