Effect of larger corneal spherical aberration in improving the near visual acuity of eyes implanted with the TECNIS Symfony.

Purpose: To explore the effect of corneal spherical aberration on the visual acuity and visual quality of eyes implanted with the TECNIS Symfony intraocular lens (IOL). Methods: A total of 43 patients with age-related cataract (60 eyes) undergoing phacoemulsification and TECNIS Symfony IOL implantation were enrolled in this study. The uncorrected distance (UDVA), intermediate (UIVA), near visual acuity (UNVA), corrected distance visual acuity (CDVA), contrast sensitivity, and ocular spherical aberration were recorded 3 months after surgery. Preoperative and postoperative corneal spherical aberration were also measured using the iTrace device. Objective scattering index (OSI), modulation transfer function cut-off frequency (MTF cut-off), and Strehl ratio (SR) were measured by the Optical Quality Analyzing System. Catquest-9SF questionnaire were applied too. Spearman's correlation analysis was used to evaluate the relationship between spherical aberration and visual quality parameters. Results: Patients were satisfied with their postoperatively visual quality. And the postoperative logMAR UDVA, UIVA, UNVA, and CDVA was 0.05 ± 0.07, 0.04 ± 0.06, 0.15 ± 0.07, and 0.03 ± 0.05, respectively. The mean preoperative corneal spherical aberration was 0.24 ± 0.10 µm, which is the only factor influencing postoperatively UNVA, and it was negatively correlated with UNVA and glare contrast sensitivity under 18 cpd (cycle/degree, cpd) spatial frequency (r = -0.403, -0.300, -0.360; all P < 0.05). Additionally, the greater the residual spherical aberration of the cornea, the better the near vision after operation. The mean postoperative ocular spherical aberration was -0.03 ± 0.07 µm, it was not correlated with visual acuity, contrast sensitivity, and visual quality (all P > 0.05). Conclusion: Preoperative positive spherical aberration can benefit near vision while decrease contrast sensitivities at high spatial frequencies when implanted with the TECNIS Symfony IOL.

The Aldose Reductase Inhibitor Epalrestat Maintains Blood-Brain Barrier Integrity by Enhancing Endothelial Cell Function during Cerebral Ischemia.

Excessive activation of aldose reductase (AR) in the brain is a risk factor for aggravating cerebral ischemia injury. Epalrestat is the only AR inhibitor with proven safety and efficacy, which is used in the clinical treatment of diabetic neuropathy. However, the molecular mechanisms underlying the neuroprotection of epalrestat remain unknown in the ischemic brain. Recent studies have found that blood-brain barrier (BBB) damage was mainly caused by increased apoptosis and autophagy of brain microvascular endothelial cells (BMVECs) and decreased expression of tight junction proteins. Thus, we hypothesized that the protective effect of epalrestat is mainly related to regulating the survival of BMVECs and tight junction protein levels after cerebral ischemia. To test this hypothesis, a mouse model of cerebral ischemia was established by permanent middle cerebral artery ligation (pMCAL), and the mice were treated with epalrestat or saline as a control. Epalrestat reduced the ischemic volume, enhanced BBB function, and improved the neurobehavior after cerebral ischemia. In vitro studies revealed that epalrestat increased the expression of tight junction proteins, and reduced the levels of cleaved-caspase3 and LC3 proteins in mouse BMVECs (bEnd.3 cells) exposed to oxygen-glucose deprivation (OGD). In addition, bicalutamide (an AKT inhibitor) and rapamycin (an mTOR inhibitor) increased the epalrestat-induced reduction in apoptosis and autophagy related protein levels in bEnd.3 cells with OGD treatment. Our findings suggest that epalrestat improves BBB function, which may be accomplished by reducing AR activation, promoting tight junction proteins expression, and upregulating AKT/mTOR signaling pathway to inhibit apoptosis and autophagy in BMVECs.

Capsulotomy opening diameter outcomes in aphakic eyes after primary congenital cataract removal and its association.

