Life expectancy, long-term care demand and dynamic financing mechanism simulation: an empirical study of Zhejiang Pilot, China.

BACKGROUND: China has piloted Long-Term Care Insurance (LTCI) to address increasing care demand. However, many cities neglected adjusting LTCI premiums since the pilot, risking the long-term sustainability of LTCI. Therefore, using Zhejiang Province as a case, this study simulated mortality-adjusted long-term care demand and the balance of LTCI funds through dynamic financing mechanism under diverse life expectancy and disability scenarios. METHODS: Three-parameter log-quadratic model was used to estimate the mortality from 1990 to 2020. Mortality with predicted interval from 2020 to 2080 was projected by Lee-Carter method extended with rotation. Cohort-component projection model was used to simulate the number of older population with different degrees of disability. Disability data of the older people is sourced from China Health and Retirement Longitudinal Study 2018. The balance of LTCI fund was simulated by dynamic financing actuarial model. RESULTS: Life expectancy of Zhejiang for male (female) is from 80.46 (84.66) years in 2020 to 89.39 [86.61, 91.74] (91.24 [88.90, 93.25]) years in 2080. The number of long-term care demand with severe disability in Zhejiang demonstrates an increasing trend from 285 [276, 295] thousand in 2023 to 1027 [634, 1657] thousand in 2080 under predicted mean of life expectancy. LTCI fund in Zhejiang will become accumulated surplus from 2024 to 2080 when annual premium growth rate is 5.25% [4.20%, 6.25%] under various disability scenarios, which is much higher than the annual growth of unit cost of long-term care services (2.25%). The accumulated balance of LTCI fund is sensitive with life expectancy. CONCLUSIONS: Dynamic growth of LTCI premium is essential in dealing with current deficit around 2050 and realizing Zhejiang's LTCI sustainability in the long-run. The importance of dynamic monitoring disability and mortality information is emphasized to respond immediately to the increase of premiums. LTCI should strike a balance between expanding coverage and controlling financing scale. This study provides implications for developing countries to establish or pilot LTCI schemes.

Network Analysis of Dyadic Burdens, Psychological Disorders, Psychological Resilience, and Illness- or Caregiving-Related Beliefs in Patients With Chronic Heart Failure and Their Caregivers.

BACKGROUND: Previous research has examined the dyadic health components consisting of dyadic burdens, psychological disorders, psychological resilience, and illness- or caregiving-related beliefs independently from each other in patients with chronic heart failure (CHF) and their caregivers, but there is a need for further insights into their interconnections. OBJECTIVE: We aimed to explore the interconnections among dyadic health components in patients with CHF and their caregivers. METHODS: We conducted a cross-sectional study, recruiting in a total of 355 patients with CHF and their 355 respective caregivers, totaling 710 individuals across the dyads. Assessments were conducted on symptom burden, caregiver burden, anxiety, depression, psychological resilience, perceived control, and caregiver self-efficacy. Network analysis was used regarding these constructs as nodes and their associations as edges. RESULTS: The strongest edge weight was observed between patients' anxiety and depression, followed by caregivers' anxiety and depression. Patients' depression exhibited the strongest edge weight with dyadic burdens. Caregiver burden was independently correlated with all nodes. Patients' symptom burden had fewer associations with the nodes within the caregiver community. Patients' anxiety, depression, and psychological resilience demonstrated the strongest and most influential correlations with other nodes. CONCLUSIONS: The findings illustrated extensive interconnections among dyadic health components in CHF dyads. These findings underscored the significance of managing and intervening with patients and caregivers as a dyadic whole. Given the strong and frequent associations of patients' anxiety, depression, and psychological resilience with other nodes in the network, interventions targeting these nodes may enhance the overall network health of CHF dyads.

Multi-Trajectories of Symptoms and their Associations with Unplanned 30-day Hospital Readmission among Patients with Heart Failure: A longitudinal study.

