Nomograms for predicting survival in patients with micropapillary bladder cancer: a real-world analysis based on the surveillance, epidemiology, and end results database and external validation in a tertiary center.

BACKGROUND: The present study aimed to construct and validate nomograms that can be used to predict cancer-specific survival (CSS) and overall survival (OS) in patients with micropapillary bladder cancer. METHODS: The data of 627 patients diagnosed with micropapillary bladder cancer between 2000 and 2018 were obtained from the surveillance, epidemiology, and end results database. Patients were randomly divided into the training and internal validation sets (7:3). The Cox proportional hazards regression model was applied to evaluate the association between variables and survival and then nomograms were constructed to predict the survival of an individual patient. The performance of nomograms was validated by using calibration curves, concordance index, receiver operating characteristic curves with the calculated area under the curve and decision curve analysis in the training and internal validation set. Data from 41 micropapillary bladder cancer patients at Qilu Hospital of Shandong University from 2000 to 2022 were collected for external validation. RESULTS: Several independent risk factors were taken into the two nomograms (CSS and OS), including age, marital status, AJCC TMN stage, surgical approach, lymph node ratio, and tumor size while the OS nomogram additionally contained race. The concordance index of the training set, internal validation set, and external verification set were all over 0.7. The calibration curve indicated good consistence between the nomogram prediction and actual survival. Area under the curve and decision curve analysis results indicated great clinical usefulness of nomograms. CONCLUSIONS: The nomograms predicting the survival outcome of patients with micropapillary bladder cancer would provide a valuable tool to help clinicians to evaluate the risk of patients and make individual treatment strategies.

Kv1.3 Channel Is Involved In Ox-LDL-induced Macrophage Inflammation Via ERK/NF-κB signaling pathway.

Macrophage inflammatory response is crucial for the initiation and progression of atherosclerosis. The voltage-gated potassium channel Kv1.3 plays an important role in the modulation of macrophage function. The aim of this study was to investigate the effect and possible mechanism of Kv1.3 on inflammation in oxidized low-density lipoprotein (ox-LDL)-induced RAW264.7 macrophages. Treatment with Kv1.3-siRNA attenuated the expression of IL-6 and TNF-α and reduced the phosphorylation of ERK1/2 and NF-κB in ox-LDL-induced macrophages. In contrast, overexpression of Kv1.3 with Lv-Kv1.3 promoted the expression of IL-6 and TNF-α, and increased ERK1/2 and NF-κB phosphorylation in macrophages. PD-98059, a specific inhibitor of ERK, reversed the expression of IL-6 and TNF-α in ox-LDL-treated macrophages. Kv1.3-siRNA did not inhibit inflammation any further when cells were treated with PD-98059. This suggests that ERK acts as a downstream regulator of the Kv1.3 channel. In conclusion, Kv1.3 may be an indispensable membrane protein in ox-LDL-induced RAW264.7 macrophage inflammation in atherosclerosis through the ERK/NF-κB pathway.

The effect of biofeedback treatment for children with non-neurogenic voiding dysfunction: A systematic review and meta-analysis.

