Efficacy and safety of traditional Chinese medicine combined with azithromycin sequential therapy for mycoplasma pneumonia among children: a meta-analysis of randomized controlled trials.

Background: Traditional Chinese medicine (TCM) is used to treat mycoplasma pneumonia (MP) in children with favorable treatment outcome in China. In the present study, we evaluated the clinical efficacy of TCM combined with azithromycin (AZM) for the treatment of MP among children, providing high evidence-based reference for clinical treatment. Method: We retrieved eligible randomized controlled trials (RCTs) from CQVIP, CNKI, WanFang, NSTL, PubMed, Embase, and Embase databases from January 2000 to November 2023. Data extraction and quality assessment of the enrolled studies were independently by two reviewers. Review Manager 5.3 was used for meta-analysis. Result: A total of 51 RCTs involving 5,799 children aged 1-14 enrolled. Meta-analysis demonstrated that TCM combined with AZM improved the cure rate (odds ratio [OR] = 2.34, 95% CI: 2.06 to 2.64) and the effective rate (OR = 5.21, 95% CI: 4.22 to 6.43), shorted the disappearance duration of cough (WMD = -1.62, 95% CI: -1.90 to -1.34), the duration of fever (WMD = -1.62, 95% CI: -1.96 to -1.29), and the disappearance time of lung rales (WMD = -1.15, 95% CI: -1.32 to -0.98), improved CRP levels (WMD = -2.06, 95% CI: -2.57 to -1.55), IL-6 levels (WMD = -1.92,95% CI: -2.51 to -1.34), and TNF-α levels (WMD = -1.59, 95% CI: -2.14 to -1.04), and reduced adverse reactions (OR = 0.37, 95% CI: 0.32 to 0.44). Conclusion: TCM combined with AZM in the treatment of MP among children has favorable clinical efficacy and safety.

Serum uric acid trajectories and the risk of cardiovascular disease: a longitudinal association and pathway analysis.

BACKGROUND: Age-specifically longitudinal associations and potential pathways between serum uric acid (SUA) and cardiovascular disease (CVD) remained unclear. This study aimed to explore SUA trajectories in different age populations and to determine their associations and potential pathways with incident CVD. METHODS: This prospective cohort included 41,367 participants from the Kailuan study, including 30,938 participants aged <55 years and 10,419 participants aged ≥55. The SUA trajectories during year 2006-2012 were identified by latent class growth models. RESULTS: Three SUA trajectories were identified in the overall, aged <55 and aged ≥55 years participants, as "low-stable" (51.9%, 54.4%, and 43.3%), "moderate-stable" (39.0%, 36.9%, and 45.6%), and "high-stable" (9.1%, 9.7%, and 11.1%), respectively. During a median follow-up of 6.75 years, incident CVD occurred in 2302 participants (5.56%). Overall, a high-stable trajectory was independently associated with a higher risk of CVD (hazard ratio [HR], 1.23; 95% [confidence interval], 1.06-1.42). Notably, the associations differed by age, a significant association was only observed in participants aged ≥55 years (HR, 1.29; 95% CI, 1.05-1.58), rather than those aged <55 years (HR, 1.08; 95% CI, 0.89-1.33). The addition of SUA trajectories to a baseline risk model for CVD improved the integrated discrimination improvement value (P < 0.05) and category-free net reclassification improvement value (P < 0.05). Bayesian network showed the conditional probability of high CVD risk associated with aging, elevated SUA trajectories, blood pressure, glucose, and inflammation was 15.5%. CONCLUSIONS: High-stable SUA trajectories were independently associated with an elevated risk of CVD, which is mainly induced by hypertension, diabetes, and inflammation, especially in participants aged ≥55 years.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for initially unresectable locally advanced colon cancer: short-term outcomes of an open-label, single-centre, randomised, controlled, phase 3 trial.