AIMS: This study aimed to uncover hidden patterns and predictors of symptom multi-trajectories within 30 days after discharge in patients with heart failure and assess the risk of unplanned 30-day hospital readmission in different patterns. METHODS AND RESULTS: The study was conducted from September 2022 to September 2023 in four third-class hospitals in Tianjin, China. A total of 301 patients with heart failure were enrolled in the cohort, and 248 patients completed a 30-day follow-up after discharge. Three multi-trajectory groups were identified: mild symptom status (24.19%), moderate symptom status (57.26%), and severe symptom status (18.55%). With the mild symptom status group as a reference, physical frailty, psychological frailty, and comorbid renal dysfunction were predictors of the moderate symptom status group. Physical frailty, psychological frailty, resilience, taking diuretics, and comorbid renal dysfunction were predictors of the severe symptom status group. Compared with the mild symptom status group, the severe symptom status group was significantly associated with high unplanned 30-day hospital readmission risks. CONCLUSIONS: This study identified three distinct multi-trajectory groups among patients with heart failure within 30 days after discharge. The severe symptom status group was associated with a significantly increased risk of unplanned 30-day hospital readmission. Common and different factors predicted different symptom multi-trajectories. Healthcare providers should assess the physical and psychological frailty and renal dysfunction of patients with heart failure before discharge. Inpatient care aimed at alleviating physical and psychological frailty and enhancing resilience may be important to improve patients' symptom development post-discharge.

The Association Between Impaired Dyadic Coping and Frailty in Elderly Patients With Hypertension: A Latent Profile Analysis.

BACKGROUND: Lifelong hypertension highlights the importance of dyadic engagement in coping with the disease. Although dyadic coping is heterogeneous in patients with other diseases, little is known about it in elderly patients with hypertension. In addition, whether impaired dyadic coping is associated with frailty has yet to be elucidated. OBJECTIVES: The aim of this study was to investigate the latent profiles and characteristics of dyadic coping and the potential association between impaired dyadic coping and frailty in elderly patients with hypertension. METHODS: We recruited a total of 741 elderly patients with hypertension. Latent profile analysis was then used to identify the best-fitting model. Then, we used regression analysis to determine profile predictors and identify the association between impaired dyadic coping and frailty. RESULTS: The 5-profile model was considered to be the best-fitting model, as follows: profile 1, severely impaired dyadic coping; profile 2, mildly impaired dyadic coping; profile 3, normal dyadic coping; profile 4, better dyadic coping; and profile 5, the highest dyadic coping. In the fully adjusted model, the probability of frailty was 1.94-fold higher in the mildly impaired dyadic coping group (odds ratio, 1.94; 95% confidence interval, 1.09-3.47) and 2.66-fold higher in the severely impaired dyadic coping group (odds ratio, 2.66; 95% confidence interval, 1.11-6.39). CONCLUSIONS: We identified heterogeneity in dyadic coping and demonstrated that impaired dyadic coping was associated with frailty. Those at risk of dyadic coping impairment need to be identified early, followed by dyadic coping-based interventions to prevent or delay frailty.

Network analysis of symptoms, physiological, psychological and environmental risk factors based on unpleasant symptom theory in patients with chronic heart failure.

BACKGROUND: Somatic symptoms and related factors in patients with chronic heart failure have been extensively researched. However, more insight into the complex interconnections among these constructs is needed, as most studies focus on them independently from each other. AIMS: The aim of this study is to gain a comprehensive understanding of how somatic symptoms and related factors are interconnected among patients with chronic heart failure. METHODS: A total of 379 patients were enrolled. Network analysis was used to explore the interconnections among the somatic symptoms and related risk factors. RESULTS: The four core symptoms of chronic heart failure were daytime dyspnea, dyspnea when lying down, fatigue and difficulty sleeping. Within the network, the edge weights of depression-anxiety, subjective social support-objective social support, and subjective social support-social support availability were more significant than others. Among physiological, psychological and environmental factors, the edge weights of NYHA-dyspnea, depression-difficulty sleeping, and social support availability-dyspnea when lying down were more significant than others. Depression and anxiety had the highest centrality, indicating stronger and closer connections with other nodes. CONCLUSIONS: Psychological and environmental factors stood out in the network, suggesting the potential value of interventions targeting these factors to improve overall health.

