Spatial spillovers of violent conflict amplify the impacts of climate variability on malaria risk in sub-Saharan Africa.

Africa carries a disproportionately high share of the global malaria burden, accounting for 94% of malaria cases and deaths worldwide in 2019. It is also a politically unstable region and the most vulnerable continent to climate change in recent decades. Knowledge about the modifying impacts of violent conflict on climate-malaria relationships remains limited. Here, we quantify the associations between violent conflict, climate variability, and malaria risk in sub-Saharan Africa using health surveys from 128,326 individuals, historical climate data, and 17,429 recorded violent conflicts from 2006 to 2017. We observe that spatial spillovers of violent conflict (SSVCs) have spatially distant effects on malaria risk. Malaria risk induced by SSVCs within 50 to 100 km from the households gradually increases from 0.1% (not significant, P>0.05) to 6.5% (95% CI: 0 to 13.0%). SSVCs significantly promote malaria risk within the average 20.1 to 26.9 °C range. At the 12-mo mean temperature of 22.5 °C, conflict deaths have the largest impact on malaria risk, with an approximately 5.8% increase (95% CI: 1.0 to 11.0%). Additionally, a pronounced association between SSVCs and malaria risk exists in the regions with 9.2 wet days per month. The results reveal that SSVCs increase population exposure to harsh environments, amplifying the effect of warm temperature and persistent precipitation on malaria transmission. Violent conflict therefore poses a substantial barrier to mosquito control and malaria elimination efforts in sub-Saharan Africa. Our findings support effective targeting of treatment programs and vector control activities in conflict-affected regions with a high malaria risk.

The Prognostic Value of Preoperative Naples Prognostic Score in Upper Tract Urothelial Carcinoma Patients after Radical Nephroureterectomy.

This study aims to determine the prognostic value of preoperative Naples prognostic score (NPS) on survival outcomes in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). We conducted a retrospective study about UTUC patients at West China Hospital from January 2015 to June 2019. The X-Tile program was used to identify the optimal cutoff value of NPS. Overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) were the endpoints of interest. Kaplan-Meier curves were used to estimate survival and Cox proportional hazard model was used for risk assessment. A total of 237 UTUC patients after RNU were identified and the threshold of NPS was determined to be 2. Preoperative high-NPS was associated with inferior OS (p = 0.004), CSS (p = 0.002) and PFS (p = 0.008), especially in locally advanced UTUC patients. Preoperative NPS was an independent predictor for OS (HR: 1.78; 95% CI: 1.08, 2.93), CSS (HR: 1.87; 95% CI: 1.11, 3.14) and PFS (HR: 1.60; 95% CI: 1.02, 2.50). The addition of NPS into the predictive model consisting of predictors from multivariate Cox regression resulted in better prediction performance. Preoperative NPS was a novel and reliable predictor for survival in UTUC patients after RNU, and should be further explored.

Serum α-hydroxybutyrate dehydrogenase as a biomarker for predicting survival outcomes in patients with UTUC after radical nephroureterectomy.

PURPOSE: We aimed to determine the prognostic value of α-hydroxybutyrate dehydrogenase (α-HBDH) in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively enrolled the data of 544 UTUC patients at West China Hospital from May 2003 to June 2019. Cancer-specific survival (CSS) was the endpoint of interest. The optimal cutoff value of α-HBDH was identified by X-Tile program. After propensity score matching (PSM), we utilized Kaplan‒Meier curves to estimate survival and Cox proportional hazard model for risk assessment. A nomogram was built based on the results of multivariate analysis, and calibration curve, time-dependent receiver operating characteristic (ROC) curves and decision curve analysis were also performed to evaluate the predictive accuracy. RESULTS: Overall, 394 and 150 patients were divided into the α-HBDH-low group and α-HBDH -high group at the cutoff value of 158 U/L, respectively. After PSM, the two groups were well matched for all confounding factors. High α-HBDH was associated with inferior CSS (P = 0.006), and preoperative α-HBDH was an independent predictor for CSS (HR: 1.36; 95% CI:1.08, 1.80), especially in localized UTUC patients (HR: 2.04; 95% CI:1.11, 3.74). Furthermore, the nomogram based on α-HBDH achieved great predictive ability for CSS with areas under the curves of 0.800 and 0.778 for 3-year and 5-year CSS, respectively. CONCLUSION: Serum α-HBDH was a novel and reliable biomarker for predicting survival outcomes in UTUC patients after RNU but should be further explored.

