Background and Objectives
COVID‐19‐related quarantine and stress have likely escalated the crisis of Internet addiction. This study aimed to determine the impact of the COVID‐19 pandemic on Internet ...use and related risk factors among the general public in China.
Methods
A large‐sample cross‐sectional online survey was conducted from March 24 to April 30, 2020, in China, and 20,472 participants completed the survey. We investigated the prevalence and severity of Internet addiction based on the Internet Addiction Test (IAT), and explored the risk factors related to increases in time spent on Internet use and severity of Internet addiction, as well as severe Internet addiction.
Results
The overall prevalence of Internet addiction was 36.7% among the general population during the pandemic, and that of severe Internet addiction was 2.8%, according to IAT scores. Time spent on recreational Internet use had significantly increased during the pandemic, and almost half of participants reported increases in the severity of Internet addiction. Risk factors for increases in time spent on Internet use and severity of Internet addiction and severe Internet addiction included having fewer social supporters, perceiving pressure and impact on mental health status due to COVID‐19, and being over‐engaged in playing videogames.
Discussion and Conclusions
The COVID‐19 pandemic adversely impacted Internet use and increased the prevalence and severity of Internet addiction among the general population in China, especially in vulnerable populations.
Scientific Significance
This study provides evidence for policymakers to refine public health policies to control the pandemic and make efforts to provide population‐specific prevention and interventions for people at risk of developing Internet addiction. (Am J Addict 2021;00:00–00)
The present meta-analytic review aimed to synthesize the global prevalence characteristics of digital addiction in the general population. We searched PubMed, Embase, Cochrane Library, and PsycINFO ...for studies reporting prevalence of various subtypes of digital addiction published before October 31, 2021. Studies were eligible if they were published in peer-reviewed journals, used a validated tool to assess digital addiction, and passed the qualify assessment. In total, 498 articles with 507 studies were included in systematic review, and the meta-analysis included 495 articles with 504 studies covering 2,123,762 individuals from 64 countries. Global pooled prevalence estimates were 26.99% (95% CI, 22.73–31.73) for smartphone addiction, 17.42% (95% CI, 12.42–23.89) for social media addiction, 14.22% (95% CI, 12.90–15.65) for Internet addiction, 8.23% (95% CI, 5.75–11.66) for cybersex addiction, and 6.04% (95% CI, 4.80–7.57) for game addiction. Higher prevalence of digital addiction was found in Eastern Mediterranean region and low/lower-middle income countries. Males had higher risk for Internet and game addiction. An increasing trend of digital addiction during the past two decades was found, which dramatically worsened during COVID-19 pandemic. This study provides the first and comprehensive estimation for the global prevalence of multiple subtypes of digital addiction, which varied between regions, economic levels, time periods of publication, genders, and assessment scales.
PROSPERO ID: CRD42020171117.
•1/4 general population could be affected by at least one subtype of digital addiction.•Prevalence differed among subtypes of digital addiction, with big geographical variation.•Low/lower-middle income countries had higher burden of digital addiction.•Males had higher prevalence of Internet addiction and game addiction than females.•Increasing trend of digital addiction was worsened by COVID-19 pandemic.
Background
Pituitary adenomas (PAs) are the second most common brain tumors, and mostly are benign tumors. However, there exists subtypes of PAs refractory to common treatments, and need novel ...therapy. Programmed death 1 (PD-1) blockade has shown durable objective response in a variety of malignancies, and the key predictive markers for this immunotherapy were PD-L1 and CD8
+
tumor-infiltrating lymphocyte (TILs) expression. To evaluate the potential immunotherapy for PAs, we investigated the expression of these two immune markers in PAs.
Methods
Immunohistochemistry (IHC) was performed to detect the expression of PD-L1 and CD8
+
TILs in PAs. The ratio of positive expression of PD-L1 and CD8
+
TILs was compared with chi-squared tests among different subtypes of PAs. The association between their expression profile and clinical parameters was analyzed using a chi-squared test, or Fisher’s exact probability test when appropriate.
