Deficiency of leucine-rich repeat kinase 2 aggravates thioacetamide-induced acute liver failure and hepatic encephalopathy in mice.

BACKGROUND: Hepatic encephalopathy (HE) is closely associated with inflammatory responses. However, as a crucial regulator of the immune and inflammatory responses, the role of leucine-rich repeat kinase 2 (LRRK2) in the pathogenesis of HE remains unraveled. Herein, we investigated this issue in thioacetamide (TAA)-induced HE following acute liver failure (ALF). METHODS: TAA-induced HE mouse models of LRRK2 wild type (WT), LRRK2 G2019S mutation (Lrrk2G2019S) and LRRK2 knockout (Lrrk2-/-) were established. A battery of neurobehavioral experiments was conducted. The biochemical indexes and pro-inflammatory cytokines were detected. The prefrontal cortex (PFC), striatum (STR), hippocampus (HIP), and liver were examined by pathology and electron microscopy. The changes of autophagy-lysosomal pathway and activity of critical Rab GTPases were analyzed. RESULTS: The Lrrk2-/--HE model reported a significantly lower survival rate than the other two models (24% vs. 48%, respectively, p < 0.05), with no difference found between the WT-HE and Lrrk2G2019S-HE groups. Compared with the other groups, after the TAA injection, the Lrrk2-/- group displayed a significant increase in ammonium and pro-inflammatory cytokines, aggravated hepatic inflammation/necrosis, decreased autophagy, and abnormal phosphorylation of lysosomal Rab10. All three models reported microglial activation, neuronal loss, disordered vesicle transmission, and damaged myelin structure. The Lrrk2-/--HE mice presented no severer neuronal injury than the other genotypes. CONCLUSIONS: LRRK2 deficiency may exacerbate TAA-induced ALF and HE in mice, in which inflammatory response is evident in the brain and aggravated in the liver. These novel findings indicate a need of sufficient clinical awareness of the adverse effects of LRRK2 inhibitors on the liver.

Early-life tobacco smoke exposure and stroke risk: a prospective study of 341,783 and 352,737 UK Biobank participants.

INTRODUCTION: Stroke is a life-threatening condition that causes a major medical burden globally. The currently used methods for the prevention or prediction of stroke have certain limitations. Exposure to tobacco in early life, including smoking during adolescence and maternal smoking during pregnancy, can affect adolescent development and lead to several negative outcomes. However, the association between early-life tobacco exposure and stroke is not known. METHODS: In this prospective cohort study, for the analyses involving exposure to maternal smoking during pregnancy and age of smoking initiation, we included 304,984 and 342,893 participants, respectively., respectively from the UK Biobank. Cox proportional hazard regression model and subgroup analyses were performed to investigate the association between early-life tobacco exposure and stroke. Mediation analyses were performed to identify the mediating role of biological aging in the association between early tobacco exposure and stroke. RESULTS: Compared with participants whose mothers did not smoke during pregnancy, participants whose mothers smoked during pregnancy showed an 11% increased risk of stroke (HR: 1.11, 95% CI: 1.05-1.18, P < 0.001). Compared with participants who never smoked, participants who smoked during adulthood, adolescence and childhood showed a 22%, 24%, and 38% increased risk of stroke during their adulthood, respectively. Mediation analysis indicated that early-life tobacco exposure can cause stroke by increasing biological aging. CONCLUSION: This study reveals that exposure to tobacco during early life is associated with an increased risk of experiencing a stroke, and increased biological aging can be the underlying mechanism.

Optimizing the detection of emerging infections using mobility-based spatial sampling.

