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The team developed the newly compiled eight methods and five steps of Tai Chi (EMFSTC), which includes introductory routines to Tai Chi characterized by simple structures. This study examined the effectiveness of EMFSTC practice on balance control. A total of 31 participants were randomly assigned to EMFSTC (n = 15, age = 66.4 ± 1.7 years, received 16-week EMFSTC practice) or control (n = 16, age = 66.7 ± 1.8 years, received no practice) groups. Significant group by training interactions were observed. After EMFSTC practice, balance control improved, as indicated by decreased root mean square and mean velocity of center of pressure, proprioception threshold during knee extension, and plantar tactile sensitivity threshold at the arch. EMFSCT can be an effective rehabilitation modality to improve balance control among older adults.

Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis. Genetic depletion of pericytes in GBM xenografts enhances TMZ-induced cytotoxicity and prolongs survival of tumor-bearing mice. Mechanistically, C-C motif chemokine ligand 5 (CCL5) secreted by pericytes activates C-C motif chemokine receptor 5 (CCR5) on GBM cells to enable DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-mediated DDR upon TMZ treatment. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ. GBM patient-derived xenografts with high CCL5 expression benefit from combined treatment with TMZ and MVC. Our study reveals the role of pericytes as an extrinsic stimulator potentiating DDR signaling in GBM cells and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.

To investigate the duration of humoral immune response in convalescent coronavirus disease 2019 (COVID-19) patients, we conduct a 12-month longitudinal study through collecting a total of 1,782 plasma samples from 869 convalescent plasma donors in Wuhan, China and test specific antibody responses. The results show that positive rate of IgG antibody against receptor-binding domain of spike protein (RBD-IgG) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the COVID-19 convalescent plasma donors exceeded 70% for 12 months post diagnosis. The level of RBD-IgG decreases with time, with the titer stabilizing at 35.7% of the initial level by the 9th month. Moreover, male plasma donors produce more RBD-IgG than female, and age of the patients positively correlates with the RBD-IgG titer. A strong positive correlation between RBD-IgG and neutralizing antibody titers is also identified. These results facilitate our understanding of SARS-CoV-2-induced immune memory to promote vaccine and therapy development., COVID-19 pandemic is a global health risk, but our understanding on the induced durable immunity remains scarce. Here the authors assess antibody responses in 869 convalescent COVID-19 patients to find that specific antibody titers reduce with time, and the RBD-IgG positive rate exceed 70% at 12 month post diagnosis, with male and older patients showing stronger responses.

MicroRNAs (miRNAs) function as post-transcriptional mediators for genes involved in cancer progression, including chronic lymphocytic leukemia. MiR-582-5p has been identified as a tumor suppressor in various tumors. The antioncogenic role of miR-582-5p was then validated in this study. Mononuclear cells were isolated from peripheral blood samples of patients with chronic lymphocytic leukemia and healthy donors. Expression of miR-582-3p in the mononuclear cells was examined by qRT-PCR. CCK8 assay was performed to detect cell viability, and cell cycle and apoptosis were evaluated by flow cytometry. Dual luciferase activity assay was performed to determine the targeting relationship between miR-582-3p and HNRNPA1, and western blot was performed to unravel the mechanism. MiR-582-5p was reduced in mononuclear cells of patients with chronic lymphocytic leukemia compared to healthy donors. Forced miR-582-5p expression reduced cell viability, and promoted apoptosis of chronic lymphocytic leukemia cells. Cell cycle was arrested in G0/G1 phase via miR-582-5p mimic. MiR-582-5p bound to HNRNPA1 (heterogeneous nuclear ribonucleoprotein A1) and down-regulated its expression. Silence of HNRNPA1 decreased cell viability, promoted apoptosis, and blocked cell cycle at G0/G1 phase through up-regulation of IκBα (IkappaBalpha). Moreover, HNRNPA1 silencing attenuated the promotive effect induced by miR-582-5p inhibitor on the progression of chronic lymphocytic leukemia. MiR-582-5p demonstrated anti-proliferative and pro-apoptotic roles in chronic lymphocytic leukemia cell growth via down-regulation of HNRNPA1 and up-regulation of IκBα, thus inactivating NF-κB.

Fibulin-1 (FBLN-1), an elastin-associated extracellular matrix protein, has been found in blood and may play a role in the pathophysiological processes leading to cardiovascular disease (CVD). We aimed to investigate the relationship between fibulin-1 levels and the risk of CVD by evaluating vascular age derived from the Framingham Heart Study and brachial-ankle Pulse Wave Velocity (baPWV) in patients with asymptomatic hyperuricemia (AHU). In total, 66 patients with AHU and 66 gender- and age-matched healthy individuals were enrolled. The plasma fibulin-1 levels were measured by immunochemistry. Patients with AHU presented significantly higher vascular age [median (interquartile range): 54 (22) vs. 48 (14) years, P=0.01] and baPWV [mean±SD: 1373±223 vs. 1291±177 cm/s, P=0.02] than the healthy subjects; however, no significant difference was observed in the plasma fibulin-1 level between the patients with AHU and healthy subjects [median (interquartile range): 4018 (3838) vs. 3099 (3405) ng/mL, P=0.31]. A correlation between fibulin-1 levels and baPWV was observed only in patients with AHU (r=0.29, P=0.02); and there was also a suggestively statistically significant correlation between fibulin-1 levels and vascular age (r=0.22, P=0.08). However, these associations were rendered insignificant after adjustments for potential confounders. In healthy subjects, no correlation was observed between fibulin-1 levels and CVD risk. This study reveals that plasma fibulin-1 levels may reflect the CVD risk in patients with AHU, but the relationship is not robust.