BACKGROUND: Children's non-neurogenic voiding dysfunction (NVD) is a syndrome characterized by lower urinary tract symptoms (LUTs) because of the inability to relax the external sphincter. Patients with NVD always suffer from urinary tract infections (UTI), incontinence, constipation. The aim of this study is to assess the efficacy of biofeedback treatment for children's NVD. METHODS: PubMed, Embase, Cochrane library database were searched for all relevant studies. Two independent reviewers decided whether to include the study, conducted quality evaluation, and extracted article data. A random-effects model was used to calculate overall effect sizes. Risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI) served as the summary statistics for meta-analysis. And sensitivity analysis was subsequently performed. RESULTS: Fifteen studies and 1274 patients were included in the systemic review, seven RCTs and 539 patients were included in meta-analysis. Meta-analysis showed efficacy of biofeedback treatment in following aspects, (1) relieving UTI (RR: 1.71, 95% CI: 1.11 to 2.64), (2) reducing PVR (MD: 9.51, 95% CI: 2.03 to 16.98), (3) increasing maximum urine flow rate (MD: 4.28, 95% CI: 2.14 to 6.42) and average urine flow rate (MD: 1.49, 95% CI: 0.53 to 2.46), (4) relieving constipation (RR: 1.59, 95% CI: 1.12 to 2.26)，(5) improving abnormal voiding pattern (RR: 1.75, 95% CI: 1.30 to 2.36) and abnormal EMG during voiding (RR: 1.55, 95% CI: 1.25 to 1.91). The improvement of UTI symptoms, maximum urine flow rate and average urine flow rate took a longer time (12 months). In terms of daytime incontinence (RR: 1.20, 95% CI [0.96, 1.50], p = 0.11), nighttime incontinence (RR: 1.20, 95% CI [0.62, 2.32], p = 0.58), no significant difference was found between biofeedback treatment and standard urotherapy. The qualitative analysis showed that biofeedback treatment was beneficial for NVD. CONCLUSION: Compared with standard urotherapy, biofeedback treatment is effective for some symptoms, such as UTI and constipation, and can improve some uroflowmetric parameters, such as PVR. Biofeedback treatment seems to have a better long-term effect.

Chaetospirolactone reverses the apoptotic resistance towards TRAIL in pancreatic cancer.

The pancreatic cancer is one of the most aggressive tumors. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can trigger apoptosis by interaction with death receptors. However, in TRAIL-resistant pancreatic cancer, responsiveness to TRAIL treatment is terribly poor. In current work, we have demonstrated that a natural product chaetospirolactone (CSL) isolated from an endophytic fungus Chaetomium sp. NF00754 can enhance the susceptibility of TRAIL-resistant pancreatic cancer cells to apoptosis. CSL can induce apoptosis in TRAIL-treated pancreatic cancer cells. Furthermore, combined CSL and TRAIL treatment significantly inhibits viability and migration of pancreatic cancer cells. Combinatorial TRAIL and CSL treatment repressed xenograft tumor growth without substantially toxic side effects. CSL can specifically upregulate expression of death receptor 4 (DR4). Further study revealed that CSL represses the activities of an epigenetic regulator enhancer of zeste homolog 2 (EZH2) and consistently reduces histone H3 lysine 27 trimethylation (H3K27me3) to allow DR4 transcription. Taken together, CSL treatment may reverse TRAIL resistance in pancreatic cancer cells via epigenetic regulation of DR4 implying that administration of CSL might represent a putative strategy for pancreatic cancer therapy.

Expression of Tim4 in Glioma and its Regulatory Role in LN-18 Glioma Cells.

BACKGROUND: Tim4 is a transmembrane protein known as T cell immunoglobulin and mucin domain containing protein-4. We speculated that Tim4 might be associated with glioma. This study aimed to investigate the expression level of Tim4 in gliomas and the regulatory role of Tim4 on the growth and apoptosis of LN-18 glioma cells. MATERIAL/METHODS: Tumor tissues and adjacent normal tissues were collected from patients with glioma. The expression level of Tim4 mRNA and protein was determined by RT-PCR and Western blot analyses, respectively to evaluate their association with glioma. Tim4 was overexpressed or silenced by siRNA interference in cultured human glioma cells LN-18. The growth and apoptosis of LN-18 cells was detected by MTT assay and flow cytometry. The colony-forming ability of LN-18 cells was assessed by the colony formation assay. The collection of human tissues was approved by the Research Ethics Committee at the Harbin Medical University Cancer Hospital and performed in strict accordance with international standards. All patients were required to sign the informed consent. RESULTS: The expression level of Tim4 mRNA and protein in tumor tissues was significantly higher compared with adjacent normal tissues. Antisense miRNA targeting Tim4 inhibited the growth of LN-18 cells, induced their apoptosis, and reduced their clonogenic capacity. In contrast, overexpression of Tim4 promoted the growth of LN-18 cells, inhibited their apoptosis, and enhanced their clonogenic potential. CONCLUSIONS: The expression level of Tim-4 is closely associated with glioma. Decreased expression of Tim4 inhibited the growth and colony-forming ability of LN-18 cells and induced their apoptosis, whereas increased expression of Tim4 stimulated the growth and clonogenic potential of LN-18 cells and suppressed their apoptosis.

