Evaluation of inpatient and emergency department healthcare resource utilization and costs pre- and post-nusinersen for the treatment of spinal muscular atrophy using United States claims.

Aim: Nusinersen, administered by intrathecal injection at a dose of 12 mg, is indicated across all ages for the treatment of spinal muscular atrophy (SMA). Evidence on real-world healthcare resource use (HRU) and costs among patients taking nusinersen remains limited. This study aimed to evaluate real-world HRU and costs associated with nusinersen use through US claims databases. Patients & methods: Using the Merative™ MarketScan® Research Databases, patients with SMA receiving nusinersen were identified from commercial (January 2017 to June 2020) and Medicaid claims (January 2017 to December 2019). Those likely to have complete information on the date of nusinersen initiation and continuous enrollment 12 months pre- and post-index (first record of nusinersen treatment) were retained. Number and costs (US$ 2020) of inpatient admissions and emergency department (ED) visits, unrelated to nusinersen administration, were evaluated for 12 months pre- and post-nusinersen initiation and stratified by age: pediatric (<18 years) and adult (≥18 years). Results: Overall, 103 individuals treated with nusinersen were retained: 59 were pediatric (mean age [range]: 9 [1-17] years), and 44 were adults (30 [18-63] years). Inpatient admissions decreased by 41% for pediatrics and 67% for adults in the 12 months post-treatment versus the 12 months pre-treatment. Average inpatient admission costs per patient for the pediatric cohort decreased by 63% ($22,903 vs $8466) and by 79% ($13,997 vs $2899) for the adult cohort when comparing the 12 months pre-index with the 12 months post-index period. Total ED visits and ED visit costs decreased by 8% and 35%, respectively, for the overall cohort over the 12-month period pre- and post-index. Conclusion: Using US claims databases, nusinersen treatment in pediatric and adult patients was associated with reductions in HRU and costs over a 12-month period post-treatment initiation relative to the pre-treatment period.

Smartphone-Based Assessment of Mobility and Manual Dexterity in Adult People with Spinal Muscular Atrophy.

Background: More responsive, reliable, and clinically valid endpoints of disability are essential to reduce size, duration, and burden of clinical trials in adult persons with spinal muscular atrophy (aPwSMA). Objective: The aim is to investigate the feasibility of smartphone-based assessments in aPwSMA and provide evidence on the reliability and construct validity of sensor-derived measures (SDMs) of mobility and manual dexterity collected remotely in aPwSMA. Methods: Data were collected from 59 aPwSMA (23 walkers, 20 sitters and 16 non-sitters) and 30 age-matched healthy controls (HC). SDMs were extracted from five smartphone-based tests capturing mobility and manual dexterity, which were administered in-clinic and remotely in daily life for four weeks. Reliability (Intraclass Correlation Coefficients, ICC) and construct validity (ability to discriminate between HC and aPwSMA and correlations with Revised Upper Limb Module, RULM and Hammersmith Functional Scale - Expanded HFMSE) were quantified for all SDMs. Results: The smartphone-based assessments proved feasible, with 92.1% average adherence in aPwSMA. The SDMs allowed to reliably assess both mobility and dexterity (ICC > 0.75 for 15/22 SDMs). Twenty-one out of 22 SDMs significantly discriminated between HC and aPwSMA. The highest correlations with the RULM were observed for SDMs from the manual dexterity tests in both non-sitters (Typing, ρ= 0.78) and sitters (Pinching, ρ= 0.75). In walkers, the highest correlation was between mobility tests and HFMSE (5 U-Turns, ρ= 0.79). Conclusions: This exploratory study provides preliminary evidence for the usability of smartphone-based assessments of mobility and manual dexterity in aPwSMA when deployed remotely in participants' daily life. Reliability and construct validity of SDMs remotely collected in real-life was demonstrated, which is a pre-requisite for their use in longitudinal trials. Additionally, three novel smartphone-based performance outcome assessments were successfully established for aPwSMA. Upon further validation of responsiveness to interventions, this technology holds potential to increase the efficiency of clinical trials in aPwSMA.

Personalized Composite Dosimetric Score-Based Machine Learning Model of Severe Radiation-Induced Lymphopenia Among Patients With Esophageal Cancer.

