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Infectious diseases, including COVID-19, are crucial public health issues and may lead to considerable fear among the general public and stigmatization of, and discrimination against, specific populations. This meta-analysis aimed to estimate the pooled prevalence of stigma in infectious disease epidemics. We systematically searched PubMed, PsycINFO, Embase, MEDLINE, Web of Science, and Cochrane databases since inception to June 08, 2021, and reported the prevalence of stigma towards people with infectious diseases including SARS, H1N1, MERS, Zika, Ebola, and COVID-19. A total of 50 eligible articles were included that contributed 51 estimates of prevalence in 92722 participants. The overall pooled prevalence of stigma across all populations was 34% [95% CI: 28-40%], including enacted stigma (36% [95% CI: 28-44%]) and perceived stigma (31% [95% CI: 22-40%]). The prevalence of stigma in patients, community population, and health care workers, was 38% [95% CI: 12- 65%], 36% [95% CI: 28-45%], and 30% [95% CI: 20-40%], respectively. The prevalence of stigma in participants from low- and middle-income countries was 37% [95% CI: 29-45%], which is higher than that from high-income countries (27% [95% CI: 18-36%]) though this difference was not statistically significant. A similar trend of prevalence of stigma was also observed in individuals with lower education (47% [95% CI: 23-71%]) compared to higher education level (33% [95% CI: 23-4%]). These findings indicate that stigma is a significant public health concern, and effective and comprehensive interventions are needed to counteract the damaging effects of the infodemics during infectious disease epidemics, including COVID-19, and reduce infectious disease-related stigma.

The complexities in the integration of carrier materials and functional materials make it challenging to promote nanoprobes for clinical translation. Carrier-free self-assembled nanosystems have been proposed as a promising strategy for synergetic anticancer therapy. In this study, carbon dots, copper ions, and doxorubicin (DOX) were assembled into nanoparticles (CCD) to achieve augmented chemodynamic therapy (CDT). The assembled CCD NPs were biodegradable and responsive to GSH and acidic pH in the tumor microenvironment resulting in the release of the DOX, Cu2+, and carbon dots. The intracellular H2O2 level was elevated by DOX activated the nicotinamide adenine dinucleotide phosphate oxidases. The GSH was depleted by Cu2+, and the generated Cu+ as well as peroxidase-like carbon dots could catalyze the intracellular H2O2 to produce cytotoxic ·OH to achieve enhanced CDT effects. Chemotherapy effects were enhanced through increasing drug sensitivity and inhibiting drug efflux after the intracellular redox balance was broken by CCD NPs. The in vivo experiments revealed that CCD NPs possessed the excellent biocompatibility and synergistic anti-tumor ability, which could completely inhibit the growth of 4T1 tumors. As a novel carrier-free nanoprobes, CCD NPs responsiveness to the tumor microenvironment may have great potential in cancer chemodynamic therapy with high specificity.

Graphical abstract, Highlights • Vitamin C reduces signs of PFOA-induced liver damage. • Protective role of vitamin C is associated with signaling networks control, suppressing linoleic acid metabolism. • Vitamin C reduces thiodiglycolic acid, and elevating glutathione in the liver. • The findings demonstrate the utility of vitamin C for preventing PFOA-induced hepatotoxicity., Introduction Perfluorooctanoic acid (PFOA) is a compound used as an industrial surfactant in chemical processes worldwide. Population and cross-sectional studies have demonstrated positive correlations between PFOA levels and human health problems. Objectives Many studies have focused on the hepatotoxicity and liver problems caused by PFOA, with little attention to remediation of these problems. As an antioxidant, vitamin C is frequently utilized as a supplement for hepatic detoxification. Methods In this study, we use a mouse model to study the possible role of vitamin C in reducing PFOA-induced liver damage. Based on comparative transcriptomic and metabolomic analysis, we elucidate the mechanisms underlying the protective effect of vitamin C. Results Our results show that vitamin C supplementation reduces signs of PFOA-induced liver damage including total cholesterol and triglyceride levels increase, liver damage markers aspartate, transaminase, and alanine aminotransferase elevation, and liver enlargement. Further, we show that the protective role of vitamin C is associated with signaling networks control, suppressing linoleic acid metabolism, reducing thiodiglycolic acid, and elevating glutathione in the liver. Conclusion The findings in this study demonstrate, for the first time, the utility of vitamin C for preventing PFOA-induced hepatotoxicity.