Timely and precise detection of emerging infections is imperative for effective outbreak management and disease control. Human mobility significantly influences the spatial transmission dynamics of infectious diseases. Spatial sampling, integrating the spatial structure of the target, holds promise as an approach for testing allocation in detecting infections, and leveraging information on individuals' movement and contact behavior can enhance targeting precision. This study introduces a spatial sampling framework informed by spatiotemporal analysis of human mobility data, aiming to optimize the allocation of testing resources for detecting emerging infections. Mobility patterns, derived from clustering point-of-interest and travel data, are integrated into four spatial sampling approaches at the community level. We evaluate the proposed mobility-based spatial sampling by analyzing both actual and simulated outbreaks, considering scenarios of transmissibility, intervention timing, and population density in cities. Results indicate that leveraging inter-community movement data and initial case locations, the proposed Case Flow Intensity (CFI) and Case Transmission Intensity (CTI)-informed spatial sampling enhances community-level testing efficiency by reducing the number of individuals screened while maintaining a high accuracy rate in infection identification. Furthermore, the prompt application of CFI and CTI within cities is crucial for effective detection, especially in highly contagious infections within densely populated areas. With the widespread use of human mobility data for infectious disease responses, the proposed theoretical framework extends spatiotemporal data analysis of mobility patterns into spatial sampling, providing a cost-effective solution to optimize testing resource deployment for containing emerging infectious diseases.

Effects of zeolite imidazole frameworks on rice seedlings (Oryza sativa L.): Phytotoxicity, transformation, and bioaccumulation.

Zeolite imidazole frameworks (ZIFs), a class of the metal organic framework, have been extensively studied in environmental applications. However, their environmental fate and potential ecological impact on plants remain unknown. Here, we investigated the phytotoxicity, transformation, and bioaccumulation processes of two typical ZIFs (ZIF-8 and ZIF-67) in rice (Oryza sativa L.) under hydroponic conditions. ZIF-8 and ZIF-67 in the concentration of 50 mg/L decreased root and shoot dry weight maximally by 55.2% and 27.5%, 53.5% and 37.5%, respectively. The scanning electron microscopy (SEM) imaging combined with X-ray diffraction (XRD) patterns revealed that ZIFs on the root surface gradually collapsed and transformed into nanosheets with increasing cultivation time. The fluorescein isothiocyanate (FITC) labeled ZIFs were applied to trace the uptake and translocation of ZIFs in rice. The results demonstrated that the transformed ZIFs were mainly distributed in the intercellular spaces of rice root, while they cannot be transported to culms and leaves. Even so, the Co and Zn contents of rice roots and shoots in the ZIFs treated groups were increased by 1145% and 1259%, 145% and 259%, respectively, compared with the control groups. These findings suggested that the phytotoxicity of ZIFs are primarily attributed to the transformed ZIFs and to a less extent, the metal ions and their ligands, and they were internalized by rice root and increased the Co and Zn contents of shoots. This study reported the transformation of ZIFs and their biological effectiveness in rice, highlighting the potential environmental hazards and risks of ZIFs to crop plants.

Graphitic carbon nitride nanosheets mitigate cadmium toxicity in Glycine max L. by promoting cadmium retention in root and improving photosynthetic performance.

Cadmium (Cd) pollution poses a serious threat to plant growth and yield. Nanomaterials have shown great application potential for alleviation of Cd toxicity to plants. In this study, we applied graphitic carbon nitride nanosheets (g-C3N4 NSs) for alleviation of Cd-toxicity to soybean (Glycine max L.). The g-C3N4 NSs supplementation significantly improved plant growth and reduced oxidative damage in the Cd-toxicated soybean seedlings through hydroponic culture. Particularly, the g-C3N4 NSs dynamically regulated the root cell wall (RCW) components by increasing pectin content and modifying its demethylation via enhancing pectin methylesterase (PME) activity, therefore greatly enhanced stronger RCW-Cd retention (up to 82.8%) and reduced Cd migration to the shoot. Additionally, the g-C3N4 NSs reversed the Cd-induced chlorosis, increased photosynthetic efficiency because of enhancement in Fv/Fm ration, Y(II) and sugars content. These results provide new insights into the alleviation of Cd toxicity to plants by g-C3N4 NSs, and shed light on the application of low-cost and environmental-friendly carbon-based NMs for alleviating heavy metal toxicity to plants.