PURPOSE: Radiation-induced lymphopenia (RIL) is common among patients undergoing radiation therapy (RT)' Severe RIL has been linked to adverse outcomes. The severity and risk of RIL can be predicted from baseline clinical characteristics and dosimetric parameters. However, dosimetric parameters, e.g. dose-volume (DV) indices, are highly correlated with one another and are only weakly associated with RIL. Here we introduce the novel concept of "composite dosimetric score" (CDS) as the index that condenses the dose distribution in immune tissues of interest to study the dosimetric dependence of RIL. We derived an improved multivariate classification scheme for risk of grade 4 RIL (G4RIL), based on this novel RT dosimetric feature, for patients receiving chemo RT for esophageal cancer. METHODS AND MATERIALS: DV indices were extracted for 734 patients who received chemo RT for biopsy-proven esophageal cancer. Nonnegative matrix factorization was used to project the DV indices of lung, heart, and spleen into a single CDS; XGBoost was employed to explore significant interactions among predictors; and logistic regression was applied to combine the resultant CDS with baseline clinical factors and interaction terms to facilitate individualized prediction of immunotoxicity. Five-fold cross-validation was applied to evaluate the model performance. RESULTS: The CDS for selected immune organs at risk (ie, heart, lung, and spleen) (OR 1.791; 95 CI [1.350, 2.377]) was a statistically significant risk determinant for G4RIL. Pearson correlation coefficients for CDS versus G4RIL risk for individual immune organs at risk were greater than any single DV indicx. Personalized prediction of G4RIL based on CDS and 4 clinical risk factors yielded an area under the curve value of 0.78. Interaction between age and CDS revealed that G4RIL risk increased more sharply with increasing CDS for patients aged ≥65 years. CONCLUSIONS: Risk of immunotoxicity for patients undergoing chemo RT for esophageal cancer can be predicted by CDS. The CDS concept can be extended to immunotoxicity in other cancer types and in dose-response models currently based on DV indices. Personalized treatment planning should leverage composite dosimetric scoring methods rather than using individual or subsets of DV indices.

P. gingivalis in oral-prostate axis exacerbates benign prostatic hyperplasia via IL-6/IL-6R pathway.

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH. METHODS: The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration. RESULTS: P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH. CONCLUSION: P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.

Human patient derived organoids: an emerging precision medicine model for gastrointestinal cancer research.

Gastrointestinal cancers account for approximately one-third of the total global cancer incidence and mortality with a poor prognosis. It is one of the leading causes of cancer-related deaths worldwide. Most of these diseases lack effective treatment, occurring as a result of inappropriate models to develop safe and potent therapies. As a novel preclinical model, tumor patient-derived organoids (PDOs), can be established from patients' tumor tissue and cultured in the laboratory in 3D architectures. This 3D model can not only highly simulate and preserve key biological characteristics of the source tumor tissue in vitro but also reproduce the in vivo tumor microenvironment through co-culture. Our review provided an overview of the different in vitro models in current tumor research, the derivation of cells in PDO models, and the application of PDO model technology in gastrointestinal cancers, particularly the applications in combination with CRISPR/Cas9 gene editing technology, tumor microenvironment simulation, drug screening, drug development, and personalized medicine. It also elucidates the ethical status quo of organoid research and the current challenges encountered in clinical research, and offers a forward-looking assessment of the potential paths for clinical organoid research advancement.

Toxic effects and mechanisms of cationic blue SD-GSL on Chlorella vulgaris before and after the biological decolorization process.

Biodegradation is regarded as an efficient way to decolorize azo dyes. However, the changes in the algal toxicity of azo dyes during biodecolorization are still unclear. In this study, the physiological responses of Chlorella vulgaris to the hydrophobic and hydrophilic components of cationic blue SD-GSL (a typical monoazo dye) and its biodecolorization products were investigated. The toxicity of each component to Chlorella vulgaris and the sources of the toxicity were analyzed. The cationic blue SD-GSL components inhibited the algal cell division and superoxide dismutase (SOD) activity at all concentrations, and inhibited the synthesis of chlorophyll-a (Chl-a) at concentrations >100 mg/L, whereas increased the malondialdehyde (MDA) content. The hydrophobic and hydrophilic components of its biodecolorization products had enhanced inhibition rates on cell density (10.7% and 15.6%, respectively), Chl-a content (31.2% and 8.4%, respectively), and SOD activity (13.5% and 1.9%, respectively) of Chlorella vulgaris, and further stimulated an increase in MDA content (4.4% and 7.0%, respectively), indicating that the biodecolorization products were more toxic than the pristine dye. Moreover, the toxic effect of hydrophobic components on Chlorella vulgaris was stronger than that of hydrophilic components. The sensitivity sequence of Chlorella vulgaris to the toxicity of cationic blue SD-GSL and its biodecolorization product components was: Chl-a synthesis > SOD activity > cell division. SUVA analysis and 3D-EEM analysis revealed that the enhanced algal toxicity of the biodecolorization products of cationic blue SD-GSL was attributed to the aromatic compounds, which were mainly concentrated in the hydrophobic components. UPLC-Q-TOF-MS was used to verify dye biodecolorization byproducts. The information obtained from this study helps to understand the decolorization products toxicities of the biologically treated azo dyes, thereby providing new insights into the environmental safety of textile wastewater after traditional biological treatment.