Bone loss remains a major health concern for astronauts during space flight. Increased osteoclast activity is one of the main causes of bone loss in astronauts subjected to microgravity conditions. However, the underlying molecular mechanisms remain unclear. Microtubule actin crosslinking factor 1 (MACF1) has been implicated in the regulation of cytoskeletal distribution, cell migration, and cell differentiation. Our previous studies have shown that MACF1 promotes the differentiation of pre-osteoclasts. However, whether MACF1 regulates the migration and cytoskeletal arrangement of pre-osteoclasts under microgravity conditions has not yet been elucidated. In this study, we used a hind-limb unloading (HLU) mouse model and a random positioning machine (RPM) to simulate the effects of microgravity on pre-osteoclasts. In the HLU mouse model, the expression of MACF1 was upregulated in primary pre-osteoclasts of mice, accompanied by enhanced migration in vivo. Moreover, simulated microgravity using the RPM also promoted MACF1 expression and migration of pre-osteoclasts in vitro. Additionally, knockdown of MACF1 disrupted cytoskeletal arrangement (F-actin and microtubules) and further inhibited the migration of pre-osteoclasts via the RhoA/ROCK1 signaling pathway. We further demonstrated that knockdown of MACF1 disrupted the enhanced migration and cytoskeleton arrangement of pre-osteoclasts induced by simulated microgravity. These data demonstrate that MACF1 positively regulates the migration and cytoskeletal organization of pre-osteoclasts under simulated microgravity, suggesting that MACF1 may be a therapeutic target for the treatment of bone loss induced by microgravity.

In the past 37 years, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has undergone various major transmission routes in China, with the world most complex co-circulating HIV-1 subtypes, even the prevalence is still low. In response to the first epidemic outbreak of HIV in injecting drug users and the second one by illegal commercial blood collection, China issued the Anti-Drug Law and launched the Blood Donation Act and nationwide nucleic acid testing, which has avoided 98,232 to 211,200 estimated infections and almost ended the blood product-related infection. China has been providing free antiretroviral therapy (ART) since 2003, which covered >80% of the identified patients and achieved a viral suppression rate of 91%. To bend the curve of increasing the disease burden of HIV and finally end the epidemic, China should consider constraining HIV spread through sexual transmission, narrowing the gaps in identifying HIV cases, and the long-term effectiveness and safety of ART in the future.

Background. Diabetic retinopathy (DR) is a leading cause of blindness in working-age populations. Proper in vitro DR models are crucial for exploring pathophysiology and identifying novel therapeutic targets. This study establishes a rational in vitro diabetic retinal neuronal-endothelial dysfunction model and a comprehensive downstream validation system. Methods. Human retinal vascular endothelial cells (HRMECs) and retinal ganglion cells (RGCs) were treated with different glucose concentrations with mannitol as matched osmotic controls. Cell proliferation and viability were evaluated by the Cell Counting Kit-8. Cell migration was measured using a transwell migration assay. Cell sprouting was assessed by a tube formation assay. The VEGF expression was assessed by ELISA. RGCs were labeled by neurons and RGC markers TUJ1 and BRN3A for quantitative and morphological analysis. Apoptosis was detected using PI/Hoechst staining and TUNEL assay and quantified by ImageJ. Results. Cell proliferation and migration in HRMECs were significantly higher in the 25 mM glucose-treated group ( p < 0.001 ) but lower in the 50 mM and 100 mM groups ( p < 0.001 ). The permeability and the apoptotic index in HRMECs were statistically higher in the 25 mM, 50 mM, and 100 mM groups ( p < 0.05 ). The tube formation assay found that all the parameters were significantly higher in the 25 mM and 50 mM groups ( p < 0.001 ) concomitant with the elevated VEGFA expression in HRMECs ( p = 0.016 ). Cell viability was significantly lower in the 50 mM, 100 mM, and 150 mM groups in RGCs ( p 50 mM = 0.013 , p 100 mM = 0.019 , and p 150 mM = 0.002 ). Apoptosis was significantly elevated, but the proportion of RGCs with neurite extension was significantly lower in the 50 mM, 100 mM, and 150 mM groups ( p 50 mM < 0.001 , p 100 m M < 0.001 , and p 150 mM < 0.001 ). Conclusions. We have optimized glucose concentrations to model diabetic retinal endothelial (25-50 mM) or neuronal (50-100 mM) dysfunction in vitro, which have a wide range of downstream applications.