The stabilities and electronic structures of single-layer bismuth oxyhalides for photocatalytic water splitting.

The stabilities and electronic/band structures of single-layer bismuth oxyhalides have been investigated by employing first-principles calculations. The results indicate that the single-layer bismuth oxyhalide materials, except for BiOF, have robust energetic and dynamical stabilities because of their low formation energies and the absence of imaginary frequencies within the entire Brillouin zone. Furthermore, calculations of the electronic structures and optical absorptions indicate that single-layer BiOI possesses a favorable band gap, suitable band edge positions, different orbital characteristics and different effective masses at the valence band maximum (VBM) and conduction band minimum (CBM), thus presenting excellent photocatalytic activity for water splitting. Moreover, the resulting compressive strains can shift the band edge positions of the single-layer materials to more suitable places to enhance their photocatalytic activities.

"Is this blueberry ripe?": a blueberry ripeness detection algorithm for use on picking robots.

Blueberries are grown worldwide because of their high nutritional value; however, manual picking is difficult, and expert pickers are scarce. To meet the real needs of the market, picking robots that can identify the ripeness of blueberries are increasingly being used to replace manual operators. However, they struggle to accurately identify the ripeness of blueberries because of the heavy shading between the fruits and the small size of the fruit. This makes it difficult to obtain sufficient information on characteristics; and the disturbances caused by environmental changes remain unsolved. Additionally, the picking robot has limited computational power for running complex algorithms. To address these issues, we propose a new YOLO-based algorithm to detect the ripeness of blueberry fruits. The algorithm improves the structure of YOLOv5x. We replaced the fully connected layer with a one-dimensional convolution and also replaced the high-latitude convolution with a null convolution based on the structure of CBAM, and finally obtained a lightweight CBAM structure with efficient attention-guiding capability (Little-CBAM), which we embedded into MobileNetv3 while replacing the original backbone structure with the improved MobileNetv3. We expanded the original three-layer neck path by one to create a larger-scale detection layer leading from the backbone network. We added a multi-scale fusion module to the channel attention mechanism to build a multi-method feature extractor (MSSENet) and then embedded the designed channel attention module into the head network, which can significantly enhance the feature representation capability of the small target detection network and the anti-interference capability of the algorithm. Considering that these improvements will significantly extend the training time of the algorithm, we used EIOU_Loss instead of CIOU_Loss, whereas the k-means++ algorithm was used to cluster the detection frames such that the generated predefined anchor frames are better adapted to the scale of the blueberries. The algorithm in this study achieved a final mAP of 78.3% on the PC terminal, which was 9% higher than that of YOLOv5x, and the FPS was 2.1 times higher than that of YOLOv5x. By translating the algorithm into a picking robot, the algorithm in this study ran at 47 FPS and achieved real-time detection well beyond that achieved manually.

Based on ARASENS trial: efficacy and safety of darolutamide as an emerging option of endocrinotherapy for metastatic hormone-sensitive prostate cancer-an updated systematic review and network meta-analysis.

PURPOSE: The newly published ARASENS trial has demonstrated the clinical efficacy of darolutamide for metastatic hormone-sensitive prostate cancer (mHSPC). However, the use of darolutamide as the latest first-line androgen receptor pathway inhibitor for mHSPC has not been compared with other androgen receptor targeted agents (ARTAs). Given the lack of head-to-head randomized trials, we performed this updated meta-analysis to conduct indirect comparison for the efficacy and safety of darolutamide with other new-generation ARTAs. METHODS: By searching the databases of PubMed, Scopus, Cochrane Library, and Embase, 9 large randomized controlled trials evaluating ARTAs for mHSPC patients were eventually screened according to PRISMA. We extracted data from overall survival, castration-resistant progression, and adverse events for network meta-analysis using the Bayesian and standard frequentist models. RESULTS: Darolutamide combination emerged with superiority (HR = 0.68, 95%CrI = 0.57-0.81) among four androgen receptor inhibitors for patients with high Gleason score (HR = 0.71, 95%CrI = 0.59-0.86). Darolutamide was best tolerated in several androgen suppression-related adverse events (AEs). CONCLUSION: Darolutamide appears to be an optional androgen receptor inhibitor for mHSPC patients, especially for patients with Gleason score ≥ 8. Its well-tolerated characteristic may provide a preferred drug option for patients with poor cardiovascular function and bone health.

