Prognosis and risk factor assessment of patients with advanced lung cancer with low socioeconomic status: model development and validation.

BACKGROUND: Lung cancer, a major global health concern, disproportionately impacts low socioeconomic status (SES) patients, who face suboptimal care and reduced survival. This study aimed to evaluate the prognostic performance of traditional Cox proportional hazards (CoxPH) regression and machine learning models, specifically Decision Tree (DT), Random Forest (RF), Support Vector Machine (SVM), and Extreme Gradient Boosting (XGBoost), in patients with advanced lung cancer with low SES. DESIGN: A retrospective study. METHOD: The 949 patients with advanced lung cancer with low SES who entered the hospice ward of a tertiary hospital in Wuhan, China, from January 2012 to December 2021 were randomized into training and testing groups in a 3:1 ratio. CoxPH regression methods and four machine learning algorithms (DT, RF, SVM, and XGBoost) were used to construct prognostic risk prediction models. RESULTS: The CoxPH regression-based nomogram demonstrated reliable predictive accuracy for survival at 60, 90, and 120 days. Among the machine learning models, XGBoost showed the best performance, whereas RF had the lowest accuracy at 60 days, DT at 90 days, and SVM at 120 days. Key predictors across all models included Karnofsky Performance Status (KPS) score, quality of life (QOL) score, and cough symptoms. CONCLUSIONS: CoxPH, DT, RF, SVM, and XGBoost models are effective in predicting mortality risk over 60-120 days in patients with advanced lung cancer with low SES. Monitoring KPS, QOL, and cough symptoms is crucial for identifying high-risk patients who may require intensified care. Clinicians should select models tailored to individual patient needs and preferences due to varying prediction accuracies. REPORTING METHOD: This study was reported in strict compliance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

ncRNA-mediated SOX4 overexpression correlates with unfavorable outcomes and immune infiltration in hepatocellular carcinoma.

BACKGROUND: The activity and number of immune cells in the tumor microenvironment are closely related to the overall survival of patients with hepatocellular carcinoma (HCC). The sex-determining region Y-box 4 (SOX4) gene is abnormally expressed in various tumor tissues and is critical for tumor development. However, the correlation between SOX4 expression in HCC and tumor immunity is unclear. METHODS: SOX4 expression was explored using data from The Cancer Genome Atlas, and UALCAN databases. Real-time reverse transcription quantitative and western blotting were used to analyze SOX4 expression in several liver cancer cell lines. Additionally, correlations among SOX4 expression, cancer immune characteristics, and infiltrated immune cell gene marker sets in patients with HCC were analyzed using data from the Tumor Immune Estimation Resource, Gene Expression Profiling Interactive Analysis, and Tumor-Immune System Interactions databases. Moreover, we evaluated SOX4 expression in HCC tissues and the correlation of SOX4 expression with survival rate. Subsequently, noncoding RNAs (ncRNAs) responsible for SOX4 overexpression were identified using expression, correlation, and survival analyses. RESULTS: SOX4 expression was significantly upregulated in HCC and correlated with a poor prognosis. Additionally, SOX4 upregulation in HCC positively correlated with immune cell infiltration, several biomarkers of immune cells, and immune checkpoint expression. Finally, the MCM3AP-AS1/hsa-miR-204-5p axis was identified as the most likely upstream ncRNA-related pathway for SOX4 in HCC. These results indicated that ncRNA-mediated upregulation of SOX4 correlated with the immune infiltration level and poor prognosis in HCC. Our findings provide new directions for the development of novel immunotherapeutic targets for HCC.

Effect of cervical pillow in phacoemulsification surgery for age-related cataract patients: a prospective randomized controlled study.

