Association between ambient temperatures and injuries: a time series analysis using emergency ambulance dispatches in Chongqing, China.

BACKGROUND: Global warming and increasing extreme weather have become a severe problem in recent years, posing a significant threat to human health worldwide. Research exploring the link between injury as one of the leading causes of death globally and ambient temperature was lacking. Based on the hourly injury emergency ambulance dispatch (IEAD) records from 2019-2021 in the main urban area of Chongqing, this study explored the role of temperature extremes on the pathogenesis of injury by different mechanisms and identified sensitive populations for different mechanisms of injury. METHODS: In this study, we collected hourly injury emergency ambulance dispatch (IEAD) records from Chongqing Emergency Dispatch Center in the main urban area of Chongqing from 2019 to 2021, and used a distributed lagged nonlinear model (DLNM) with quasi-Poisson distribution to evaluate the association between ambient temperature and IEADs. And the stratified analysis was performed by gender, age and different injury mechanisms to identify susceptible groups. Finally, the attributable burden of ambient extreme temperatures was also investigated. RESULTS: The risk for total IEADs increased significantly at high temperature (32 °C) compared with optimal temperature (9 °C) (CRR: 1.210; 95%CI[1.127,1.300]). The risks of traffic accident injury (CRR: 1.346; 95%CI[1.167,1.552]), beating injury (CRR: 1.508; 95%CI[1.165,1.952]), fall-height injury (CRR: 1.871; 95%CI[1.196-2.926]) and injury of sharp penetration (CRR: 2.112; 95%CI[1.388-3.213]) were significantly increased. At low temperature (7 °C), the risk of fall injury (CRR: 1.220; 95% CI [1.063,1.400]) increased significantly. Lag for 24 hours at extreme low temperature (5 °C), the risk of 18-45 years (RR: 1.016; 95%CI[1.009,1.024]) and over 60 years of age (RR: 1.019; 95%CI[1.011,1.025]) increased significantly. The effect of 0 h delay in extreme high temperature (36 °C) on males aged 18-45 years (RR: 1.115; 95%CI[1.071,1.162]) and 46-59 years (RR: 1.069; 95%CI[1.023,1.115]) had significant impact on injury risk. CONCLUSIONS: This study showed that ambient temperature was significantly related to the risk of injury, and different mechanisms of injury were affected differently by extreme temperature. The increasing risk of traffic accident injury, beating injury, fall-height injury and sharp penetrating injury was associated with extreme heat, while fall injury was associated with extreme cold. The risk of injury in high temperature environment was mainly concentrated in males and young adults. The results of this study can help to identify the sensitive population with different injury mechanisms in extreme temperature environment, and provide reference for public health emergency departments to respond to relevant strategies in extreme temperature environment to minimize the potential risk to the public.

Application of ultrasound markers measured at different time points of COH cycle in the prediction of ovarian response for individualised ovulation induction.

The purpose of this study was to evaluate the predictive value of ultrasound markers measured at different time points of the controlled ovarian hyperstimulation (COH) cycle on ovarian response and outcome indicators in the IVF-ET cycle. According to the oestrogen level and the number of retrieved oocytes, patients who planned for COH treatment were separated into low-response group, normal and high-response group. The ovarian stromal artery flow parameters on the day of pituitary down-regulation, day 1, day 7, day 10, and the day of hCG injection were collected prospectively. We also have collected the data of cumulus oophorus count on the day of hCG injection by transvaginal sonography. Compared with the low-response group, on the first day of the COH cycle PI, RI, and S/D were lower in the high-response group than they were in the low-response group (p < .05). PSV and EDV were significantly higher in the high-response group than they were in the low-response group (p < .01), and the PSV on the first day of the COH cycle have statistical significance in predicting the number of high-quality embryos. The number of cumulus oophorus on the day of hCG injection has statistical significance in predicting the number of oocytes retrieved and fertilised oocytes. We conclude that the ovarian stromal artery flow parameters on the first day of the COH cycle and cumulus oophorus count on hCG injection day can serve as efficient indicators for an early assessment of ovarian response and individualised ovulation induction.IMPACT STATEMENTWhat is already known on this subject? AMH, AFC, and the age of the patient are well-known effective parameters for the evaluation of ovarian response, but these are insufficient and full of individual differences. Some researchers have investigated the value of colour Doppler ultrasound and cumulus oophorus in assessing ovarian response, but no definitive conclusion has been reached.What do the results of this study add? The hemodynamic parameters of ovarian stromal artery on the first day of the COH cycle and the number of cumulus oophorus on the day of hCG injection detected by Transvaginal Colour Doppler Sonography (TV-CDS) could be used to predict the ovarian response.What are the implications of these findings for clinical practice and/or further research? Ovarian stromal artery flow parameters and cumulus oophorus detected by TV-CDS can potentially be offered as a complementary parameter for ovarian reserve.