Identification and validation of novel prognostic fatty acid metabolic gene signatures in colon adenocarcinoma through systematic approaches.

Background: Colorectal cancer (CRC) belongs to the class of significantly malignant tumors found in humans. Recently, dysregulated fatty acid metabolism (FAM) has been a topic of attention due to its modulation in cancer, specifically CRC. However, the regulatory FAM pathways in CRC require comprehensive elucidation. Methods: The clinical and gene expression data of 175 fatty acid metabolic genes (FAMGs) linked with colon adenocarcinoma (COAD) and normal cornerstone genes were gathered through The Cancer Genome Atlas (TCGA)-COAD corroborating with the Molecular Signature Database v7.2 (MSigDB). Initially, crucial prognostic genes were selected by uni- and multi-variate Cox proportional regression analyses; then, depending upon these identified signature genes and clinical variables, a nomogram was generated. Lastly, to assess tumor immune characteristics, concomitant evaluation of tumor immune evasion/risk scoring were elucidated. Results: A 8-gene signature, including ACBD4, ACOX1, CD36, CPT2, ELOVL3, ELOVL6, ENO3, and SUCLG2, was generated, and depending upon this, CRC patients were categorized within high-risk (H-R) and low-risk (L-R) cohorts. Furthermore, risk and age-based nomograms indicated moderate discrimination and good calibration. The data confirmed that the 8-gene model efficiently predicted CRC patients' prognosis. Moreover, according to the conjoint analysis of tumor immune evasion and the risk scorings, the H-R cohort had an immunosuppressive tumor microenvironment, which caused a substandard prognosis. Conclusion: This investigation established a FAMGs-based prognostic model with substantially high predictive value, providing the possibility for improved individualized treatment for CRC individuals.

How Workplace Social Capital Affects Turnover Intention: The Mediating Role of Job Satisfaction and Burnout.

Committed social workers are significant to organizational performance and service quality; therefore, it is crucial to explore the contributing factors of turnover intention to enhance social workers' commitment. To reduce social workers' turnover intention, this study used the first national survey data (N = 5620) of social workers in China to find out the relationship between workplace social capital and turnover intention in public service and explore possible solutions. This study treated workplace social capital as a comprehensive measure that captured employees' overall perceptions of their interpersonal relations in the public sector. It covered the impact of many other organizational factors on turnover intention, such as job embeddedness, social networks, social relations, communication, and organizational fairness. The results confirmed that workplace social capital had a significant negative impact on employees' turnover intention. Workplace social capital could be a better predictor of employees' turnover intention than a single organizational factor or a combination of several factors. These findings not only deepened the theoretical understanding of social capital within the organization and brought insight into how workplace social capital affected employees' turnover but also promoted a formation of a holistic organizational perspective from the fragmented organizational factors. Results also showed that job burnout and job satisfaction mediated the relation between workplace social capital and turnover intention. Public service agencies should endeavor to foster an organizational climate of cooperation and trust, encourage teamwork and altruistic behaviors among coworkers to reduce emotional exhaustion, and strengthen the professional identity and professional value of social work.

Comparison of different types of therapy for overactive bladder: A systematic review and network meta-analysis.