A dye-sensitive photocatalytic H2 evolution reaction (HER) system with photogenerated carrier directed conduction was constructed. The protonated g-C3N4 combines with the sheet-like Co MOF to form a 2D/2D heterojunction via electrostatic self-assembly. The protonated g-C3N4 and 2D Co-MOF directionally adsorb Eosin Y (EY) and triethanolamine (TEOA) molecules through hydrogen bond and complexation to achieve a whole photocatalytic system. The integral structure effectively facilitates the utilization of dye sensitizer and hole sacrificial agent to achieve the effective and stable photocatalytic H2 evolution capacity. The photocatalytic hydrogen evolution rate of g-C3N4 after protonation is 1.88 times as high as that of the original g-C3N4. On the basis of 2D/2D heterojunction, Co MOF is doped with rare earth element Sm. The 4f electrons and the difference valences (Sm3+ and Co2+) further suppress the reorganization of photogenerated excitons to achieve highly efficient photocatalytic HER. The directional coupling of sensitizer and electron sacrificial agent combined with rare earth element doping makes the photocatalytic HER rate of the composite material reached 73.42 μmol.h−1 within 5 h under simulated sunlight.

Objective The aim of this study was to examine the survival rate of patients with different bone sarcomas and to investigate homogenous and heterogenous prognostic factors for different types of bone sarcomas. Methods This is a retrospective analysis of records from the Surveillance, Epidemiology, and End Result (SEER) database. Clear information on the distant metastasis of cancer is provided in the SEER database for patients diagnosed between January 2010 and December 2016. Data for the four types of malignant bone sarcomas were extracted, including osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma. Patients with bone sarcomas originated from other sites, diagnosed at autopsy, or indicated in death certification were excluded. The overall survival was calculated for the entire cohort and across different bone sarcomas using the Kaplan–Meier method. A subgroup analysis of the different survival rates of four types of bone sarcomas in various levels of each variable was conducted and the differences were tested with the log‐rank test. Cox proportional hazard regression analysis was performed to determine the prognostic factors. Variables with P, Patients with chordoma, chondrosarcoma, Ewing sarcoma, and osteosarcoma showed homogenous and heterogenous clinicopathological characteristics, survival rates, and prognostic factors, which can potentially guide sarcoma‐specific prediction and treatments.

Background Papillary thyroid cancer (PTC) is the most common type of thyroid cancer. However, due to the lack of reliable prognostic biomarkers for PTC, overtreatment has been on the rise. Therefore, our research aims to identify new and promising prognostic biomarkers and provide fresh perspectives for clinical decision making. Methods The RNA‐seq data and clinical data of PTC samples were obtained from The Cancer Genome Atlas data portal. GSE64912 and GSE83520 datasets were downloaded through the GEOquery R package. The difference in the expression of oxoglutarate dehydrogenase like (OGDHL) between PTC and normal tissues was explored by the Wilcoxon test. Kaplan–Meier (KM) and Cox regression analyses were used to further explore the prognostic value of OGDHL. The tumor microenvironments of PTC patients were explored based on ssGSEA and Tumor Immune Estimation Resource online database. Gene Set Enrichment Analysis (GSEA) was performed to explore the biological processes associated with OGDHL. Results The expression level of OGDHL in PTC was significantly altered compared to that in normal tissues (p, Our study proved that the expression of OGDHL was closely related to the prognosis of PTC, and could be used as a new promising prognostic biomarker for PTC.

Background: This study aims to assess the sex disparities in clinical characteristics and synchronous distant metastasis occurrence at diagnosis, as well as the subsequent prognosis in non-sex-specific cancers. Methods: The study included details from patients diagnosed with non-sex-specific cancers, during the period from 2010 to 2016, in the Surveillance, Epidemiology, and End Results (SEER) program. The distant metastasis prevalence and subsequent survival time were summarized in the total population and the population with specific cancers of different systems. The multivariable logistic and the Cox proportional hazards regressions were applied to evaluate the sex effect on distant metastasis occurrence and prognosis. The results were combined using meta-analysis. Results: Across all non-sex-specific cancers, the pooled prevalence of distant metastasis was 15.2% (95% CI: 14.7-15.7%) and 7.1% (95% CI: 6.8-7.3%) for males and females, respectively. The pooled median survival time was 8.40 months (95% CI: 7.99-8.81) for male patients and 9.40 months (95% CI: 8.84-10.02) for female patients. After combining all non-sex-specific cancers, male patients displayed a higher distant metastasis occurrence than females (pooled OR=1.06, 95% CI: 1.04-1.08; P

The cooling control of the melt during the casting process is of great significance. A comprehensive closed-loop cooling control of castings by adopting a skeletal sand mold design was proposed. The skeletal sand mold consisting of an adaptive shell, functional cavities and a support was designed and created based on the finite difference meshes of a casting. It was applied to a round wall test casting. Two kinds of skeletal sand molds, one with lattice support and the other with enforcing ribs for this casting were designed and printed out by the 3D printing (3DP) method. Aluminum alloy A356 was cast by using these two sand molds. The first mold was cooled by natural convection, the other one by water spray cooling. Two sound castings were obtained. The sand mold temperature, cooling curves, microstructures, mechanical properties, residual stress and deformation were measured, compared and discussed. Water spray cooling hastened the cooling rate by 62%, increased the content of Mg and Cu in the α-Al matrix, improved the mechanical properties, and altered the surface residual stress state.