Infection of humanized mice with a novel phlebovirus presented pathogenic features of severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne emerging phlebovirus with high mortality rates of 6.0 to 30%. SFTSV infection is characterized by high fever, thrombocytopenia, leukopenia, hemorrhage and multiple organ failures. Currently, specific therapies and vaccines remain elusive. Suitable small animal models are urgently needed to elucidate the pathogenesis and evaluate the potential drug and vaccine for SFTSV infection. Previous models presented only mild or no pathogenesis of SFTS, limiting their applications in SFTSV infection. Therefore, it is an urgent need to develop a small animal model for the investigation of SFTSV pathogenesis and evaluation of therapeutics. In the current report, we developed a SFTSV infection model based on the HuPBL-NCG mice that recapitulates many pathological characteristics of SFTSV infection in humans. Virus-induced histopathological changes were identified in spleen, lung, kidney, and liver. SFTSV was colocalized with macrophages in the spleen and liver, suggesting that the macrophages in the spleen and liver could be the principle target cells of SFTSV. In addition, histological analysis showed that the vascular endothelium integrity was severely disrupted upon viral infection along with depletion of platelets. In vitro cellular assays further revealed that SFTSV infection increased the vascular permeability of endothelial cells by promoting tyrosine phosphorylation and internalization of the adhesion molecule vascular endothelial (VE)-cadherin, a critical component of endothelial integrity. In addition, we found that both virus infection and pathogen-induced exuberant cytokine release dramatically contributed to the vascular endothelial injury. We elucidated the pathogenic mechanisms of hemorrhage syndrome and developed a humanized mouse model for SFTSV infection, which should be helpful for anti-SFTSV therapy and pathogenesis study.

Efficacy of short pulse and conventional deep brain stimulation in Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND: Deep brain stimulation (DBS) is a common treatment for Parkinson's disease. However, the clinical efficacy of short pulse width DBS (spDBS) compared with conventional DBS (cDBS) is still unknown. OBJECTIVE: This meta-analysis investigated the effectiveness of spDBS versus cDBS in patients with PD. METHODS: Four databases (PubMed, Cochrane, Web of Science, and Embase) were independently searched until October 2021 by two reviewers. We utilized the following scales and items: therapeutic windows (TW), efficacy threshold, side effect threshold, Movement Disorder Society-Sponsored Revision Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III off-medication score, Speech Intelligence Test (SIT), and Freezing of Gait Questionnaire (FOG-Q). RESULTS: The analysis included seven studies with a total of 87 patients. The results indicated that spDBS significantly widened the therapeutic windows (0.99, 95% CI = 0.61 to 1.38) while increasing the threshold amplitudes of side effects (2.25, 95% CI = 1.69 to 2.81) and threshold amplitudes of effects (1.60, 95% CI = 0.84 to 2.36). There was no statistically significant difference in UPDRS part III, SIT, and FOG-Q scores between spDBS and cDBS groups, suggesting that treatment with both cDBS and spDBS may result in similar effects of improved dysarthria and gait disorders. CONCLUSIONS: Compared with cDBS, spDBS is effective in expanding TW. Both types of deep brain stimulation resulted in improved gait disorders and speech intelligibility.

Directional and Ultrafast Charge Transfer in Oxygen-Vacancy-Rich ZnO@Single-Atom Cobalt Core-Shell Junction for Photo-Fenton-Like Reaction.

In photosynthesis, solar energy is harvested by photosensitizers, and then, the excited electrons transfer via a Z-Scheme mode to enzymatic catalytic centers to trigger redox reactions. Herein, we constructed a core-shell Z-scheme heterojunction of semiconductor@single-atom catalysts (SACs). The oxygen-vacancy-rich ZnO core and single-atom Co-N4 sites supported on nitrogen-rich carbon shell (SA-Co-CN) act as the photosensitizer and the enzyme-mimicking active centers, respectively. Driven by built-in electric field across the heterojunction, photoexcited electrons could rapidly (2 ps) transfer from the n-type ZnO core to the p-type SA-Co-CN shell, finally boosting the catalytic performance of the surface-exposed single-atom Co-N4 sites for peroxymonosulfate (PMS) activation under light irradiation. The synergies between photocatalysis and heterogeneous Fenton-like reaction lead to phenomenally enhanced production of various reactive oxygen species for rapid degradation of various microcontaminants in water. Experimental and theoretical results validate that the interfacial coupling of SA-Co-CN with ZnO greatly facilitates PMS adsorption and activation by reducing the adsorption energy and enhancing the cascade electron transfer processes for the photo-Fenton-like reaction.