Results
One hundred and ninety one patients with PAs were retrospectively involved in this study, consisting of 106 non-functioning PAs (NF-PAs, 55.5%), 40 PRL-secreting PAs (PRL-PAs, 20.9%), 31 GH-secreting PAs (GH-PAs, 16.2%), 9 ACTH-secreting PAs (ACTH-PAs, 4.7%) and 5 plurihormonal adenomas (2.6%) respectively. 36.6% of them were PD-L1 positive and 86.9% were CD8
+
TILs positive. The positive PD-L1 immunostaining presented more frequently in functioning PAs (58.8%), compared with that (34.3%) in nonfunctioning group (p = 0.000). Moreover, the rates of PD-L1 expression were more associated with increased blood levels of PRL, GH, ACTH and cortisol. Contrastly, positive CD8
+
TILs immunostaining was only correlated with elevated blood level of GH. For the analysis of immune markers with pathological results, PD-L1 expression was associated with PRL and GH immunostaining and higher Ki-67 index. But CD8
+
TILs was only correlated with PRL immunostaining.
Conclusion
Our results showed that PD-L1 was frequently expressed in functioning PAs with association of aggressive behaviors in PAs. The immunotherapy could be a promising treatment option of PAs.
Increased glucose production and reduced hepatic glycogen storage contribute to metabolic abnormalities in diabetes. Irisin, a newly identified myokine, induces the browning of white adipose tissue, ...but its effects on gluconeogenesis and glycogenesis are unknown. In the present study, we investigated the effects and underlying mechanisms of irisin on gluconeogenesis and glycogenesis in hepatocytes with insulin resistance, and its therapeutic role in type 2 diabetic mice. Insulin resistance was induced by glucosamine (GlcN) or palmitate in human hepatocellular carcinoma (HepG2) cells and mouse primary hepatocytes. Type 2 diabetes was induced by streptozotocin/high-fat diet (STZ/HFD) in mice. In HepG2 cells, irisin ameliorated the GlcN-induced increases in glucose production, phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) expression, and glycogen synthase (GS) phosphorylation; it prevented GlcN-induced decreases in glycogen content and the phosphoinositide 3-kinase (PI3K) p110α subunit level, and the phosphorylation of Akt/protein kinase B, forkhead box transcription factor O1 (FOXO1) and glycogen synthase kinase-3 (GSK3). These effects of irisin were abolished by the inhibition of PI3K or Akt. The effects of irisin were confirmed in mouse primary hepatocytes with GlcN-induced insulin resistance and in human HepG2 cells with palmitate-induced insulin resistance. In diabetic mice, persistent subcutaneous perfusion of irisin improved the insulin sensitivity, reduced fasting blood glucose, increased GSK3 and Akt phosphorylation, glycogen content and irisin level, and suppressed GS phosphorylation and PEPCK and G6Pase expression in the liver. Irisin improves glucose homoeostasis by reducing gluconeogenesis via PI3K/Akt/FOXO1-mediated PEPCK and G6Pase down-regulation and increasing glycogenesis via PI3K/Akt/GSK3-mediated GS activation. Irisin may be regarded as a novel therapeutic strategy for insulin resistance and type 2 diabetes.
Insomnia is one of the most common and burdensome disorders in adults. We compared and ranked insomnia medication on the basis of their efficacy and tolerability.
We performed a systematic review and ...network meta-analysis of placebo-controlled or head-to-head randomized controlled trials for primary insomnia in adults comparing 20 drugs. We searched eight databases and seven trial registers from inception to March 1st, 2022. Primary outcomes included sleep latency (SL), awake time after sleep onset (WASO) and discontinuation for adverse events (AED), and secondary outcomes included total sleep time (TST), sleep efficiency (SE), sleep quality (SQ) and adverse events (ADE). Pooled standardized mean differences or odds ratios with 95% credible intervals were estimated using pairwise and network meta-analysis with random-effects. Differences among trial findings were explored in subgroup and sensitivity analyses. Confidence in evidence was assessed using GRADE. The PROSPERO registered number is CRD42020182144.