To compare the efficacy and safety of different interventions [including antimuscarinics, mirabegron, OnabotulinumtoxinA, sacral neuromodulation (SNM) and peripheral tibial nerve stimulation (PTNS)] for treating idiopathic overactive bladder (OAB). PubMed, Embase, Cochrane Library, and other sources were searched for randomized controlled trials (RCTs) comparing interventions for overactive bladder from 1 January 2000 to 19 April 2021. A systematic review and network meta-analysis were performed by two authors independently. Fifty-five RCTs involving 32,507 patients were included in this analysis. Overall, antimuscarinics, mirabegron, OnabotulinumtoxinA, sacral neuromodulation, and peripheral tibial nerve stimulation were more efficacious than placebo, and sacral neuromodulation showed the best effect for reducing micturition frequency, urgency episodes and urgency urinary incontinence episodes. OnabotulinumtoxinA was the best intervention for achieving reductions of 100 and ≥50% in the number of urinary incontinence episodes/day, and peripheral tibial nerve stimulation was the best intervention for reducing urinary incontinence episodes. Antimuscarinics, mirabegron and peripheral tibial nerve stimulation had a similar efficacy for reducing micturition frequency, urinary incontinence episodes and urgency urinary incontinence episodes. The results revealed that all interventions examined herein were efficacious for managing adult overactive bladder syndrome compared with placebo. Furthermore, sacral neuromodulation and OnabotulinumtoxinA were the most efficient treatments for overactive bladder. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=251966], identifier [CRD42021251966].

The Outcome of Sutureless in Partial Nephrectomy: A Systematic Review and Meta-Analysis.

Purpose: To compare the effect of sutureless versus standard suture (double-layer suture) during renorrhaphy in laparoscopic or robotic-assisted partial nephrectomy on perioperative and renal function outcomes. Methods: PubMed, Embase, and other sources were searched for randomized controlled trials or retrospective studies comparing sutureless partial nephrectomy versus standard suture partial nephrectomy. A systematic review and meta-analysis were performed by two reviewers independently. Results: Five retrospective studies were included with a total of 634 patients. The results showed that there was a significant difference in the decline of estimated glomerular filtration rate (I 2 = 98.5%; WMD, -4.19 ml/min; 95% CI, -7.64 to -0.73; P < 0.001) and no significant difference in postoperative complications (I 2 = 0; RR, 1.31; 95% CI, 0.61 to 2.81; P = 0.623). A significant advantage in terms of operating time (I 2 = 53.9%; WMD, -29.08 min; 95% CI, -33.06 to -25.10; P = 0.069) and warm ischemia time (I 2 = 38.5%; WMD, -6.17 min; 95% CI, -6.99 to -5.36; P = 0.165) favored sutureless, while there was no significant difference in blood loss (I 2 = 58.1%; WMD, 3.10 ml; 95% CI, -39.18 to 45.38; P = 0.049). Conclusion: Sutureless during renorrhaphy is feasible and safe compared with standard suture. Sutureless can shorten the operating time and warm ischemia time without increasing postoperative complications, and thus, it protects renal function.

Preoperative sarcopenia and systemic immune-inflammation index can predict response to intravesical Bacillus Calmette-Guerin instillation in patients with non-muscle invasive bladder cancer.

Background: To explore the prognostic significance of sarcopenia and systemic immune-inflammation index (SII) for response to intravesical Bacillus Calmette-Guerin (BCG) in patients with intermediate-, and high-risk non-muscle invasive bladder cancer (NMIBC). Methods: We retrospectively analyzed 183 consecutive patients treated in Qilu hospital of Shandong University for a first diagnosis of intermediate and high risk NMIBC. Using computed tomography scans at the third lumbar vertebra level, we calculated skeletal muscle index (SMI). Sarcopenia was defined as SMI <43 cm2/m2 for males with BMI < 25 kg/m2, <53 cm2/m2 for males with BMI ≥ 25 kg/m2, and <41 cm2/m2 for females. The response to intravesical BCG immunotherapy and relapse-free survival (RFS) were analyzed. Results: Compared with BCG responders, BCG non-responders were associated with sarcopenia (P < 0.001), carcinoma in situ (P < 0.001), T1 stage (P < 0.001), multiple tumor (P < 0.001), tumor diameter >=3cm (P < 0.001), and have a significant increase of neutrophil-to-lymphocyte ratio (NLR) (P < 0.001), platelet to lymphocyte ratio (PLR) (P = 0.004), SII (P < 0.001). The area under the ROC curve (AUC) of the BMI, NLR, PLR, and SII for response to intravesical BCG immunotherapy were 0.425, 0.693, 0.631, and 0.702 respectively. Logistic regression analysis demonstrated that sarcopenia and SII were predictors of response to intravesical BCG immunotherapy. The Kaplan-Meier survival analysis showed that the RFS of patients with BCG response, lower SII and no sarcopenia was significantly increased compared with that of patients with BCG non-response, higher SII and sarcopenia, respectively. Subgroup analysis demonstrated that the RFS of patients with high SII and sarcopenia was significantly decreased compared with those with low SII and no sarcopenia in Ta stage subgroup, T1 stage subgroup, non-Cis subgroup, multiple tumor subgroup, single tumor subgroup, tumor diameter≥3cm subgroup and tumor diameter<3cm subgroup, respectively (P < 0.05). However, there was no significant difference in RFS for patients in CIS subgroup (P > 0.05). Multivariate Cox analysis shown that sarcopenia (p=0.005) and high SII (p = 0.003) were significantly associated with poor RFS. Conclusions: Both sarcopenia and high SII are useful predictors of response to intravesical BCG in intermediate- and high-risk NMIBC patients. Patients with intermediate- and high-risk NMIBC that had sarcopenia or high SII at diagnosis were associated with poor RFS, and the combination of sarcopenia and SII may be a better predictor of RFS.

