Lower Serum Albumin Level: A Prospective Risk Predictor of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Virus Infection.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumours in China, at high annual incidence and mortality. Chronic hepatitis B virus infection (CHB) is considered as a leading cause to bring about HCC in China. Serum albumin (ALB) level has been adopted to verify its risk with HCC development as a combination variable with other factors. However, the predictive value of a single ALB level on HBV-related HCC risk remained unclear. The aim of this study was to evaluate the prediction ability of serum ALB concentration on the risk of HBV-related HCC development. A prospectively enrolled clinical cohort compromising 2932 cases of CHB patients with at least 1-year exclusion window was selected to explore the predictive role of serum ALB level on incident HCC risk. Baseline clinical data including host characters and laboratory test were collected at the initial period of hospitalisation. The hazard ratio of ALB level associated with HCC development was assessed by Cox proportional hazards regression model using univariate and multivariate analyses. We evaluated the discrimination accuracy of ALB level in predicting HCC development by receiver operating characteristic (ROC) curves. Dose-dependent and time-dependent effects of ALB level on HCC risk prediction were demonstrated, respectively, using a restricted cubic spline and a Fine and Grey competing risk model. Referred to patients with higher ALB level, those with lower ALB level exhibited significantly increased risk of HCC development after adjustment for host variables (dichotomised analyses: hazard ratio = 3.12, 95% confidence interval 1.63-5.97, p = 8.23 × 10-4, plog-rank = 5.97 × 10-4; tertile analyses: hazard ratio = 2.07, 95% confidence interval 1.63-2.64, p = 3.77 × 10-9, plog-rank < 2.00 × 10-16; quartile analyses: hazard ratio = 2.10, 95% confidence interval 1.56-2.84, p = 9.87 × 10-7, plog-rank < 2.00 × 10-16). There was a statistically increasing trend on HCC risk which was found following by the decrease of ALB level (ptrend < 0.0001). Similar findings were present by the Kaplan-Meier analysis, cumulative incidences of HCC development were significantly higher in patients with lower ALB levels, with the p value obtained from log-rank test were all < 0.0001. The result of dose-dependent effect showed hazard ratio (HR) value of HCC risk was gradually decreasing as the increasing of ALB level, with non-linear correlation being statistically significant (Wald χ2 = 20.59, p = 0.000). HR value in lower ALB level remained persistently prominent by fluctuating around 2.73 in the whole follow-up time by adjusting for host variables. Sub-cohort analysis by ROC revealed that the discrimination ability of the ALB model was performed better than Child-Pugh (C-P) model in both cohort of patients with 1-year (area under curve [AUC] 0.762 vs. 0.720) and 2-year exclusion window (AUC 0.768 vs. 0.728). The AUC added by ALB level was demonstrated significantly from host model to full model. Lower ALB level was significantly associated with an increased risk of HBV-related HCC and could provide extra useful clinical utility to other host features, which might be a promising non-invasive indicator for surveillance on HCC development.

Surgical vs. drug therapy in patients with patent foramen ovale and cryptogenic stroke.

OBJECTIVE: This study aimed to investigate the effectiveness of risk scoring for predicting stroke recurrence after percutaneous patent foramen ovale (PFO) closure or medication therapy in patients with PFO and a history of cryptogenic stroke. METHODS: This study included 559 patients with PFO and cryptogenic stroke who were treated in our hospital from January 2013 to January 2018 and were followed up for 15-72 months. After calculating the risk scores for stroke recurrence, we randomly divided the patients into two groups (ratio, 1:1): Patients in one group underwent PFO closure and those in the other received drug therapy. RESULTS: Patients in the PFO closure group had a lower risk of recurrent stroke than those in the drug therapy group (1.1% vs. 4.2%). Moreover, serious bleeding was less frequent in the PFO closure group than in the drug therapy group (0% vs. 3.2%), although the incidence of atrial fibrillation or flutter did not significantly differ between the groups (p = 0.67). Interestingly, a subgroup analysis revealed no inter-treatment group difference in the rate of cryptogenic stroke recurrence among patients with risk scores of 0-1. By contrast, PFO closure yielded superior outcomes among patients with risk scores of ≥2. CONCLUSION: Compared with drug therapy, PFO closure reduced the risk of recurrent stroke among patients with a risk score of ≥2 and reduced the incidence of serious bleeding without increasing the risk of new-onset atrial fibrillation or atrial flutter.