PURPOSE: To explore the application effect of cervical pillow in phacoemulsification surgery for age-related cataract patients. METHODS: 104 cases of age-related cataract patients admitted to our hospital in June 2023 were enrolled and divided into the control group (traditional supine position) and the experimental group (the cervical pillow supine position) by the digital parity method (52 cases per group). The two groups were evaluated for the discomfort score, the satisfaction of patients and doctors, the head displacement rate, the number of displacement, the operation time and the time of body position during the operation and after the operation. RESULTS: There was no significant difference in the gender (P = 0.84), age (P = 0.86), course of disease (P = 0.82) and the time spent on position placement (P = 0.15) of the two groups. The patient in the experimental group had lower discomfort score (P = 0.0001), higher patients satisfaction (P = 0.0001) and higher doctors satisfaction (P = 0.0001) than patients in the control group. There was no significant difference between the experimental group and the control group in the proportion of intraoperative (P = 0.36) and postoperative pain (P = 0.65). Besides, the number of head transfers (P = 0.001), number of head shifts (P = 0.0001), the surgical time (P = 0.0001) and laparoscopic time (P = 0.0001) in the experimental group were significantly lower than those in the control group. CONCLUSION: The additional cervical pillow for age-related cataract patients in the traditional supine position during the operation will not increase the preparation time before the operation, but will help improve the patient satisfaction, improve the comfort and maintain a good position of the operative eye field, bringing obvious comfort and smooth operation for the surgeon in the operation, thus reducing the risk of the operation, shortening the operation time.

Holographic 3D renal segments reconstruction protects renal function by promote choice of selective renal artery clamping during robot-assisted partial nephrectomy.

OBJECTIVE: To investigate the impact of selective artery clamping (SAC) and main artery clamping (MAC) during robot-assisted partial nephrectomy (RAPN) on renal function and the influence of holographic three-dimensional (3D) reconstruction of renal segments on the selection between SAC and MAC. METHODS: This retrospective observational study included patients who underwent RAPN at First Hospital Affiliated to the Army Medical University between December 2016 and July 2022. According to the clamping methods, the patients were divided into the SAC group and the MAC group. The primary outcome was renal function. RESULTS: A total of 422 patients (194 in the SAC group and 228 in the MAC group) were included. The RAPN procedures were all completed successfully. The patients in SAC group had less glomerular filtration rate (GFR) decline in the affected kidney (8.6 ± 7.0 ml/min vs. 18.7 ± 10.9 ml/min, P < 0.001) and minor estimated glomerular filtration rate (eGFR) decrease (4.3 ± 10.5 ml/min vs. 12.6 ± 12.1 ml/min, P < 0.001) than those in MAC group. Among 37 patients with baseline renal insufficiency, the GFR decline of the affected kidney in the SAC subgroup was significantly lower than in the MAC subgroup (5.5 ± 6.5 ml/min vs. 14.3 ± 9.2 ml/min, P = 0.002). The proportion of patients who underwent 3D reconstruction was significant higher in the SAC group than in the MAC group. (65.46% vs. 28.07%, P < 0.001). CONCLUSION: The SAC technique during RAPN may serve as a protective measure for renal function, while the implementation of holographic 3D renal segment reconstruction technique may facilitate optimal selection of SAC.

Identification of immune-related target and prognostic biomarkers in PBMC of hepatocellular carcinoma.

BACKGROUND:  Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and is characterized by insidious onset, rapid progression, and poor prognosis. Immunotherapy is a first-line treatment for advanced HCC. The identification of immune-related prognostic markers may be an effective strategy to predict and improve clinical response rate of immunotherapy. METHODS:  The DESeq2, edgeR, and limma R packages were used to compare the transcriptomes of HCC with different prognoses. Cancer-related databases such as UALCAN, TNMplot, GEPIA, muttarget and Human Protein Atlas (HPA), and the Kaplan-Meier Plotter platform were used to analyze the relationship between CLDN18 and the clinical characteristics, as well as prognosis of HCC. The co-expressed genes of CLDN18 were obtained from LinkedOmics platform, and GO functional enrichment and KEGG pathway analysis were performed. The CIBERSORT, TIMER, Timer 2.0 and TISIDB algorithms were used to analyze immune infiltration. RESULTS:  CLDN18 was differentially expressed in HCC patients with different prognoses, and its expression level in PBMC was positively correlated with the stage of BCLC. In addition, CLDN18 was significantly overexpressed in HCC tumor tissues compared to adjacent non-tumor tissues, which was consistent with PBMC sequencing results and immunohistochemical data from human protein profiles. CLDN18 was also positively correlated with HCC staging and grading, and high expression levels of CLDN18 predicted shorter overall survival. Functional annotation of CLDN18 in HCC revealed enrichment of the cellular senescence and protein activation cascade, along with biological processes such as cell cycle, inflammatory response, and cellular ketone metabolism. In addition, CLDN18 was also associated with tumor infiltrating immune cells, suppressive immune cell markers, T lymphocyte depletion and activation of HCC, and low expression of CLDN18 was associated with higher CD8 + T cell infiltration and better survival rates. CONCLUSIONS: CLDN18 is a potential prognostic marker and immunotherapeutic target for HCC.