Endogenous Labile Iron Pool-Mediated Free Radical Generation for Cancer Chemodynamic Therapy.

Current chemodynamic therapy (CDT) primarily relies on the delivery of transition metal ions with Fenton activity to trigger hydroxyl radical production from hydrogen peroxide. However, administration of an excess amount of exogenous Fenton-type heavy metals may cause potential adverse effects to human health, including acute and chronic damages. Here, we present a new CDT strategy that uses intracellular labile iron pool (LIP) as the endogenous source of Fenton-reactive metals for eliciting free radical generation, and the discovery of hydroperoxides (R'OOH) as an optimal LIP-mediated chemodynamic agent against cancer. By simulating the metabolic fates of peroxo compounds within cells, R'OOH was found to have excellent free radical-producing ability in the presence of labile iron(II) and to suffer only moderate elimination by glutathione/glutathione peroxidase, which contributes to its superior chemodynamic efficacy. The LIP-initiated nontoxic-to-toxic transition of R'OOH, together with increased LIP levels in tumor cells, enabled efficient and specific CDT of cancer. Moreover, pH/labile iron(II) cascade-responsive nanomedicines comprising encapsulated methyl linoleate hydroperoxide and LIP-increasing agent in pH-sensitive polymer particles were fabricated to realize enhanced CDT. This work not only paves the way to using endogenous Fenton-type metals for cancer therapy but also offers a paradigm for the exploration of high-performance chemodynamic agents activated by intracellular LIP.

Gadolinium Metallofullerene-Based Activatable Contrast Agent for Tumor Signal Amplification and Monitoring of Drug Release.

Activatable imaging probes are promising to achieve increased signal-to-noise ratio for accurate tumor diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is a noninvasive imaging technique with excellent anatomic spatial resolution and unlimited tissue penetration depth. However, most of the activatable MRI contrast agents suffer from metal ion-associated potential long-term toxicity, which may limit their bioapplications and clinical translation. Herein, an activatable MRI agent with efficient MRI performance and high safety is developed for drug (doxorubicin) loading and tumor signal amplification. The agent is based on pH-responsive polymer and gadolinium metallofullerene (GMF). This GMF-based contrast agent shows high relaxivity and low risk of gadolinium ion release. At physiological pH, both GMF and drug molecules are encapsulated into the hydrophobic core of nanoparticles formed by the pH-responsive polymer and shielded from the aqueous environment, resulting in relatively low longitudinal relativity and slow drug release. However, in acidic tumor microenvironment, the hydrophobic-to-hydrophilic conversion of the pH-responsive polymer leads to amplified MR signal and rapid drug release simultaneously. These results suggest that the prepared activatable MRI contrast agent holds great promise for tumor detection and monitoring of drug release.

Enhanced Antitumor Efficacy by a Cascade of Reactive Oxygen Species Generation and Drug Release.

Reactive oxygen species (ROS) can be used not only as a therapeutic agent for chemodynamic therapy (CDT), but also as a stimulus to activate release of antitumor drugs, achieving enhanced efficacy through the combination of CDT and chemotherapy. Here we report a pH/ROS dual-responsive nanomedicine consisting of ß-lapachone (Lap), a pH-responsive polymer, and a ROS-responsive polyprodrug. In the intracellular acidic environment, the nanomedicine can realize pH-triggered disassembly. The released Lap can efficiently generate hydrogen peroxide, which will be further converted into highly toxic hydroxyl radicals via the Fenton reaction. Subsequently, through ROS-induced cleavage of thioketal linker, doxorubicin is released from the polyprodrug. In vivo results indicate that the cascade of ROS generation and antitumor-drug release can effectively inhibit tumor growth. This design of nanomedicine with cascade reactions offers a promising strategy to enhance antitumor efficacy.

Intracranial meningioma surgery in the elderly (over 65 years): prognostic factors and outcome.