This study aimed to develop a model that fused multiple features (multi-feature fusion model) for predicting metachronous distant metastasis (DM) in breast cancer (BC) based on clinicopathological characteristics and magnetic resonance imaging (MRI). A nomogram based on clinicopathological features (clinicopathological-feature model) and a nomogram based on the multi-feature fusion model were constructed based on BC patients with DM (n=67) and matched patients (n=134) without DM. DM was diagnosed on average (17.31±13.12) months after diagnosis. The clinicopathological-feature model included seven features: reproductive history, lymph node metastasis, estrogen receptor status, progesterone receptor status, CA153, CEA, and endocrine therapy. The multi-feature fusion model included the same features and an additional three MRI features (multiple masses, fat-saturated T2WI signal, and mass size). The multi-feature fusion model was relatively better at predicting DM. The sensitivity, specificity, diagnostic accuracy and AUC of the multi-feature fusion model were 0.746 (95% CI: 0.623-0.841), 0.806 (0.727-0.867), 0.786 (0.723-0.841), and 0.854 (0.798-0.911), respectively. Both internal and external validations suggested good generalizability of the multi-feature fusion model to the clinic. The incorporation of MRI factors significantly improved the specificity and sensitivity of the nomogram. The constructed multi-feature fusion nomogram may guide DM screening and the implementation of prophylactic treatment for BC.

We aimed to perform a pan-metastatic cancer analysis on survival and prognostic factors and to create a prognosis-based classification system. We selected distant metastasis patients from the Surveillance, Epidemiology, and End Results (SEER) database. The associations between the characteristics of the patients at admission and overall survival were determined. A prognosis-based metastatic cancer classification was established based on the identified prognostic factors. The differences in prognosis among these categories were tested. The survival rate and prognostic factors were not consistent across cancers. Three metastatic cancer categories were generated, each with different prognoses. The prognostic differences among the categories were satisfactorily validated. Different metastatic cancer types had homogeneous and heterogeneous survival rates and prognostic factors. A prognosis-based classification system for synchronous distant metastasis cancer patients at admission was created. This classification system reflects the grade of malignancy in metastatic cancers and may guide the prediction of survival and individualized treatment. Moreover, it may have important implications for the management of synchronous metastatic cancers and aid clinicians in properly allocating medical resources to metastatic patients.

Objectives: The present study aimed to evaluate the early mortality rate and associated factors for early death in bone and soft tissue tumors, and to construct predictive nomogram. Methods: Patients diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) dataset were enrolled. The early death (survival time ≤ 3 months) rate was calculated and associated risk factors were evaluated by the logistic regression models. The significant factors were used to construct predictive nomograms. Results: A total of 2,003 (8.5%) patients died within 3 months after cancer diagnosis, among whom 1,146 (4.9%) patients died from cancer-specific cause. Older age (19-50 and >50 years), grade (III and IV), reginal or distant stage were associated with higher odds of total, cancer-specific and non-cancer-specific early death. T2 stage, metastasis to brain and lung were risk factors for total and cancer-specific early death. Surgical interventions significantly decreased the odds of total, cancer-specific and non-cancer-specific early death. Female and black race were associated with lower odds of non-cancer-specific early death. The area under the curve (AUC) of the nomograms for total early death, cancer-specific and non-cancer-specific early death prediction was 88.0%, 89.0% and 83.2%, respectively. Conclusions: A total of 8.5% patients with bone and soft tissue tumors suffered early death. Several risk factors were associated with higher odds of early death while surgery can decrease the possibility of early death. Nomograms based on all related factors can be used to estimate the early death in bone and soft tissue tumors.

Glioblastoma multiforme (GBM) is the most malignant form of glioma, and the overall survival time of patients with GBM is usually less than 14 months. Therefore, it is urgent to find new and effective medicine for GBM. Recently, marine natural products have been shown to exhibit strong inhibitory effects on cancer cells, providing a new avenue for exploring novel drugs for GBM treatment. In this study, we investigated the inhibitory effect of the Grincamycin (GCN) B-F, newly isolated from marine-derived Streptomyces Lusitanus SCSIO LR32, on GBM cells, and evaluated the mechanism of GCN B on GBM. The results, for the first time, showed that GCN B acted as a potent inhibitor to suppress growth and invasion of two human GBM cell lines U251 and 091214 in vitro. In addition, GCN B could effectively target GSCs in GBM evidenced by attenuated formation of tumor spheres and decrease of several markers of GSCs. Furthermore, we performed gene expression microarray followed by Signal-Net analysis. The result revealed that RHOA and PI3K/AKT axis played critical roles for a GCN B-mediated inhibitory effect on GSCs. Altogether, our findings highlighted GCN B as a promising inhibitor for GSCs via targeting RHOA and PI3K/AKT.