Aim: To observe the change of capsulotomy opening diameter (COD) in aphakic eyes after primary congenital cataract removal and investigate its influencing factors. Methods: Ocular parameters, including corneal diameter (CD), axial length (AL), anterior and posterior COD (ACOD, PCOD), and age at surgery were recorded at primary congenital cataract removal and secondary intraocular lens implantation. The concentrations of 15 kinds of cytokines in aqueous humor samples collected at the primary surgery were detected. The change (Δ) of COD between two surgeries were described, and its association was analyzed. Results: Fifty eyes from 33 patients with congenital cataract who underwent primary and secondary surgery were enrolled. The changes in ACOD and PCOD were not statistically significant on the whole. ΔACOD was positively correlated with ΔCD and the concentrations of PDGF-AA, VEGF and TGF-ß1. The concentration of FGF-2 and the interval between two surgeries showed negative correlations with ΔACOD and ΔPCOD. Conclusion: COD in aphakic eyes kept changing after primary surgery. The positive correlation between ΔACOD and ΔCD manifested the enlargement of ACOD was influenced by lateral eye growth. Meanwhile, ΔACOD was also associated with cytokines, indicating postoperative inflammation promoted the ACOD constriction.

Systemic Inflammatory Response Syndrome on Admission and Clinical Outcomes After Intracerebral Hemorrhage.

Background: Since studies on systemic inflammatory response syndrome (SIRS) in patients with acute intracerebral hemorrhage (ICH) are insufficient. This study investigated the associations between SIRS on admission and clinical outcomes after acute ICH. Patients and Methods: The study included 1159 patients with acute spontaneous ICH from January 2014 to September 2016. In accordance with standard criteria, SIRS was defined as two or more of the following: (1) body temperature >38°C or <36°C, (2) respiratory rate >20 per minute, (3) heart rate >90 per minute, and (4) white blood cell count >12,000/µL or <4000/µL. The clinical outcomes of interest were death and major disability (defined as a modified Rankin Scale of 6 and 3-5), combined and separate at 1 month, 3 months and 1 year follow-up. Results: SIRS was observed in 13.5% (157/1159) of patients and independently increased the risk of death at 1 month, 3 months, or 1 year: hazard ratio (HR) 2.532 (95% confidence interval [CI] 1.487-4.311), HR 2.436 (95% CI 1.499-3.958), HR 2.030 (95% CI 1.343-3.068), respectively (P<0.05 for all). The relationship between SIRS and ICH mortality was more pronounced in older patients or patients with larger hematoma volumes. Patients with in-hospital infections were at greater risk of major disability. The risk was enhanced when SIRS was incorporated. Conclusion: The presence of SIRS at the time of admission was associated with mortality in patients with acute ICH, particularly in older patients and those with large hematomas. SIRS may exacerbate the disability caused by in-hospital infections in patients with ICH.

Association between the VEGFR-2 -604T/C polymorphism (rs2071559) and type 2 diabetic retinopathy.

This retrospective case-control study examined the association between the rs2071559 (-604T/C) single nucleotide polymorphism (SNP) in the vascular endothelial growth factor receptor (VEGFR)-2 gene and the risk of diabetic retinopathy (DR) in Northern Han Chinese. This study included patients diagnosed with diabetes mellitus (DM) in Shijiazhuang between 07/2014 and 07/2016. The healthy controls were unrelated individuals who received routine physical examinations. The diabetic patients were grouped as DM (diabetes but no fundus examination abnormalities), proliferative DR (PDR), and non-proliferative DR (NPDR). Finally, 438 patients were included: 114 controls and 123, 105, and 96 patients in the DM, NPDR, and PDR groups, respectively. In the multivariable analyses and all genetic models, the VEGFR-2 rs2071559 SNP was not associated with DR (among all diabetic patients) or with PDR (among the patients with DR) after adjustment for age, sex, duration of DM, blood glucose, systolic blood pressure, diastolic blood pressure, and body mass index (all P > 0.05). In conclusion, the VEGFR-2- 604T/C rs2071559 SNP is not associated with DR or PDR in the Han Chinese population of Shijiazhuang (China).

Axenic and gnotobiotic insect technologies in research on host-microbiota interactions.

Insects are one of the most important animal life forms on earth. Symbiotic microbes are closely related to the growth and development of the host insects and can affect pathogen transmission. For decades, various axenic insect-rearing systems have been developed, allowing further manipulation of symbiotic microbiota composition. Here we review the historical development of axenic rearing systems and the latest progress in using axenic and gnotobiotic approaches to study insect-microbe interactions. We also discuss the challenges of these emerging technologies, possible solutions to address these challenges, and future research directions that can contribute to a more comprehensive understanding of insect-microbe interactions.

Association between Arachidonic Acid and the Risk of Schizophrenia: A Cross-National Study and Mendelian Randomization Analysis.