Transmission in home environment associated with the second wave of COVID-19 pandemic in India.

India has suffered from the second wave of COVID-19 pandemic since March 2021. This wave of the outbreak has been more serious than the first wave pandemic in 2020, which suggests that some new transmission characteristics may exist. COVID-19 is transmitted through droplets, aerosols, and contact with infected surfaces. Air pollutants are also considered to be associated with COVID-19 transmission. However, the roles of indoor transmission in the COVID-19 pandemic and the effects of these factors in indoor environments are still poorly understood. Our study focused on reveal the role of indoor transmission in the second wave of COVID-19 pandemic in India. Our results indicated that human mobility in the home environment had the highest relative influence on COVID-19 daily growth rate in the country. The COVID-19 daily growth rate was significantly positively correlated with the residential percent rate in most state-level areas in India. A significant positive nonlinear relationship was found when the residential percent ratio ranged from 100 to 120%. Further, epidemic dynamics modelling indicated that a higher proportion of indoor transmission in the home environment was able to intensify the severity of the second wave of COVID-19 pandemic in India. Our findings suggested that more attention should be paid to the indoor transmission in home environment. The public health strategies to reduce indoor transmission such as ventilation and centralized isolation will be beneficial to the prevention and control of COVID-19.

Sex-Related Differences in Sitagliptin Treatment in Type 2 Diabetes: Results from the PROLOGUE Trial.

BACKGROUND At present, whether sitagliptin has sex-related differences in effect on atherosclerosis in type 2 diabetes mellitus (T2DM) patients is unknown. The purpose of this study was to investigate whether there is sex-related difference in the effect of sitagliptin on atherosclerosis in T2DM patients. MATERIAL AND METHODS In the PROLOGUE trial, 222 patients were allocated to the sitagliptin group and 220 patients were allocated to the conventional group. Carotid artery intima-media thickness (IMT) was assessed at baseline, 12 months, and 24 months. RESULTS In male patients, sitagliptin significantly reduced the mean IMT (0.84±0.41 mm vs 1.02±0.67 mm, P=0.013) and the maximum IMT (1.14±0.59 mm vs 1.39±0.88 mm, P=0.016) in the right internal carotid arteries (ICA) compared to the conventional group at 12 months. Similarly, sitagliptin significantly reduced the maximum IMT (1.09±0.52 mm vs 1.28±0.77 mm, P=0.049) in the right ICA compared to the conventional group at 24 months, but no difference was found in the mean IMT in the right ICA between groups at 24 months. In female patients, sitagliptin significantly reduced the mean IMT (1.01±0.47 mm vs 1.23±0.51 mm, P=0.049) and the maximum IMT (1.39±0.65 mm vs 1.71±0.77 mm, P=0.042) in the right bulb compared to the conventional group at 12 months. However, the group differences were not observed in mean IMT and maximum IMT at 24 months. CONCLUSIONS Our results suggest that sitagliptin slows the progression of right carotid IMT in male patients. However, more research is needed to validate this finding in female patients.

Impacts of worldwide individual non-pharmaceutical interventions on COVID-19 transmission across waves and space.

Governments worldwide have rapidly deployed non-pharmaceutical interventions (NPIs) to mitigate the COVID-19 pandemic. However, the effect of these individual NPI measures across space and time has yet to be sufficiently assessed, especially with the increase of policy fatigue and the urge for NPI relaxation in the vaccination era. Using the decay ratio in the suppression of COVID-19 infections and multi-source big data, we investigated the changing performance of different NPIs across waves from global and regional levels (in 133 countries) to national and subnational (in the United States of America [USA]) scales before the implementation of mass vaccination. The synergistic effectiveness of all NPIs for reducing COVID-19 infections declined along waves, from 95.4% in the first wave to 56.0% in the third wave recently at the global level and similarly from 83.3% to 58.7% at the USA national level, while it had fluctuating performance across waves on regional and subnational scales. Regardless of geographical scale, gathering restrictions and facial coverings played significant roles in epidemic mitigation before the vaccine rollout. Our findings have important implications for continued tailoring and implementation of NPI strategies, together with vaccination, to mitigate future COVID-19 waves, caused by new variants, and other emerging respiratory infectious diseases.