Study on the deterioration characteristics of aeolian sand concrete under the coupling effect of multiple factors in harsh environments.

This study takes the aeolian sand concrete as a research object, uses the relative dynamic elastic modulus to study its macro characteristics, and combines nuclear magnetic resonance、scanning electron microscope to study its pore characteristics and micro morphology under the action of prestress, freeze-thaw and salt intrusion. The results show that with the increase of the amount of aeolian sand, the dynamic elastic modulus of aeolian sand concrete shows a pattern of first decreasing, then increasing, and then decreasing; when no prestress is applied, the porosity of aeolian sand concrete first increases, then decreases, and then continues to increase. Among them, the porosity of aeolian sand concrete with a 40% content of aeolian sand decreases by 0.06% compared to that with a 0% content of aeolian sand, and decreases by 0.003% compared to that with a 60% content of aeolian sand; with the increase of prestress, the porosity of aeolian sand concrete with the same amount of aeolian sand increases gradually with the increase of damage degree. The porosity of concrete with 40% aeolian sand content increases by 0.33% when the damage degree is 0.0 compared to 0.3, with a 6.31% increase in the number of multi damage pores; under the coupling effect of multiple factors, when the amount of aeolian sand is 40%, the damage degree of the four groups of aeolian sand concrete before and after the coupling effect is 0.0, 0.1, 0.2, and 0.3, respectively, increases by 25.8%, 32.2%, 73.8%, and 85.8%, respectively; under the coupling effect of multiple factors, the content of aeolian sand is 60%, the damage degree is 0.2 and 0.3 groups, and the content of aeolian sand is 20%, the damage degree is 0.3 groups, which does not meet the standard requirements; under the coupling action of stress, freeze-thaw, salt intrusion and the amount of aeolian sand, the filling effect of aeolian sand on the internal pores of aeolian sand concrete decreases first, then increases, and then decreases with the increase of the amount of aeolian sand. The filling effect is further weakened after the action of stress. After the superposition of freeze-thaw and salt intrusion, the coupling effect of water and salt solution in frost heaving medium makes the variation law and range of physical and chemical characteristics of aeolian sand concrete show a great difference.

Superconductivity and phase transitions in Kagome compound Pd3P2S8from first-principles calculation.

Pd3P2S8is a semiconductor that contains Kagome lattices, which exhibits various physical phenomena. Structural searches of Pd3P2S8in the pressure range from 0 to 120 GPa have revealed two phases of the space groupP3‾m1(designated asP3‾m1-1 andP3‾m1-2) and two phases of the space groupC2/m(designated asC2/m-1 andC2/m-2), with all butC2/m-2 phase being dynamically stable. Electron-phonon calculations combined with Bardeen-Cooper-Schrieffer's argument have shown that both phases are superconductors. Notably, theP3‾m1-1 phase undergoes a semiconductor-to-superconductor transition, with superconducting critical temperature (Tc) increasing up to a maximum of 9.13 K at 70 GPa. BothC2/m-1 andP3‾m1-2 phases exhibit superconductivity at 0 GPa. Our calculations demonstrate several new superconducting phases of Pd3P2S8, providing a pathway and platform for exploring superconductivity in materials with Kagome lattices and expanding the options for studying such lattices.

Continued benefit of nusinersen initiated in the presymptomatic stage of spinal muscular atrophy: 5-year update of the NURTURE study.