Long noncoding RNAs (LncRNAs) play a pivotal role in gastric tumorigenesis, while exosomes facilitate the LncRNAs transferring to recipient cells. However, the roles of exosomal LncRNAs in gastric premalignant lesions (GPL) remain unclear. We analyzed the expression of LncHOXA10 and its role in GPL progression. The protective effect of all-trans retinoic acid (ATRA) on GPL was explored in vitro and in vivo. Here, we found that LncHOXA10 expression was obviously increased in serum exosomes and gastric tissues from individuals with GPL, and exosomal LncHOXA10 from patients with GPL markedly promoted the malignant progression of human gastric epithelial cell line GES-1. Furthermore, RNA-pulldown assay revealed that LncHOXA10 mainly interacted with pyruvate carboxylase (PC), an essential enzyme in various cellular metabolic pathways. In gastric tissues from patients with GPL and gastric cancer (GC), PC was also upregulated and positively correlated with LncHOXA10 expression, which predicted a poor prognosis as well. Moreover, PC silencing attenuated the malignant effects of exosomal LncHOXA10 on GES-1 cells. ATRA also ameliorated the deterioration of GPL and prevented the malignant progression of GPL by reducing exosomal LncHOXA10 and PC expression. Collectively, the LncHOXA10–PC axis participated in the early stage of GC tumorigenesis, and ATRA might be useful to prevent GPL from developing into GC because it targets this axis.

Genome-wide association studies (GWAS) have identified a large number of schizophrenia risk variants, and most of them are mapped to noncoding regions. By leveraging multiple joint-tissue gene expression data and GWAS data, we herein performed a transcriptome-wide association study (TWAS) and Mendelian randomization (MR) analysis and identified 144 genes whose mRNA levels were related to genetic risk of schizophrenia. Most of these genes exhibited diametrically opposite trends of expression in prenatal and postnatal brain tissues, despite that their expression levels in dorsolateral prefrontal cortex (DLPFC) tissues did not significantly differ between schizophrenics and healthy controls. We then found significant enrichment of these genes in dopamine-related pathways that were repeatedly implicated in schizophrenia pathogenesis and in the action of antipsychotic drugs. Gene expression analysis using single cell RNA-sequencing (scRNA-seq) data of mid-gestation fetal brains further revealed enrichment of these genes in glutamatergic excitatory neurons and cycling progenitors. These lines of evidence, in consistency with previous findings, confirmed the polygenic nature of schizophrenia and highlighted involvement of early neurodevelopment aberrations in this disorder. Further investigations using advanced algorithms in both bulk brain tissues and in single cells and at different developmental stages are necessary to characterize transcriptomic features of schizophrenia pathogenesis along brain development.

Background The present study aims to investigate the preliminary mechanism underlying the peritoneal metastasis of gastric cancer cells. Methods Exosomes from GC9811 cells (Con-Exo) and from GC9811-P cells (PM-Exo) were extracted by ultracentrifugation, which were identified with transmission electron microscopy (TEM) and nanoparticle trafficking analysis, as well as the expression of CD9, CD63, and CD81 detected by Western blot assay. α-SMA expression was determined by immunofluorescence assay and Western blot assay. The levels of Snail1, E-cadherin, and Actin-related protein 3 (ACTR3) were evaluated by Western blot assay. MiRNA array was performed on exosomes to screen the differentially expressed miRNAs. The expressions of miRNAs, SMAD2, CDK4, and ACTR3 were determined by QRT-PCR. The delivery of miR-486-5p was confirmed by laser confocal detection. Results Firstly, TEM, nanoparticle trafficking analysis, and Western blot assays were used to confirm the successful extraction of Con-Exo and PM-Exo. The incubation of Con-Exo and PM-Exo could decrease E-cadherin expression and increase of α-SMA respectively in HMrSV5 cells, with the increased proportion of fusiform cells. More significant changes were observed in PM-Exo-treated HMrSV5 cells. Secondary, compared to Con-Exo, miR-486-5p and miR-132-3p were found downregulated, and miR-132-5p was found upregulated in PM-Exo. The transfection of miR-486-5p and miR-132-3p was observed to suppress EMT, and the transfection of miR-132-3p was observed to induce EMT. Laser confocal detection confirmed the delivery of miR-486-5p from gastric cancer cells to HMrSV5 cells through exosomes. Lastly, the expression of Mothers against decapentaplegic homolog 2 (SMAD2), cyclin-dependent kinase 4 (CDK4), and ACTR3 was found to be downregulated via miR-486-5p. Conclusion Decreased delivery of miR-486-5p via exosomes might be responsible for the peritoneal metastasis of gastric cancer cells by promoting epithelial-mesenchymal transition progress.