Disease burden of mental disorders among children and adolescents considering both co-morbidities and suicide in Northeastern China.

BACKGROUND: Few studies have assessed the burden of mental disorders among children and adolescents considering the impact of co-morbidities and suicide on disability adjusted life years (DALYs). METHODS: This was a multicenter cross-sectional study. Our survey data in Liaoning Province (LN) were used to estimate the burden of six mental disorders, supplemented with data from other investigative studies conducted in China to assess four other disorders. DALYs were derived from the sum of years lived with a disability (YLDs) adjusted for co-morbidities, and the years of life lost (YLLs) adjusted for suicide. The changes in DALYs, YLDs, and YLLs were compared with and without adjustment for co-morbidities and suicide. RESULTS: The DALYs rate of mental disorders among children and adolescents in LN decreased from 1579.6/105 to 1391.4/105, after adjusting for both co-morbidities and suicide (-11.9%). The DALYs rate for major depression, anxiety disorder, and conduct disorder (-80.8/105, -75.0/105 and -30.2/105, respectively) were the top three contributors to the DALYs reduction (-188.2/105). The YLDs decreased from 72724.8 to 62478.5 after co-morbidity adjustment (-17.8%), mainly due to the reduction by major depression (-35.3%) and attention deficit/hyperactivity disorder [ADHD] (-34.2%). The YLLs increased from 130 to 1697.8 after adjusting for suicides (+ 56.9% of all suicide YLLs), mainly due to the contribution of major depression (+ 32.4%) and anxiety disorder (+ 10.4%). Compared to GBD 2010, the estimated DALY rate for mental disorders in LN was to be about 80%, with the proportion of DALYs and DALY rates explained by major depressive disorder accounted for only approximately one-third (14.6% vs. 41.9% and 202.6 vs. 759.9, respectively). But the proportion and absolute level of DALY rates explained by anxiety disorders were approximately 2-fold higher (39.7% vs. 19.6% and 552.2 vs. 323.3, respectively). CONCLUSIONS: The DALYs of mental disorders among Chinese children and adolescents were approximately 80% of the global level, with anxiety disorders imposing about 2 times the global level. Co-morbidity and suicide must be adjusted when calculating DALYs.

Promoting Electrocatalytic CO2 Reduction to CH4 by Copper Porphyrin with Donor-Acceptor Structures.

Molecular catalysts have been receiving increasingly attention in the electrochemical CO2 reduction reaction (CO2 RR) with attractive features such as precise catalytic sites and tunable ligands. However, the insufficient activity and low selectivity of deep reduction products restrain the utilization of molecular catalysts in CO2 RR. Herein, a donor-acceptor modified Cu porphyrin (CuTAPP) is developed, in which amino groups are linked to donate electrons toward the central CuN4 site to enhance the CO2 RR activity. The CuTAPP catalyst exhibited an excellent CO2 -to-CH4 electroreduction performance, including a high CH4 partial current density of 290.5 mA cm-2 and a corresponding Faradaic efficiency of 54.8% at -1.63 V versus reversible hydrogen electrode in flow cells. Density functional theory calculations indicated that CuTAPP presented a much lower energy gap in the pathway of producing *CHO than Cu porphyrin without amino group modification. This work suggests a useful strategy of introducing designed donor-acceptor structures into molecular catalysts for enhancing electrochemical CO2 conversion toward deep reduction products.

Amelioration of cadmium cytotoxicity to human cells by nutrient cation contents and the building of a biotic ligand model.

A variety of important major and trace elements may competitively inhibit cadmium (Cd) absorption in human cells and reduce Cd toxicity. However, the impact of essential elements on the cytotoxicity of metals can be difficult to quantify and anticipate. Cd acute toxicity to Caco-2 cell viability was studied in culture solutions and modeled by a biotic ligand model (BLM). The individual effects of the cations potassium (K+), calcium (Ca2+), magnesium (Mg2+), ferrous ion(Fe2+), zinc (Zn2+) and manganese (Mn2+) on Cd toxicity were also investigated. The results indicated that the toxicity of Cd in culture solutions to cell viability declined with increasing concentrations of Zn2+ and Mn2+ in the solutions, while K+, Ca2 +, Mg2 + and Fe2+ had no significant effect. Using the BLM, the stability constants for the binding of Cd2 +, Zn2+, and Mn2+ to biotic ligands were determined to be logKCdBL = 5.76, logKZnBL = 4.39 and logKMnBL = 5.31, respectively. Moreover, it was calculated that 51% occupancy of the biotic ligand sites for Cd by Cd was required to cause a 50% reduction in Caco-2 cell viability. A BLM was successfully established using the estimated constants to predict the Cd cytotoxicity to Caco-2 cell viability as a function of solution characteristics, so that the effective concentrations that reduced cell viability by 50% (EC50) could be predicted by the BLM within 1.6 fold changes of the observed EC50. The application's viability and precision for foretelling Cd toxicity in Caco-2 cells are discussed.