Background: Neoadjuvant chemotherapy (NACT) is commonly used to downstage the tumor in locally advanced colon cancer (LACC) and improve the R0 resection rate. Neoadjuvant chemoradiotherapy (NACRT) is the standard treatment for locally advanced rectal and esophageal cancers, but its benefits in LACC remain poorly understood. This study aimed to compare the effects and safety of NACRT and NACT on R0 resection and survival rates in initially unresectable LACC. Methods: This was an open-label, single-center, randomized, controlled trial conducted between May 11, 2019 and May 30, 2022. Forty-five patients with initially unresectable LACC were randomly allocated to the NACT (control, n = 20) or NACRT (research, n = 25) group. The NACT group received XELOX (oxaliplatin 100-130 mg/m2, qd, d1, every 3 weeks; and capecitabine 1000 mg/m2, bid, d1-d14, every 3 weeks) for 4 cycles. The NACRT group, in addition to chemotherapy, received daily irradiation (GTV 45-50 Gy/25 F; CTV 42.5-45 Gy/25 F). Surgery was scheduled 6-12 weeks after neoadjuvant treatment and adjuvant chemotherapy was administered if the patient developed resectable LACC. The primary endpoint was the 5-year overall survival (OS) rate. The secondary outcomes included the 3-year progression-free survival (PFS) and R0 resection rates. This study was registered with ClinicalTrials.gov (NCT03970694). Findings: In short-term outcome analysis, NACRT significantly improved the R0 resection rate (80% for NACRT vs. 20% for NACT, P < 0.001). The NACRT and NACT groups had a 3-year OS of 87.6% and 75% (P = 0.037) and a 3-year PFS of 76% and 45% (P = 0.049), respectively. The 5-year OS was not reached. In the NACRT group, no local or regional recurrence was observed in patients who underwent surgery during the follow-up period, compared to two patients in the NACT group. Both NACT and NACRT were well tolerated, with no significant differences in severe adverse events. The most commonly observed grade 3-4 AE was myelosuppression (39% for NACRT and 47% for NACT, P = 0.609). No grade 5 AEs were observed between the two groups. Interpretation: Adding radiation to NACT increased the R0 resection rate, prolonged the PFS, and potentially improved OS in selected patients with initially unresectable LACC. The trial findings indicate that this approach is safe, feasible, and may confer a survival benefit. Funding: This study was supported by grants from the National Natural Science Foundation of China (82373213 to Dr Gao, 82202952 to Dr Wang); and the Natural Science Foundation of Guangdong Province (2023A1515010290 to Dr Chang). Funding sources were not involved in the study design, data collection, analysis and interpretation, writing of the report, or decision to submit the article for publication.

Time in target range for systolic blood pressure and glucose with cardiovascular disease and all-cause mortality risks.

Evidence on the combined effect of time in the target range (TTR) for systolic blood pressure (SBP) and fasting blood glucose (FBG) in real-world settings was scarce. We aimed to evaluate the separate and combined effects of SBP TTR and FBG TTR on cardiovascular disease (CVD) and all-cause mortality risks among participants with comorbidity of hypertension and diabetes. The data was derived from the Kailuan study. The target ranges for SBP and FBG were set as 110-140 mmHg and 3.9-7.0 mmol/L, and linear interpolation to calculate TTR. Cox proportional hazard regression models were used to estimate the separate and combined effects of SBP TTR and FBG TTR on CVD and all-cause mortality risks. We included 11,899 participants with hypertension and diabetes comorbidity whose mean age was 54.52 ± 10.36 years, and 9,873 (83.00%) were male. After a follow-up of 6.67 years, 1,381 cases of CVD and 2,148 cases of all-cause mortality were documented. In the fully adjusted model, compared with the participants with both SBP TTR and FBG TTR lower than 25%, participants with both greater SBP TTR and FBG TTR had the lowest risks of CVD (HR: 0.53; 95%CI: 0.57-0.78) and mortality (HR: 0.59; 95%CI: 0.47-0.74). Per 1 SD increase in SBP TTR was associated with a 14% reduction in CVD risk (HR, 0.86; 95% CI, 0.80-0.92) and a 10% reduction in mortality risk (HR, 0.90; 95% CI, 0.85-0.95), all significant results were maintained in the FBG TTR analyses. Both higher SBP TTR and FBG TTR were associated with lower risks of CVD and all-cause mortality in participants with comorbidity of hypertension and diabetes. Simultaneous control of SBP and FBG within the target ranges is a beneficial strategy for CVD prevention.