Effects of the family customised online FOCUS programme on patients with heart failure and their informal caregivers: a multicentre, single-blind, randomised clinical trial.

Background: Living with heart failure can severely affect the physical and mental health of patients with heart failure and their caregivers. Available dyadic self-care interventions for heart failure are scarce, especially in China. We aimed to develop and test the family FOCUS programme. Methods: This single-blind, randomised, controlled study was conducted at four hospitals in Tianjin, China. Patients with heart failure (aged at least 18 years) and their caregiver (dyads) were randomly assigned to either the intervention (n = 71) or control (n = 71) group in a 1:1 ratio. The primary outcomes of this study were patient self-care, with three specific dimensions (self-care maintenance, symptom perception, and self-care management), and caregiver contribution to self-care, mirroring these three dimensions. The outcomes were assessed at baseline (T0) and 4 (T1), 12 (T2), and 24 (T3) weeks post-discharge, respectively. This work is registered on ChiCTR, ChiCTR2100053168. Findings: Between May 20, 2022, and September 30, 2022, 142 dyads with heart failure were enrolled. The intervention group exhibited dropout rates of 6%, 8.5%, and 18.3% at 4, 12, and 24 weeks after discharge, while the control group showed 9.9%, 12.3%, and 25.4%. Compared with the control group, patients in the intervention group reported improved self-care maintenance (ß: 8.5, 95% CI: 0.7, 16.4) and management (ß: 7.2, 95% CI: 0.1, 14.3) at T1, as well as improved symptom perception at both T1 (ß: 9.7, 95% CI: 1.5, 17.9) and T2 (ß: 9.6, 95% CI: 0.6, 18.6). Furthermore, caregiver contributions to self-care maintenance, self-care management, and symptom perception (excluding T3) exhibited significant improvements at all timepoints. Interpretation: Although the significant improvements in patients' self-care were not long-lasting, this study suggested that the family FOCUS programme consistently enhanced caregivers' contributions to self-care. Future work could explore the effect of the family FOCUS programme on families with multiple chronic conditions. Funding: The National Natural Science Foundation of China.

Latent transition analysis of instrumental activities of daily living in Chinese elderly: based on the 2014-2018 wave of the Chinese Longitudinal Healthy Longevity Survey.

BACKGROUND: The instrumental activities of daily living (IADL) among the elderly have been found to be heterogeneous, with different trajectories. However, the transition of the IADL over time remains unclear. We aimed to explore the transition probabilities and the predictors of IADL among the elderly. METHODS: Longitudinal data from the 2014 (T1) and 2018 (T2) waves of the Chinese Longitudinal Healthy Longevity Survey were extracted. A sample of 2,944 participants aged 65 years or older, with complete responses to the IADL scale, was included. Latent profile analysis (LPA) and latent transition analysis (LTA) were employed to identify latent profiles of IADL and investigate the transition probabilities between profiles from T1 to T2. The predictors of latent profiles and transition probabilities were examined using multinomial regression analysis. RESULTS: The results of LPA at both T1 and T2 supported a 4-profile model solution. They were labeled as the "Normal function profile," "Mildly impaired profile," "Moderately impaired profile," and "Highly impaired profile". The Normal function profile and Highly impaired profile were characterized by maintaining stability rather than transitioning over time, with transition probabilities of 0.71 and 0.68, respectively, for maintaining stability. The Mildly impaired profile and Moderately impaired profile were characterized by a stronger tendency towards transition rather than stability, with transition probabilities of 0.29 and 0.45, respectively, of transitioning to the Highly impaired profile. The transition probabilities from the three impaired function profiles to the Normal function profile ranged from 0.05 to 0.19. Age, gender, place of residence, and social participation were significant predictors of profile attribution at T1 and transition probabilities over time. CONCLUSIONS: This study employed the LTA to examine the transition probability of IADL among the Chinese elderly. By recognizing the different profiles of IADL and understanding the factors associated with transitions among the elderly, interventions can be tailored to improve their functional independence and successful reintegration into families and society.