Association of mitochondrial DNA copy number with chronic kidney disease in older adults.

BACKGROUND: Mitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of chronic kidney disease (CKD). Estimation of mitochondrial DNA copy number (mtDNA-CN) is considered a convenient method for representing mitochondrial function in large samples. However, no study has investigated the association between mtDNA-CN and CKD in older adults with the highest prevalence. The objective is to examine cross-sectional and prospective associations between mtDNA-CN values and CKD risk in older adults to determine whether mtDNA-CN represents a novel potential biomarker for the recognition of CKD risk. PATIENTS AND METHODS: In a Chinese community-based cohort of over 65-year-olds, we included 14,467 participants (52.6% females). CKD was defined by eGFR < 60 mL/min/1.73 m2 or ICD-10 codes (patients = 3831 (26.5%)). Participants had peripheral blood levels of mtDNA-CN calculated from probe intensities of the Axiom CAS Array. RESULTS: The risk of CKD prevalence decreased with mtDNA-CN per 1-SD increment, independent of established risk factors for older CKD (odds ratio [OR] per SD 0.90, 95% confidence interval [CI] 0.86, 0.93, P < 0.001), and has comparable strength of association with these established risk factors. Furthermore, the progression of kidney function was stratified according to the worsening of eGFR categories. The risk of kidney function progression to a more severe stage gradually decreased as the mtDNA-CN increased (P trend < 0.001). Non-CKD participants in the highest quartile of mtDNA-CN had a lower risk of developing CKD compared to the lowest quartile within 2 years of follow-up, reducing the risk of CKD by 36% (95% CI 0.42, 0.97; P = 0.037). CONCLUSIONS: Based on the analysis of the largest sample to date investigating the association between mtDNA-CN and CKD in older adults, higher levels of mtDNA-CN were found to be associated with a lower risk of CKD, suggesting that a reduced level of mtDNA-CN is a potential risk factor for CKD.

Detection and monitoring of HBV-related hepatocellular carcinoma from plasma cfDNA fragmentation profiles.

Most hepatocellular carcinomas (HCCs) are associated with hepatitis B virus infection (HBV) in China. Early detection of HCC can significantly improve prognosis but is not yet fully clinically feasible. This study aims to develop methods for detecting HCC and studying the carcinogenesis of HBV using plasma cell-free DNA (cfDNA) whole-genome sequencing (WGS) data. Low coverage WGS was performed for 452 participants, including healthy individuals, hepatitis B patients, cirrhosis patients, and HCC patients. Then the sequencing data were processed using various machine learning models based on cfDNA fragmentation profiles for cancer detection. Our best model achieved a sensitivity of 87.10% and a specificity of 88.37%, and it showed an increased sensitivity with higher BCLC stages of HCC. Overall, this study proves the potential of a non-invasive assay based on cfDNA fragmentation profiles for the detection and prognosis of HCC and provides preliminary data on the carcinogenic mechanism of HBV.

Experimental study on the effect of chrysin on skin injury induced by amiodarone extravasation in rats.

OBJECTIVE: Amiodarone is the first choice for the treatment of arrhythmia, but it is easy to cause extravasation during infusion, after extravasation, it often cause skin injury. The healing of skin injury induced by amiodarone is an inflammatory process. Chrysin, a natural flavonoid, has been investigated to have anti-inflammatory and antioxidant effects. It was reported that chrysin can promote wound healing. So this study aims to investigate the effect of chrysin on amiodarone extravasation-induced skin injury model in rats. METHODS: The rat model of skin extravasation injury was established by subcutaneous injection of 0.5 mL of amiodarone. After successful modeling, the rats were randomly assigned to the five groups: control group, 10% DMSO group, and low-dose, medium-dose, and high-dose chrysin groups (10, 20 and 40 mg/mL). The extravasation injury model was given locally on the same day for seven days. On day 0, 3, 7 and 10 of administration, the lesion's image were taken to calculate the area, and the tissue of the lesion were collected for H&E staining. Then, the level of IL-6 and TNF-α were measured by ELISA, and the protein expression level of bFGF in the wound tissue were detected by immunohistochemical staining. RESULTS: It was found that chrysin groups (20 and 40 mg/mL) compared to contronl group and 10% DMSO solvent group significantly decreased area injury, IL-6 and TNF-α(P < 0.05) on day 3, 7, 10. On the other hand, the chrysin group (40 mg/mL) compared to contronl group and 10% DMSO group significantly increase bFGF(P < 0.05) on day 3, 7. CONCLUSION: Chrysin were effective in reducing injury area, reducing inflammation, and promoting the secretion of bFGF, it can promote the healing of skin injury induced by amiodarone extravasation in rats. These findings provide a good theoretical and experimental basis for the prevention and treatment of amiodarone extravasation-induced skin injury, and provide evidence for finding potential healing agents for the prevention and treatment of amiodarone and other corrosive extravasation-induced injuries from the molecular and cytological levels, thus solving the clinical problems.