Profiling mechanism of Hippophae rhamnoides phytoremediation on microecosystem of rhizosphere soil surrounding a magnetite tailings pond in North China.

Tailings pond poses a serious threat to the surrounding environment. This study aimed to explore the current status and mechanism of Hippophae rhamnoides (H. rhamnoides) restoration in the Zhoutaizi magnetite tailings pond in Chengde city by analyzing the physicochemical properties, heavy metal content, and microbial community characteristics of the rhizosphere soil of H. rhamnoides. Rhizosphere soil samples were collected from the planting areas (10 m, 50 m, and 80 m) at distances of 10, 50, and 80 m from the mountain, the dead plants areas (D) at a distance of 80 m from the mountain, and the unplanted areas (U) in the center of the Zhoutaizi magnetite tailings pond. The available manganese (Mn) content in groups 10 m, 50 m, 80 m, and D was higher than in group U (p< 0.05). Mn contributed to the relative abundances of Articulospora, Mortierella, Minimedusa, and Knufia, but negatively correlated with that of Fusarium and Cistella (p< 0.05). These results indicated that H. rhamnoides can improve soil quality and microbial community structure by increasing Mn content. The Chao and Ace indices in groups 10 m, 50 m, 80 m and D were higher than in group U (p< 0.05), implying that H. rhamnoides can increase the total number of soil microbial species. The electrical conductivity (EC) of groups D and U was higher than that of the other groups (p< 0.05). EC was positively correlated with Cistella, while negatively correlated with Minimedusa and Knufia (p< 0.05). Therefore, we speculated that the increase of harmful bacteria and the decrease of beneficial bacteria caused by high EC were one of the reasons for H. rhamnoides death. In short, H. rhamnoides can be used to some extent for restoring magnetite tailings pond, but high EC is the main obstacle to its restoration. This study provides a theoretical basis for the construction of green mines.

Cognitive function characteristics and influencing factors in patients with depressive disorders: a 5-year follow-up report based on the epidemiological survey of mental disorders in Shandong Province, China.

Objective: Cognitive impairment represents a notable feature of depressive disorders. Comprehending its characteristics and influencing factors is vital for patient rehabilitation. Methods: This study is based on the 2015 Shandong Province epidemiological survey of mental disorders, from which 871 individuals meeting DSM-IV criteria for depressive disorders were selected as the research group. Using 1:1:1 matching by sex, age, and residence, we randomly selected 825 individuals with no DSM-IV diagnosis but positive on GHQ-12 and additional risk assessments as the elevated risk control group, and 825 with negative screenings as the minimal risk control group. In 2020, a follow-up survey was conducted, resulting in a final analysis of 1,855 cases. The survey included demographic data, various clinical information, and a series of screening and questionnaire assessments. Results: The current depressive group scored lower on the MoCA than the non-depressive group (t=8.86, P<0.01). The research group scored lower on the MoCA than the elevated and minimal risk group (F=11.98, P<0.01). The depression-unremitted group scored lower than the depression-remitted group (t=6.44, P<0.01). The Analysis indicated that males, with better life quality, poor early psychological status and, and longer education were associated with higher MoCA scores. Conversely, older age, rural residency, employment, current depression, and poor marital were associated with lower MoCA scores. Conclusion: Individuals with depression commonly suffer cognitive impairment, which tends to partially improve as depression remits. Individual cognitive function is influenced by early psychological health, depressive status, quality of life, age, sex, educational level, residence, occupational, and marital status.

Estimated glucose disposal rate, high sensitivity C-reactive protein and cardiometabolic multimorbidity in middle-aged and older Chinese adults: A nationwide prospective cohort study.