The induction and characterization of monoclonal antibodies specific to GP of Ebola virus.

The Ebola virus is highly infectious and characterized by hemorrhagic fever, headache, and so on with a high mortality rate. Currently, there are neither therapeutic drugs or vaccines against the Ebola virus nor fast diagnostic methods for the detection of Ebola virus infection. This study reported the induction and isolation of two monoclonal antibodies that specifically recognized the glycoprotein (GP) and secreted glycoprotein (sGP) of the Ebola virus. Plasmids encoding either GP or sGP were constructed and immunized BALB/c mice, accordingly purified sGP was boosted. The antisera were analyzed for binding activity against sGP protein in enzyme-linked immunosorbent assay (ELISA) and neutralization activity in a pseudotyped virus neutralization assay. A number of reactive clones were isolated and two monoclonal antibodies T231 and T242 were identified to react with both GP and sGP. Western blot and ELISA assays showed that the monoclonal antibodies could react with GP and sGP, respectively. Moreover, they could recognize Ebola pseudovirus by cellular immunochemistry assay. We labeled the monoclonal antibody T231 with biotin and analyzed the competitiveness of the two antibodies by the ELISA test. The results showed that the binding epitopes of the two monoclonal antibodies to sGP were partially overlapped. In summary, two GP-specific mAbs were identified, which will be used to detect the Ebola virus or investigate GP.

Metformin treatment improves the spatial memory of aged mice in an APOE genotype-dependent manner.

Aging and apolipoprotein E4 (ApoE4) can increase the risk of cognitive impairment and neurodegenerative disorders, including Alzheimer's disease (AD), and patients with type 2 diabetes mellitus are highly susceptible to cognitive dysfunction. Recent research has indicated that metformin, a prescribed drug for type 2 diabetes, may affect cognitive function; however, findings regarding its efficacy are largely controversial. The current study reported that a 5-mo metformin administration (300 mg/kg/d) starting at 13 mo old improved the spatial memory of ApoE3-target replacement (TR) mice, not ApoE4-TR mice. It found that in aged ApoE3-TR mice, metformin treatment, at a molecular level, inhibited AMPK activity, increased insulin signaling, and activated mammalian target of rapamycin signaling, resulting in an enhanced expression of postsynaptic proteins; but the response of the neuronal AMPK activity and insulin signaling to metformin was blunt in aged ApoE4-TR mice. Meanwhile, metformin treatment also increased the phosphorylation of tau in both ApoE3-TR and ApoE4-TR mice, implying that metformin may have side effects in human. These findings suggest that metformin can improve the cognitive performance of aged mice in an APOE genotype-dependent manner, which provides empirical insights into the clinical value of metformin for ApoE4- and age-related AD prevention and treatment.-Zhang, J., Lin, Y., Dai, X., Fang, W., Wu, X., Chen, X. Metformin treatment improves the spatial memory of aged mice in an APOE genotype-dependent manner.

Dual active sites of the Co2N and single-atom Co-N4 embedded in nitrogen-rich nanocarbons: a robust electrocatalyst for oxygen reduction reactions.

The development of low-cost, highly efficient and durable non-precious-metal (NPM) electrocatalysts for the oxygen reduction reaction (ORR) is of great significance. Herein, we report an ingenious two-step strategy for the fabrication of NPM electrocatalysts containing multifarious cobalt species embedded in nitrogen-rich nanocarbons (Co-N-C). Firstly, Co ions were fixed by coordination with 1H-Imidazo[4,5-f][1,10]phenanthroline (Hip), and secondly the Co-Hip precursor with abundant Co, C and N sources was subjected to calcination at various temperatures (700-900 °C). The obtained Co-N-C catalysts exhibited excellent activity in terms of the ORR in alkaline conditions, with a half-wave potential of 0.82 eV versus the reversible hydrogen electrode, which is close to that of commercial Pt/C. Moreover, the Co-N-C exhibited an unexpected catalytic activity with long-term stability and immunity to methanol which is better than commercial Pt/C catalyst, suggesting that Co-N-C with dual active sites of the single-atom Co sites (Co-N4) and Co2N can be a promising alternative to replace Pt-based electrocatalysts in fuel cells. This work can provide a new route to designing promising catalysts with dual active sites for ORR.