Hydrological regimes and water quality variations in the Yangtze River basin from 1998 to 2018.

Understanding the long-term variations in basins that undergo large-scale hydroelectric projects is crucial for effective dam operation and watershed management. In this study, comprehensive analyses were conducted on a dataset spanning over 20 years (1998-2018) of hydrological regime and physicochemical parameters from the Yangtze River basin to evaluate the potential impacts of the Three Gorges Dam. Water level significantly increased from 128.75±58.18 m in 2002 to 136.78±55.05 m in 2005, and the mean flow velocity significantly decreased from 2004 to 2010. However, no significant change in the flow was observed in the basin. Meanwhile, remarkable fluctuations in physicochemical parameters, including dissolved oxygen, chemical oxygen demand, conductivity, hardness, and alkalinity, were mainly observed during impoundment (2003-2009). After that, the above parameters tended to stabilize, and some even returned to their original levels. The dam's retention effect significantly reduced the suspended solids (SS) in both up- and downstream, to only one-third of the pre-operation level. And total phosphorus and chemical oxygen demand also significantly decreased with the decline of SS. Particularly, ammonium also showed a significant downward trend, with the up- and downstream of the dam falling by 36.8 % and 26.1 %, respectively. However, the increasing total nitrogen (7.5 % and 20.0 % up- and downstream of the dam, respectively) still threatened the water quality of the basin, especially in the estuaries. Additionally, the significant decline in dissolved oxygen downstream (from 8.53±1.08 mg/L to 8.11±1.36 mg/L) also exacerbated the hypoxia in the Yangtze River estuary. The results demonstrated the long-term impact of the construction of the Three Gorges Dam on the environmental elements of the Yangtze River basin, which provides reference data and guidance for the construction of big dams in major rivers in the future.

Association of MTHFR C667T Polymorphism, Homocysteine, and B Vitamins with Senile Cataract.

Senile cataract has become the leading cause of visual impairment and even blindness in the world, but there are few reports on its relationship with methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms. This study is aimed to investigate the correlation between MTHFR gene polymorphisms or its enzyme metabolites and senile cataract. From January 2019 to June 2020, 663 patients with senile cataract at the Mianyang Central Hospital were enrolled as the observation group, and 646 healthy subjects were randomly selected as the control group. MTHFR gene polymorphisms (i.e., CC, CT, or TT genotypes) and serum homocysteine (HCY), folic acid (FOL), vitamin B12 (VitB12), and vitamin B6 (VitB6) levels were detected. The mutation rate of MTHFR C677T and HCY levels in the observation group were significantly higher than those in the control group, whereas FOL, VitB12, and VitB6 were significantly lower. With an increase in the MTHFR C677T mutation, HCY showed an upward trend, whereas FOL and VitB12 showed a decreasing trend in both the observation and control groups. Multiple logistic regression analysis showed that HCY and FOL were associated with senile cataract and MTHFR mutations; VitB12 was only associated with senile cataract. Compared to that with the CC genotype, CT and TT genotypes were associated with an increased senile cataract risk. Monitoring MTHFR gene polymorphisms and changes in serum HCY, FOL, and VitB12 levels could provide references in predicting senile cataract.

Spatiotemporal Patterns in pCO2 and Nutrient Concentration: Implications for the CO2 Variations in a Eutrophic Lake.