ß-cyclocitral, a novel AChE inhibitor, contributes to the defense of Microcystis aeruginosa against Daphnia grazing.

ß-cyclocitral is one of the major compounds in cyanobacterial volatile organic compound (VOCs) and can poison other aquatic organisms. To investigate the effect of ß-cyclocitral on cyanobacterial-grazer interactions, Daphnia sinensis was fed Microcystis aeruginosa and exposed to ß-cyclocitral. Our present study demonstrated that M. aeruginosa could significantly inhibit D. sinensis grazing. And the grazing inhibition by Microcystis aeruginosa results from the suppression of feeding rate, heart rate, thoracic limb activity and swimming speed of D. sinensis. In addition, M. aeruginosa could also induce intestinal peristalsis and emptying in D. sinensis. Interestingly, our present study found that the exposure to ß-cyclocitral could mimic a range of phenotypes induced by M. aeruginosa in D. sinensis. These results suggested that M. aeruginosa could release ß-cyclocitral to inhibit Daphnia grazing. To further examine the toxic mechanism of ß-cyclocitral in Daphnia, several in vivo and in vitro experiments displayed that ß-cyclocitral was a novel inhibitor of acetylcholinesterase (AChE). It could induce the accumulation of acetylcholine (ACh) by inhibiting AchE activity in D. sinensis. High level of endogenous Ach could inhibit feeding rate and induce intestinal peristalsis and emptying in D. sinensis.

Design and Preparation of Avermectin Nanopesticide for Control and Prevention of Pine Wilt Disease.

Pine wilt disease is a devastating forest disaster caused by Bursaphelenchus xylophilus, which has brought inestimable economic losses to the world's forestry due to lack of effective prevention and control measures. In this paper, a porous structure CuBTC was designed to deliver avermectin (AM) and a control vector insect Japanese pine sawyer (JPS) of B. xylophilus, which can improve the biocompatibility, anti-photolysis and delivery efficacy of AM. The results illustrated the cumulative release of pH-dependent AM@CuBTC was up to 12 days (91.9%), and also effectively avoided photodegradation (pH 9.0, 120 h, retention 69.4%). From the traceable monitoring experiment, the AM@CuBTC easily penetrated the body wall of the JPS larvae and was transmitted to tissue cells though contact and diffusion. Furthermore, AM@CuBTC can effectively enhance the cytotoxicity and utilization of AM, which provides valuable research value for the application of typical plant-derived nerve agents in the prevention and control of forestry pests. AM@CuBTC as an environmentally friendly nanopesticide can efficiently deliver AM to the larval intestines where it is absorbed by the larvae. AM@CuBTC can be transmitted to the epidemic wood and dead wood at a low concentration (10 mg/L).

Defected MoS2 Modified by Vanadium-Substituted Keggin-Type Polyoxometalates as Electrocatalysts for Triiodide Reduction in Dye-Sensitized Solar Cells.

The rational design of efficient triiodide reduction reaction catalysts that are dependent on cheap and ample elements on Earth has become a challenge. As an extremely encouraging non-noble metallic catalyst, MoS2 requires effective strategies to improve the site accessibility, inherent conductivity, and structural stability. Here, vanadium-substituted Keggin-type polyoxometalates (POMs) can be used as electron aggregates to modify manganese (Mn)-doped MoS2 through the electrochemical deposition strategy, thereby improving the charge transfer ability of MoS2 to I-/I3- redox pairs and accelerating the reduction of I3-. Additionally, with the increase in the number of vanadium atoms substituted in POMs, the conduction band of POMs and MoS2 can also match better, which effectively reduces the energy loss and is more conducive to charge transfer. Meanwhile, the deposition of POMs can improve the stability of metastable MoS2. When POMs/MoS2 materials are used as the counter electrodes of dye-sensitized solar cells, the power conversion efficiency (PCE) obtained is 7.27%, which is higher than that of platinum (Pt) (6.07%). The PCE can still maintain the initial 96% after 9 days. This work provides a valuable way for the improvement of platinum-free catalysts with minimal expense, basic process, high efficiency, and good stability.