BACKGROUND: Meningiomas are more prevalent in elderly individuals; however, the surgical outcome and prognostic factors in this age group are unclear. This retrospective study aimed to identify the prognostic factors of elderly patients with intracranial meningiomas who underwent surgical resection. METHODS: Eighty-six patients (aged ≥ 65) diagnosed with an intracranial meningioma were surgically treated at our department. The clinical, radiological, and follow-up data were retrospectively reviewed. Univariate and multivariate logistic analyses were performed to identify relationships between factors [age, sex, neurological condition, concomitant disease, American Society of Anesthesiology (ASA) classification, preoperative Karnofsky Performance Scale (KPS) score, tumor location and size, peritumoral edema, and Simpson resection grade] and outcome. RESULTS: One patient (1.2 %) died within 30 days of surgery. The morbidity rate was 37.2 %. Postoperative morbidities occurred more frequently in the patients with preoperative neurological deficits than in those without (p = 0.049). Univariate analysis identified significant relationships between a low KPS score (≤ 70) at discharge and preoperative neurological deficits, low preoperative KPS score (≤ 70), and critical tumor location (p < 0.001, p < 0.001, and p = 0.04, respectively). In the multivariate logistic analysis, only the preoperative KPS score remained significant for the KPS score at discharge (p = 0.005); there was no significant association with the most recent KPS score. CONCLUSION: The outcome of intracranial meningioma resection in elderly individuals is favorable if the preoperative KPS score is >70 and no neurological deficits are present. Treatment decisions should be patient-specific, and additional factors should be considered when operations are performed in patients with a low preoperative KPS score or neurological deficits.

A 3-bp deletion in the HBS1L-MYB intergenic region on chromosome 6q23 is associated with HbF expression.

Fetal hemoglobin (HbF) is regulated as a multigenic trait. By genome-wide association study, we confirmed that HBS1L-MYB intergenic polymorphisms (HMIP) and BCL11A polymorphisms are highly associated with HbF in Chinese ß-thalassemia heterozygotes. In this population, the variance in HbF resulting from the HMIP is 13.5%; that resulting from the BCL11A polymorphism is 6.4%. To identify the functional variant in HMIP, we used 1000 Genomes Project data, single nucleotide polymorphism imputation, comparisons of association results across populations, potential transcription factor binding sites, and analysis of phylogenetic conservation. Based on these studies, a hitherto unreported association between HbF expression and a 3-bp deletion, between 135 460 326 and 135 460 328 bp on chromosome 6q23 was found. This 3-bp deletion is in complete linkage disequilibrium with rs9399137, which is the single nucleotide polymorphism in HMIP most significantly associated with HbF among Chinese, Europeans, and Africans. Chromatin immunoprecipitation assays confirmed erythropoiesis-related transcription factors binding to this region in K562 cells. Based on transient expression of a luciferase reporter plasmid, the DNA fragment encompassing the 3-bp deletion polymorphism has enhancer-like activity that is further augmented by the introduction of the 3-bp deletion. This 3-bp deletion polymorphism is probably the most significant functional motif accounting for HMIP modulation of HbF in all 3 populations.

Gene therapy for cardiovascular disease mediated by ultrasound and microbubbles.

Gene therapy provides an efficient approach for treatment of cardiovascular disease. To realize the therapeutic effect, both efficient delivery to the target cells and sustained expression of transgenes are required. Ultrasound targeted microbubble destruction (UTMD) technique has become a potential strategy for target-specific gene and drug delivery. When gene-loaded microbubble is injected, the ultrasound-mediated microbubble destruction may spew the transported gene to the targeted cells or organ. Meanwhile, high amplitude oscillations of microbubbles increase the permeability of capillary and cell membrane, facilitating uptake of the released gene into tissue and cell. Therefore, efficiency of gene therapy can be significantly improved. To date, UTMD has been successfully investigated in many diseases, and it has achieved outstanding progress in the last two decades. Herein, we discuss the current status of gene therapy of cardiovascular diseases, and reviewed the progress of the delivery of genes to cardiovascular system by UTMD.

Study of the UTMD-based delivery system to induce cervical cancer cell apoptosis and inhibit proliferation with shRNA targeting Survivin.