Polyunsaturated fatty acids (PUFAs), especially long-chain PUFAs (LCPUFAs), are crucial for both the structural and functional integrity of cells. PUFAs have been reported to be insufficient in schizophrenia, and the resulting cell membrane impairments have been hypothesized as an etiological mechanism. However, the impact of PUFA deficiencies on the onset of schizophrenia remain uncertain. We investigated the associations between PUFAs consumption and schizophrenia incidence rates through correlational analyses and conducted Mendelian randomization analyses to reveal the causal effects. Using dietary PUFA consumption and national schizophrenia incidence rates in 24 countries, we found that incidence rates of schizophrenia were inversely correlated with arachidonic acid (AA) and ω-6 LCPUFA consumption (rAA = -0.577, p < 0.01; rω-6 LCPUFA = -0.626, p < 0.001). Moreover, Mendelian randomization analyses revealed that genetically predicted AA and gamma-linolenic acid (GLA) were protective factors against schizophrenia (ORAA = 0.986, ORGLA = 0.148). In addition, no significant relationships were observed between schizophrenia and docosahexaenoic acid (DHA) or other ω-3 PUFAs. These findings show that the deficiencies of ω-6 LCPUFAs, especially AA, are associated with schizophrenia risk, which sheds novel insight into the etiology of schizophrenia and a promising diet supplementation for the prevention and treatment of schizophrenia.

IFIH1 was predicted as a key biomarker in primary Sjögren's syndrome based on transcriptome analysis and experimental verification in patients and mice.

OBJECTIVES: To investigate the novel key genes and biological processes that may lead to primary Sjögren' s syndrome (pSS). METHODS: We downloaded datasets about peripheral blood samples of pSS patients and healthy controls (GSE51092, GSE84844, and GSE66795) from Gene Expression Omnibus database. The weighted co-expression network analysis and differential expression analysis first were implemented. After that, protein-protein network interaction and Support Vector Machines were applied in the meantime to take intersection for key genes. Moreover, we conducted immune cell infiltration analysis to explore the relationship between the gene expression and concentration of immune cells in peripheral blood. Lastly, the expression of key genes was verified in pSS patients and murine models by reverse-transcription polymerase chain reaction. Meanwhile, correlation analysis of gene expression and disease activity was also performed. RESULTS: Only 1 key gene, interferon induced with helicase c domain 1 (IFIH1), was identified to be both significantly up-regulated and important for the diagnosis of pSS. The increased expression of IFIH1 in peripheral blood was confirmed in data sets, patients and non-obese diabetic (NOD) mice. Its expression was correlated with disease activity in patients as well. In addition, the IFIH1 expression was also increased in spleen and salivary glands infiltrated with lymphocytes in NOD mice. Furthermore, immune cell infiltration analysis showed that the expression of IFIH1 was positively correlated with the proportion of memory B cells and activated dendritic cells, and negatively correlated with the proportion of macrophage M0. CONCLUSIONS: Here, bioinformatics analyses and experimental assays were performed to provide a new insight for understanding of pSS. IFIH1 may be a new diagnostic marker or therapeutic target for pSS.

Shotgun metagenomics reveals abnormal short-chain fatty acid-producing bacteria and glucose and lipid metabolism of the gut microbiota in patients with schizophrenia.

Evidence has shown that the gut microbiota is closely related to the pathogenesis of schizophrenia, but temporal changes in the gut microbiota of patients with schizophrenia (SZ) during treatment remain unclear. Here, to evaluate temporal changes in the gut microbiota in schizophrenia, we performed whole-genome shotgun metagenomics on fecal samples from 36 healthy controls (HCs) and 19 baseline-period patients, and followed up with patients upon treatment. Compared to that in HCs, beta diversity in SZ was significantly distinct. The genera Bacteroides, Prevotella and Clostridium were the top 3 altered genera between SZ and HCs, and the Bacteroides-Prevotella ratio was significantly increased in SZ. Thirty-three percent of differentially abundant species were short-chain fatty acid (SCFA)-producing bacteria. Functional analysis showed that glucose and lipid metabolism of the gut microbiota was decreased in SZ compared with those in HCs. The abundances of two rate-limiting enzymes in glucose and lipid metabolism, phosphofructokinase (PFK) and acetyl-CoA carboxylase (ACC), were significantly decreased in SZ, and differentially abundant metabolism-related enzymes were significantly associated with SCFA-producing bacteria. Next, we found that the abundance of SCFA-producing bacteria also changed after treatment and that Clostridium was significantly negatively correlated with the total positive and negative syndrome scale (PANSS) score in patients. Functional analysis showed that glycoside hydrolase family 30 incrementally increased in abundance during treatment and were significantly associated with SCFA-producing bacteria. Our findings help to provide evidence for the role of gut microbiota in the occurrence and development of schizophrenia.