Electrocatalytic CO2 Upgrading to Triethanolamine by Bromine-Assisted C2 H4 Oxidation.

The electrocatalytic carbon dioxide (CO2 ) reduction is a promising approach for converting this greenhouse gas into value-added chemicals, while the capability of producing products with longer carbon chains (Cn >3) is limited. Herein, we demonstrate the Br-assisted electrocatalytic oxidation of ethylene (C2 H4 ), a major CO2 electroreduction product, into 2-bromoethanol by electro-generated bromine on metal phthalocyanine catalysts. Due to the preferential formation of Br2 over *O or Cl2 to activate the C=C bond, a high partial current density of producing 2-bromoethanol (46.6 mA⋅cm-2 ) was obtained with 87.2 % Faradaic efficiency. Further coupling with the electrocatalytic nitrite reduction to ammonia at the cathode allowed the production of triethanolamine with six carbon atoms. Moreover, by coupling a CO2 electrolysis cell for in situ C2 H4 generation and a C2 H4 oxidation/nitrite reduction cell, the capability of upgrading of CO2 and nitrite into triethanolamine was demonstrated.

Prediabetes and the incidence of dementia in general population: a systematic review and meta-analysis of prospective studies.

BACKGROUND: Continuous hyperglycaemia has been related with dementia. However, it remains unclear whether prediabetes poses a higher risk of dementia. A meta-analysis was therefore conducted to comprehensively investigate the possible role of prediabetes as a risk factor of dementia. METHODS: Prospective cohort studies reporting the association of prediabetes and dementia were identified from PubMed, Web of Science, and Embase databases. A random-effects model was applied to combine the results by incorporating the influence of heterogeneity. Subgroup analyses were also conducted to explore the influences of study features on the relationship. Sensitivity analysis re-estimated the combined effect size after excluding single studies separately to explore the robustness of the results. RESULTS: Nine studies involving 29 986 adults from the general population, 6265 (20.9%) of whom had prediabetes, were included. It was shown that prediabetes was not independently associated with a higher incidence of dementia compared with normoglycaemia (adjusted risk ratio (RR): 1.01, 95% confidence interval (CI): 0.85-1.21, P = 0.89, I2  = 39%). Subgroup analyses according to the definitions of prediabetes, follow-up duration, method for diagnosis of dementia, and quality score produced similar findings (P for all subgroup differences >0.05). In addition, prediabetes was not independently associated with the incidence of Alzheimer's disease (RR: 1.24, 95% CI: 0.98-1.56, P = 0.07, I2  = 0%) or vascular dementia (RR: 1.16, 95% CI: 0.70-1.92, P = 0.56, I2  = 0%). Different definitions of prediabetes have the potential to influence the results, as reflected in the subgroup analysis for Alzheimer's disease (RR: 1.30, 95% CI: 1.06-1.60, P = 0.01, I2  = 0%). CONCLUSIONS: Prediabetes may not be an independent risk factor of all-cause dementia or vascular dementia in the general adult population. However, changing the definition of prediabetes may have an impact on the outcome for Alzheimer's disease.

Effects of water-soluble components of atmospheric particulates from rare earth mining areas in China on lung cancer cell cycle.