Background To evaluate the association between apolipoprotein B gene polymorphism and coronary heart disease in some populations at home and abroad by means of meta-analysis. Methods Using the strict exclusion criteria for primary screening of the literature and applying the Hardy-Weinberg equilibrium to test the genetic balance of the selected literature. The corresponding models were selected according to the results of the heterogeneity test. The Begg’s test and Egger’s test were used to evaluate publication bias, and meta-analysis was performed using Stata 12.0. Results The study included twelve articles. In the literature, a total of 1596 patients with coronary heart disease and 1431 controls.Meta-analysis results showed no statistical value in the following three genetic models: allelic comparison (a vs A,P = 0.811,OR = 0.95, 95%CI = 0.62–1.46), recessive genetic models (aa vs Aa/AA, P = 0.86,OR = 0.94, 95%CI = 0.45–1.96), or dominant genetic models (aa/Aa vs AA, P = 0.73,OR = 0.92, 95%CI = 0.58–1.47). Subgroup analysis based on ethnicity showed allelic comparison (a vs A,P = 0.464,OR = 1.32, 95%CI = 0.63–2.78), recessive genetic models (aa vs Aa/AA, P = 0.422,OR = 1.52, 95%CI = 0.55–4.21), and dominant genetic models (aa/Aa vs AA, P = 0.551,OR = 1.26, 95%CI = 0.58–2.73) in Asians, allelic comparison (a vs A,P = 0.410,OR = 0.79, 95%CI = 0.45–1.39), recessive genetic models (aa vs Aa/AA, P = 0.041,OR = 0.75,95%CI = 0.57–0.99),dominant genetic models (aa/Aa vs AA, P = 0.385,OR = 0.75, 95%CI = 0.40–1.43) in Caucasian; Conclusion The ApoB(apolipoprotein B) XbaI locus is not a risk factor when it comes to the development of coronary heart disease in the domestic and international populations included in this paper. In Caucasians, people carrying the aa genotype may be less susceptible to CHD (coronary heart disease). The results of recessive genetic models have to take the effect of heterogeneity and sample sizes into account. Further research may require a larger and more rigorous research design.

Background: Melanoma is a cancer of the skin with potential to spread to other organs and is responsible for most deaths due to skin cancer. It is imperative to identify immune biomarkers for early melanoma diagnosis and treatment. Results: 63 immune-related genes of the total 1039 unique IRGs retrieved were associated with overall survival of melanoma. A multi-IRGs classifier constructed using eight IRGs showed a powerful predictive ability. The classifier had better predictive power compared with the current clinical data. GSEA analysis showed multiple signaling differences between high and low risk score group. Furthermore, biomarker was associated with multiple immune cells and immune infiltration in tumor microenvironment. Conclusions: The immune-related genes prognosis biomarker is an effective potential prognostic classifier in the immunotherapies and surveillance of melanoma. Methods: Melanoma samples of genes were retrieved from TCGA and GEO databases while the immune-related genes (IRGs) were retrieved from the ImmPort database. WGCNA, Cox regression analysis and LASSO analysis were used to classify melanoma prognosis. ESTIMATE and CIBERSORT algorithms were used to explore the relationship between risk score and tumor immune microenvironment. GSEA analysis was performed to explore the biological signaling pathway.

Background Stair descent is one of the most common and challenging daily activities for several populations, particularly under dual-task conditions. This study investigated the effects of cognitive or manual task on kinematics and kinetics during stair descent. Methods A total of 37 participants performed stair descent under three conditions: stair descending only, stair descending while performing a cognitive task and stair descending while performing a manual task. Kinematic and kinetic data were collected. Multivariate analysis of variance with repeated measures was conducted to test the significant differences among the three conditions. Results The gait performance, loading rate, lower limb joint moments and powers were significantly lower under the two dual-task conditions compared with stair descending only. The participants had lower knee flexion/extension range of motion, loading rate, peak hip flexion moment, first peak knee extensor moment, second peak ankle plantar flexion moment, first knee power absorption and less stride width under the manual task compared with the cognitive task. Conclusions Dual tasks during stair descent had a significant impact on the kinematics and kinetics of motion, and the effect was more significant while performing a concurrent manual task in healthy young adults. Further studies could focus on the complexity level of dual tasks on the biomechanical parameters during stair walking.

Chidamide has demonstrated significant clinical benefits for patients with relapsed/refractory (R/R) PTCL in previous studies. This multi-center observational study was aimed to evaluate the objective response rate (ORR), overall survival (OS), and safety of chidamide. From February 2015 to December 2017, 548 patients with R/R PTCL from 186 research centers in China were included in the study. Among the 261 patients treated with chidamide monotherapy, ORR was 58.6% and 55 patients (21.1%) achieved complete response (CR). Among the 287 patients receiving chidamide-containing combination therapies, ORR was 73.2% and 73 patients (25.4%) achieved CR. The median OS of all patients was 15.1 months. The median OS of patients receiving chidamide monotherapy and combination therapies was 433 and 463 days, respectively. These results demonstrate a significant survival advantage of chidamide treatments as compared with international historical records. Common adverse effects (AEs) were hematological toxicities. Most AEs in both monotherapy and combined treatments were grade 1–2. No unanticipated AEs occurred. In conclusion, chidamide-based therapy led to a favorable efficacy and survival benefit for R/R PTCL. Future studies should explore the potential advantage of chidamide treatment combined with chemotherapy.

One new phenolic glycoside, methyl 3,4-dihydroxyphenylacetate-4-O-[2-O-β-D-apisoyl-6-O-(2-hydroxybenzoyl)]-β-D-glucopyranoside (1), together with 10 known compounds (2–11), were isolated from the r...