Exploring interactions in water-related ecosystem services nexus in Loess Plateau.

Scientific understanding of the driving relationship between water-related ecosystem services (WESs) and influencing factors, as well as the trade-off and synergy relationship between WESs and WESs, is the premise of reasonably bringing them into management decisions. However, the existing research often separates the above-mentioned two relationships and conducts independent research, which leads to the conflict of research conclusions and cannot be well adopted by managers. Therefore, based on the panel data of Loess Plateau in 2000-2019, this paper uses the simultaneous equation model to combine the two kinds of relationships existing between WESs and influencing factors, establish a feedback loop, and reveal the interactions mechanism of WESs nexus. The results show that: (1) The fragmentation of land use leads to the uneven spatial-temporal distribution of WESs. (2) Vegetation factors and land factors are the main driving factors that affect WESs, and the impact of climate factors on WESs is decreasing year by year. (3) The increase of water yield ecosystem services will lead to the obvious increase in soil export ecosystem services, and there is a synergistic relationship between soil export ecosystem services and nitrogen export ecosystem services. The conclusion can provide an important reference for implementing the strategy of ecological protection and high-quality development.

Ultrasound-guided Aspiration Combined with Medical Treatment for an Unexpected Rectal Endometriotic Cyst: A Case Report.

Most bowel endometriotic lesions are ill-defined serosal and subserosal nodules, and no case of cystic bowel endometriosis has been reported in the literature. This is the first report of an unexpected presentation of bowel endometriosis as a primary cyst located inside the posterior rectal wall. The patient was a 26-year-old nulliparous woman with progressive lower abdominal pain for 6 days and difficult defecation for 1 day. Colorectal surgeons recommended bowel resection owing to the giant rectal mass. However, the patient refused to undergo surgery. Ultrasound-guided aspiration of the rectal endometriotic cyst followed by gonadotropin-releasing hormone agonist injection was individually scheduled, which finally brought significant improvement both in symptoms and in the size of the rectal endometriotic lesion.

Anti-inflammatory effect of Danhong injection through inhibition of GSDMD-mediated pyroptosis.

BACKGROUND: Pyroptosis is an inflammatory form of cell death that has been implicated in various infectious and non-infectious diseases. Gasdermin family proteins are the key executors of pyroptotic cell death, thus they are considered as novel therapeutic targets for inflammatory diseases. However, only limited gasdermin specific inhibitors have been identified to date. Traditional Chinese medicines have been applied in clinic for centuries and exhibit potential in anti-inflammation and anti-pyroptosis. We attempted to find candidate Chinese botanical drugs which specifically target gasdermin D (GSDMD) and inhibit pyroptosis. METHODS: In this study, we performed high-throughput screening using a botanical drug library to identify pyroptosis specific inhibitors. The assay was based on a cell pyroptosis model induced by lipopolysaccharides (LPS) and nigericin. Cell pyroptosis levels were then evaluated by cell cytotoxicity assay, propidium iodide (PI) staining and immunoblotting. We then overexpressed GSDMD-N in cell lines to investigate the direct inhibitory effect of the drug to GSDMD-N oligomerization. Mass spectrometry studies were applied to identify the active components of the botanical drug. Finally, a mouse model of sepsis and a mouse model of diabetic myocardial infarction were constructed to verify the protective effect of the drug in disease models of inflammation. RESULTS: High-throughput screening identified Danhong injection (DHI) as a pyroptosis inhibitor. DHI remarkably inhibited pyroptotic cell death in a murine macrophage cell line and bone marrow-derived macrophages. Molecular assays demonstrated the direct blockade of GSDMD-N oligomerization and pore formation by DHI. Mass spectrometry studies identified the major active components of DHI, and further activity assays revealed salvianolic acid E (SAE) as the most potent molecule among these components, and SAE has a strong binding affinity to mouse GSDMD Cys192. We further demonstrated the protective effects of DHI in mouse sepsis and mouse myocardial infarction with type 2 diabetes. CONCLUSION: These findings provide new insights for drug development from Chinese herbal medicine like DHI against diabetic myocardial injury and sepsis through blocking GSDMD-mediated macrophage pyroptosis.