We identified 22,538 records and included 69 studies (17,319 patients). Orexin receptor antagonists (ORAs) are more efficacious than benzodiazepine-like drugs (Z-drugs) and placebo for WASO and SE, and better than melatonin receptor agonists (MRAs) for SL, WASO and SE. ORAs ranked the best in SL (SUCRA value: 0.84), WASO (0.93), TST (0.86) and SE (0.96). Lemborexant and daridorexant (two ORAs) showed greater efficacy than placebo for SL, WASO, and TST, with good tolerability. Z-drugs were more efficacious than placebo for SL, WASO, TST and SE, but with higher risk to safety. Zaleplon and eszopiclone had better efficacy than placebo for TST and SQ respectively. MRAs may also be efficacious for sleep-onset insomnia with good safety. However, the long-term adverse effects of all medications are unclear.
Insomnia medications differ in their efficacy and tolerability. ORAs have superior efficacy and tolerability. These findings should aid clinicians in matching risk/benefits of drugs available in their countries to insomnia symptoms.
Ki-67 is a typical immunohistochemical marker for cell proliferation. Higher expression of Ki-67 is correlated with poor clinical outcomes in several cancers. However, the prognostic value of Ki-67 ...on the prognosis of meningiomas is still controversial. The purpose of this meta-analysis was to evaluate the prognostic value of Ki-67 in meningiomas.
We searched Medline and EMBASE from inception to December 31, 2018, to identify relevant articles. Using a fixed or random effects model, pooled hazard ratios (HRs) for overall survival (OS) and disease/progression/recurrence-free survival (D/P/RFS) were estimated.
A total of 43 studies, comprising 5012 patients, were included in this analysis. Higher Ki-67 expression levels were significantly associated with worse OS (HR = 1.565; 95% CI: 1.217-2.013) and D/P/RFS (HR = 2.644; 95% CI: 2.264-3.087) in meningiomas. Subgroup analysis revealed that all the included factors (ethnicity, tumor grade, HR sources, definition of cutoffs, cutoff values) for heterogeneity investigation can affect the pooled results. Among them, the definitions of cutoffs and cutoff values factor are the two main contributors toward heterogeneity. Multivariable meta-regression analysis also showed that methodologies used for cutoff value definition contributed to the high inner-study heterogeneity.
Higher Ki-67 expression levels negatively influenced survival in meningiomas. A higher cutoff value (>4%) is more appropriate for prognosis prediction. It is highly recommended that Ki-67 expression profile could be assessed in meningiomas treatment for predicting survival. And patients with elevated expression of Ki-67 need to have close follow-ups.
Fibronectin type III domain-containing 5 (FNDC5) protein induces browning of subcutaneous fat and mediates the beneficial effects of exercise on metabolism. However, whether FNDC5 is associated with ...hepatic steatosis, autophagy, fatty acid oxidation (FAO), and lipogenesis remains unknown. Herein, we show the roles and mechanisms of FNDC5 in hepatic steatosis, autophagy, and lipid metabolism. Fasted FNDC5
mice exhibited severe steatosis, reduced autophagy, and FAO, and enhanced lipogenesis in the liver compared with wild-type mice. Energy deprivation-induced autophagy, FAO, and AMPK activity were attenuated in FNDC5
hepatocytes, which were restored by activating AMPK with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Inhibition of mammalian target of rapamycin (mTOR) complex 1 with rapamycin enhanced autophagy and FAO and attenuated lipogenesis and steatosis in FNDC5
livers. FNDC5 deficiency exacerbated hyperlipemia, hepatic FAO and autophagy impairment, hepatic lipogenesis, and lipid accumulation in obese mice. Exogenous FNDC5 stimulated autophagy and FAO gene expression in hepatocytes and repaired the attenuated autophagy and palmitate-induced steatosis in FNDC5
hepatocytes. FNDC5 overexpression prevented hyperlipemia, hepatic FAO and autophagy impairment, hepatic lipogenesis, and lipid accumulation in obese mice. These results indicate that FNDC5 deficiency impairs autophagy and FAO and enhances lipogenesis via the AMPK/mTOR pathway. FNDC5 deficiency aggravates whereas FNDC5 overexpression prevents the HFD-induced hyperlipemia, hepatic lipid accumulation, and impaired FAO and autophagy in the liver.