Esophageal squamous cell carcinoma (ESCC) is a highly malignant gastrointestinal cancer with a high recurrence rate and poor prognosis. Although N6-methyladenosine (m6A), the most abundant epitranscriptomic modification of mRNAs, has been implicated in several cancers, little is known about its participation in ESCC progression. We found reduced expression of ALKBH5, an m6A demethylase, in ESCC tissue specimens with a more pronounced effect in T3-T4, N1-N3, clinical stages III-IV, and histological grade III tumors, suggesting its involvement in advanced stages of ESCC. Exogenous expression of ALKBH5 inhibited the in vitro proliferation of ESCC cells, whereas depletion of endogenous ALKBH5 markedly enhanced ESCC cell proliferation in vitro. This suggests ALKBH5 exerts anti-proliferative effects on ESCC growth. Furthermore, ALKBH5 overexpression suppressed tumor growth of Eca-109 cells in nude mice; conversely, depletion of endogenous ALKBH5 accelerated tumor growth of TE-13 cells in vivo. The growth-inhibitory effects of ALKBH5 overexpression are partly attributed to a G1-phase arrest. In addition, ALKBH5 overexpression reduced the in vitro migration and invasion of ESCC cells. Altogether, our findings demonstrate that the loss of ALKBH5 expression contributes to ESCC malignancy.

In this study, the characteristic patterns of ferroptosis in clear cell renal cell carcinoma (ccRCC) were systematically investigated with the interactions between ferroptosis and the tumor microenvironment (TME). On the mRNA expression profiles of 57 ferroptosis-related genes (FRGs), three ferroptosis patterns were constructed, with distinct prognosis and immune cell infiltrations (especially T cells and dendritic cells). The high ferroptosis scores were characterized by poorer prognosis, increased T cell infiltration, higher immune and stromal scores, elevated tumor mutation burden, and enhanced response to anti-CTLA4 immunotherapy. Meanwhile, the low ferroptosis scores were distinctly associated with enhanced tumor purity and amino acid and fatty acid metabolism pathways. Following validation, the ferroptosis score was an independent and effective prognostic factor. Collectively, ferroptosis could be involved in the diverse and complex TME. Evaluation of the ferroptosis patterns may heighten the comprehension about immune infiltrations in the TME, assisting oncologists to generate individualized immunotherapeutic strategies., Graphical abstract, Characteristics of ferroptosis in clear cell renal cell carcinoma (ccRCC) were systematically investigated. Ferroptosis scores associated with increased T cell infiltration, higher immune and stromal scores, elevated tumor mutation burden, and enhanced anti-CTLA4 response involved in tumor microenvironment therefore are likely to affect the immunotherapy cohorts (GEO: GSE78220 and IMvigor210) in anti-PD-1 treatment.

The majority of smokers relapse even after successfully quitting because of the craving to smoking after unexpectedly re-exposed to smoking-related cues. This conditioned craving is mediated by reward memories that are frequently experienced and stubbornly resistant to treatment. Reconsolidation theory posits that well-consolidated memories are destabilized after retrieval, and this process renders memories labile and vulnerable to amnestic intervention. This study tests the retrieval reconsolidation procedure to decrease nicotine craving among people who smoke. In this study, 52 male smokers received a single dose of propranolol (n = 27) or placebo (n = 25) before the reactivation of nicotine-associated memories to impair the reconsolidation process. Craving for smoking and neural activity in response to smoking-related cues served as primary outcomes. Functional magnetic resonance imaging was performed during the memory reconsolidation process. The disruption of reconsolidation by propranolol decreased craving for smoking. Reactivity of the postcentral gyrus in response to smoking-related cues also decreased in the propranolol group after the reconsolidation manipulation. Functional connectivity between the hippocampus and striatum was higher during memory reconsolidation in the propranolol group. Furthermore, the increase in coupling between the hippocampus and striatum positively correlated with the decrease in craving after the reconsolidation manipulation in the propranolol group. Propranolol administration before memory reactivation disrupted the reconsolidation of smoking-related memories in smokers by mediating brain regions that are involved in memory and reward processing. These findings demonstrate the noradrenergic regulation of memory reconsolidation in humans and suggest that adjunct propranolol administration can facilitate the treatment of nicotine dependence. The present study was pre-registered at ClinicalTrials.gov (registration no. ChiCTR1900024412).