INTRODUCTION/AIMS: NURTURE (NCT02386553) is an open-label study of nusinersen in children (two SMN2 copies, n = 15; three SMN2 copies, n = 10) who initiated treatment in the presymptomatic stage of spinal muscular atrophy (SMA). A prior analysis after ~3 y showed benefits on survival, respiratory outcomes, motor milestone achievement, and a favorable safety profile. An additional 2 y of follow-up (data cut: February 15, 2021) are reported. METHODS: The primary endpoint is time to death or respiratory intervention (≥6 h/day continuously for ≥7 days or tracheostomy). Secondary outcomes include overall survival, motor function, and safety. RESULTS: Median age of children was 4.9 (3.8-5.5) y at last visit. No children have discontinued the study or treatment. All were alive. No additional children utilized respiratory intervention (defined per primary endpoint) since the prior data cut. Children with three SMN2 copies achieved all World Health Organization (WHO) motor milestones, with all but one milestone in one child within normal developmental timeframes. All 15 children with two SMN2 copies achieved sitting without support, 14/15 walking with assistance, and 13/15 walking alone. Mean Hammersmith Functional Motor Scale Expanded total scores showed continued improvement. Subgroups with two SMN2 copies, minimum baseline compound muscle action potential amplitude ≥2 mV, and no baseline areflexia had better motor and nonmotor outcomes versus all children with two SMN2 copies. DISCUSSION: These results demonstrate the value of early treatment, durability of treatment effect, and favorable safety profile after ~5 y of nusinersen treatment. Inclusion/exclusion criteria and baseline characteristics should be considered when interpreting presymptomatic SMA trial data.

Programmable Proteolysis-Activated Transcription for Highly Sensitive Ratiometric Electrochemical Detection of Viral Protease.

Viral proteases play a crucial role in viral infection and are regarded as promising targets for antiviral drug development. Consequently, biosensing methods that target viral proteases have contributed to the study of virus-related diseases. This work presents a ratiometric electrochemical sensor that enables highly sensitive detection of viral proteases through the integration of target proteolysis-activated in vitro transcription and the DNA-functionalized electrochemical interface. In particular, each viral protease-mediated proteolysis triggers the transcription of multiple RNA outputs, leading to amplified ratiometric signals on the electrochemical interface. Using the NS3/4A protease of the hepatitis C virus as a model, this method achieves robust and specific NS3/4A protease sensing with sub-femtomolar sensitivity. The feasibility of this sensor was demonstrated by monitoring NS3/4A protease activities in virus-infected cell samples with varying viral loads and post-infection times. This study provides a new approach to analyzing viral proteases and holds the potential for developing direct-acting antivirals and novel therapies for viral infections.

Genome-scale analysis of ABC transporter genes and characterization of the ABCC type transporter genes in the oriental armyworm, Mythimna separata (Walker).

The oriental armyworm Mythimna separata is a polyphagous, migratory corn pest in China and other Asian countries. Transgenic Bacillus thuringiensis (Bt) corn may effectively control this insect pest. Several reports have suggested that ATP-binding cassette (ABC) transporter proteins may act as receptors that bind Bt toxins. However, our knowledge about ABC transporter proteins in M. separata is limited. We identified 43 ABC transporter genes in the M. separata genome by bioinformatics prediction. Evolutionary tree analysis grouped these 43 genes into 8 subfamilies, ABCA to ABCH. Among the 13 ABCC subfamily genes, the transcript levels of MsABCC2 and MsABCC3 were upregulated. In addition, RT-qPCR analyses of these two potentials showed that both were predominantly expressed in the midgut tissue. Knock-down of MsABCC2, but not MsABCC3, decreased Cry1Ac susceptibility as indicated by increased larval weight and reduced larval mortality. This suggested that MsABCC2 might play a more important role in Cry1Ac toxicity and that it is a putative Cry1Ac receptor in M. separata. Together, these findings provide unique and valuable information for future elucidating of the role of ABC transporter genes in M. separata, which is highly valuable and important for the long-term application of Bt insecticidal protein.

Synthesis and Antibacterial Activity of Erythromycin 9-Acylhydrazone Derivates.

BACKGROUND: Some species of Marine bacteria pose great risks to human and mariculture organisms. Meanwhile, Vibrio harveyi and Vibrio parahaemolyticus strains have acquired resistance to many antibiotics. OBJECTIVE: A novel series of erythromycin 9-acylhydrazone derivatives were synthesized and evaluated for their in vitro antibacterial activity against marine pathogens. METHODS: The site-selective N-acylation of erythromycin hydrazone was achieved using acid chloride/ triethylamine in methanol as the reaction system. All the synthesized target compounds were evaluated for their antibacterial activity by determination of minimum inhibitory concentrations (MICs) using the broth microdilution method. RESULTS: All the tested acylhydrazone compounds showed moderate to high activity with MIC value 0.125-1 µg/mL against Vibrio parahaemolyticus and Vibrio harveyi. CONCLUSION: The introduction of the acylhydrazone moiety at the C-9 position of erythromycin improved its activity against the above-mentioned marine bacteria strains.