The Factors Affecting Volunteers' Willingness to Participate in Disaster Preparedness.

Disaster preparedness is crucial for providing an effective response to, and reducing the possible impacts of, disasters. Although volunteers' participation plays an important role in disaster preparedness, their actual participation in disaster preparedness activities is still low. To find ways to encourage more volunteers to participate, this study analyzed the social background and organizational and attitudinal factors affecting the volunteers' willingness to participate. Questionnaires were distributed to 990 registered disaster volunteers across Beijing and the data were analyzed using linear regression models. Results revealed a weak willingness to participate in disaster preparedness. Only 28.08% of the respondents indicated that they were "very ready" to participate in voluntary disaster preparedness, and 14.65% showed "a little bit" of interest. The following was concluded: (1) Disaster volunteers' social background variables were related to their willingness to participate in disaster preparedness. Compared to male volunteers, female volunteers were more willing to participate. Chinese Communist Party members were more willing to participate than non-members. (2) Providing accidental life insurance for the volunteers had a positive effect on their willingness to participate in disaster preparedness. Provision of more training had a negative effect on the volunteers' willingness to participate, indicating a low quality of training. (3) Organizational identification was positively related to the volunteers' willingness to participate. According to these results, we suggest that volunteer organizations should improve their standards and procedures for disaster volunteer recruitment and selection, and gain a deeper understanding of the needs of the disaster volunteers in order to better motivate them to participate.

miR-142 suppresses proliferation and induces apoptosis of osteosarcoma cells by upregulating Rb.

It has been reported that microRNA-142 (miR-142) is a tumor suppressor gene. The present study primarily investigated whether the overexpression of miR-142 was able to inhibit the proliferation, apoptosis and expression of apoptosis-associated proteins in osteosarcoma (OS) cells. Different concentrations of miR-142 were transfected into the OS MG-63 cell line using Lipofectamine 2000. The cell lines were divided into three groups: Normal group (non-transfected group), miR-142 transfected group, and negative group, which were transfected with random miR-142 fragment. The proliferation of cells was detected by MTT assay. The expression of miR-142 was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). DAPI staining was performed to investigate the influence of miR-142 on the morphology of MG-63c ells. The apoptotic cell percentages were determined by flow cytometry with Annexin V-fluorescein isothiocyanate/propidium iodide double staining. Expression of tumor suppressors, phosphatase and tensin homolog (PTEN) and Retinoblastoma-associated protein (Rb), and apoptosis-associated proteins were evaluated by western blotting. RT-qPCR indicated a higher expression of miR-142 in the transfected group (miR-142 was transfected into the MG-63 cell line) compared with that in the normal (non-transfected group) and negative control groups. The proliferation of miR-142 transfected cells was significantly lower compared with that in the normal and negative groups. Furthermore, an increased apoptosis rate accompanied by a statistically significant upregulation of PTEN, Rb phosphorylation, cleaved caspase-3 and cytochrome c protein levels were detected in the transfected group, indicating an internal apoptosis pathway was involved in this process. Furthermore, no significant changes were identified between the normal and negative groups (P>0.05). The present study demonstrated that miR-142 overexpression by liposomal transfection resulted in an inhibitory effect on MG-63 cell proliferation. The underlying mechanisms may relate to the upregulation of tumor suppressor and activation of caspase signaling pathway, which may provide a novel horizon in short nucleotide drugs on the management of OS.