AIM: To explore the separate and joint association of estimated glucose disposal rate (eGDR) and high-sensitivity C-reactive protein (hsCRP) with cardiometabolic multimorbidity (CMM). METHODS: A total of 6900 participants aged 45 years or older with available data on eGDR and hsCRP and without cardiometabolic diseases at baseline from the China Health and Retirement Longitudinal Study were included. CMM was defined as the coexistence of two or more cardiometabolic diseases, including heart diseases, stroke, and diabetes. RESULTS: During a median follow-up of 9.0 years, 464 (6.7 %) participants developed CMM. Low eGDR and high hsCRP separately and jointly increased the risk of CMM. The adjusted hazard ratio (HR) was 1.67 (95 % confidence interval [CI] 1.33-2.09) for low eGDR versus high eGDR, 1.43 (95 % CI 1.12-1.82) for high hsCRP versus low hsCRP) and 2.40 (95 % CI 1.77-3.27) for low eGDR plus high hsCRP versus high eGDR plus low hsCRP. The C-statistic, discriminatory power and risk reclassification significantly improved with the addition of combined eGDR and hsCRP for CMM (P < 0.001). CONCLUSIONS: Low eGDR and high hsCRP were individually and jointly associated with increased risk of incident CMM. The findings highlighted the importance of joint evaluation of eGDR and hsCRP for primary prevention of CMM.

Isolation and identification of endophytic fungi from Alhagi sparsifolia Shap. and their antibacterial activity.

In order to explore the endophytic resources of Alhagi sparsifolia Shap. and identified novel antibacterial substances. Thirty endophytic fungal strains were isolated from the stems and roots of A. sparsifolia Shap. Morphological and molecular biology methods were used to identify ten strains of fungi, including four strains of Aspergillus niger, three strains of Alternaria alternata, two strains of Aspergillus flavus, and one strain of Fusarium incarnatum. All these strains were isolated from A. sparsifolia Shap. for the first time, and of these Aspergillus was the dominant genus. Antibacterial activity of the ten strains against Escherichia coli, Staphylococcus aureus, Candida albicans, and Pseudomonas aeruginosa were evaluated using the disc diffusion method. The results demonstrated that the metabolites from all the strains had inhibitory effects on at least one indicator bacterium. Notably, the endophytic fungi AFJ3 and AFG6 demonstrated strong broad-spectrum antibacterial activity, particularly against E. coli, with inhibition zones measuring 32.0 ± 0.3 and 31.3 ± 0.3 mm, respectively. The three endophytic fungi (AFG1, AFG2, and AFG3) isolated from the roots demonstrated significant antibacterial activity against P. aeruginosa forming an inhibition zone of diameter 31.3 ± 0.1, 25.6 ± 0.2, and 25.6 ± 0.2 mm, respectively. However, the strains of endophytic fungi demonstrated no significant inhibitory effects on C. albicans. Ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry/mass spectrometry (UPLC-QTOF-MS/MS) analysis depicted that the ethyl acetate phase of AFJ3 and AFG6 fermentation broth predominantly contained organic acids, phenolic acids, flavonoids, and fatty acids. These secondary metabolites often exhibited good antibacterial activity. This study broadens our understanding of endophytic fungi in A. sparsifolia Shap. The antibacterial activity of some strains of endophytic fungi was significant, making it worthy of further research on their active material.

The legacy effect of long-term nitrogen fertilization on nitrous oxide emissions.

The primary driver of increasing atmospheric concentrations of nitrous oxide (N2O) is the use of organic and synthetic fertilizer to increase agricultural crop production. Current global estimates are based on IPCC N2O emission factor (EF) calculations, although there are shortcomings as many of the N2O EFs are derived from measurements during the cropping season. These neglect the fallow season, and do not adequately account for double or even triple cropping systems or legacy effects on soil N2O emissions in the following year. In this study, we assessed the legacy effect of fertilization on soil N2O fluxes using data from a long-term double-cropping field experiment with summer maize and winter wheat in rotation, in which no nitrogen (N; NN) and balanced manure with synthetic N (MN) fertilized treatments were switched to allow an assessment of legacy effects. Based on high-frequency measurements of N2O and previous data, we calculated that the historical N fertilization, or legacy effect, explained 23 % of the annual flux of 0.81 kg N ha-1 yr-1 in the first season of observation. In the following three seasons, the legacy effect of the previous N fertilization regime decreased to a negligible level, with N2O emissions mainly driven by in-season fertilization. Our data show that, on average, the seasonal EF for N2O was about 0.11 % higher in response to the previous N fertilization. Our study indicates that the current N2O EF may severely underestimate emissions because studies ignore legacy effects on N2O emissions from zero N plots and only compare zero N with N fertilization treatments for a given season or year to derive seasonal or annual N2O EF.