Round ligament suspending treatment in orthotopic ileal-neobladder after radical cystectomy in women: a single-centre prospective randomised trial.

OBJECTIVES: To compare the occurrence of emptying dysfunction between surgical techniques for orthotopic neobladder suspended with round ligament (rONB) and the standard procedure (sONB). PATIENTS AND METHODS: A prospective randomised controlled trial was performed in a single centre of female patients undergoing creation of an ONB using rONB or sONB. Patients were followed for ≥24 months after ONB. The primary endpoints were significant post-void residual urine volume (sPVR) and need for clean intermittent catheterisation (CIC) at 24 months postoperatively. The secondary endpoints included early and late complications, urodynamic profile, and ONB continence. RESULTS: Between January 2011 and October 2017, the trial enrolled 85 patients, of whom 82 were randomised. A total of 41 patients had a rONB and 41 a sONB. At 24 months, 17 of the 37 patients with a sONB and nine of the 39 patients with a rONB had a sPVR. The cumulative risk of a sPVR was significantly lower in the rONB group (23.1%) vs the sONB group (45.9%) (hazard ratio [HR] 0.43, 95% confidence interval [CI], 0.19-0.96; P = 0.040). In all, 15 of the 37 patients with a sONB and four of the 39 patients with a rONB needed CIC. The cumulative risk of requiring CIC was significantly lower in the rONB group (10.3%) vs the sONB group (40.5%) (HR 0.22, 95% CI 0.07-0.67; P = 0.008) at 24 months. Multivariable Cox regression analysis also showed that the rONB type was an independently protective factor for sPVR and CIC. The rates of early (0-90 days) and late complication (>90 days) were 54.1% and 13.5% in the sONB group, and 64.1% and 10.3% in the rONB group, respectively. There were no significant differences in complications, urodynamic profile or ONB continence. A major limitation is the small sample size at a single centre. CONCLUSION: Posterior support with round ligament for an ONB significantly improved the emptying of the ONB and resulted in a reduced need for CIC. The surgical modification is a feasible and safe technique without additional complication-related surgeries.

Photoselective sharp enucleation of the prostate with a front-firing 532-nm laser: an innovative surgical technique for benign prostatic hyperplasia-a single-center study of 475 cases.

PURPOSE: To describe the novel technique of photoselective sharp enucleation of the prostate (PSEP) with a front-firing 532-nm laser and evaluate its efficacy and safety. METHODS: A seven-step standardized surgical procedure was established, and PSEP was performed in an en bloc or lobulate manner according to the size of the middle lobe of the prostate. The following clinical data of 583 patients who underwent PSEP in our center from November 2016 to May 2018 were retrospectively reviewed: maximum flow rate (Qmax), International Prostate Symptom Score (IPSS), quality of life score (Qols), post-void residual volume (PVR), prostate volume, operation time, serum prostate-specific antigen (PSA) concentration, and complications at 1, 6, and 12 months postoperatively. RESULTS: Of the 583 patients, 475 had complete clinical information and were included in the study. The median operation time was 39 min. There were significant improvements in the Qmax, IPSS, Qols, PVR and PSA concentration at each follow-up time point postoperatively. Postoperative hemorrhage occurred in 22 patients (4.6%), urinary retention in 29 (6.1%), urinary tract infection in 55 (11.6%), bladder neck contracture in 8 (1.7%), urethral strictures in 11 (2.3%), and stress urinary incontinence in 9 (1.9%). CONCLUSIONS: PSEP is effective and safe for the treatment of benign prostatic hyperplasia. The innovative technique integrates the excellent hemostatic property of the 532-nm laser and the high efficiency of enucleation. It decreases the occurrence of postoperative incontinence associated with "blunt" enucleation of 532-nm laser and eliminates the lack of tissue samples problem associated with photoselective vaporization of the prostate.