Lakes are considered sentinels of terrestrial environmental change. Nevertheless, our understanding of the impact of catchment anthropogenic activities on nutrients and the partial pressure of carbon dioxide (pCO2, an important parameter in evaluating CO2 levels in water) is still restrained by the scarcity of long-term observations. In this study, spatiotemporal variations in nutrient concentrations (total nitrogen: TN, total phosphorus: TP, nitrate: NO3--N, and ammonium: NH4+-N) pCO2 in Taihu Lake were analyzed from 1992 to 2006, along with the gross domestic product (GDP) and wastewater discharge (WD) of its catchment. The study area was divided into three zones to characterize spatial heterogeneity in water quality: the inflow river mouth zone (Liangxi River and Zhihugang River), transition zone (Meiliang Bay), and central Taihu Lake, respectively. It is abundantly obvious that external nutrient inputs from the catchment have a notable impact on the water parameters in Taihu Lake, because nutrient concentrations and pCO2 were substantially higher in the inflow river mouth zone than in the open water of Meiliang Bay and central Taihu Lake. The GDP and WD of Taihu Lake's catchment were significantly and positively correlated with the temporal variation in nutrient concentrations and pCO2, indicating that catchment development activities had an impact on Taihu Lake's water quality. In addition, pCO2 was negatively correlated with chlorophyll a and the saturation of dissolved oxygen, but positively correlated with nutrient concentrations (e.g., TN, TP, and NH4+-N) in inflow river mouth zone of Taihu Lake. The findings of this study reveal that the anthropogenic activities of the catchment not only affect the water quality of Taihu Lake but also the CO2 concentrations. Consequently, catchment effects require consideration when modeling and estimating CO2 emissions from the extensively human-impacted eutrophic lakes.

Source, Distribution and Potential Risk of Antimony in Water and Sediments of Danjiangkou Reservoir: Impact from Dam.

Danjiangkou Reservoir is the water source of the mid-route of the South-to-North Water Transfer Project. The source, distribution and potential risk of antimony in its water and sediments are rarely reported. In this study, symmetrical investigation results demonstrated that the concentration of antimony in the Han sub-reservoir and water in front of the dam fluctuated at about 0.9 mg L-1, while it was relatively higher and increased with the distance from the dam in Dan sub-reservoir water, with an annual average of 0.93~3.15 mg L-1. In recent years, the concentration of antimony in the Danjiangkou Reservoir showed a downward trend, and the difference between the Han and Dan sub-reservoirs decreased significantly. The antimony in the sediments in the reservoir was primarily derived from the inflowing rivers, and it was higher in the Dan sub-reservoir than in the Han sub-reservoir. The concentration of antimony in the water in the reservoir was considerably higher than the background value in the watersheds, indicating that there is an external input with decreasing input intensity. The content of antimony in the sediments in the reservoir and its inflow rivers was substantially higher than the background value of watersheds, indicating that there is a certain degree of enrichment. In addition, the antimony mining industry in the water source area poses a risk to the water safety of the reservoir. Antimony is not a conventional pollutant. Consequently, the collection of antimony monitoring results is a challenging task. Additionally, this study fills the gap in regional antimony research. Furthermore, the ecological risk assessment of antimony in China is still in its infancy. Unquestionably, the study of the temporal and spatial distribution of antimony concentration will be beneficial for the protection of water sources in relevant regions.

Developmental neurotoxicity of reserpine exposure in zebrafish larvae (Danio rerio).

Reserpine is widely used for treatment of hypertension and schizophrenia. As a specific inhibitor of monoamine transporters, reserpine is known to deplete monoamine neurotransmitters and cause decreased movement symptoms. However, how zebrafish larvae respond to reserpine treatment is not well studied. Here we show that swimming distance and average velocity are significantly reduced after reserpine exposure under various stimulatory conditions. Using liquid chromatograph-mass spectrometer analysis, decreased levels of monoamines (e.g. dopamine, noradrenaline, and serotonin) were detected in reserpine-treated larvae. Moreover, reserpine treatment significantly reduced the number of dopaminergic neurons, which was identified with th (Tyrosine Hydroxylase) in situ hybridization in the preoptic area. Interestingly, dopaminergic neuron development-associated genes, such as otpa, otpb, wnt1, wnt3, wnt5 and manf, were downregulated in reserpine treated larvae. Our data indicates that 2 mg/L reserpine exposure induces dopaminergic neuron damage in the brain, demonstrating a chemical induced depression-like model in zebrafish larvae for future drug development.