Artesunate is a widely used derivative of artemisinin for malaria. Recent researches have shown that artesunate has a significant anti‐inflammatory effect on many diseases. However, its effect on acute kidney injury with a significant inflammatory response is not clear. In this study, we established a cisplatin‐induced AKI mouse model and a co‐culture system of BMDM and tubular epithelial cells (mTEC) to verify the renoprotective and anti‐inflammatory effects of artesunate on AKI, and explored the underlying mechanism. We found that artesunate strongly down‐regulated the serum creatinine and BUN levels in AKI mice, reduced the necroptosis of tubular cells and down‐regulated the expression of the tubular injury molecule Tim‐1. On the other hand, artesunate strongly inhibited the mRNA expression of inflammatory cytokines (IL‐1β, IL‐6 and TNF‐α), protein levels of inflammatory signals (iNOS and NF‐κB) and necroptosis signals (RIPK1, RIPK3 and MLKL) in kidney of AKI mouse. Notably, the co‐culture system proved that Mincle in macrophage can aggravate the inflammation and necroptosis of mTEC induced by LPS, and artesunate suppressed the expression of Mincle in macrophage of kidney in AKI mouse. Overexpression of Mincle in BMDM restored the damage and necroptosis inhibited by artesunate in mTEC, indicating Mincle in macrophage is the target of artesunate to protect tubule cells in AKI. Our findings demonstrated that artesunate can significantly improve renal function in AKI, which may be related to the inhibition of Mincle‐mediated macrophage inflammation, thereby reducing the damage and necroptosis to tubular cells that provide new option for the treatment of AKI.

The use of lytic bacteriophages for treating harmful bacteria (phage therapy) is faced with the challenge of bacterial resistance evolution. Phage strains with certain traits, for example, rapid growth and relatively broad infectivity ranges, may enjoy an advantage in slowing bacterial resistance evolution. Here, we show the possibility for laboratory selection programs (“evolutionary training”) to yield phage genotypes with both high growth rate and broad infectivity, traits between which a trade‐off has been assumed. We worked with a lytic phage that infects the bacterium Pseudomonas fluorescens and adopted three types of training strategies: evolution on susceptible bacteria, coevolution with bacteria, and rotation between evolution and coevolution phases. Overall, there was a trade‐off between growth rate and infectivity range in the evolved phage isolates, including those from the rotation training programs. A small number of phages had both high growth rate and broad infectivity, and those trade‐off‐overcoming phages could slow or even completely prevent resistance evolution in initially susceptible bacterial populations. Our findings show the promise of well‐designed evolutionary training programs, in particular an evolution/coevolution rotation selection regime, for obtaining therapeutically useful phage materials.

Introduction: Autoimmune hemolytic anemia is a potentially lethal disease characterized by autoimmune hemolysis. Although human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been reported as a promising therapy, there is limited evidence regarding warm autoimmune hemolytic anemia (wAIHA) patients. This study aimed to investigate the potential therapeutic effects of hUC-MSCs via immune regulation in wAIHA patients. Methods: Peripheral blood mononuclear cells (PBMCs) from 10 wAIHA patients and 8 healthy controls were isolated from peripheral blood and cultured for 3 days with or without the presence of hUC-MSCs; PBMCs were co-cultured with hUC-MSCs using Transwell assays. The supernatant cytokine levels were measured after culture through AimPlex Multiple Immunoassays for Flow, including IL-2, IL-4, IL-10, IFN-γ, TNF-α, and IL-17A. The percentages of regulatory T cells, regulatory B cells, and Th1/Th2 in PBMCs were also assessed before and after culturing. Results: In the wAIHA group, hUC-MSCs could upregulate the Treg and Breg proportions after culturing for 3 days, and the Treg and Breg percentages increased after co-culturing with hUC-MSCs in the wAIHA group compared with PBMC cultured alone for 3 days (8.29 ± 8.59 vs. 6.82 ± 1.32, 3.82 ± 1.87 vs. 1.75 ± 1.20, respectively). Compared with the PBMC wAIHA group, the levels of TNF-α (2.13 ± 2.07 vs. 16.20 ± 21.13 pg/mL, p = 0.019) and IL-10 (10.51 ± 18.42 vs. 37.78 ± 44.20 pg/mL, p = 0.012) were significantly elevated in the PBMC + hUC-MSCs wAIHA group. Conclusion: The hUC-MSCs contributed to the increasing proportion of regulatory cell populations in PBMCs of wAIHA patients, thereby potentially regulating autoimmune response; thus, hUC-MSCs may be a promising approach for wAIHA treatment.