Impacts of mutations on dynamic allostery of adenylate kinase.

Escherichia coli adenylate kinase (AK) is composed of CORE domain and two branch domains: LID and AMP-binding domain (AMPbd). AK exhibits considerable allostery in a reversible phosphoryl transfer reaction, which is largely attributed to the relative motion of LID and AMPbd with respect to CORE. Such an allosteric conformational change is also evident in the absence of ligands. Recent studies showed that the mutations in branch domains can adjust dynamic allostery and alter the substrate affinity and enzyme activity. In this work, we use all-atom molecular dynamics simulation to study the impacts of mutations in branch domains on AK's dynamic allostery by comparing two double mutants, i.e., LID mutant (Val135Gly, Val142Gly) and AMPbd mutant (Ala37Gly, Ala55Gly), with wild-type. Two mutants undergo considerable conformational fluctuation and exhibit deviation from the initially extended apo state to more compact structures. The LID domain in the LID mutant adjusts its relative position and firmly adheres to CORE. More strikingly, AMPbd mutations affect the relative positions of both the AMPbd domain and remote LID domain. Both domains undergo considerable movement, especially the inherent hinge swing motion of the flexible LID domain. In both mutants, the mutations can enhance the inter-domain interaction. The results about the conformation change of AK in both mutants are in line with the experiment of AK's affinity and activity. As revealed by our findings, the flexibility of branch domains and their inherent motions, especially LID domain, is highly relevant to dynamic allostery in the AK system.

Research on Discrete Semantics in Continuous Hand Joint Movement Based on Perception and Expression.

Continuous movements of the hand contain discrete expressions of meaning, forming a variety of semantic gestures. For example, it is generally considered that the bending of the finger includes three semantic states of bending, half bending, and straightening. However, there is still no research on the number of semantic states that can be conveyed by each movement primitive of the hand, especially the interval of each semantic state and the representative movement angle. To clarify these issues, we conducted experiments of perception and expression. Experiments 1 and 2 focused on perceivable semantic levels and boundaries of different motion primitive units from the perspective of visual semantic perception. Experiment 3 verified and optimized the segmentation results obtained above and further determined the typical motion values of each semantic state. Furthermore, in Experiment 4, the empirical application of the above semantic state segmentation was illustrated by using Leap Motion as an example. We ended up with the discrete gesture semantic expression space both in the real world and Leap Motion Digital World, containing the clearly defined number of semantic states of each hand motion primitive unit and boundaries and typical motion angle values of each state. Construction of this quantitative semantic expression will play a role in guiding and advancing research in the fields of gesture coding, gesture recognition, and gesture design.

The prognostic value of routine preoperative blood parameters in muscle-invasive bladder cancer.

BACKGROUND: A routine blood examination is one of the most rapid, convenient and inexpensive clinical examinations that can reflect a patient's inflammatory status and other blood conditions, and the prognostic value of routine preoperative blood parameters in MIBC patients is still unclear, so we evaluated the prognostic value of routine preoperative blood parameters in muscle-invasive bladder cancer (MIBC) following radical cystectomy (RC). METHODS: Data on 202 patients with MIBC who underwent RC at our institution were retrospectively collected between October 2007 and August 2018. The median preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and hemoglobin (HGB) values were used as cutoffs to form the low and high NLR, low and high PLR, and low and high HGB groups, respectively. The clinicopathologic characteristics of each group were compared by chi-square and t tests. Kaplan-Meier survival and multivariate Cox regression analyses were used to analyze prognosis. RESULTS: The median NLR, PLR and HGB values were 2.42, 112 and 125 g/L, respectively. Kaplan-Meier results showed that the low HGB group had poor progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). A high NLR and high PLR groups correlated only with poor OS. Multivariate Cox analyses showed that pathological T3/4 stage, positive lymph node status and low HGB were independent risk factors for PFS, CSS and OS, and age was the only independent risk factor for OS. CONCLUSION: Preoperative peripheral blood HGB is an independent risk factor for the prognosis of MIBC patients. These data suggest that HGB may be a useful prognostic marker for MIBC patients undergoing RC.

Clinical efficacy of submucosal injection of triamcinolone acetonide in the treatment of type II/III interstitial cystitis/bladder pain syndrome.