Apoptosis induction by short hairpin RNA (shRNA) expression vectors could be an efficient and promising strategy for cancer gene therapy. Ultrasound-targeted microbubble destruction (UTMD) is an appealing technique. In this study, we investigated the apoptosis induction and suppression of cell proliferation in vivo transfected by the UTMD-based shRNA delivery system. Nude mice with transplanted tumors of cervical cancer were randomly arranged into three groups: control group, plasmid injection and ultrasound (P + US), P + UTMD group. Expressions of Survivin and proliferating cell nuclear antigen (PCNA), Bcl-2, Bax, Caspase-3, Ki-67, nucleostemin (NS) were investigated by immunohistochemistry. Furthermore, microvessel density (MVD) was detected by CD34 protein expressions and apoptotic index (AI) was measured by TUNEL. As compared with those in the control and P + US groups, protein expressions of PCNA, Ki-67, Bcl-2, Survivin and NS in P + UTMD groups were down-regulated markedly, while those of Bax, Caspase-3 were up-regulated significantly (p < 0.05). MVD decreased significantly, whereas AI increased remarkably (p < 0.05). We suggested that UTMD-based shRNA delivery system could induce apoptosis and inhibit proliferation significantly, without causing any apparently adverse effect, representing a new, promising technology that would be used in the future gene therapy and research.

A Spatio-temporal Bayesian model to estimate risk and influencing factors related to tuberculosis in Chongqing, China, 2014-2020.

BACKGROUND: Tuberculosis (TB) is a serious infectious disease that is one of the leading causes of death worldwide. This study aimed to investigate the spatial and temporal distribution patterns and potential influencing factors of TB incidence risk, and to provide a scientific basis for the prevention and control of TB. METHODS: We collected reported cases of TB in 38 districts and counties in Chongqing from 2014 to 2020 and data on environment, population characteristics and economic factors during the same period. By constructing a Bayesian spatio-temporal model, we explored the spatio-temporal distribution pattern of TB incidence risk and potential influencing factors, identified key areas and key populations affected by TB, compared the spatio-temporal distribution characteristics of TB in populations with different characteristics, and explored the differences in the influence of various social and environmental factors. RESULTS: The high-risk areas for TB incidence in Chongqing from 2014 to 2020 were mainly concentrated in southeastern and northeastern regions of Chongqing, and the overall relative risk (RR) of TB showed a decreasing trend during the study period, while RR of TB in main urban area and southeast of Chongqing showed an increasing trend. The RR of TB was relatively high in the main urban area for the female population and the population aged 0-29 years, and the RR of TB for the population aged 30-44 years in the main urban area and the population aged 60 years or older in southeast of Chongqing had an increasing trend, respectively. For each 1 µg/m3 increase in SO2 and 1% increase in the number of low-income per 1000 non-agricultural households (LINA per 1000 persons), the RR of TB increased by 0.35% (95% CI: 0.08-0.61%) and 0.07% (95% CI: 0.05-0.10%), respectively. And LINA per 1000 persons had the greatest impact on the female population and the over 60 years old age group. Although each 1% increase in urbanization rate (UR) was associated with 0.15% (95% CI: 0.11-0.17%) reduction in the RR of TB in the whole population, the RR increased by 0.18% (95% CI: 0.16-0.21%) in the female population and 0.37% (95% CI: 0.34-0.45%) in the 0-29 age group. CONCLUSION: This study showed that high-risk areas for TB were concentrated in the southeastern and northeastern regions of Chongqing, and that the elderly population was a key population for TB incidence. There were spatial and temporal differences in the incidence of TB in populations with different characteristics, and various socio-environmental factors had different effects on different populations. Local governments should focus on areas and populations at high risk of TB and develop targeted prevention interventions based on the characteristics of different populations.

Ultrasound- and liposome microbubble-mediated targeted gene transfer to cardiomyocytes in vivo accompanied by polyethylenimine.