Spatial-temporal evolution and driving force analysis of eco-quality in urban agglomerations in China.

Urban agglomerations are important spatial carriers of regional economic development, and their ecological quality (EQ) is closely related to economic growth and human development. However, the rapid urbanization in China has generated a series of EQ problems that threaten the sustainable development of the country. Therefore, it is essential to explore changes in EQ for the development of sustainable "human-land" relations in urban agglomerations. Using GIS, GeoDetector, Stepwise multiple regression, and Sen'trend analysis, to reveal the spatial-temporal evolution of EQ in urban agglomerations along with the spatial heterogeneity of its driving forces in China. Results show that: (1) The annual change rate of EQ of urban agglomerations ranges from -0.0312 to 0.0334. Taking the Hu-line as a boundary, the EQ of urban agglomerations is spatially high in the east and low in the west. (2) The Global Moran's I index ranged from 0.740 to 0.687 during the study period, indicating a positive correlation in the EQ spatial distribution. The EQ of urban agglomerations has significant spatial agglomeration, with hot spots concentrated in the eastern region and cold spots in the northwestern region. (3) Main drivers of EQ of urban agglomerations are elevation, population density, nighttime light index, arable land area, real GDP per capita, precipitation, and built-up urban area (q > 10 %). (4) The stepwise multiple regression model spatially reveals that the nighttime light index, built-up urban area land and GDP per capita dominate the ecological quality changes of urban agglomerations, accounting for 73.68 % of the total number of urban agglomerations. This study provides an effective method for assessing spatial-temporal changes of EQ in urban agglomerations, supports scientific decision-making support for the construction of ecological civilization and the development of human-land harmony in urban agglomerations, and promotes the development and construction of "Beautiful China."

[Effect of Polygonati Rhizoma in improving pyroptosis injury of diabetic macroangiopathy via NLRP3/caspase-1/GSDMD pathway].

This study aims to explore the influence of Polygonati Rhizoma on the pyroptosis in the rat model of diabetic macroangiopathy via the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/gasdermin D(GSDMD) pathway. The rat model of diabetes was established by intraperitoneal injection of streptozotocin(STZ) combined with a high-fat, high-sugar diet. The blood glucose meter, fully automated biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, and Western blot were employed to measure blood glucose levels, lipid levels, vascular thickness, inflammatory cytokine levels, and expression levels of pyroptosis-related proteins. The mechanism of pharmacological interventions against the injury in the context of diabetes was thus explored. The results demonstrated the successful establishment of the model of diabetes. Compared with the control group, the model group showed elevated levels of fasting blood glucose, total cholesterol(TC), triglycerides(TG) and low-density lipoprotein cholesterol(LDL-c), lowered level of high-density lipoprotein cholesterol(HDL-c), thickened vascular intima, and elevated serum and aorta levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß) and interleukin-18(IL-18). Moreover, the model group showed increased NLRP3 inflammasomes and up-regulated levels of caspase-1 and GSDMD in aortic vascular cells. Polygonati Rhizoma intervention reduced blood glucose and lipid levels, inhibited vascular thickening, lowered the levels of TNF-α, IL-1ß, IL-18 in the serum and aorta, attenuated NLRP3 inflammasome expression, and down-regulated the expression levels of caspase-1 and GSDMD, compared with the model group. In summary, Polygonati Rhizoma can slow down the progression of diabetic macroangiopathy by inhibiting pyroptosis and alleviating local vascular inflammation.

Access to Sulfur-Containing Bisheterocycles through Base-Promoted Consecutive Tandem Cyclization/Sulfenylation with Elemental Sulfur.

A convenient and efficient tandem cyclization/sulfenylation of o-alkynyl-phenols/-anilines/enaminones for the synthesis of diverse sulfur-containing bisheterocycles has been developed using stable, odorless, and easy-to-handle elemental S8 as a building block under green chemistry conditions. Notably, a one-step simple base-mediated organic transformation affords a benzofuran (indole or chromone) ring and two C-S bonds. Attractive features of this methodology include the absence of a metal catalyst, mild conditions, good functional group tolerance, and valuable product structures.