Association Between Cystatin C and Cardiac Function and Long-Term Prognosis in Patients with Chronic Heart Failure.

BACKGROUND The aim of this study was to investigate the association between cystatin C and cardiac function and long-term prognosis in patients with chronic heart failure (CHF). MATERIAL AND METHODS We selected 418 CHF patients admitted to our hospital as subjects. Patients were divided into 3 groups according to the cystatin C level (Quantile 1 group: 0.65-1.04 mg/L, Quantile 2 group: 1.05-1.35 mg/L, and Quantile 3 group: 1.36-7.84 mg/L), and patients were followed up for 5 years. We used odds ratio (OR) and 95% confidence interval (CI) to compare the results. RESULTS The cystatin C and NT-ProBNP level in the cardiac function grade (NYHA) class IV group were higher than those in the class III group (P<0.05). Pearson correlation analysis showed that there was a positive correlation between cystatin C and NT-ProBNP log10 transform in CHF patients (r=0.411). During 5-year follow-up, 231 patients died and the 5-year all-cause mortality rate was 55.26% (231/418). There was a significant difference in 5-year all-cause mortality among the 3 groups (P for trend=0.010). After adjusting for potential confounders by multivariate regression analysis, the Quantile 2 group vs. Quantile 1 group were OR=0.83, 95% CI 0.51 to 1.35, P=0.448, and the Quantile 3 group vs. Quantile 1 group were OR=1.71, 95% CI. 1.04 to 2.82, P=0.034. Curve fitting showed that cystatin C was positively correlated with 5-year all-cause mortality in CHF patients. CONCLUSIONS Cystatin C was positively correlated with cardiac function and NT-ProBNP in CHF patients. Cystatin C could be used as a serological index to evaluate the long-term prognosis of CHF patients.

Nitrogen Doped Nanoporous Carbon Derived from Zizania Latifolia for Adsorptive Removal of Bisphenol A.

Nitrogen doped nanoporous activated carbon (N-NPAC) was prepared via the facile and effective KOH activation method using Zizania latifolia (ZL), a common Chinese aquatic vegetable, as the raw material. The biomass derived N-NPAC exhibited high content of nitrogen (18.4 at%), large surface area (1493.4 m²/g) and abundant nanopores. The unique physical-chemical structure endows the N-NPAC with great application potential in adsorbents. The performance of the N-NPAC for the adsorptive removal of bisphenol A (BPA) was studied. The results showed the adsorption processes were barely affected by solution pH. The adsorption kinetics are well-fitted by the pseudo-second-order kinetic model and the adsorption isotherms followed the Langmuir isotherm model. The maximum adsorption capacity calculated by the Langmuir isotherm model is 555.5 mg/g at 313 K, demonstrating the promise of the N-NPAC for the application in water cleanup. This study provides an example using the inexpensive and abundantly available biomass as the raw materials for the large scale production of nanocarbons and paves an avenue for the development of bio-derived nanomaterials.

Sustainable biodegradation of phenol by immobilized Bacillus sp. SAS19 with porous carbonaceous gels as carriers.

In this study, high-efficient phenol-degrading bacterium Bacillus sp. SAS19 which was isolated from activated sludge by resuscitation-promoting factor (Rpf) addition, were immobilized on porous carbonaceous gels (CGs) for phenol degradation. The phenol-degrading capabilities of free and immobilized Bacillus sp. SAS19 were evaluated under various initial phenol concentrations. The obtained results showed that phenol could be removed effectively by both free and immobilized Bacillus sp. SAS19. Furthermore, for degradation of phenol at high concentrations, long-term utilization and recycling were more readily achieved for immobilized bacteria as compared to free bacteria. Immobilized bacteria exhibited significant increase in phenol-degrading capabilities in the third cycle of recycling and reuse, which demonstrated 87.2% and 100% of phenol (1600 mg/L) degradation efficiency at 12 and 24 h, respectively. The present study revealed that immobilized Bacillus sp. SAS19 can be potentially used for enhanced treatment of synthetic phenol-laden wastewater.