A Generic Nomogram Predicting the Stage of Liver Fibrosis Based on Serum Biochemical Indicators Among Chronic Hepatitis B Patients.

Introduction: Liver fibrosis staging is of great importance for reducing unnecessary injuries and prompting treatment in chronic viral hepatitis B patients. Liver biopsy is not suitable to act a screening method although it is a gold standard because of various shortcomings. This study aimed to establish a predictive nomogram as a convenient tool to effectively identify potential patients with different stages of liver fibrosis for patients with chronic hepatitis B. Methods: A nomogram for multinomial model was developed in a training set to calculate the probability for each stage of fibrosis and tested in a validation set. Fibrosis stages were subgrouped as followed: severe fibrosis/cirrhosis (F3-F4), moderate fibrosis (F2), and nil-mild fibrosis (F0-F1). The indicators were demographic characteristics and biochemical indicators of patients. Continuous indicators were divided into several groups according to the optimal candidate value generated by the decision tree. Results: This study recruited 964 HBV patients undergoing percutaneous liver biopsy. The multinomial model with 10 indicators was transformed into the final nomogram. The calibration plot showed a good agreement between nomogram-predicted and observed probability of different fibrosis stages. Areas under the receiver operating characteristics (AUROCs) for severe fibrosis/cirrhosis were 0.809 for training set and 0.879 for validation set. For moderate fibrosis, the AUROCs were 0.75 and 0.781. For nil-mild fibrosis, the AUROCs were 0.792 and 0.843. All the results above showed great predictive performance in predicting the stage of fibrosis by our nomogram. Conclusion: Our model demonstrated good discrimination and extensibility in internal and external validation. The proposed nomogram in this study resulted in great reliability and it can be widely used as a convenient and efficient way.

Heteropoly Blue/Protonation-Defective Graphitic Carbon Nitride Heterojunction for the Photo-Driven Nitrogen Reduction Reaction.

The establishment of a heterojunction is a crucial strategy to design highly effective nonnoble metal nanocatalysts for the photocatalytic nitrogen reduction reaction (PNRR). Heteropoly blues (r-POMs) can act as electron-transfer mediators in PNRR, but its agglomeration limits the further promotion of PNRR productivity. In this work, we construct a protonation-modified surface of N-vacancy g-C3N4 (HV-C3N4), achieving the high dispersion of r-POMs via the surface modification strategy. Enlightened by the synergy effect of the nitrogenase, r-POMs were anchored onto HV-C3N4 nanosheets through an electrostatic self-assembly method for preparing r-POMs-based protonation-defective graphitic carbonitride (HV-C3N4/r-POMs). As an electron donor, r-PW12 can match with the energy level of HV-C3N4 to build a heterojunction. The electron redistribution of the heterojunction facilitates the optimization of the electronic structure for enhancing the performance of PNRR. HV-C3N4/r-PW12 exhibits the best PNRR efficiency of 171.4 µmol L-1 h-1, which is boosted by 94.39% (HV-C3N4) and 86.98% (r-PW12). The isotope 15NH4+ experiment proves that ammonia is derived from N2, not carbon nitride. This study opens up a crucial view to achieve the high dispersion of r-POMs nanoparticles and develop high-efficiency nonnoble metal photocatalysts for the PNRR.

Effect of socio-demographic characteristics on social security in northeast China.