BACKGROUND: This study aims to investigate the effects of water soluble particulate matter (WSPM) on the viability and protein expression profile of human lung adenocarcinoma cell A549 in the Bayou Obo rare earth mining area, and explore the influence of WSPM on the A549 cell cycle. RESULTS: It was found that WSPM can inhibit the viability of A549 cells and induce cell arrest in the G2/M phase. Compared with controls, exposure to WSPM10 and WSPM2.5 induced 134 and 116 proteins to be differentially expressed in A549 cells, respectively. In addition, 33 and 31 differentially expressed proteins were further confirmed, and was consistent with the proteomic analysis. The most prominent enrichment in ribosome-associated proteins were presented. When RPL6, RPL13, or RPL18A gene expression was inhibited, A549 cells were arrested in the G1 phase, affecting the expression of Cyclin D1, p21, RB1, Cyclin A2, Cyclin B1, CDC25A, CDK2, CHEK2 and E2F1. Furthermore, the La3+, Ce3+, Nd3+ and F- in WSPM also inhibited the viability of A549 cells. After 24 h of exposure to 2 mM of NaF, A549 cells were also arrested in the G2/M phase, while the other three compounds did not have this effect. These four compounds affected the cell cycle regulatory factors in A549 cells, mainly focusing on effecting the expression of CDK2, CDK4, RB1, ATM, TP53 and MDM2 genes. These results are consistent with the those from WSPM exposure. CONCLUSIONS: These results revealed that WSPM from rare earth mines decreased the viability of A549 cells, and induced cell cycle G2/M phase arrest, and even apoptosis, which may be independent of the NF-κB/MYD88 pathway, and be perceived by the TLR4 receptor. The dysfunction of the cell cycle is correlated to the down-expression of ribosomal proteins (RPs). However, it is not the direct reason for the A549 cell arrest in the G2/M phase. La3+, Ce3+, and F- are probably the main toxic substances in WSPM, and may be regulate the A549 cell cycle by affecting the expression of genes, such as MDM2, RB1, ATM, TP53, E2F1, CDK2 and CDK4. These results indicate the importance for further research into the relationship between APM and lung cancer.

Electrocatalytic Methane Oxidation Greatly Promoted by Chlorine Intermediates.

Renewable energy-powered methane (CH4 ) conversion at ambient conditions is an attractive but highly challenging field. Due to the highly inert character of CH4 , the selective cleavage of its first C-H bond without over-oxidation is essential for transforming CH4 into value-added products. In this work, we developed an efficient and selective CH4 conversion approach at room temperature using intermediate chlorine species (*Cl), which were electrochemically generated and stabilized on mixed cobalt-nickel spinels with different Co/Ni ratios. The lower overpotentials for *Cl formation enabled an effective activation and conversion of CH4 to CH3 Cl without over-oxidation to CO2 , and Ni3+ at the octahedral sites in the mixed cobalt-nickel spinels allowed to stabilize surface-bound *Cl species. The CoNi2 Ox electrocatalyst exhibited an outstanding yield of CH3 Cl (364 mmol g-1 h-1 ) and a high CH3 Cl/CO2 selectivity of over 400 at room temperature, with demonstrated capability of direct CH4 conversion under seawater working conditions.

[Transcriptomics study on mechanism of Aconiti Lateralis Radix Praeparata in treatment of rats with acute heart failure].

In this study,transcriptomics technique was used to investigate the mechanism of action of Aconiti Lateralis Radix Praeparata on acute heart failure rats induced by propafenone hydrochloride.First,rats were randomly divided into normal group,model group and administration group(1.25,2.5,5 g·kg-1).A rat with acute heart failure was constructed by intravenous femoral administration of proparone hydrochloride.The changes of heart rate,+dp/dtmaxand-dp/dtmaxat 5,10,20,30 and 60 min were recorded.Then another group of rats were given the same drug delivery method.In another group of animals,serum TNF-α could be determined by ELISA with the same dosage method.High-throughput sequencing technology was used to detect all gene expression differences in cardiac tissue samples of rats with acute heart failure.Through functional annotation and enrichment analysis,gene expression signaling pathways of rats with acute heart failure and rats with post-administration heart failure were screened out.The results showed that heart rate and LV+dp/dtmaxand LV-dp/dtmaxwere significantly decreased in the model group(P<0.05),while heart rate and LV+dp/dtmax and LV-dp/dtmaxwere significantly increased in the drug group(P<0.05,P<0.01).Moreover,ANP,BNP and TNF-α in acute heart failure rats was significantly decreased in high-dose aconite decoction group(P<0.05).Transcriptomics analysis showed that the mechanism of action was mainly related to activation of PI3 K-AKT signaling pathway and Jak-STAT pathway.Compared with the model group,aconite decoction up-regulated the expression of phosphatidylinostol 3-kinase(PI3 K),lysophosphatidic acid(LAP3),Bcl-3 and STAT genes,and down-regulated the expression of integrin(ITGA),nuclear orphan receptor(Nur77) genes.It could be concluded that the mechanism of aconite in treating acute heart failure rats may be related to the regulation of the PI3 k-Akt/Jak-STAT pathway.