The variation and the spatial–temporal distribution of soil water content have significant effects on heat balance, agricultural moisture, etc. A soil moisture (SM) retrieval model can provide a ...theoretical basis for realizing a rapid test and revealing the spatial–temporal variation of the surface water. However, remote sensors do not measure soil water content directly. Therefore, it is of great importance to establish a SM retrieval model. In this paper, the relationship between SM and diffuse reflectance was first derived using the absorption coefficient and scattering coefficient related to SM. Then, based on Kubelka–Munk (KM) theory, the SM retrieval model using reflectance information was further derived, which is a semi-empirical model with an unknown parameter obtained either from fitting or from experimental measurements. The validity and reliability of the model were confirmed with the validation set. The results showed that the root mean square errors of prediction (RMSEPs) of four soils were generally less than 0.017, while the coefficients of determination (R2s) of four soils were generally more than 0.85, and the ratios of the performance to deviation (RPDs) of four soils were greater than 2.5 (470–2400 nm). Therefore, the model has high prediction accuracy, and can be well applied to the prediction of water content in different sorts of soils.
Background and aims
Genomic and transcriptomic findings greatly broaden the biological knowledge regarding substance use. However, systematic convergence and comparison evidence of genome‐wide ...findings is lacking for substance use. Here, we combined all the genome‐wide findings from both substance use behavior and disorder (SUBD) and identified common and distinguishing genetic factors for different SUBDs.
Methods
Systemic literature search for genome‐wide association (GWAS) and RNA‐seq studies of alcohol/nicotine/drug use behavior (partially meets or not reported diagnostic criteria) and alcohol use behavior and disorder (AUBD), nicotine use behavior and disorder (NUBD) and drug use behavior and disorder (DUBD) was performed using PubMed and the GWAS catalog. Drug use was focused upon cannabis, opioid, cocaine and methamphetamine use. GWAS studies required case–control or case/cohort samples. RNA‐seq studies were based on brain tissues. The genes which contained significant single nucleotide polymorphism (P ≤ 1 × 10−6) in GWAS and reported as significant in RNA‐seq studies were extracted. Pathway enrichment was performed by using Metascape. Gene interaction networks were identified by using the Protein Interaction Network Analysis database.
Results
Total SUBD‐related 2910 genes were extracted from 75 GWAS studies (2 773 889 participants) and 17 RNA‐seq studies. By overlapping the genes and pathways of AUBD, NUBD and DUBD, four shared genes (CACNB2, GRIN2B, PLXDC2 and PKNOX2), four shared pathways two Gene Ontology (GO) terms of ‘modulation of chemical synaptic transmission’, ‘regulation of trans‐synaptic signaling’, two Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of ‘dopaminergic synapse’, ‘cocaine addiction’ were identified (significantly higher than random, P < 1 × 10−5). The top shared KEGG pathways (Benjamini–Hochberg‐corrected P‐value < 0.05) in the pairwise comparison of AUBD versus DUBD, NUBD versus DUBD, AUBD versus NUBD were ‘Epstein–Barr virus infection’, ‘protein processing in endoplasmic reticulum’ and ‘neuroactive ligand‐receptor interaction’, respectively. We also identified substance‐specific genetic factors: i.e. ADH1B and ALDH2 were unique for AUBD, while CHRNA3 and CHRNA4 were unique for NUBD.
Conclusions
This systematic review identifies the shared and unique genes and pathways for alcohol, nicotine and drug use behaviors and disorders at the genome‐wide level and highlights critical biological processes for the common and distinguishing vulnerability of substance use behaviors and disorders.
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