Adefovir dipivoxil induced hypophosphatemic osteomalacia in chronic hepatitis B: a comparative study of Chinese and foreign case series.

BACKGROUND: Adefovir dipivoxil (ADV)-induced renal tubular dysfunction and hypophosphatemic osteomalacia (HO) have been given great consideration in the past few years. However, no standard guidance is available due to a lack of powerful evidence from appropriate long-term prospective case-control studies and variations in the definition of renal adverse events. The aim of this study is to clarify clinical features of ADV-related HO in Chinese chronic hepatitis B patients with long-term ADV treatment in Chinese and non-Chinese comparative case series. METHODS: Retrieval of case reports was based on Pubmed, CNKI, Wan Fang and VIP databases using the key words adefovir dipivoxil, hypophosphatemia, osteomalacia and Fanconi syndrome. We divided patients into Chinese (C group) and Foreign (F group) groups according to their nationality. Comparisons involving demographics, clinical manifestations, tests, treatment and prognosis were conducted between the two groups. RESULTS: Of the patients screened, 120 Chinese patients were identified in the C group, and 32 non-Chinese patients were identified in the F group. The average age of the C group was younger than that of the F group (51.89 years ±10.96 years versus 56.47 years ±11.36 years, t = - 2.084, P = 0.039). No significant difference was found in gender (male to female, 3.29:1 versus 3:1, χ 2 = 0.039, P = 0.844). Although there was no significant difference in the duration of ADV therapy before ostalgia onset, the C group tended to develop adverse events earlier, by 2-3 years, while the F group developed adverse events at 4-5 years (Z = - 1.517, P = 0.129). Prognosis was good after adjustment of the ADV dose and supplemental administration of phosphate and calcitriol. Time to resolution of tubular dysfunction was commenced at the first month, and Chinese patients were more prone to recover in the first 3 months than non-Chinese patients (91.3% of patients in the C group versus 56.3% in the F group, Z = - 3.013, P = 0.003). CONCLUSIONS: Sufficient attention is required for middle-aged males before and during exposure to long-term ADV therapy, regardless of nationality. The clinical picture, laboratory and radiograph alterations are important clues for those patients and are usually characterized by polyarthralgia, renal tubular dysfunction and mineralization defects. Implementation of an early renal tubular injury index is recommended for patients with higher risk, which would prevent further renal injury.

INHIBITORY ACTIVITY OF MANGIFERIN ON HELICOBACTER PYLORI-INDUCED INFLAMMATION IN HUMAN GASTRIC CARCINOMA AGS CELLS.

BACKGROUND: Gastric cancer is a serious health issue caused by H. pylori and claims more lives in developing and undeveloped countries. Hence, the need for a natural drug with several pharmacological activities with no adverse effect are highly recommended. The target of this study was to verify the anti-H. pyloric efficacy of mangiferin (MF) on H. pylori-infected AGS cells. MATERIALS AND METHODS: AGS cells were co-cultured with H. pylori and incubated with increased concentration of MF (10, 20, 50 and 100 µg/mL) or amoxicillin (AMX) and DMSO (control) group to assess its anti-H. pyloric effect by checking inhibitory zone, bacterial drug sensitivity test (MIC and MBC), adhesion and invasive property and various inflammatory markers. RESULTS: Co-culturing of H. pylori-infected AGS cells with MF (100 µg) considerably increased (p<0.05) the inhibitory zone as well as substantially lowered (p<0.05) in the levels of MBC and MIC with decreased adhesion and invasive property in a dose-dependent manner and thus endorsing its anti H. pyloric activity and are almost equivalent to antibiotic AMX. Meanwhile, inflammatory markers such as NF-κΒ subunit p65, interleukins-1ß, IL-8, and TNF-α were also markedly suppressed (p<0.01) on treatment with MF. In addition, the protein expression of inflammatory enzymes like COX-2 and iNOS were notably downregulated (p<0.05) in AGS cells incubated with MF. CONCLUSION: We, concluded that MF treatment with H. pylori-infected AGS cells significantly suppressed the adhesion and invasion process as well as deactivated NF-p65 thereby blocking inflammatory response and thus lower the incidence of gastric carcinoma.