AIM: To update and investigate the clinical outcomes and complications between femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification cataract surgery (CPCS). METHODS: A Meta-analysis was performed using databases, including Pubmed, Embase, and the Cochrane library. At least one of the clinical outcomes and/or complications data in each included randomized controlled trials (RCT) was reported. The quality of the RCT was assessed with the Cochrane risk assessments tool. RESULTS: Overall, 25 RCTs including 3781 eyes were included. No statistically significant difference detected between FLACS and CPCS in terms of corrected distant visual acuity (CDVA), uncorrected distant visual acuity (UDVA), and central corneal thickness (CCT) at the long-term follow up, although FLACS showed better CDVA at 1wk postoperatively, and less increase in CCT at 1d and 1wk. FLACS had better postoperative endothelial cell count (ECC) at 1 and 4-6wk, while there was no significantly difference between FLACS and CPCS at 1d, 3 and 6mo [weighted mean difference (WMD): 51.54, 95% confidence interval (CI): -5.46 to 108.54, P=0.08; WMD: 48.52, 95%CI: -17.54 to 114.58, P=0.15; WMD: 12.17, 95%CI: -48.61 to 72.94, P=0.69, respectively]. Postoperative endothelial cell loss (ECL) of the FLACS was significantly lower than that of the CPCS at 1, 4-6wk, and 3mo (P=0.02, 0.008, 0.03, respectively). However, there was no significant difference between two groups at 6mo (WMD: -30.36, 95%CI: -78.84 to 18.12, P=0.22). No significant difference was discovered with respect to the macular edema [odds ratio (OR): 0.93, 95%CI: 0.42 to 2.05, P=0.85], capsular complication excluding posterior capsular tears (OR: 0.79, 95%CI: 0.42 to 1.50, P=0.47) and intraocular pressure change (OR: 0.82, 95%CI: 0.39 to 1.72, P=0.60). However, posterior capsular tears were more common in CPCS group (OR: 0.12, 95%CI: 0.01 to 0.98, P=0.05). The effective phacoemulsification times were significantly lower in the FLACS group compared to the CPCS group (WMD: -0.78, 95%CI: -1.23 to -0.34, P=0.0006). CONCLUSION: No statistically significant difference is discovered between FLACS and CPCS in clinical outcomes at the long-term follow up. However, higher rate of posterior capsular tears is detected in patients receiving CPCS.

Osteosarcoma is a quickly developing, malignant cancer of the bone, which is associated with a bad prognosis. In osteosarcoma, hypoxia promotes the malignant phenotype, which results in a cascade of immunosuppressive processes, poor prognosis, and a high risk of metastasis. Nonetheless, additional methodologies for the study of hyperoxia in the tumor microenvironment also need more analysis. We obtained 88 children patients with osteosarcoma from the Therapeutically Applicable Research to Generate Effective Treatment (TARGET) database and 53 children patients with RNA sequence and clinicopathological data from the Gene Expression Omnibus (GEO). We developed a four-gene signature related to hypoxia to reflect the immune microenvironment in osteosarcoma that predicts survival. A high-risk score indicated a poor prognosis and immunosuppressive microenvironment. The presence of the four-gene signature related to hypoxia was correlated with clinical and molecular features and was an important prognostic predictor for pediatric osteosarcoma patients. In summary, we established and validated a four-gene signature related to hypoxia to forecast recovery and presented an independent prognostic predictor representing overall immune response strength within the osteosarcoma microenvironment.

The Intensive Supervision Mechanism (hereafter referred to as ISM) is one of the most important institutional management innovations for air pollution control in China, but there is currently no consensus on the effects of the ISM on air quality improvement. In this study, a reliable quantitative model based on the Difference-in-Differences (DID) analysis was designed to evaluate the impacts of ISM on air quality (as indicated by good air quality days (hereafter referred to as GAD) and the concentrations of six major air pollutants (i.e. PM

BACKGROUND Endometrial lesions include endometrial cancer and inferior fibroids. Among them, endometrial cancer as a malignant tumor seriously endangers the life and health of patients. Ultrasonography is an important means of diagnosing female reproductive system diseases, and it is of critical value for the early diagnosis of endometrial cancer. However, different ultrasound inspection programs have achieved different results. It is of great significance to choose a suitable inspection program. AIM To explore the diagnostic efficacy of different ultrasonic examination methods in clinical endometrial lesions. METHODS The 140 patients with endometrial lesions who were treated in our hospital from April 2018 to October 2019 were used as the research subjects. All patients underwent transvaginal color ultrasound and transabdominal color ultrasound. We compared the diagnostic coincidence and image display effects of the two different examination methods, and the endometrial thickness, blood flow, uterine effusion and resistance index of different diseases were observed by transvaginal color ultrasound. RESULTS The diagnostic coincidence rate of all types of diseases of transvaginal color ultrasound was significantly higher than that of transabdominal color ultrasound (P = 0.001, 0.005, 0.001 and 0.001). In addition, the excellent and good rate of image display of transvaginal color ultrasound was higher than that of transabdominal color ultrasound (P = 0.001). There were significant differences in endometrial thickness in patients with different types of endometrial lesions through the transvaginal color examination (P = 0.001). The incidence rate of uterine effusion in patients with endometrial carcinoma was significantly higher than that in patients with other types of endometrial lesions (P = 0.001), and the rate of the blood flow was the highest (P = 0.001). The comparison of blood flow resistance index indicated that the blood flow resistance index in endometrial cancer patients was the lowest, which shows that the difference was statistically significant (P = 0.001). CONCLUSION The overall diagnostic efficacy of transvaginal color ultrasound in the clinical diagnosis of endometrial lesions is better than that of transabdominal color ultrasound, which held higher diagnostic coincidence rate and image display effect. There were significant differences in the thickness of the endometrium and the blood flow in different types of lesions.