Multifunctional natamycin modified chondroitin sulfate eye drops with anti-inflammatory, antifungal and tissue repair functions possess therapeutic effects on fungal keratitis in mice.

Fungal keratitis (FK) is recognized as a stubborn ocular condition, caused by intense fungal invasiveness and heightened immune reaction. The glycosaminoglycan chondroitin sulfate exhibits properties of immunomodulation and tissue regeneration. In prior investigations, oxidized chondroitin sulfate (OCS) ameliorated the prognosis of FK in murine models. To further improve the curative efficacy, we used the antifungal drug natamycin to functionalize OCS and prepared oxidized chondroitin sulfate-natamycin (ON) eye drops. The structure of ON was characterized by FTIR, UV-vis, and XPS, revealing that the amino group of natamycin combined with the aldehyde group in OCS through Schiff base reaction. Antifungal experiments revealed that ON inhibited fungal growth and disrupted the mycelium structure. ON exhibited exceptional biocompatibility and promoted the proliferation of corneal epithelial cells. Pharmacokinetic analysis indicated that ON enhanced drug utilization by extending the mean residence time in tears. In murine FK, ON treatment reduced the clinical score and corneal fungal load, restored corneal stroma conformation, and facilitated epithelial repair. ON effectively inhibited neutrophil infiltration and decreased the expression of TLR-4, LOX-1, IL-1ß, and TNF-α. Our research demonstrated that ON eye drops achieved multifunctional treatment for FK, including inhibiting fungal growth, promoting corneal repair, enhancing drug bioavailability, and controlling inflammatory reactions.

Higher Flower Hydraulic Safety, Drought Tolerance and Structural Resource Allocation Provide Drought Adaptation to Low Mean Annual Precipitation in Caragana Species.

Determining the differences in flower hydraulic traits and structural resource allocation among closely related species adapted to low mean annual precipitation (MAP) can provide insight into plant adaptation to arid environments. Here, we measured the maximum flower hydraulic conductance (Kmax-flower), water potential at induction 50% loss of Kmax-flower (P50-flower), flower pressure-volume parameters, dry mass of individual flowers and structural components (vexillum, wings, keels, stamens and sepals) of six Caragana species growing in regions ranging from 110 to 1400 mm MAP. Compared with species from high-MAP environments, those from low-MAP environments presented lower Kmax-flower, more negative P50-flower, osmotic potential at full turgor (πo) and turgor loss points (πtlp), and a greater bulk modulus of elasticity (ε). Consequently, a negative correlation between Kmax-flower (hydraulic efficiency) and P50-flower (hydraulic safety) was observed across Caragana species. Furthermore, the dry masses of individual flowers and structural components (vexillum, wings, keels, stamens and sepals) were greater in the species from the low-MAP environment than in those from the high-MAP environment. These findings suggest that greater flower hydraulic safety and drought tolerance combined with greater structural resource allocation promote drought adaptation in Caragana species to low-MAP environments.

The Genome-Wide Identification of the Dihydroflavonol 4-Reductase (DFR) Gene Family and Its Expression Analysis in Different Fruit Coloring Stages of Strawberry.

Dihydroflavonol 4-reductase (DFR) significantly influences the modification of flower color. To explore the role of DFR in the synthesis of strawberry anthocyanins, in this study, we downloaded the CDS sequences of the DFR gene family from the Arabidopsis genome database TAIR; the DFR family of forest strawberry was compared; then, a functional domain screen was performed using NCBI; the selected strawberry DFR genes were analyzed; and the expression characteristics of the family members were studied by qRT-PCR. The results showed that there are 57 members of the DFR gene family in strawberry, which are mainly expressed in the cytoplasm and chloroplast; most of them are hydrophilic proteins; and the secondary structure of the protein is mainly composed of α-helices and random coils. The analysis revealed that FvDFR genes mostly contain light, hormone, abiotic stress, and meristem response elements. From the results of the qRT-PCR analysis, the relative expression of each member of the FvDFR gene was significantly different, which was expressed throughout the process of fruit coloring. Most genes had the highest expression levels in the full coloring stage (S4). The expression of FvDFR30, FvDFR54, and FvDFR56 during the S4 period was 8, 2.4, and 2.4 times higher than during the S1 period, indicating that the DFR gene plays a key role in regulating the fruit coloration of strawberry. In the strawberry genome, 57 members of the strawberry DFR gene family were identified. The higher the DFR gene expression, the higher the anthocyanin content, and the DFR gene may be the key gene in anthocyanin synthesis. Collectively, the DFR gene is closely related to fruit coloring, which lays a foundation for further exploring the function of the DFR gene family.