Secular trends of morbidity and mortality of prostate, bladder, and kidney cancers in China, 1990 to 2019 and their predictions to 2030.

BACKGROUND: Prostate, bladder and kidney cancers are common age-related genitourinary cancers. China's population is aging at an increasing rate, so predicting the morbidity and mortality of prostate, bladder, and kidney cancer in China is of great significance to provide epidemiological evidence for forward planning and implementation of national health policies. METHODS: Numbers of incidences and deaths by cancer (prostate, bladder and kidney), sex (male and female) and age groups from 1990 to 2019 were extracted from the Global Burden of Disease (GBD) Study. We applied Bayesian age-period-cohort models to predict incidences and deaths to 2030. We also calculated Age-standardized incidence rate (ASIR) and mortality rate (ASMR), their trends were quantified by estimated average percentage change (EAPC) and 95% confidence interval (CI). RESULTS: Predictions suggest that by 2030, there will be 315,310 prostate cancer cases, 192,390 bladder cancer cases and 126,980 kidney cancer cases. The ASIRs will increase to 25.54/100,000 for prostate cancer (EAPC: 2.88, 95% CI, 2.84, 2.93), 7.54/100,000 for bladder cancer (EAPC: 2.58, 95% CI, 2.54, 2.61) and 5.63/100,000 for kidney cancer (EAPC: 4.78, 95% CI, 4.54, 5.02). Number of deaths in 2030 will be 81,540, 61,220, and 41,940, respectively. Different ASMR changes are observed, the ASMR for prostate cancer will drop to 7.69/100,000 (EAPC: -0.29, 95% CI, -0.31, -0.27), the ASMR for bladder cancer will stabilize at 2.49/100,000 (EAPC: 0.00, 95% CI, -0.02, 0.03), the ASMR of kidney cancer will increase to 1.84/100,000 (EAPC: 3.45, 95% CI, 3.22, 3.67). From 1990 to 2030, higher numbers of cases and rates are reported among males and in the 60 plus age group, both ASIR and ASMR of bladder and kidney cancers presents progressively widening differences between both males and females and between the < 60 and the ≥ 60 age groups. CONCLUSION: Morbidity and mortality of the three genitourinary cancers are predicted to increase further over the next decade. It highlights the need for timely development and implementation of optimal health policies to curb the epidemic trends.

School assets and bullying in Chinese youth: A multiple mediation model of intentional self-regulation and internet gaming disorder.

Bullying is a severe social problem affecting young people all over the world. Previous studies suggested that engagement in bullying had massive effects on teenagers' physical and psychological development. It is critical and necessary to investigate the antecedents and underlying mechanisms of this phenomenon among young generations. The present study, based on the positive youth development perspective and the developmental assets theory, attempts to explore the positive factors in the school subsystem that could effectively prevent adolescents from bullying, as well as the multiple mediation effects of intentional self-regulation (ISR) and internet gaming disorder (IGD). In this study, we adopted a two-wave design and recruited a sample of 768 Chinese adolescents using a randomized cluster sampling method in the post-pandemic era. The results revealed that T1 school assets significantly and negatively predicted T2 adolescent bullying. Furthermore, T2 ISR and T2 IGD mediated the association between T1 school assets and T2 bullying separately and sequentially. Overall, school resources play a protective role in adolescent development and could effectively prevent them from negative outcomes. These current findings contribute to the literature by providing a further understanding of the direct and indirect protective effects of school assets on adolescent bullying. Moreover, practitioners could also benefit from these findings in preventing and intervening in bullying in the school subsystem.

Using Haemocoagulase Agkistrodon in Patients Undergoing Transurethral Plasmakinetic Resection of the Prostate: A Pilot, Real-World, and Propensity Score-Matched Study.