BACKGROUND: To evaluate the efficacy of submucosal injection of triamcinolone acetonide for the treatment of type II/III interstitial cystitis/bladder pain syndrome. METHODS: A retrospective analysis of the clinical data of type II/III interstitial cystitis/bladder pain syndrome patients treated in our department from April 2016 to August 2018 was conducted, and changes in International Prostate Symptom Scores and the Pelvic Pain and Urgency/Frequency symptom scale after surgery were evaluated to explore factors that may affect patient outcomes. RESULTS: A total of 27 female patients and 8 male patients were enrolled, with type II patients accounting for 62.9% of the sample, and the median follow-up duration was 31 months (range: 12-40 months). Twenty-two patients (74.3%) had significantly improved questionnaire scores at 4 weeks postoperatively. Treatment efficacy was sustained for at least 1 year in 15 patients, and persistent effectiveness was noted in 10 (28.6%) patients. Patients with an advanced age (p = 0.015), high pain scores (p = 0.040), and higher International Prostate Symptom Scores (p = 0.037) and Pelvic Pain and Urgency/Frequency symptom scale scores (p = 0.020) were more likely to benefit from submucosal injection of triamcinolone acetonide. Gender, disease duration, and the presence of Hunner's lesions had no predictive value for treatment outcomes. CONCLUSION: Submucosal injection of triamcinolone acetonide can improve the clinical symptoms and quality of life in both men and women with type II/III interstitial cystitis/bladder pain syndrome. Patients with an advanced age and more severe interstitial cystitis/bladder pain syndrome related symptoms may benefit more from triamcinolone acetonide injection.

Enhanced recovery after surgery for radical cystectomy with ileal urinary diversion: a multi-institutional, randomized, controlled trial from the Chinese bladder cancer consortium.

PURPOSE: Enhanced recovery after surgery (ERAS) has played an important role in recovery management for radical cystectomy with ileal urinary diversion (RC-IUD). This study is to evaluate ERAS compared with the conventional recovery after surgery (CRAS) for RC-IUD. METHODS: From October 2014 and July 2016, bladder cancer patients scheduled for curative treatment from 25 centers of Chinese Bladder Cancer Consortium were randomly assigned to either ERAS or CRAS group. Primary endpoint was the 30-day complication rate. Secondary endpoints included recovery of fluid and regular diet, flatus, bowel movement, ambulation, and length of stay (LOS) postoperatively. Follow-up period was 30-day postoperatively. RESULTS: There were 144 ERAS and 145 CRAS patients. Postoperative complications occurred in 25.7 and 30.3% of the ERAS and CRAS patients with 55 complications in each group, respectively (p = 0.40). There was no significant difference between groups in major complications (p = 0.82), or type of complications (p = 0.99). The ERAS group had faster recovery of bowel movements (median 88 versus 100 h, p = 0.01), fluid diet tolerance (68 versus 96 h, p < 0.001), regular diet tolerance (125 versus 168 h, p = 0.004), and ambulation (64 versus 72 h, p = 0.047) than the CRAS group, but similar time to flatus and LOS. CONCLUSIONS: ERAS did not increase 30-day complications compared with CRAS after RC. ERAS may be better than CRAS in terms of bowel movement, tolerance of fluid and regular diet, and ambulation.

ent-Jungermannenone C Triggers Reactive Oxygen Species-Dependent Cell Differentiation in Leukemia Cells.

Acute myeloid leukemia (AML) is a hematologic malignancy that is characterized by clonal proliferation of myeloid blasts. Despite the progress that has been made in the treatment of various malignant hematopoietic diseases, the effective treatment of AML remains very challenging. Differentiation therapy has emerged as a promising approach for leukemia treatment, and new and effective chemical agents to trigger the differentiation of AML cells, especially drug-resistant cells, are urgently required. Herein, the natural product jungermannenone C, a tetracyclic diterpenoid isolated from liverworts, is reported to induce cell differentiation in AML cells. Interestingly, the unnatural enantiomer of jungermannenone C (1) was found to be more potent than jungermannenone C in inducing cell differentiation. Furthermore, compound 1 targets peroxiredoxins I and II by selectively binding to the conserved cysteine residues and leads to cellular reactive oxygen species accumulation. Accordingly, ent-jungermannenone C (1) shows potential for further investigation as an effective differentiation therapy against AML.