Blocking IL-23 Signaling Mitigates Cigarette Smoke-Induced Murine Emphysema.

Inflammatory cell infiltration is a characteristic feature of COPD and correlates directly with the severity of the disease. Interleukin-23 (IL-23) is a pro-inflammatory cytokine that regulates Th-17 inflammation, which mediates many pathophysiological events in COPD. The primary goal of this study was to determine the role of IL-23 as a mediator of key pathologic processes in cigarette smoke-induced COPD. In this study, we report an increase in IL23 gene expression in the lung biopsies of COPD patients compared to controls and identified a positive correlation between IL23 gene expression and disease severity. In a cigarette smoke-induced murine emphysema model, the suppression of IL-23 with a monoclonal blocking antibody reduced the severity of cigarette smoke-induced murine emphysema. Mechanistically, the suppression of IL-23 was associated with a reduction in immune cell infiltration, oxidative stress injury, and apoptosis, suggesting a role for IL-23 as an essential immune mediator of the inflammatory processes in the pathogenesis of CS-induced emphysema.

Time course of remnant cholesterol and the risk of heart failure.

BACKGROUND AND AIM: Previous studies have shown that remnant cholesterol (RC) was associated with heart failure (HF). However, lack of evidence regarding the long-term trend of RC with HF risk. We aimed to investigate the association between cumulative RC exposure with incident HF and to further explore the modulating effects of the time course of RC accumulation. METHODS AND RESULTS: We enrolled 41,168 participants free of CVD from the Kailuan Study who completed the first three health examinations from 2006 to 2010. Cumulative RC exposure included cumulative RC and time-weighted cumulative RC. The combination of cumulative RC and RC slope over time was characterized as the time course of RC accumulation. Multivariable adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for HF risk. We also considered non-HF-related death as a competing event by performing competing risk models as a sensitivity analysis. During 8.84 years, 839 participants developed HF events. Cumulative RC exposure increased the HF risk, with HRs for cumulative RC of 1.72 (1.41-2.10) and for time-averaged cumulative RC of 1.54 (1.25-1.89). There was a nonlinear relationship between cumulative RC exposure and HF risk. Participants with higher cumulative RC and negative slope had the highest HF risk (HR, 1.46; 95% CI, 1.16-1.83). CONCLUSIONS: Both cumulative long-term exposure and the time course of RC accumulation were associated with HF risk. Early RC accumulation resulted in a greater increase in risk compared to later accumulation. This finding suggests that long-term exposure to RC may be useful in identifying individuals at high risk of developing HF and highlights the need for early initiation of appropriate RC control to prevent or reduce incident HF.

Effect of Alloying on Microstructure and Mechanical Properties of AlCoCrFeNi2.1 Eutectic High-Entropy Alloy.

In order to explore the effect of alloying on the microstructures and mechanical properties of AlCoCrFeNi2.1 eutectic high-entropy alloys (EHEAs), 0.1, 0.2, and 0.3 at.% V, Mo, and B were added to the AlCoCrFeNi2.1 alloy in this work. The effects of the elements and contents on the phase composition, microstructures, mechanical properties, and fracture mechanism were investigated. The results showed that the crystal structures of the AlCoCrFeNi2.1 EHEAs remained unchanged, and the alloys were still composed of FCC and BCC structures, whose content varied with the addition of alloying elements. After alloying, the aggregation of Co, Cr, Al, and Ni elements remained unchanged, and the V and Mo were distributed in both dendritic and interdendritic phases. The tensile strengths of the alloys all exceeded 1000 MPa when the V and Mo elements were added, and the Mo0.2 alloy had the highest tensile strength, of 1346.3 MPa, and fracture elongation, of 24.6%. The alloys with the addition of V and Mo elements showed a mixed ductile and brittle fracture, while the B-containing alloy presented a cleavage fracture. The fracture mechanism of Mo0.2 alloy is mainly crack propagation in the BCC lamellae, and the FCC dendritic lamellae exhibit the characteristics of plastic deformation.