Social security is the most important and even the only source of income for Chinese older people. It is an important guarantee for the medical care and living of older people. However, the backward economy may bring great hidden troubles to the social security of resource-exhausted cities in the future. Our aims were to explore effects of socio-demographic characteristics on social security in the resource-exhausted city. We set up panel data models for social security contributions, social security benefits, newly insured individuals and ex-insured individuals, respectively, to track changes in social security of different age, genders and workplaces from 2011 to 2015. There were 175,194 individuals who eventually entered our database. We found that individuals working in enterprises and individuals aged 55 to 60 had relatively less social security contributions and more social security benefits. Individuals under 25 years of age were more willing to participate in social security. Individuals working in enterprises and men were likely to withdraw from social security. We have concluded that there are some problems that cannot be ignored in the social security of resource-exhausted cities. Our research makes a certain contribution to better guaranteeing the life of older people and improving their qualities of life in resource-exhausted cities.

Activities of daily living, life orientation, and health-related quality of life among older people in nursing homes: a national cross-sectional study in China.

PURPOSE: This study aimed to explore the current status of activities of daily living (ADLs), life orientation, and health-related quality of life (HRQoL) among older people in nursing homes and to further examine the mediating role of life orientation in the impact of ADLs on HRQoL. METHODS: A national cross-sectional study was conducted among older people aged 60 and above in nursing homes by the randomly stratified cluster sampling method. The status of ADLs, life orientation and HRQoL were measured using an ADL scale, a life orientation scale and the SF-12v2 scale, respectively. Multiple linear regression models were used to identify explanatory factors associated with ADLs, life orientation, and HRQoL. The potential mediating role of life orientation in the relationship between ADL and HRQoL was explored by mediation analysis. RESULTS: The overall prevalence of ADL disability was 52.67%, and 84.37% of older people in nursing homes had a negative life orientation. The mean scores of physical health and mental health among older people in nursing homes were 45.44 ± 6.46 and 42.67 ± 8.48, respectively. Some sociodemographic characteristics were associated with poor physical health and mental health. After adjustments were made for covariates, the life orientation score mediated 13.81% of the total effect of the ADL score on physical component score of HRQoL and mediated 45.33% of the mental component score of HRQoL. CONCLUSION: A sizeable proportion of older people had ADL disability and negative life orientation, and HRQoL was poor among older Chinese people in nursing homes. Life orientation partially mediates the relationship between ADLs and HRQoL.

Exosome-transmitted lncRNA UFC1 promotes non-small-cell lung cancer progression by EZH2-mediated epigenetic silencing of PTEN expression.

Long non-coding RNAs (LncRNAs) have been suggested as important regulators of cancer development and progression in non-small cell lung cancer (NSCLC). Nevertheless, the biological roles and clinical significance of lncRNA UFC1 in NSCLC remain unclear. We detected the expression of UFC1 in tumor tissues, serum, and serum exosomes of NSCLC patients by qRT-PCR. Gene overexpression or silencing were used to examine the biological roles of UFC1 in NSCLC. RNA immunoprecipitation and ChIP assays were performed to evaluate the interaction between UFC1 and enhancer of zeste homolog 2 (EZH2) and the binding of EZH2 to PTEN gene promoter. Rescue study was used to access the importance of PTEN regulation by UFC1 in NSCLC progression. UFC1 expression was upregulated in tumor tissues, serum, and serum exosomes of NSCLC patients and high level of UFC1 was associated with tumor infiltration. UFC1 knockdown inhibited NSCLC cell proliferation, migration and invasion while promoted cell cycle arrest and apoptosis. UFC1 overexpression led to the opposite effects. Mechanistically, UFC1 bound to EZH2 and mediated its accumulation at the promoter region of PTEN gene, resulting in the trimethylation of H3K27 and the inhibition of PTEN expression. UFC1 knockdown inhibited NSCLC growth in mouse xenograft tumor models while the simultaneous depletion of PTEN reversed this effect. NSCLC cells derived exosomes could promote NSCLC cell proliferation, migration and invasion through the transfer of UFC1. Moreover, Exosome-transmitted UFC1 promotes NSCLC progression by inhibiting PTEN expression via EZH2-mediated epigenetic silencing. Exosome-mediated transmit of UFC1 may represent a new mechanism for NSCLC progression and provide a potential marker for NSCLC diagnosis.