Backgrounds Myopia has become a global public health problem. Children with early onset of myopia are at particular risk of complications associated with myopia. Younger children and children with greater initial myopic refractive errors are at a greater risk of myopia progression. Therefore, it is essential to identify subjects at high risk of developing myopia to facilitate myopia prevention in the early stage, especially during the preschool period. The purpose of this study was to determine whether premyopia and myopia in preschool children can be predicted by easily obtainable parameters. Methods Data was collected in a population-based cohort. Comprehensive examinations included height, weight, refraction, axial length (AL), and corneal radius of curvature (CR), with a follow-up of 2 years. Parental myopia history was obtained from a questionnaire. Myopia was defined as spherical equivalent (SE) ≤ − 0.50 D. Premyopia was defined as − 0.50 D Results A total of 830 children (433 boys and 397 girls) were included (40.83 ± 3.43 months old at baseline). A significantly negative relationship was observed in the multivariate analysis between baseline AL, AL/CR, two myopic parents, and the future SE after adjusting for age and gender (coefficient = − 0.291, coefficient = − 5.791, coefficient = − 0.273, respectively, both p p p = 0.001) were associated with a higher risk of future onset of premyopia. From the nomogram, AL/CR was found to have the most enormous effect on survival. Different baseline AL and AL/CR values (both Log Rank p Conclusions AL and AL/CR could be used as obtainable indicators for identifying subjects at high risk of developing premyopia and myopia in young preschool children.

A series of 1,3-diphenylurea quinoxaline derivatives were synthesized and characterized by 1H, 13C NMR, and HR-ESI-MS analyses. In vitro cytotoxicity of the synthesized compounds was evaluated by MTT assay against MGC-803, H460, T-24, HeLa, HepG2, and SMMC-7721 human cancer cell lines. The results showed that most of the compounds exhibited effective cytotoxicity to the tested cancer cell lines. The mechanism of action of the two best active quinoxaline derivatives, compounds 2d and 2g was also investigated. They may be potent anticancer agents.

Summary The purpose of this study is to conduct a meta-analysis to evaluate the efficacy of screening and decolonization protocol for Staphylococcus aureus (SA) in total joint arthroplasty (TJA). We systematically searched the electronic databases of PubMed, Embase and Cochrane databases for relevant literatures from January 2000 to September 2020. The outcomes were colonization rate, total-surgical site infection (SSI) rate, SA-SSI rate and methicillin-resistant Staphylococcus aureus (MRSA)-SSI rate. All calculations and statistical tests were performed using Stata 14.0 software. A total of 12 studies were eligible in this study. Compared with control group, the screening and decolonization group had lower risks in total-SSI (risk ratio (RR) = 0.52; 95% confidence interval (CI): 0.40–0.67), SA-SSI (RR = 0.48; 95% CI: 0.32–0.72) and MRSA-SSI (RR = 0.45; 95% CI: 0.21–0.96). The nasal SA colonization was found to be associated with higher accidences of SSI involving total-SSI (RR = 1.49; 95% CI: 1.02–2.18), SA-SSI (RR = 2.51; 95% CI: 0.97–6.50) and MRSA-SSI (RR = 7.84; 95% CI: 1.67–36.79). The colonization rate of SA was significantly reduced after decolonization. No difference was observed between universal decolonization and screening-based decolonization. In conclusion, colonization of SA is associated with increased risk of SSI in TJA. Screening and decolonization protocol are proven to be effective to reduce colonization of SA and present protective effects against SSI in TJA. Moreover, universal decolonization protocol is non-inferior to screening-based decolonization.