Necrosis with inflammation plays a crucial role in acute respiratory distress syndrome (ARDS). Receptor-interacting protein 3 (RIPK3) regulates a newly discovered programmed form of necrosis called necroptosis. However, the underlying mechanism of necroptosis in ARDS remains unknown. Thus, the purpose of this study was to examine the possible involvement of RIPK3 in ARDS-associated necroptosis. RIPK3 protein levels were found to be significantly elevated in the plasma and bronchoalveolar lavage fluid of ARDS patients. Next, we utilised a mouse model of severe ARDS induced with high-dose lipopolysaccharide and found that lung injury was mainly due to RIPK3-mixed lineage kinase domain-like pseudokinase (MLKL)-mediated necroptosis and endothelial dysfunction. The activation of RIPK3-MLKL by tumour necrosis factor receptor 1 (TNFR1) and TNFR1-associated death domain protein (TRADD) required catalytically active RIPK1 and the inhibition of Fas-associated protein with death domain (FADD)/caspase-8 catalytic activity. We further showed that the molecular chaperone heat shock protein 90 (Hsp90)/p23, as a novel RIPK3- and MLKL-interacting complex, played an important role in RIP-MLKL-mediated necroptosis, inflammation and endothelial dysfunction in the pulmonary vasculature, which resulted in ARDS. Collectively, the results of our study indicate that necroptosis is an important mechanism of cell death in ARDS and the inhibition of necroptosis may be a therapeutic intervention for ARDS. KEY MESSAGES: Lung injury in high-dose LPS-induced severe ARDS is mainly due to RIP3-MLKL-mediated necroptosis and endothelial dysfunction. Chaperone HSP90/p23 is a novel RIP3- and MLKL-interacting complex in HPAECs. HSP90/p23 is a novel RIP3- and MLKL-interacting complex in RIP-MLKL-mediated necroptosis, inflammation and endothelial dysfunction.

This paper uses computer technology combined with regression model to analyze the risk factors of children with sepsis, determine the relevant factors and establish a corresponding early warning model of sepsis, and then verify the clinical application value of the regression model. The paper collected severe infections and sepsis in children who came to our hospital from 2014 to 2018, including 129 patients with infection and 86 patients with sepsis. The general conditions, clinical symptoms, laboratory tests and other factors were used. Analysis, to identify the risk of infection development into sepsis, and use Logistic regression model combined with computer technology to construct an early warning model of sepsis. The experimental results show that early warning of sepsis is closely related to skin spots, platelets, procalcitonin, creatinine and international normalized ratio. The experiment demonstrates that the early warning model has higher sensitivity and specificity, and has higher accuracy for predicting whether infection develops into sepsis in advance, and has certain clinical value. Keywords: Logistic regression analysis, Computer technology, Early warning model for children with sepsis

PURPOSE: In contrast to other studies, our previous study showed that adding induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) significantly worsened the prognosis of patients with stage II nasopharyngeal carcinoma (NPC). However, the population used was small; therefore, there is an urgent need to confirm the result in a larger population because IC is still widely used in certain sections of china for stage II NPC. METHODS AND MATERIALS: We retrospectively analyzed an additional 272 patients. Therefore, in total, we report the results for 445 patients with stage II NPC treated with IC + CCRT or CCRT between June 2003 to June 2016 at the Zhejiang Cancer Hospital and Sun Yat-Sen University Cancer Center. RESULTS: This study included 445 patients treated with IC + CCRT (n = 195) or CCRT (n = 250). By last analysis, 22 (11.3%) patients in the IC + CCRT group developed local-regional recurrence and 23 (11.8%) patients developed distant metastases. Twenty-four (9.6%) patients in the CCRT group developed local-regional recurrence and 12 (4.8%) patients developed distant metastases. Univariate analyses showed that adding IC to CCRT significantly decreased the 5-year disease-free survival (DFS) (80.6% vs. 88.5%, P = .043); however, there was no statistically significant difference in 5-year overall survival (OS) (90.5% vs. 95.0%, P = .375). CONCLUSION: Using a larger population, the present study showed that adding IC to CCRT had a negative effect on patients with stage II NPC, which warrants further investigation.

One of the most effective methods to improve electron-transfer efficiency and photocatalytic reaction activity is to construct a photocatalyst with a heterojunction interface. Herein, a WO3/CoS2 n–n heterojunction composite catalyst was synthesized, and used in photocatalytic hydrogen evolution, and was optimized by adjusting the pH of the triethanolamine solution, the amount of Eosin Y added, and the content of WO3 in the composite catalyst. After 5 h of photocatalytic reaction, WO3/CoS2 (WCS-2) had a H2 production of 221.15 μmol, which was 80.41 times that of single WO3 and 2.17 times that of CoS2, and had good stability. XRD, SEM, TEM, and XPS characterization results indicated that WO3/CoS2 was successfully prepared. Fluorescence test and electrochemical test results showed that the WO3/CoS2 catalyst had a higher photoelectron transfer efficiency. Finally, it is pointed out that WO3/CoS2 enhanced the photocatalytic activity, which may be due to the electron migration of WO3 and CoS2 following the Z-scheme mechanism. This work presents a new idea for constructing n–n heterojunction to enhance the activity in photocatalytic hydrogen production.

The development of new drugs for nonalcoholic steatohepatitis (NASH) is a current focus of research in the management of liver disease. Here we provided an overview of NASH drug pipelines and the challenges faced in conducting phases II and III clinical trials. These challenges include the selection and definition of research populations, rational selection of study end-points, choice of noninvasive diagnostic indicators, accounting for confounding factors and safety assessments. Furthermore, we discussed how to establish guidelines for study design and end-points in complex clinical trials of anti-NASH drugs.