The Impact of Prostate Volume on Prostate Cancer Detection: Comparing Magnetic Resonance Imaging with Transrectal Ultrasound in Biopsy-naïve Men.

Background and objective: This study aimed to determine the difference in prostate volume (PV) derived from transrectal ultrasound (TRUS) and multiparametric magnetic resonance imaging (mpMRI), and to further investigate the role of TRUS prostate-specific antigen density (PSAD) and mpMRI-PSAD in prostate cancer (PCa) detection in biopsy-naïve men. Methods: Patients who underwent an initial prostate biopsy within 3 mo after mpMRI between January 2016 and December 2021 were analyzed retrospectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of both TRUS-PSAD and mpMRI-PSAD for PCa detection were calculated and compared. The Pearson correlation coefficient, Bland-Altman plot, and receiver operating characteristic curve were also utilized to explore the interests of this study. Key findings and limitations: The median prostate-specific antigen level of 875 patients was 9.79 (interquartile range [IQR]: 7.09-13.50) ng/ml. The median mpMRI-PV and TRUS-PV were 41.92 (IQR: 29.29-60.73) and 41.04 (IQR: 29.24-57.27) ml, respectively, demonstrating a strong linear correlation (r = 0.831, 95% confidence interval: 0.809, 0.850; p < 0.01) and sufficient agreement. No significant difference was observed in terms of the sensitivity, specificity, PPV, and NPV between TRUS-PSAD and mpMRI-PSAD for any PCa and clinically significant PCa (csPCa) detection. The overall discriminative ability of TRUS-PSAD for detecting PCa or non-PCa, as well as csPCa and non-csPCa, was comparable with that of mpMRI-PSAD, and similar results were also observed in the subsequent analysis stratified by mpMRI-PV quartiles, prostate-specific antigen level, and age. The limitations include the retrospective and single-center nature and a lack of follow-up information. Conclusions and clinical implications: TRUS-PV and MRI-PV exhibited a strong linear correlation and reached sufficient agreement. The efficiency of TRUS-PSAD and mpMRI-PSAD for PCa detection was comparable. TRUS could be used for PV estimation and dynamic monitoring of PSAD, and TRUS-PSAD could effectively guide clinical decision-making and optimize diagnostic strategies. Patient summary: In this work, prostate volume (PV) derived from transrectal ultrasound (TRUS) exhibited a strong linear correlation with the PV derived from multiparametric magnetic resonance imaging (mpMRI). The efficiency of TRUS prostate-specific antigen density (PSAD) and mpMRI-PSAD for the detection of prostate cancer was comparable. TRUS could be used for PV estimation and TRUS-PSAD could help in clinical decision-making and optimizing diagnostic strategies.

Rapidly reducing cadmium from contaminated farmland soil by novel magnetic recyclable Fe3O4/mercapto-functionalized attapulgite beads.

Reducing cadmium (Cd) content from contaminated farmland soils remains a major challenge due to the difficulty in separating commonly used adsorbents from soils. This study synthesized novel millimeter-sized magnetic Fe3O4/mercapto-functionalized attapulgite beads (MFBs) through a facile one-step gelation process incorporating alginate. The MFBs inherit the environmental stability of alginate and enhance its mechanical strength by hybridizing Fe3O4 and clay mineral components. MFBs can be easily separated from flooded soils by magnets. When applied to 12 Cd-polluted paddy soils and 14 Cd-polluted upland soils, MFBs achieved Cd(II) removal rates ranging from 16.9% to 62.2% and 9.8%-54.6%, respectively, within a 12-h period. The MFBs predominantly targeted the exchangeable and acid soluble, and reducible fractions of Cd, with significantly enhanced removal efficiencies in paddy soils compared to upland soils. Notably, MFBs exhibited superior adsorption performance in soils with lower pH and organic matter (OM) content, where the bioavailability and mobility of Cd are heightened. The reduction of Cd content by MFBs is a sustainable and safe method, as it permanently removes the bioavailable Cd from soil, rather than temporarily reducing its bioavailability. The functional groups such as -SH, -OH, present in attapulgite and alginate of MFBs, played a crucial role in Cd(II) adsorption. Additionally, attapulgite and zeolite provided a porous matrix structure that further enhanced Cd(II) adsorption. The results of X-ray photoelectron spectroscopy suggested that both chemical precipitation and surface complexation contributed to Cd(II) removal. The MFBs maintained 87.6% Cd removal efficiency after 5 regeneration cycles. The surface of the MFBs exposed new adsorption sites and increased the specific surface area during multiple cycles with Cd-contaminated soil. This suggests that MFBs treatment with magnetic retrieval is a potentially effective pathway for the rapid removal of Cd from contaminated farmland soils.