MiR-101-3p inhibits the growth and metastasis of non-small cell lung cancer through blocking PI3K/AKT signal pathway by targeting MALAT-1.

BACKGROUND: MiR-101-3p is an important tumor suppressor miRNA in many human cancers. This study was to investigate the role of miR-101-3p in the progression of non-small cell lung cancer (NSCLC) and its potential underlying mechanism. METHODS: In this study, the endogenous expression of miR-101-3p or MALAT-1 in cells was modulated by cell transfection assays. The regulatory interaction of miR-101-3p and MALAT-1 was examined by Luciferase reporter gene and RNA pull-down assays. The effect of miR-101-3p or MALAT-1 on NSCLC cells was evaluated by cell proliferation assays, wound-healing assays and transwell invasion assays. The mice tumor model was established to test the role of miR-101-3p and MALAT-1 in the growth and metastasis of NSCLC in vivo. RESULTS: The relative expression of miR-101-3p in NSCLC cells was significantly decreased; while MALAT-1 was significantly increased. Moreover, overexpression of miR-101-3p could significantly inhibit the proliferation, migration and invasion of NSCLC cells in vitro, as well as MALAT-1 expression. Further studies confirmed that miR-101-3p could specifically repress MALAT-1 expression through direct binding; MALAT-1 overexpression completely reversed the miR-101-3p-induced suppression on the viability, migration and invasion of NSCLC cells and MALAT-1 expression. Finally, we confirmed that miR-101-3p could block the MALAT-1-induced activation of PI3K/AKT signal pathway and resulted in the inhibition on the growth and metastasis of NSCLC cells in vivo. CONCLUSION: MiR-101-3p inhibited the growth and metastasis of NSCLC through blocking PI3K/AKT signal pathway by targeting MALAT-1.

[Evaluation of Temporal and Spatial Variation Characteristics of Nutrients in Surface Sediment in the Three Gorges Reservoir Area].

With the construction of the Three Gorges Dam, the river flow pattern and sediment dynamics are expected to be affected. As a consequence, the sediment traits could be impacted by these changes. The temporal and spatial variation characteristics of the nutrient content from 2000 to 2015 in surface sediment were analyzed in the main stream from Jiangjin to the dam site section of the Yangtze River and in the estuaries of the representative input tributaries of the Three Gorges Reservoir, such as the Jialing River, Yulin River, Wujiang River, Xiaojiang River, Daning River, and Xiangxi River. Then, the state of the pollution was assessed. Results revealed that the average concentrations of total phosphorus (TP) in the surface sediments of the main stream ranged from 678.2 to 928.6 mg·kg-1, the average contents of total nitrogen (TN) ranged from 0.203% to 0.362%, the average contents of potassium ranged from 1.74% to 2.37%, and the average contents of organic matter ranged from 0.94% to 1.54%. The average concentrations of TP in the estuaries of the representative input tributaries ranged from 490.1 to 832.3 mg·kg-1, the average contents of TN ranged from 0.257% to 0.495%, the average contents of potassium ranged from 1.69% to 2.32%, and the average contents of organic matter ranged from 1.21% to 2.27%. The concentrations of TP and potassium in the study sections were generally within background concentration ranges, while the concentrations of TN were obviously above background levels, and the concentrations of organic matter were obviously below background levels. The nutrient contents in the surface sediment did not display significant differences among the study sites; however, the distributions of different nutrient contents along the river varied widely. Although the nutrient contents in the surface sediments fluctuated somewhat during different flow periods, they were seemingly unaffected by the impoundment, since no obvious enrichment was observed throughout the impoundment. The evaluation of organic index indicated a clean state for the surface sediments in the majority of the study area, while there was a moderately polluted state in some local sections. The evaluation of nitrogen pollution indicated a polluted state for most sections. Overall, the nutrients in the surface sediments of the Three Gorges Reservoir showed moderate ecological risks, possibly caused by TP and TN.