Downregulated XPA promotes carcinogenesis of bladder cancer via impairment of DNA repair.

Bladder cancer is the most common malignant tumor of urinary system, largely resulting from failure of repair of DNA damage to the environmental insults. The function of XPA in nucleotide excision repair pathway has been well documented. However, participation of XPA in the repair of DNA double-strand break remains unknown. Here, we reported that bladder cancer expressed low XPA levels compared to adjacent non-tumor bladder tissue, and this phenotype was closely associated with chromosomal aberrations. Moreover, downregulated XPA appeared to increase incidence of chromosome aberration. XPA reduction increased cell viability of a bladder cancer cell line RT4, while XPA re-expression decreased the cell viability of RT4 cells. Since high mutation frequency is the basis of mutations of oncogenes and anti-oncogenes, and may be the essence of bladder cancer susceptibility, our study suggests that downregulated XPA may promote carcinogenesis of bladder cancer via impairment of DNA repair.

Ginkgolide B Inhibits Human Bladder Cancer Cell Migration and Invasion Through MicroRNA-223-3p.

BACKGROUND/AIMS: Ginkgolide B (GB) is currently used as an anticancer drug for treatment of some malignant cancers. However, whether it may have therapeutic effects on bladder cancer remains unknown. Here, we studied the effects of GB on bladder cancer cells. METHODS: Bladder cells were treated with different doses of GB, and the effects on ZEB1 and microRNA-223-3p (miR-223-3p) were analyzed by RT-qPCR and/or Western blot. Prediction of a regulatory relationship between miR-93 and 3'-UTR of Beclin-1 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. RESULTS: We found that GB dose-dependently decreased ZEB1 protein, but not mRNA, in bladder cancer cells, resulting in suppression of cell invasion. Moreover, in bladder cancer cells, GB dose-dependently decreased the levels of miR-223-3p, which suppressed the protein translation of ZEB1 through binding to 3'-UTR of ZEB1 mRNA. Overexpression of miR-223-3p decreased ZEB1 protein, while depletion of miR-223-3p increased ZEB1 protein in bladder cancer cells. CONCLUSION: GB inhibits bladder cancer cell invasiveness through suppressing ZEB1 protein translation via upregulating miR-223-3p.

Deficiency in perlecan/HSPG2 during bone development enhances osteogenesis and decreases quality of adult bone in mice.

Perlecan/HSPG2 (Pln) is a large heparan sulfate proteoglycan abundant in the extracellular matrix of cartilage and the lacunocanalicular space of adult bones. Although Pln function during cartilage development is critical, evidenced by deficiency disorders including Schwartz-Jampel Syndrome and dyssegmental dysplasia Silverman-Handmaker type, little is known about its function in development of bone shape and quality. The purpose of this study was to understand the contribution of Pln to bone geometric and mechanical properties. We used hypomorph mutant mice that secrete negligible amount of Pln into skeletal tissues and analyzed their adult bone properties using micro-computed tomography and three-point-bending tests. Bone shortening and widening in Pln mutants was observed and could be attributed to loss of growth plate organization and accelerated osteogenesis that was reflected by elevated cortical thickness at older ages. This effect was more pronounced in Pln mutant females, indicating a sex-specific effect of Pln deficiency on bone geometry. Additionally, mutant females, and to a lesser extent mutant males, increased their elastic modulus and bone mineral densities to counteract changes in bone shape, but at the expense of increased brittleness. In summary, Pln deficiency alters cartilage matrix patterning and, as we now show, coordinately influences bone formation and calcification.

Action Speaks Louder: The Role of Proactive Behavior between Creative Leadership and Employees' Creativity.

Drawing on social learning theory, this study presents a moderated mediation model to examine the role of proactive behavior and conformity value in the positive relationship between creative leadership and employees' creativity. Two-wave data are collected from 230 employees and their leaders in an automobile manufacturing enterprise in China, in which employees are encouraged to be creative because they need to implement novel designs and proposals to attract consumers. Statistical analysis reveals that proactive behavior partially mediates the influence of creative leadership on employees' creativity. Conformity value moderates not only the relationship between creative leadership and proactive behavior but also the indirect effect of creative leadership on employees' creativity via proactive behavior. The relationship and the mediating mechanism are stronger in the presence of employees' higher conformity value. We discuss the theoretical and practical implications as well as future research directions of the findings.