Objectives: To compare the clinical outcomes of using different hemostatic agents after transurethral plasmakinetic resection of the prostate (TUPKP) in benign prostatic hyperplasia (BPH) patients. Methods: The patients were divided into 5 groups according to the hemostatic agents used after TUPKP, including the haemocoagulase agkistrodon for injection (HCA), hemocoagulase for injection (HC), hemocoagulase bothrops atrox for injection (HCB), ethylenediamine diaceturate injection (EDD), and tranexamic acid (TXA). Propensity score matching was performed based on age, body mass index, prostate volume, hypertension status, fasting blood glucose, smoking, and drinking history. The hospitalization time, bladder irrigation time, indwelling catheterization time, the patency of urine flow, and blood transfusion records were used as outcome indicators to compare the clinical effects of these five agents. Results: We finally matched 65 pairs receiving HCA or HC, 71 pairs receiving HCA or HCB, 38 pairs receiving HCA or TXA, and 29 pairs receiving HCA or EDD. Compared with HC, HCA given during the perioperative period significantly reduced the median hospitalization time [7.00 days (5.00, 8.00) vs. 9.00 days (8.00, 10.00); p < 0.001] and median catheterization time (109.00 hours [88.00, 129.00] vs. 164.00 hours [114.00, 189.00], p < 0.001). Compared with EDD, the median hospitalization time (7.00 days [6.00, 8.00] vs. 10.00 days [8.00, 11.00]; p < 0.001) and median catheterization time (113.00 hours [95.00, 143.00] vs. 160.00 hours [139.00, 168.00]; p < 0.001) were also significant shorter in HCA group. Compared with HCB, median bladder irrigation time (45.00 hours [27.00, 71.00] vs. 49.00 hours [45.00, 72.00]; p = 0.04) was shorter in the HCA group. However, there were no statistical differences in outcomes between HCA and TXA. Conclusions: HCA probably has an advantage over HC, HCB, and EDD in reducing the hospitalization time, catheterization time, and bladder irrigation time among BPH patients undergoing TUPKP.

Cumulative Family Risk and Cyberbullying Among Chinese Adolescents: The Chain Mediating Role of School Connectedness and Cyber Victimization.

Abundant evidence has demonstrated that cumulative family risk is associated with cyberbullying. However, few studies to date have investigated how cumulative family risk links to cyberbullying. To fill in these gaps, the present study examined the mediating role of school connectedness and cyber victimization in the relation between cumulative family risk and cyberbullying. A sample of 1,804 Chinese adolescents was recruited to complete measures of cumulative family risk, cyberbullying, school connectedness, cyber victimization, and demographic variables through convenience sampling. There were 813 boys and 991 girls, aged from 13 to 18, with an average age of 16 years (SD = 1.71). Correlational analyses and SPSS macro PROCESS (Model 6) were used for major data analysis. Results indicated that cumulative family risk was positively associated with cyberbullying, and this link could be mediated by school connectedness and cyber victimization. The present study identifies the potential underlying mechanism by which cumulative family risk is associated with adolescent cyberbullying, which has important implications for theory and prevention.

Interactive effects of aquatic nitrogen and plant biomass on nitrous oxide emission from constructed wetlands.

Understanding of mechanisms in nitrous oxide (N2O) emission from constructed wetland (CW) is particularly important for the establishment of related strategies to reduce greenhouse gas (GHG) production during its wastewater treatment. However, plant biomass accumulation, microbial communities and nitrogen transformation genes distribution and their effects on N2O emission from CW as affected by different nitrogen forms in aquatic environment have not been reported. This study investigated the interactive effects of aquatic nitrogen and plant biomass on N2O emission from subsurface CW with NH4+-N (CW-A) or NO3--N (CW-B) wastewater. The experimental results show that NH4+-N and NO3--N removal efficiencies from CW mesocosms were 49.4% and 87.6%, which indirectly lead to N2O emission fluxes of CW-A and CW-B maintained at 213 ± 67 and 462 ± 71 µg-N/(m2·h), respectively. Correlation analysis of nitrogen conversion dynamic indicated that NO2--N accumulation closely related to N2O emission from CW. Aquatic NH4+-N could up-regulate plant biomass accumulation by intensifying citric acid cycle, glycine-serine-threonine metabolism etc., resulting in more nitrogen uptake and lower N2O emission/total nitrogen (TN) removal ratio of CW-A compared to CW-B. Although the abundance of denitrifying bacteria and N2O reductase nosZ in CW-B were significantly higher than that of CW-A, after fed with mixed NH4+-N and NO3--N influent, N2O fluxes and N2O emission/TN removal ratio in CW-A were extremely close to that of CW-B, suggesting that nitrogen form rather than nitrogen transformation microbial communities and N2O reductase nosZ determines N2O emission from CW. Hence, the selection of nitrate-loving plants will play an important role in inhibiting N2O emission from CW.