The ability of different imputation methods for missing values in mental measurement questionnaires.

BACKGROUND: Incomplete data are of particular important influence in mental measurement questionnaires. Most experts, however, mostly focus on clinical trials and cohort studies and generally pay less attention to this deficiency. We aim is to compare the accuracy of four common methods for handling items missing from different psychology questionnaires according to the items non-response rates. METHOD: All data were drawn from the previous studies including the self-acceptance scale (SAQ), the activities of daily living scale (ADL) and self-esteem scale (RSES). SAQ and ADL dataset, simulation group, were used to compare and assess the ability of four imputation methods which are direct deletion, mode imputation, Hot-deck (HD) imputation and multiple imputation (MI) by absolute deviation, the root mean square error and average relative error in missing proportions of 5, 10, 15 and 20%. RSES dataset, validation group, was used to test the application of imputation methods. All analyses were finished by SAS 9.4. RESULTS: The biases obtained by MI are the smallest under various missing proportions. HD imputation approach performed the lowest absolute deviation of standard deviation values. But they got the similar results and the performances of them are obviously better than direct deletion and mode imputation. In a real world situation, the respondents' average score in complete data set was 28.22 ± 4.63, which are not much different from imputed datasets. The direction of the influence of the five factors on self-esteem was consistent, although there were some differences in the size and range of OR values in logistic regression model. CONCLUSION: MI shows the best performance while it demands slightly more data analytic capacity and skills of programming. And HD could be considered to impute missing values in psychological investigation when MI cannot be performed due to limited circumstances.

MiRNA Polymorphisms and Hepatocellular Carcinoma Susceptibility: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is an intractable public health threat worldwide, representing the second leading cause of cancer-related mortality, with limited early detection and therapeutic options. Recent findings have revealed that the susceptibility of HCC is closely related to microRNA (miRNA). We performed this systematic review with a network meta-analysis to investigated four single nucleotide polymorphisms (SNPs) that most regularly reported in miRNAs, exploring their involvement in HCC susceptibility and interaction with hepatitis B virus (HBV). METHODS: Databases were reviewed for related studies published up to May 2019 to identify all studies that compared genotypes of miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913, and miR-499 rs3746444 with no language and date restrictions. A pairwise meta-analysis was performed to estimate pooled odds ratios and 95% confidence intervals incorporating heterogeneity to assess the relationship between four miRNA polymorphisms and HCC. To further clarify the effect of polymorphisms on HCC, a Bayesian network meta-analysis was conducted to combine the effective sizes of direct and indirect comparisons. Calculations were performed by R version 3.6.1 and STATA 14.0. All steps were performed according to PRISMA guidelines. RESULTS: A total of 20 studies were enrolled in this network meta-analysis, providing 5,337 hepatocellular carcinoma cases and 6,585 controls. All included studies had an acceptable quality. Pairwise meta-analysis demonstrated that miR-196a2 rs11614913 was significantly associated with the susceptibility of HCC, while the other three SNPs were not found to have a significant association. In the analysis of HCC patients under different HBV infection status, only miR-196a2 revealed correlation of threefold risk. The network results showed no significant difference in the distribution of genotype frequencies except for miR-196a2, which appeared to have the highest superiority index when comparing and ranking four SNPs. CONCLUSION: MiR-196a2 rs11614913 was significantly associated with the susceptibility of HCC, especially for HBV- related HCC, and that individuals with TC/CC were more susceptible. No significant association was found in the other three miRNA genes. MiR-196a2 could serve as the best predictor of susceptibility in HCC.

miR-370 Sensitizes TMZ Response Dependent of MGMT Status in Primary Central Nervous System Lymphoma.