Endurance exercise preconditioning alleviates ferroptosis induced by doxorubicin-induced cardiotoxicity through mitochondrial superoxide-dependent AMPKα2 activation.

Doxorubicin-induced cardiotoxicity (DIC) adversely impacts patients' long-term health and quality of life. Its underlying mechanism is complex, involving regulatory cell death mechanisms, such as ferroptosis and autophagy. Moreover, it is a challenge faced by patients undergoing cardiac rehabilitation. Endurance exercise (E-Exe) preconditioning effectively counters DIC injury, potentially through the adenosine monophosphate-activated protein kinase (AMPK) pathway. However, detailed studies on this process's mechanisms are scarce. Here, E-Exe preconditioning and DIC models were established using mice and primary cultured adult mouse cardiomyocytes (PAMCs). Akin to ferrostatin-1 (ferroptosis inhibitor), rapamycin (autophagic inducer), and MitoTEMPO (mitochondrial free-radical scavenger), E-Exe preconditioning effectively alleviated Fe2+ accumulation and oxidative stress and improved energy metabolism and mitochondrial dysfunction in DIC injury, as demonstrated by multifunctional, enzymatic, and morphological indices. However, erastin (ferroptosis inducer), 3-methyladenine (autophagic inhibitor), adenovirus-mediated AMPKα2 downregulation, and AMPKα2 inhibition by compound C significantly diminished these effects, both in vivo and in vitro. The results suggest a non-traditional mechanism where E-Exe preconditioning, under mild mitochondrial reactive oxygen species generation, upregulates and phosphorylates AMPKα2, thereby enhancing mitochondrial complex I activity, activating adaptive autophagy, and improving myocardial tolerance to DIC injury. Overall, this study highlighted the pivotal role of mitochondria in myocardial DIC-induced ferroptosis and shows how E-Exe preconditioning activated AMPKα2 against myocardial DIC injury. This suggests that E-Exe preconditioning could be a viable strategy for patients undergoing cardiac rehabilitation.

Three-year follow-up study reveals improved survival rate in NSCLC patients underwent guideline-concordant diagnosis and treatment.

Background: No studies in China have assessed the guideline-concordance level of the first-course of non-small cell lung cancer (NSCLC) diagnosis and treatment and its relationship with survival. This study comprehensively assesses the current status of guideline-concordant diagnosis (GCD) and guideline-concordant treatment (GCT) of NSCLC in China and explores its impact on survival. Methods: First course diagnosis and treatment data for NSCLC patients in Liaoning, China in 2017 and 2018 (n=1828) were used and classified by whether they underwent GCD and GCT according to Chinese Society of Clinical Oncology (CSCO) guidelines. Pearson's chi-squared test was used to determine unadjusted associations between categorical variables of interest. Logistic models were constructed to identify variables associated with GCD and GCT. Kaplan-Meier analysis and log-rank tests were used to estimate and compare 3-year survival rates. Multivariate Cox proportional risk models were constructed to assess the risk of cancer mortality associated with guideline-concordant diagnosis and treatment. Results: Of the 1828 patients we studied, 48.1% underwent GCD, and 70.1% underwent GCT. The proportions of patients who underwent both GCD and GCT, GCD alone, GCT alone and neither GCD nor GCT were 36.7%, 11.4%, 33.5% and 18.4%, respectively. Patients in advanced stage and non-oncology hospitals were significantly less likely to undergo GCD and GCT. Compared with those who underwent neither GCD nor GCT, patients who underwent both GCD and GCT, GCD alone and GCT alone had 35.2%, 26.7% and 35.7% higher 3-year survival rates; the adjusted lung cancer mortality risk significantly decreased by 29% (adjusted hazard ratio[aHR], 0.71; 95% CI, 0.53-0.95), 29% (aHR, 0.71; 95% CI, 0.50-1.00) and 32% (aHR, 0.68; 95% CI, 0.51-0.90). Conclusion: The 3-year risk of death is expected to be reduced by 29% if patients with NSCLC undergo both GCD and GCT. There is a need to establish an oncology diagnosis and treatment data management platform in China to monitor, evaluate, and promote the use of clinical practice guidelines in healthcare settings.