Background The thoracic radiotherapy (TRT) target volume for limited-stage small-cell lung cancer (SCLC) has been controversial for decades. In this report, the final results of a prospective randomized trial on the TRT target volume before and after induction chemotherapy are presented. Methods After 2 cycles of etoposide and cisplatin, patients arm were randomized to receive TRT to the postchemotherapy or prechemotherapy tumor volume in a study arm and a control arm. Involved-field radiotherapy was received in both arms. TRT consisted of 1.5 grays (Gy) twice daily in 30 fractions to up to a total dose of 45 Gy. Lymph node regions were contoured, and intentional and incidental radiation doses were recorded. Results The study was halted early because of slow accrual. Between 2002 and 2017, 159 and 150 patients were randomized to the study arm or the control arm, respectively; and 21.4% and 19.1% of patients, respectively, were staged using positron emission tomography/computed tomography (P = .31). With a median follow-up of 54.1 months (range, 19.9-165.0 months) in survivors, the 3-year local/regional progression-free probability was 58.2% and 65.5% in the study and control arms, respectively (P = .44), and the absolute difference was -7.3% (95% CI, -18.2%, 3.7%). In the study and control arms, the median overall survival was 21.9 months and 26.6 months, respectively, and the 5-year overall survival rate was 22.8% and 28.1%, respectively (P = .26). Grade 3 esophagitis was observed in 5.9% of patients in the study arm versus 15.5% of those in the control arm (P = .01). The isolated out-of-field failure rate was 2.6% in the study arm versus 4.1% in the control arm (P = .46), and all such failures were located in the supraclavicular fossa or contralateral hilum. The regions 7, 3P, 4L, 6, 4R, 5, and 2L received incidental radiation doses >30 Gy. Conclusions TRT could be limited to the postchemotherapy tumor volume, and involved-field radiotherapy could be routinely applied for limited-stage SCLC.

Sm2MoO6/Ni(OH)2 was successfully immersed in water first, and the sensitizer is Eosin Y and the sacrificial agent is triethanolamine agent for high-efficiency photocatalytic production of H2. When Sm2MoO6 was loaded onto the surface of Ni(OH)2, the photocatalytic activity (2407.48 μmol g−1 h−1) was 2.6 times that of Ni(OH)2 (925.36 μmol g−1 h−1), which was Sm2MoO6 (169.36 μmol g−1 h−1) is 14.2 times. From a series of characterizations, Sm2MoO6 is an effective cocatalyst to improve the separation of photo-generated charges and the efficiency of electron transfer. Large specific surface areas are a primary requirement for high efficiency catalysts, and the catalyst is sufficiently into contact with the sensitizer and the sacrificial agent to soar the photocatalytic activity. The first condition for an excellent catalyst is that it has a large specific surface area and can provide more active sites. In the dye sensitization system, the photocatalytic activity of Sm2MoO6/Ni(OH)2 is 2.6 times that of Ni(OH)2 and 14.2 times that of Sm2MoO6. Sm2MoO6 is an effective co-catalyst.

Background and objectives: Ovarian cancer is the most fatal primary malignancy among gynecological cancers. Circular RNAs (circRNAs) play an important role in the development of various cancers, but the functions of circRNAs in ovarian cancer development have not been studied. We aim to explore the function and mechanism of CDR1as in the progression of ovarian cancer and to provide a new target for the diagnosis and treatment of ovarian cancer. Methods: Ovarian cancer cell proliferation was assessed according to proliferating cell nuclear antigen (PCNA) and Ki67 protein expression levels and MTT and CCK8 assays. The migration ability of cells was detected by scratch-wound assays, and the invasion ability of the cells was determined by Transwell® assays. qRT-PCR and Western blotting were used to verify miRNA and protein expression. Results: CDR1as expression in ovarian tissues was significantly lower in ovarian cancer patients than in patients without ovarian cancer. CDR1as overexpression inhibited the proliferation, invasion and migration of ovarian cancer cells. Silencing CDR1as increased the expression of miR-135b-5p and decreased the expression of hypoxia-inducible factor 1-alpha inhibitor (HIF1AN), thus increasing the proliferation capacity of ovarian cancer cells. Conclusions: CDR1as, acting as a sponge of miR-135b-5p, promotes the expression of HIF1AN and therefore plays a role in tumor inhibition.

Osteosarcoma is the most common primary malignant bone tumor. Raddeanin A (RA) is an active oleanane-type triterpenoid saponin extracted from the traditional Chinese herb Anemone raddeana Regel that exerts antitumor activity against several cancer types. However, the effect of RA on osteosarcoma remains unclear. In the present study, we showed that RA inhibited proliferation and induced apoptosis of osteosarcoma cells in a dose- and time-dependent way in vitro and in vivo. RA treatment resulted in excessive reactive oxygen species (ROS) generation and JNK and ERK1/2 activation. Apoptosis induction was evaluated by the activation of caspase-3, caspase-8, and caspase-9 and poly-ADP ribose polymerase (PARP) cleavage. RA-induced cell death was significantly restored by the ROS scavenger glutathione (GSH), the pharmacological inhibitor of JNK SP600125, or specific JNK knockdown by shRNA. Additionally, signal transducer and activator of transcription 3 (STAT3) activation was suppressed by RA in human osteosarcoma, and this suppression was restored by GSH, SP600125, and JNK-shRNA. Further investigation showed that STAT3 phosphorylation was increased after JNK knockdown. In a tibial xenograft tumor model, RA induced osteosarcoma apoptosis and notably inhibited tumor growth. Taken together, our results show that RA suppresses proliferation and induces apoptosis by modulating the JNK/c-Jun and STAT3 signaling pathways in human osteosarcoma. Therefore, RA may be a promising candidate antitumor drug for osteosarcoma intervention.