A comprehensive genome-wide analysis of long noncoding RNA expression profile in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, especially in East Asia and China. Long noncoding RNAs (lncRNAs) are emerging as critical regulators that may be involved in the development and progression of cancers in humans. However, the contributions of lncRNAs to HCC development, metastasis, and recurrence remain largely unknown. In this study, we comprehensively investigated lncRNA expression profile in HCC and normal tissues using TCGA RNA sequencing data, one RNA sequencing dataset, and two microarray datasets from GEO. By analyzing these four datasets, we identified hundreds of expression-dysregulated lncRNAs in HCC tissues compared with normal tissues. Genomic copy number variation analysis showed that many of those lncRNAs disorder are related to the copy number amplification or deletion. Moreover, several lncRNAs expression levels are associated with HCC patients' overall and recurrence-free survival, such as RP1-228H13.5, TMCC1-AS1, LINC00205, and RP11-307C12.11. Furthermore, we identified two lncRNAs termed PVT1 and SNHG7 that may be involved in HCC cells metastasis by comparing lncRNAs expression profiles between early recurrence HCC tissues with metastasis and late recurrence HCC tissues without metastasis. Finally, loss-of-function assays confirmed that knockdown of SNHG7 and PVT1 impaired HCC cells invasion. Taken together, these findings may provide a valuable resource for further identification of novel biomarkers and therapeutic targets for HCC patients.

HOX transcript antisense intergenic RNA represses E-cadherin expression by binding to EZH2 in gastric cancer.

AIM: To clarify the mechanisms of HOX transcript antisense intergenic RNA (HOTAIR) in gastric cancer (GC) migration and invasion. METHODS: Quantitative real-time polymerase chain reaction (qPCR) was used to detect the expression level of HOTAIR in GC tissues. The correlation of its expression with clinicopathological features was analyzed. Area under receiver operating characteristic curve (AUCROC) was constructed to evaluate the diagnostic value of HOTAIR. Wound-healing assay and Transwell assay were performed to detect the biological effects of HOTAIR in GC cells. qPCR, western blot and immunohistochemistry were used to evaluate the mRNA and protein expression of E-cadherin. RNA-binding protein immunoprecipitation was used for the analysis of EZH2 interactions with HOTAIR. Chromatin immunoprecipitation assay was performed to investigate direct interactions between EZH2 and E-cadherin. RESULTS: The expression of HOTAIR was up-regulated in GC tumorous tissues compared with the para-tumorous tissues (P < 0.001). Its over-expression was correlated with tumor-node-metastasis (TNM) stage (P = 0.024), tumor invasion (P = 0.018), lymph node metastasis (P = 0.023), and poor prognosis (P < 0.001). Multivariate Cox regression analysis confirmed expression of HOTAIR as an independent predictor of overall survival (P = 0.033), together with TNM stage (P = 0.002) and lymph node metastasis (P = 0.002). The AUCROC was up to 0.709 (95%CI: 0.623-0.785, P < 0.001). Knockdown of HOTAIR by siRNA in GC cells suppressed the migration and invasion of GC cells. Significantly negative correlation between HOTAIR and E-cadherin was found in GC tissues and cell lines, and HOTAIR contributed to the regulation of E-cadherin through binding to EZH2 with the E-cadherin promoter. CONCLUSION: HOTAIR may play a pivotal role in tumor cell migration and invasion. It can be used as a potential diagnostic and prognostic biomarker for GC.