Salidroside pretreatment alleviates ferroptosis induced by myocardial ischemia/reperfusion through mitochondrial superoxide-dependent AMPKα2 activation.

BACKGROUND: Ferroptosis, a form of regulated cell death (RCD) that relies on excessive reactive oxygen species (ROS) generation, Fe2+accumulation, abnormal lipid metabolism and is involved in various organ ischemia/reperfusion (I/R) injury, expecially in myocardium. Mitochondria are the powerhouses of eukaryotic cells and essential in regulating multiple RCD. However, the links between mitochondria and ferroptosis are still poorly understood. Salidroside (Sal), a natural phenylpropanoid glycoside isolated from Rhodiola rosea, has mult-bioactivities. However, the effects and mechanism in alleviating ferroptosis caused by myocardial I/R injury remains unclear. PURPOSE: This study aimed to investigate whether pretreated with Sal could protect the myocardium against I/R damage and the underlying mechanisms. In particular, the relationship between Sal pretreatment, AMPKα2 activity, mitochondria and ROS generation was explored. STUDY DESIGN AND METHODS: Firstly, A/R or I/R injury models were employed in H9c2 cells and Sprague-Dawley rats. And then the anti-ferroptotic effects and mechanism of Sal pretreatment was detected using multi-relevant indexes in H9c2 cells. Further, how does Sal pretreatment in AMPKα2 phosphorylation was explored. Finally, these results were validated by I/R injury in rats. RESULTS: Similar to Ferrostatin-1 (a ferroptosis inhibitor) and MitoTEMPO, a mitochondrial free radical scavenger, Sal pretreatment effectively alleviated Fe2+ accumulation, redox disequilibrium and maintained mitochondrial energy production and function in I/R-induced myocardial injury, as demonstrated using multifunctional, enzymatic, and morphological indices. However, these effects were abolished by downregulation of AMPKα2 using an adenovirus, both in vivo and in vitro. Moreover, the results also provided a non-canonical mechanism that, under mild mitochondrial ROS generation, Sal pretreatment upregulated and phosphorylated AMPKα2, which enhanced mitochondrial complex I activity to activate innate adaptive responses and increase cellular tolerance to A/R injury. CONCLUSION: Overall, our work highlighted mitochondria are of great impotance in myocardial I/R-induced ferroptosis and demonstrated that Sal pretreatment activated AMPKα2 against I/R injury, indicating that Sal could become a candidate phytochemical for the treatment of myocardial I/R injury.

Preoperative Systemic Inflammation Score Predicts the Prognosis of Patients with Upper Tract Urothelial Carcinoma Undergoing Radical Nephroureterectomy.

Background: To investigate the prognostic significance of systemic inflammation score (SIS) in upper tract urothelial carcinoma (UTUC) in patients undergoing radical nephroureterectomy (RNU). Methods: A total of 313 UTUC patients who underwent RNU at West China Hospital from May 2014 to June 2019 were retrospectively analyzed. The predictive value of SIS for relevant endpoints, including overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS), was assessed by Kaplan-Meier curves and the Cox proportional hazards model. Results: According to inclusion and exclusion criteria, 218 UTUC patients were ultimately included in this cohort study. Statistical analysis shows that increased SIS was significantly associated with higher TNM stage (p = 0.017), lower BMI (p = 0.037), absence of hemoglobin (p < 0.001), and pathologic necrosis (p = 0.007). Kaplan-Meier survival curves clearly visually stratified survival for the three outcomes. After adjusting for tumor grade, the multivariate Cox proportional hazards model results showed that SIS was an independent risk factor for poor OS and CSS (HR = 1.89, 95% CI: 1.11-3.21, p = 0.0183, HR = 1.89, 95% CI: 1.07-3.33, p = 0.0285) in the advanced group. Conclusions: SIS was an independent risk factor for OS and CSS after RNU in patients with high-grade UTUC. It may be a novel and conducive tool for preoperative risk stratification and guiding individualized therapy for high-risk UTUC patients.

A rare case report of a primary lung cancer comprising adenocarcinoma and atypical carcinoid tumor, with the carcinoid component harboring EML4-ALK rearrangement.