Objective: Uric acid is thought to be associated with the occurrence of atherosclerosis, which is closely related to cardio-cerebrovascular disease. However, the present study examined serum uric acid (SUA) and its correlation with carotid intima-media thickness (CIMT), which is a major issue. The purpose of this paper is to examine serum uric acid concentration and its correlation with carotid artery atherosclerosis according to age and sex groups.Methods: Individuals who underwent physical examinations at the First Affiliated Hospital of Chongqing Medical University from 2016 to 2020 were selected. The physical examination information of the subjects was recorded, and biochemical indexes such as blood uric acid levels were collected. The intima media thickness of the carotid artery was measured by ultrasound. Using traditional atherosclerosis risk factors as adjustment variables, the association between blood uric acid levels and atherosclerosis was assessed by logistic regression analysis.Results: A total of 15,843 subjects (73.90% male) were included, with an average age of 52±12 (20-92) years. The prevalence of CIMT thickened was 9.51%, and the plaque prevalence was 28.59%. Univariate analysis results showed that there were significant differences in CIMT thickening and plaque occurrence among different SUA level groups in both men and women (P430 μmol/L: OR=1.857, 95% CI: 1.264-2.73;P < 0.05. female: ≤210 μmol/L as the reference group, 260-310 μmol/L: OR=1.419, 95% CI: 1.059-1.901; 310-360 μmol/L: OR=1.432, 95% CI: 1.048-1.957; >360 μmol/L: OR=1.557, 95% CI: 1.113-2.177; P < 0.05). Correlation analysis in each age subgroup showed that CIMT was significantly associated with SUA in men ≥60 years old and women 45-60 years old and ≥60 years old (male: ≤220 μmol/L as the reference group, >430 μmol/L: OR=1.972, 95% CI: [1.2,3.238]. female: ≤210 μmol/L as the reference group, >360 μmol/L (45-60 years old): OR=1.77, 95% CI:[1.107,2.832]; > 360 μmol/L (≥60 years old), OR = 1.65, 95% CI: [1.067, 2.551]. P < 0.05).Conclusions: In both men and women, increased SUA levels are closely associated with thickened CIMT, which is associated with a higher risk of cardio-cerebrovascular disease. The age at which this association was observed in women was lower than in men, and whether this result is due to changes in hormone levels before and after menopause remains to be prospectively studied.

Rationale: The etiology of acute respiratory distress syndrome (ARDS) may play an important role in the failure of noninvasive ventilation (NIV). Objectives: To explore the association between ARDS...

Background: Osteosarcoma (OS) is the most common malignant bone cancer. Recently, more studies have shown that TPX2, a potential oncogene considered to be an important prognostic biomarker, is widely expressed in various tumors. However, until now, little is known about the impacts of TPX2 on the pathogenesis of OS. Methods: TPX2 expression of in OS cells and tissues was detected by Western blot and immunohistochemical analyses. Various assays were used to analyze OS cell proliferation and metastasis in vitro and in vivo. The effect of TPX2 on the expression of E2F1 and proteins encoded by E2F1-regulated genes was evaluated by Western blotting. Coimmunoprecipitation, immunofluorescence and in vitro ubiquitination assays were employed to explore the molecular mechanisms underlying the effect of TPX2 on stabilizing E2F1 and maintaining E2F1 signaling. Findings TPX2 is overexpressed in OS and is significantly correlated with the malignant progression of OS. TPX2 probably plays a critical role in the proliferation and metastasis of OS cells in vitro. Furthermore, TPX2 regulates E2F1 signaling by affecting the stability of E2F1, thereby affecting the proliferation and metastasis of OS cells. In addition, PSMD14 impacts the degradation and regulates the stability of E2F1. Most importantly, TPX2 regulates the interaction of E2F1 and PSMD14 to influence E2F1 degradation. Interpretation: Collectively, our research not only identifies TPX2 ground as a promising therapeutic target in cancer but also illuminates its underlying molecular mechanism. We showed that TPX2 promotes the malignant progression of OS by regulating E2F1 signaling. Funding: This project was supported by the NSFC (81802985), and a Research Grant from the Shanghai Hospital Development Center (SHDC2020CR2037B). Declaration of Interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethical Approval: All animal experiments were performed under the protocols approved by the Shanghai General Hospital Institutional Animal Care and Use Committee. Six-week-old female BABL/c nude mice were obtained from SLRC laboratory Animal (Shanghai, China). The Central Laboratory of Shanghai General Hospital approved this study.