Early onset of hyperuricemia is associated with the risk of nonalcoholic fatty liver disease across life course.

BACKGROUND AND AIM: Hyperuricemia is associated with nonalcoholic fatty liver disease (NAFLD), whereas whether the association differed by hyperuricemia onset age remained unclear. This study sought to investigate the associations of hyperuricemia onset age with the risk of incident NAFLD across adulthood. METHODS AND RESULTS: Based on Kailuan prospective cohort, our analysis comprised 3318 new-onset hyperuricemia cases from 2006 to 2015 and 3318 age- and sex-matched controls who were randomly selected from the general population. The risk of NAFLD across the onset age groups (<45, 45-54, 55-64, and ≥65 years) were compared using multivariable-adjusted Cox regression models. During a median follow-up of 6.78 years, 744 (22.42%) hyperuricemia participants and 586 (17.66%) normouricemia participants were diagnosed with incident NAFLD. After adjusted for potential confounders, the risk of NAFLD was gradually attenuated with each decade increase in hyperuricemia onset age. The adjusted hazard ratio (95% confidence interval) was 1.62 (1.33-1.97) for hyperuricemia onset age <45 years, 1.26 (1.01-1.57) for age of 45-54 years, 1.24 (1.00-1.59) for age of 55-64 years, and 1.19 (0.90-1.71) for age ≥65 years, respectively. The trend remained robust among the multiple sensitivity analyses. CONCLUSIONS: The relative risk of incident NAFLD differed across hyperuricemia onset age-group, and the association was more evident in those with a younger age of hyperuricemia onset, highlighting the importance of performing early strategies on the prevention of NAFLD.

Environmental and economic impact analysis of levying VOCs environmental protection tax in China.

China is one of the largest volatile organic compounds (VOCs) emitters worldwide. The emission levels of and harm caused by VOCs have attracted much attention. China has implemented multiple policies for VOCs prevention and control but lacks economic control measures for VOCs In this study, the input-output (IO) price model was used to simulate and analyze the emission reduction and economic effects resulting from the imposition of a VOCs environmental protection tax (EPT) in 31 provinces in China. The results show that, first, the collection of a VOCs-EPT can achieve not only VOCs emission reductions but also the synergistic emission reductions of other major pollutants. Second, the collection of a VOCs-EPT could have a negative impact on the macroeconomy, i.e., the greater the tax scope and the higher the tax rate are, the greater the negative economic impact. Third, differences in the level of economic development, the structure of pollution emissions and the stringency of tax policies among regions would cause the emission reduction effect and related negative economic impact to vary across regions. Finally, the collection of a VOCs-EPT could have heterogeneous impacts on various industries, as high-emission industries would suffer greater negative impacts. Therefore, each region should set tax rates that match its provincial economic and environmental development levels. Furthermore, a VOCs-EPT can be levied on key industries, and reasonable preferential tax policies can be formulated to reduce negative macroeconomic benefits.

Association of hyperuricemia with risk of cardiovascular disease according to the number of risk factors within target range.

BACKGROUND AND AIMS: Risk factor modification may decrease the risk of cardiovascular disease (CVD). Whether risk factor modification can mitigate the effect of hyperuricemia on CVD is unclear. This study aimed to investigate the risk of CVD among individuals with hyperuricemia, according to risk factors on target, compared with controls without hyperuricemia. METHODS AND RESULTS: This prospective study included 91,722 participants free of CVD at baseline (2006-2007) of the Kailuan study. Individuals with hyperuricemia were categorized according to the number of seven selected risk factors within the guideline-recommended target range (nonsmoking, physical activity, healthy diet, guideline-recommended levels of body mass index, blood pressure, fasting blood glucose, and total cholesterol). During a median follow-up of 13.00 years, 671 out of 6740 individuals (9.96%) with hyperuricemia and 6301 out of 84,982 control subjects (7.41%) had incident CVD. Compared with control subjects without hyperuricemia, individuals with hyperuricemia who had 4 or 5 to 7 risk factors on target had no significant excess CVD risk, the hazard ratio (HR) (95% confidence internal [CI]) was 0.93 (0.79-1.10) and 0.88 (0.71-1.10), respectively. Among individuals with hyperuricemia, excess CVD risk decreased stepwise for a higher number of risk factors on target, the HR of CVD associated with per additional risk factor within target range was 0.82 (95% CI, 0.77-0.87). Similar results were yielded for CVD subtypes. CONCLUSIONS: Among individuals with hyperuricemia, excess CVD risk decreased stepwise for a higher number of risk factors within target.