Background: The occurrence of pulmonary adenocarcinoma coexisting with atypical carcinoid tumors is a rare phenomenon. The presence of EML4-ALK fusion in an atypical carcinoid component of a histologically mixed tumor is even more uncommon. Due to their infrequency, the origin and pathogenesis of these mixed tumors remain largely unknown. The advances of therapy development in such patients are still limited and there is no standard treatment. We present a case of collision tumor in the lung consisting of atypical carcinoid and adenocarcinoma to better understand the clinical characteristics of this disease. Case Description: We report an extremely rare case of EML4-ALK rearrangement in a pulmonary atypical carcinoid tumor that coexisting with adenocarcinoma. A 58-year-old woman, who was asymptomatic, underwent pulmonary lobectomy due to the detection of a gradually enlarging solitary pulmonary nodule in the right upper lung. Histological examination of the resected tumor revealed the presence of both atypical carcinoid (approximately 80%) and adenocarcinoma (approximately 20%) components. Metastases by the carcinoid component were observed in mediastinal lymph nodes (station 2R and 4R) and in the primary tumor. Anaplastic lymphoma kinase (ALK) rearrangement was detected in both the primary and metastatic lesions of the carcinoid tumor. Four cycles of chemotherapy with etoposide and carboplatin were dispensed after surgery. Conclusions: This is the first reported case of coexisting pulmonary adenocarcinoma and atypical carcinoid tumor with an ALK fusion only detected in the carcinoid component. The presence of ALK rearrangement in pulmonary carcinoid tumor is very uncommon, and there is currently no standard treatment for advanced stages. Therefore, comprehensive molecular testing, including ALK rearrangement analysis, should be recommended for mixed tumors exhibiting features of atypical carcinoid. ALK inhibitors could represent a potential treatment strategy for selected patients.

Tumor-promoting roles of HMMR in lung adenocarcinoma.

Searching for differential genes in lung adenocarcinoma (LUAD) is vital for research. Hyaluronan mediated motility receptor (HMMR) promotes malignant progression of cancer patients. However, the molecular regulators of HMMR-mediated LUAD onset are unknown. This work aimed to study the relevance of HMMR to proliferation, migration and invasion of LUAD cells. Let-7c-5p and HMMR levels in LUAD cells and HLF-a cells were assessed, and their correlation was also detected. Their interaction was determined by dual-luciferase experiments and qRT-PCR. Cell proliferation, migration and invasion potentials in vitro were validated through cell counting kit-8 (CCK-8), colony formation, scratch healing, and transwell assays. The expression of HMMR was examined by qRT-PCR and western blot and the expression of let-7c-5p was assayed by qRT-PCR. It was found that HMMR level was increased in LUAD and negatively correlated with let-7c-5p level. Let-7c-5p directly targeted HMMR to repress LUAD cell proliferation, migration and invasion. The above data illustrated that the let-7c-5p/HMMR axis may provide certain therapeutic value for LUAD patients.

Removal of Cd from contaminated farmland soil by washing with residues of traditional Chinese herbal medicine extracts.

Soil washing is one of the effective methods for permanent removal of heavy metals from farmland soil, and selection of washing agents determines heavy metal removal efficiency. However, there is still a lack of cost-efficient and eco-friendly washing agents. In this study, three residues of traditional Chinese herbal medicine (RTCHM) extracts: residues of Prunus mume (Sieb.) Sieb. et Zucc. (RPM), residues of Schisandra chinensis (Turcz.) Baill. (RSC), and residues of Crataegus pinnatifida Bunge (RCP), were tested for their potential of Cd removal. The variations in amounts and compositions of dissolved organic carbon (DOC) and citric acid were responsible for the difference in Cd removal efficiencies of RTCHM extracts. Fourier-transform infrared spectrophotometer (FTIR) analysis showed that hydroxyl, carboxyl, and amine were the main functional groups of RTCHM extracts to chelate with heavy metals. The optimum conditions for RTCHM extracts were 100 g L-1 concentration, solid-liquid ratio 1:10, pH 2.50, and contact time of 1 h, and the highest Cd removal efficiencies of RPM, RSC, and RCP extracts reached 35%, 11%, and 15%, respectively. The ecological risk of Cd decreased significantly due to the decrease of exchangeable and reducible Cd fractions. RTCHM extracts washing alleviated soil alkalinity and had little effect on soil cation exchange capacity. Meanwhile, the concentrations of soil organic matter and nitrogen were enhanced significantly by RPM extracts and the activities of soil catalase and urease were also improved. Overall, among the tested extracts, RPM extracts was a much more feasible and environment-friendly washing agent for the remediation of Cd-contaminated farmland soil.