The clinical controversy of rosiglitazone as a hypoglycemic agent is potentially associated with heart failure, mainly due to its potent activation of peroxisome proliferator-activated receptor γ (PPARγ). PPARγ partial agonists showed superior pharmacological profiles to rosiglitazone. This study compared differences in cardiac morphology and function of the PPARγ partial agonist CMHX008 with rosiglitazone. High-fat diet (HFD) induced obese mice, ob/ob mice and cardiomyocytes overexpressing PPARγ2 were treated with CMHX008 or rosiglitazone. Heart function, myocardial morphology, and hypertrophy-related gene expression were examined. Clinical information from patients with type 2 diabetes mellitus (T2DM) who had taken rosiglitazone and undergone Doppler echocardiography was collected. HFD and ob/ob mice significantly developed cardiac contractile dysfunction, with upregulated PPARγ2 protein levels in heart tissues. Cardiomyocytes of HFD and ob/ob mice were disorderly arranged, the cell areas expanded, and collagen accumulated. In vitro cardiomyocytes overexpressing PPARγ2 displayed obvious structural abnormalities and high mRNA levels of ANP and BNP, critical cardiac hypertrophy-related genes. HFD-fed mice treated with rosiglitazone or CMHX008 had significantly improved cardiac function, but rosiglitazone induced higher expression of ANP and βMHC and hypertrophic cardiomyopathy, while CMHX008 did not. Patients with T2DM taking rosiglitazone exhibited increased thickness of the posterior wall and the ventricular septum, suggesting cardiac hypertrophy. Our findings show that diabetic cardiomyopathy was associated with ectopic overexpression of PPARγ2. The full agonist rosiglitazone prevents cardiac dysfunction at the expense of compensatory hypertrophy, while the partial agonist CMHX008 shared a comparable protective effect without altering the structure of cardiomyocytes.

Non-alcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) are the most prevalent metabolic liver diseases globally. Due to the complex pathogenic mechanisms of NAFLD and AFLD, no specific drugs were approved at present. Lipid accumulation, oxidative stress, insulin resistance, inflammation, and dietary habits are all closely related to the pathogenesis of NAFLD and AFLD. However, the mechanism that promotes disease progression has not been fully elucidated. Meanwhile, the gut microbiota and their metabolites also play an important role in the pathogenesis and development of NAFLD and AFLD. This article comparatively reviewed the shared and specific signaling pathways, clinical trials, and potential intervention effectors of NAFLD and AFLD, revealing their similarities and differences. By comparing the shared and specific molecular regulatory mechanisms, this paper provides mutual reference strategies for preventing and treating NAFLD, AFLD, and related metabolic diseases. Furthermore, it provides enlightenment for discovering novel therapies of safe and effective drugs targeting the metabolic liver disease.

In this study, we aimed to investigate treatment options and the prognosis of patients with WM in China. This retrospective study included 1141 patients diagnosed with symptomatic WM between January 2003 and December 2019 at 35 tertiary hospitals in 22 provinces of China. Fifty-four patients (7.3%) received monotherapy, 264 (36.0%) received chemoimmunotherapy, 395 (53.8%) received other combination regimens without rituximab, and 21 (2.9%) received ibrutinib. Using a multivariable Cox regression model, age > 65 years old, platelets 65 years, LDH ≥250 IU/L, ALB

Background The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) was developed to accurately assess the pain, urinary symptoms, and quality of life related to chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). This study aimed to evaluate the cross-cultural adaptations of the NIH-CPSI. Method PubMed, Embase, CINAHL, and SciELO databases were searched from their established year to September 2020. Cross-cultural adaptations and the quality control of measurement properties of adaptations were conducted by two reviewers independently according to the Guidelines for the Process of Cross-Cultural Adaptation of Self-Report Measures and the Quality Criteria for Psychometric Properties of Health Status Questionnaire. Results Area total of 21 papers with 16 adaptations, and six studies of the original version of the NIH-CPSI were enrolled in the systematic review. Back translation was the weakest process for the quality assessment of the cross-cultural adaptations of the NIH-CPSI. Internal consistency was analyzed for most of the adaptations, but none of them met the standard. Only 11 adaptations reported test reliability, then only the Arabic-Egyptian, Chinese-Mainland, Danish, Italian, Persian, and Turkish adaptations met the criterion. Most adaptations reported the interpretability, but only the Danish adaptation reported the agreement. The other measurement properties, including responsiveness, and floor as well as ceiling effects were not reported in any of the adaptations. Conclusions The overall quality of the NIH-CPSI cross-cultural adaptations was not organized as expected. Only the Portuguese-Brazilian, Italian, and Spanish adaptations reached over half the process for the cross-cultural adaptation. Only the Turkish adaptations finished half of the measurement properties of cross-cultural adaptations.

Background As a new noninvasive diagnostic technique, computed tomography (CT)-based fraction flow reserve (FFR) has been used to identify hemodynamically significant coronary artery stenosis. This meta-analysis used invasive FFR as the standard to evaluate the diagnostic performance of FFRCT. Methods We searched the PubMed, Cochrane library, and EMBASE for articles published between January 2009 and January 2021. The synthesized sensitivity and specificity of invasive FFR and FFRCT were analyzed at both the patient and vessel levels. We generated a summary receiver operating characteristic curve (SROC) and then calculated the area under the curve (AUC). Results We included a total of 23 studies, including 2,178 patients and 3,029 vessels or lesions. Analysis at each patient level demonstrated a synthesized sensitivity of 88%, specificity of 79%, LR+ of 4.16, LR-of 0.15, and AUC of 0.89 for FFRCT. Analysis at the level of each vessel or lesion showed a synthesized sensitivity of 85%, specificity of 81%, LR+ of 4.44, LR-of 0.19, and AUC of 0.87 for FFRCT. Conclusion Our research reveals that FFRCT has high diagnostic performance in patients with coronary artery stenosis, regardless of whether it is at the patient level or the vessel level.

This study investigated the effects of a 16-week Tai Chi (TC) intervention on cutaneous sensitivity and proprioception among older adults with and without sensory loss. Thirty-six older adults were divided into sensory loss and control groups, and they underwent a 16-week TC intervention. Significant interactions were detected in heel cutaneous sensitivity (