The PGC-1α/ERRα/ULK1 pathway contributes to Perioperative neurocognitive disorders by inducing mitochondrial dysfunction and activating NLRP3 inflammasome in aged mice.

Perioperative neurocognitive disorders (PND) are intractable, indistinct, and considerably diminish the postoperative quality of life of patients. It has been proved that Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) was involved in neurodegenerative diseases by regulating mitochondrial biogenesis. The underlying mechanisms of PGC-1α and Nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in PND are not well understood. In this study, we constructed a model of laparotomy in aged mice, and then examined the cognition changes with novel object recognition tests and fear condition tests. The protein levels of PGC-1α and NLRP3 in the hippocampus were detect after surgery. Our results showed that NLRP3 and downstream PI3K/AKT pathway expressions were augmented in the hippocampus after surgery, whereas, the expressions of PGC-1α/estrogen-related receptor α (ERRα)/Unc-51-like autophagy activating kinase 1 (ULK1) pathway were diminished after surgery. In addition, we found that NLRP3 was mainly co-localized with neurons in the hippocampus, and synaptic-related proteins were reduced after surgery. At the same time, transmission electron microscopy (TEM) showed that mitochondria were impaired after surgery. Pharmacological treatment of MCC950, a selective NLRP3 inhibitor, effectively alleviated PND. Activation of PGC-1α with ZLN005 significantly ameliorated PND by enhancing the PGC-1α/ERRα/ULK1 signaling pathway, and further suppressing NLRP3 activation. As a result, we conclude that suppression of the PGC-1α/ERRα/ULK1 signaling pathway is the primary mechanism of PND which caused mitochondrial dysfunction, and activated NLRP3 inflammasome and downstream PI3K/AKT pathway, eventually improved cognitive dysfunction.

Therapeutic effect of oxidized bletilla striata polysaccharide-natamycin eye drops on fungal keratitis.

OBJECTIVE: Fungal keratitis (FK) usually develops to a poor clinical prognosis due to the fungal invasion and excessive inflammatory reaction. In order to enhance the therapeutic effect of natamycin (NAT), we used the anti-inflammatory biological polysaccharide bletilla striata polysaccharide (BSP) combined with NAT to prepare a new eye drop -- oxidized bletilla striata polysaccharide-natamycin (OBN). METHODS: UV-vis, FT-IR, and fluorescence spectroscopy were used to identify the synthesis of OBN. Biocompatibility of OBN was determined by CCK-8, scratch assay, and corneal toxicity test. RAW264.7 cells and C57BL/6 mice were stimulated with A. fumigatus and treated with PBS, OBN, or NAT. The anti-inflammatory activity of OBN was detected by RT-PCR and ELISA. In mice with FK, the clinical scores were used to evaluate the effect of OBN; HE staining was performed to assess the corneal pathological changes; MPO assay and immunofluorescence staining were used to investigate neutrophil infiltration. RESULTS: OBN was synthesized by combining oxidized bletilla striata polysaccharide (OBSP) with NAT through Schiff base reaction. OBN did not affect cell viability at a concentration of 160 µg/mL in HCECs, RAW264.7 cells, and mouse corneas. OBN versus NAT significantly improved the prognosis of A. fumigatus keratitis by reducing disease severity, neutrophil infiltration, and expression of inflammatory factors in vivo. Additionally, OBN treatment down-regulated the mRNA and protein expression levels of inflammatory factors IL-1ß, TNF-α, and IL-6 in RAW264.7 and mouse models. CONCLUSION: OBN is a compound prepared by covalently linking OBSP to the imino group of NAT through Schiff base reaction. OBN treatment down-regulated inflammation and improved the prognosis of mice with A. fumigatus keratitis.