Overexpression of NgBR inhibits high-fat diet-induced atherosclerosis in ApoE-deficiency mice.

BACKGROUND: Hyperlipidemia (hypercholesterolemia and/or hypertriglyceridemia) is a risk factor for atherosclerosis. Nogo-B receptor (NgBR) plays important roles in hepatic steatosis and cholesterol transport. However, the effect of NgBR overexpression on atherosclerosis remains unknown. MATERIALS AND METHODS: Apolipoprotein E deficient (ApoE-/-) mice infected with adeno-associated virus (AAV)-NgBR expression vector were fed a high-fat diet for 12 weeks, followed by determination of atherosclerosis and the involved mechanisms. RESULTS: We determined that high expression of NgBR by AAV injection mainly occurs in the liver and it can substantially inhibit en face and aortic root sinus lesions. NgBR overexpression also reduced levels of inflammatory factors in the aortic root and serum, and levels of cholesterol, triglyceride, and free fatty acids in the liver and serum. Mechanistically, NgBR overexpression increased the expression of scavenger receptor type BI and the genes for bile acid synthesis, and decreased the expression of cholesterol synthesis genes by reducing sterol regulatory element-binding protein 2 maturation in the liver, thereby reducing hypercholesterolemia. In addition, NgBR overexpression activated AMP-activated protein kinase α via the Ca2+ signaling pathway, which inhibited fat synthesis and improved hypertriglyceridemia. CONCLUSIONS: Taken together, our study demonstrates that overexpression of NgBR enhanced cholesterol metabolism and inhibited cholesterol/fatty acid synthesis to reduce hyperlipidemia, and reduced vascular inflammation, thereby inhibiting atherosclerosis in ApoE-/- mice. Our study indicates that NgBR might be a potential target for atherosclerosis treatment.

ACT001 inhibited CD133 transcription by targeting and inducing Olig2 ubiquitination degradation.

Lung cancer is the most lethal malignancies with high aggressive and poor prognosis. Until now, the five-year survival rate has not been improved which brings serious challenge to human health. Lung cancer stem cells (LCSCs) serve as the root of cancer occurrence, progression, recurrence, and drug resistance. Therefore, effective anti-cancer agents and molecular mechanisms which could specifically eliminate LCSCs are urgently needed for drug design. In this article, we discovered Olig2 was overexpressed in clinical lung cancer tissues and acted as a transcription factor to regulate cancer stemness by regulating CD133 gene transcription. The results suggested Olig2 could be a promising target in anti-LCSCs therapy and new drugs targeted Olig2 may exhibit excellent clinical results. Furthermore, we verified ACT001, a guaianolide sesquiterpene lactone in phase II clinical trial with excellent glioma remission, inhibited cancer stemness by directly binding to Olig2 protein, inducing Olig2 ubiquitination degradation and inhibiting CD133 gene transcription. All these results suggested that Olig2 could be an excellent druggable target in anti-LCSCs therapy and lay a foundation for the further application of ACT001 in the treatment of lung cancer in clinical.

Mesenchymal stem cells inhibit MRP-8/14 expression and neutrophil migration via TSG-6 in the treatment of lupus nephritis.

Abnormal infiltration and activation of neutrophils play a pathogenic role in the development of lupus nephritis (LN). Myeloid-related proteins (MRPs), MRP-8 and -14, also known as the damage-associated molecular patterns (DAMPs), are mainly secreted by activated neutrophils in systemic lupus erythematosus (SLE). Mesenchymal stem cells (MSCs) regulate a variety of immune cells to treat LN, but it is not clear whether MSCs can regulate neutrophils and the expression of MRP-8/14 in LN. Here, we demonstrated that neutrophil infiltration and MRP-8/14 expression were increased in the kidney of MRL/lpr mice and both decreased after MSCs transplantation. Further, the results showed that tumor necrosis factor- (TNF) stimulated gene-6 (TSG-6) in MSCs is necessary for MSCs to inhibit MRP-8/14 expression in neutrophils and neutrophil migration. In addition, small-molecule immunosuppressant had no significant effect on the expression of MRP-8/14 in neutrophils. Therefore, our results suggest that MSCs inhibited MRP-8/14 expression and neutrophil migration by secreting TSG-6 in the treatment of LN.

Genome-Wide Genetic Structure of Henan Indigenous Chicken Breeds.