Primary central nervous system lymphoma (PCNSL) is an aggressive and rare subtype of non-Hodgkin lymphoma, arising exclusively in the CNS with a poor prognosis. Previous evidence has proved that MGMT was a promising target involving in TMZ resistance of PCNSL. Our study described a new miR-370-mediated mechanism of MGMT regulation in PCNSL. We first showed that miR-370 was downregulated in PCNSL tissues, while MGMT was inversely overexpressed. It was also observed that miR-370 suppressed the expression of MGMT. Additionally, upregulation of miR-370 significantly increased TMZ sensitivity dependent of MGMT, thus suppressed Raji cell proliferation and induced apoptosis in vitro. In conclusion, these results suggest that miR-370 is a potential target in PCNSL treatment.

Pharmacokinetic and pharmacodynamic profiling of four antimicrobials against Acinetobacter baumannii infection.

BACKGROUND: The aim of this study was to evaluate common antimicrobial regimens used in eradicating Acinetobacter baumannii in Shenyang, China. METHODS: Monte Carlo simulation was conducted to estimate the probability target attainment (PTA) and cumulative fraction of response (CFR) for imipenem, cefoperazone/sulbactam (2:1), tigecycline and colistin methanesulfonate. RESULTS: For the results of PTAs, imipenem following administration of 0.5 g q6 h, 1 g q8 h, and 1 g q6 h for both 0.5 h and 2 h infusion achieved＞90% PTAs when MIC was 8 µg/ml; cefoperazone/ sulbactam (2:1) following administration of 4.5 g q6 h and 6 g q6 h achieved＞90% PTAs when MIC was 64µg/ml; tigecycline following administration of 50 mg q12 h and 100 mg q12 h achieved＞90% PTAs when MIC was 1 µg/ml; colistin methanesulfonate with high dosages (3MU q8 h) could provide high PTA (95.13%) in patients with CLCr＜60 ml/min when MIC was 2 µg/ml. As for CFR values of four antibiotics, imipenem achieved the lowest CFR values. For cefoperazone/sulbactam (2:1) and tigecycline, with simulated regimens improvement, the CFR values were both increased, and there were obviously increasing CFR values against Acinetobacter baumannii. For colistin methanesulfonate, the most aggressive dosage of 3MU q8 h could provide satisfactory CFR values (≥86.94%) against Acinetobacter baumannii in patients at various CLCr. CONCLUSION: This study suggested that measurement of MICs, individualized therapy and therapeutic drug-level monitoring should be considered together to achieve the optimal drug exposure. That will provide the best chance of achieving the highest probability of a successful clinical or microbiological response, and avoiding the induced resistance.

LINC00978 promotes the progression of hepatocellular carcinoma by regulating EZH2-mediated silencing of p21 and E-cadherin expression.

Long non-coding RNAs (lncRNAs) have been suggested as important regulators of cancer development and progression in hepatocellular carcinoma (HCC). Nevertheless, the clinical value and biological roles of LINC00978 in HCC remain unclear. In this study, we detected the expression of LINC00978 in tumor tissues and serum of HCC patients, examined the roles of LINC00978 in HCC progression and elucidated the underlying molecular mechanisms. We found that LINC00978 expression was upregulated in tumor tissues and serum of HCC patients. Higher serum levels of LINC00978 could distinguish HCC patients from hepatitis and liver cirrhosis patients and healthy controls. LINC00978 knockdown inhibited HCC cell proliferation, migration and invasion while promoted cell cycle arrest and apoptosis. Overexpression of LINC00978 led to the opposite effects. LINC00978 knockdown also inhibited HCC growth and metastasis in mouse tumor models. Mechanistically, LINC00978 bound to EZH2 and mediated its accumulation at the promoter region of p21 and E-cadherin genes, leading to the trimethylation of H27K3 and the inhibition of p21 and E-cadherin expression. Moreover, the simultaneous depletion of p21 and E-cadherin expression reversed the inhibitory effects of LINC00978 knockdown on HCC cell proliferation, migration, and invasion. Taken together, these findings suggest that LINC00978 promotes HCC progression by inhibiting p21 and E-cadherin expression via EZH2-mediated epigenetic silencing. LINC00978 may represent a novel biomarker for HCC diagnosis, prognosis, and therapy.