In the past two decades, significant progress has been made in the past two decades towards the understanding of the basic mechanisms underlying cancer growth and angiogenesis. In this context, receptor tyrosine kinases (RTKs) play a pivotal role in cell proliferation, differentiation, growth, motility, invasion, and angiogenesis, all of which contribute to tumor growth and progression. Mutations in RTKs lead to abnormal signal transductions in several pathways such as Ras-Raf, MEK-MAPK, PI3K-AKT and mTOR pathways, affecting a wide range of biological functions including cell proliferation, survival, migration and vascular permeability. Increasing evidence demonstrates that multiple kinases are involved in angiogenesis including RTKs such as vascular endothelial growth factor, platelet derived growth factor, epidermal growth factor, insulin-like growth factor-1, macrophage colony-stimulating factor, nerve growth factor, fibroblast growth factor, Hepatocyte Growth factor, Tie 1 & 2, Tek, Flt-3, Flt-4 and Eph receptors. Overactivation of RTKs and its downstream regulation is implicated in tumor initiation and angiogenesis, representing one of the hallmarks of cancer. This review discusses the role of RTKs, PI3K, and mTOR, their involvement, and their implication in pro-oncogenic cellular processes and angiogenesis with effective approaches and newly approved drugs to inhibit their unrestrained action.

Background: Despite the better prognosis given by surgical resection and chemotherapy in low-grade glioma (LGG), progressive transformation is still a huge concern. In this case, the S100A gene family, being capable of regulating inflammatory responses, can promote tumor development. Methods: The analysis was carried out via ONCOMINE, GEPIA, cBioPortal, String, GeneMANIA, WebGestalt, LinkedOmics, TIMER, CGGA, R 4.0.2 and immunohistochemistry. Results: S100A2, S100A6, S100A10, S100A11, and S100A16 were up-regulated and S100A1 and S100A13 were down-regulated in LGG compared to normal tissues. S100A3, S100A4, S100A8, and S100A9 expression was up-regulated during the progression of glioma grade. In addition, genetic variation of the S100A family was high in LGG, and the S100A family genes mostly function through IL-17 signaling pathway, S100 binding protein, and inflammatory responses. The TIMER database also revealed a relationship between gene expression and immune cell infiltration. High expression of S100A2, S100A3, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, S100A13, and S100A16 was significantly associated with poor prognosis in LGG patients. S100A family genes S100A2, S100A3, S100A6, S100A10, and S100A11 may be prognosis-related genes in LGG, and were significantly associated with IDH mutation and 1p19q codeletion. The immunohistochemical staining results also confirmed that S100A2, S100A3, S100A6, S100A10, and S100A11 expression was upregulated in LGG. Conclusion: The S100A family plays a vital role in LGG pathogenesis, presumably facilitating LGG progression via modulating inflammatory state and immune cell infiltration.

Background Tau pathology is a hallmark of Alzheimer’s disease (AD) and other tauopathies. During disease progression, abnormally phosphorylated forms of tau aggregate and accumulate into neurofibrillary tangles, leading to synapse loss, neuroinflammation, and neurodegeneration. Thus, targeting of tau pathology is expected to be a promising strategy for AD treatment. Methods The effect of rutin on tau aggregation was detected by thioflavin T fluorescence and transmission electron microscope imaging. The effect of rutin on tau oligomer-induced cytotoxicity was assessed by MTT assay. The effect of rutin on tau oligomer-mediated the production of IL-1β and TNF-α in vitro was measured by ELISA. The uptake of extracellular tau by microglia was determined by immunocytochemistry. Six-month-old male Tau-P301S mice were treated with rutin or vehicle by oral administration daily for 30 days. The cognitive performance was determined using the Morris water maze test, Y-maze test, and novel object recognition test. The levels of pathological tau, gliosis, NF-kB activation, proinflammatory cytokines such as IL-1β and TNF-α, and synaptic proteins including synaptophysin and PSD95 in the brains of the mice were evaluated by immunolabeling, immunoblotting, or ELISA. Results We showed that rutin, a natural flavonoid glycoside, inhibited tau aggregation and tau oligomer-induced cytotoxicity, lowered the production of proinflammatory cytokines, protected neuronal morphology from toxic tau oligomers, and promoted microglial uptake of extracellular tau oligomers in vitro. When applied to Tau-P301S mouse model of tauopathy, rutin reduced pathological tau levels, regulated tau hyperphosphorylation by increasing PP2A level, suppressed gliosis and neuroinflammation by downregulating NF-kB pathway, prevented microglial synapse engulfment, and rescued synapse loss in mouse brains, resulting in a significant improvement of cognition. Conclusion In combination with the previously reported therapeutic effects of rutin on Aβ pathology, rutin is a promising drug candidate for AD treatment based its combinatorial targeting of tau and Aβ.