Meta-analysis for the efficacy of S-1-based regimens as the first-line treatment in Asian chemotherapy-naive patients with advanced non-small-cell lung cancer.

AIM: We performed a meta-analysis to evaluate the efficacy and safety for S-1-based regimens as the first-line treatment in Asian chemotherapy-naive patients with advanced non-small-cell lung cancer. PATIENTS & METHODS: Eligible randomized clinical trials (RCTs) were included, of which data were extracted by inclusion criteria and exclusion one. Odds ratio and hazard ratio (HR) of outcomes including objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse effects (AEs) were explored for the final analysis. RESULTS: Twenty-one RCTs including 3263 patients were fit into the analysis. Pooled HR for PFS was 1.01 (95% CI: 0.92-1.10; p = 0.88), the pooled HR for OS was 0.95 (95% CI: 0.85-1.06; p = 0.33) and the pooled odds ratio for ORR was 0.74 (95% CI: 0.61-0.90; p = 0.003). S-1-based regimens showed milder AEs in high-grade nausea/vomit, anorexia, leukopenia, neutropenia and febrile neutropenia (all p < 0.05). CONCLUSION: The present study has revealed that S-1-based regimens are accompanied by the similar efficacy and slighter AEs compared with standard regimens as the first-line treatment in Asian chemotherapy-naive patients with advanced non-small-cell lung cancer.

Prevalence of consistent condom use with various types of sex partners and associated factors among money boys in Changsha, China.

INTRODUCTION: Money boys with inconsistent condom use (less than 100% of the time) are at high risk of infection by human immunodeficiency virus (HIV) or sexually transmitted infection (STI), but relatively little research has examined their risk behaviors. AIM: We investigated the prevalence of consistent condom use (100% of the time) and associated factors among money boys. METHODS: A cross-sectional study using a structured questionnaire was conducted among money boys in Changsha, China, between July 2012 and January 2013. MAIN OUTCOME MEASURE: Independent variables included socio-demographic data, substance abuse history, work characteristics, and self-reported HIV and STI history. Dependent variables included the consistent condom use with different types of sex partners. RESULTS: Among the participants, 82.4% used condoms consistently with male clients, 80.2% with male sex partners, and 77.1% with female sex partners in the past 3 months. A multiple stepwise logistic regression model identified four statistically significant factors associated with lower likelihoods of consistent condom use with male clients: age group, substance abuse, lack of an "employment" arrangement, and having no HIV test within the prior 6 months. In a similar model, only one factor associated significantly with lower likelihoods of consistent condom use with male sex partners was identified in multiple stepwise logistic regression analyses: having no HIV test within the prior six months. As for female sex partners, two significant variables were statistically significant in the multiple stepwise logistic regression analysis: having no HIV test within the prior 6 months and having STI history. CONCLUSIONS: Interventions which are linked with more realistic and acceptable HIV prevention methods are greatly warranted and should increase risk awareness and the behavior of consistent condom use in both commercial and personal relationship.

Association between serum uric acid and cardiovascular fitness among US adults: A cross-sectional study.

Background: While serum uric acid (SUA) is known as a cardiovascular disease risk factor and is associated with increased cardiovascular mortality, the relationship between SUA and cardiovascular adaptability under exercise stress remains unclear. Aims: This study aims to elucidate the relationship between SUA levels and cardiovascular fitness, particularly as manifested during cardiopulmonary exercise testing. Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, this study included 5765 participants aged 12-49 years. Heart rate recovery (HRR) during cardiopulmonary exercise testing was measured as an indicator of cardiovascular fitness. Multivariate linear regression analysis was used to explore the association between SUA levels and heart rate recovery at 1 min (HRR1) and 2 min (HRR2) post-exercise. Results: After adjusting for potential confounders, an inverse relationship was found between SUA levels and both HRR1 and HRR2. Multivariate adjusted smoothing spline plots demonstrated a decrease in HRR1 and HRR2 with increasing SUA levels. This negative correlation was observed across nearly all subgroups. Conclusions: Elevated SUA levels are indicative of poorer cardiovascular adaptability in the adult US population.