There are five indigenous chicken breeds in Henan Province, China. These breeds have their own unique phenotypic characteristics in terms of morphology, behavior, skin and feather color, and productive performance, but their genetic basis is not well understood. Therefore, we analyzed the genetic structure, genomic diversity, and migration history of Henan indigenous chicken populations and the selection signals and genes responsible for Henan gamecock unique phenotypes using whole genome resequencing. The results indicate that Henan native chickens clustered most closely with the chicken populations in neighboring provinces. Compared to other breeds, Henan gamecock's inbreeding and selection intensity were more stringent. TreeMix analysis revealed the gene flow from southern chicken breeds into the Zhengyang sanhuang chicken and from the Xichuan black-bone chicken into the Gushi chicken. Selective sweep analysis identified several genes and biological processes/pathways that were related to body size, head control, muscle development, reproduction, and aggression control. Additionally, we confirmed the association between genotypes of SNPs in the strong selective gene LCORL and body size and muscle development in the Gushi-Anka F2 resource population. These findings made it easier to understand the traits of the germplasm and the potential for using the Henan indigenous chicken.

Portable Paper-Based Nucleic Acid Enrichment for Field Testing.

Point-of-care testing (POCT) can be the method of choice for detecting infectious pathogens; these pathogens are responsible for not only infectious diseases such as COVID-19, but also for certain types of cancers. For example, infections by human papillomavirus (HPV) or Helicobacter pylori (H. pylori) are the main cause of cervical and stomach cancers, respectively. COVID-19 and many cancers are treatable with early diagnoses using POCT. A variety of nucleic acid testing have been developed for use in resource-limited environments. However, questions like unintegrated nucleic acid extraction, open detection systems increase the risk of cross-contamination, and dependence on expensive equipment and alternating current (AC) power supply, significantly limit the application of POCT, especially for on-site testing. In this paper, a simple portable platform is reported capable of rapid sample-to-answer testing within 30 min based on recombinase polymerase amplification (RPA) at a lower temperature, to detect SARS-CoV-2 virus and H. pylori bacteria with a limit of detection as low as 4 × 102 copies mL-1 . The platform used a battery-powered portable reader for on-chip one-pot amplification and fluorescence detection, and can test for multiple (up to four) infectious pathogens simultaneously. This platform can provide an alternative method for fast and reliable on-site diagnostic testing.

Integrating metabolomics, bionics, and culturomics to study probiotics-driven drug metabolism.

Many drugs have been shown to be metabolized by the human gut microbiome, but probiotic-driven drug-metabolizing capacity is rarely explored. Here, we developed an integrated metabolomics, culturomics, and bionics framework for systematically studying probiotics-driven drug metabolism. We discovered that 75% (27/36 of the assayed drugs) were metabolized by five selected probiotics, and drugs containing nitro or azo groups were more readily metabolized. As proof-of-principle experiments, we showed that Lacticaseibacillus casei Zhang (LCZ) could metabolize racecadotril to its active products, S-acetylthiorphan and thiorphan, in monoculture, in a near-real simulated human digestion system, and in an ex vivo fecal co-culture system. However, a personalized effect was observed in the racecadotril-metabolizing activity of L. casei Zhang, depending on the individual's host gut microbiome composition. Based on data generated by our workflow, we proposed a possible mechanism of interactions among L. casei Zhang, racecadotril, and host gut microbiome, providing practical guidance for probiotic-drug co-treatment and novel insights into precision probiotics.

Associations Between Problematic Internet Use and Mental Health Outcomes of Students: A Meta-analytic Review.

The increasing prevalence of problematic internet use has heightened concerns about its adverse impact on internet users' mental health. Despite reviews investigating the associations between problematic internet use and mental health outcomes, there is a lack of understanding of various aspects of students' mental health. This study aimed to bridge this gap by providing a more comprehensive overall picture of this issue through a quantitative synthesis based on three-level random-effects meta-analytic models. In total, 223 studies with a cumulative total of 498,167 participants and 512 effect sizes were included in this synthesis. The results showed that problematic internet use was moderately and positively associated with depressive symptoms, anxiety, loneliness, and other mental health outcomes, and negatively related to subjective well-being. Moderator analyses revealed that several study features (i.e., school grade, region, measure of problematic internet use, publication year, and gender) could explain the variations in the findings across individual studies. These research results provide solid evidence for the link between problematic internet use and different mental health outcomes and have implications for future research and interventions on students' problematic internet use. Supplementary Information: The online version contains supplementary material available at 10.1007/s40894-022-00201-9.