OBJECTIVES: Gene transfer to cardiomyocytes in vivo has received much research attention in the last decade but remains a substantial hurdle. Gene transfer using ultrasound-targeted microbubble destruction is a promising tool for gene therapy. Little data have shown the feasibility and optimization of this method for primary myocardial disease. In this study, we sought to determine the feasibility and efficiency of in vivo gene transfer to the myocardium mediated by ultrasound-targeted microbubble destruction accompanied by polyethylenimine. METHODS: Three plasmids (luciferase reporter, red fluorescent protein reporter, and enhanced green fluorescent protein reporter) were used in this study. The ultrasound parameters were also optimized. A solution containing phosphate-buffered saline, a plasmid, plasmid complex, or polyethylenimine/plasmid, and liposome microbubbles was injected via a tail vein with (study) or without (control) transthoracic ultrasound irradiation. The efficiency of reporter gene transfer was determined by detection of luciferase activity or microscopy, and histologic investigations of the tissue specimens were performed. RESULTS: Ultrasound-targeted microbubble destruction significantly increased luciferase activity in vivo compared to plasmids and microbubbles alone (P < .001). More importantly, the increase in transgene expression was significantly related to ultrasound-targeted microbubble destruction in the presence of polyethylenimine (P < .001). In addition, fluorescein expression was present in all sections that received ultrasound-targeted microbubble destruction. The fluorescent reporter genes and luciferase plasmid all had similar results. Regardless of ultrasound exposure, expression in other organs was close to a background level except for the liver and lung. Hematoxylin-eosin staining showed no notable myocardial injury or death in control and treated mice. CONCLUSIONS: An atraumatic targeted gene delivery technique based on ultrasound-targeted microbubble destruction and polyethylenimine has been developed to transfect cardiomyocytes in vivo. If a suitable target gene is added, the novel technique could be highly effective in many kinds of heart disease.

Inducing Tumor Cell Apoptosis: Mediated Survivin miRNA by Ultrasound and Cationic Lipid Contrast Agent.

BACKGROUND: Non-viral delivery systems is a promising method for gene or drug delivery. Polyethyleneimine (PEI) is a double-edged sword. It internalizes itself into the cell through endocytosis and promotes gene transfer efficiency. However, the strong positive charge also makes PEI highly toxic to cells. Ultrasound-targeted microbubble destruction (UTMD) is a promising non-viral method for gene and drug delivery, but its efficiency still needs to be improved. OBJECTIVE: The aim of this study was to explore a system that combines ultrasound with non-viral gene delivery for the treatment of cervical cancer HeLa cells. METHODS: In this study, we synthesized a kind of cationic ultrasound contrast agent(CUCA) that the physical and chemical properties, gene carrying capacity and cytotoxicity were verified. On the basis of previous studies, we further optimized the following transfusion parameters including ultrasound parameters, microbubble concentration, plasmid concentration, cell density and other parameters. The experiment was designed to compare the following six groups: (1) Plasmid group (P group), plasmid 15 µg; (2) PEI + plasmid group (PEI + P group),1 µl of PEI containing 10 nmol nitrogen and 1 µg of DNA containing 3 nmol phosphate for a PEI/DNA ratio equal to a nitrogen/phosphate ratio of 7 for transfection; (3) Ultrasound + plasmid group (US + P), plasmid 15 µg; (4) Ultrasound + cationic liposomal ultrasound contrast agent + plasmid group (UTMD + P group), plasmid 15 µg and cationic liposomal ultrasound contrast agent 5%; (5) Ultrasound + cationic liposomal ultrasound contrast agent + PEI + plasmid group (UTMD + PEI + P group), PEI/DNA ratio equal to a nitrogen/phosphate ratio of 7 for transfection and cationic liposomal ultrasound contrast agent 5%; and (6) Blank group, no treatment), The influence on Hela cells was observed under microscope, the efficiency of apoptosis was measured by flow cytometry, and cell viability was tested in CCK 8. RESULTS: The optimized transfection parameters can improve the transfection efficiency of ultrasound combined with C-UCA to a certain extent, but its transfection efficiency is still lower than that of branched polyethyleneimine (bPEI) 25 kDa. By investigating the effect of HeLa cells apoptosis induced by UTMD in combination with PEI mediated survivin miRNA, we found that both PEI alone and ultrasound in combination with CUCA were able to transfect cells with survivin miRNA to effectively induce HeLa cell apoptosis. However, the synergistic effect between the two methods was not significant. CONCLUSION: In contrast, the combined use of ultrasound, C-UCA and PEI may significantly reduce the transfection efficiency of UTMD and PEI, and the specific mechanism remains to be further studied.

Conditional deletion of Cited2 results in defective corneal epithelial morphogenesis and maintenance.

Cited2 is an important transcriptional cofactor involved in multiple organ development. Gene profile analysis has identified Cited2 as one of the transcription factors expressed at high levels in adult mouse cornea. To address the function of Cited2 in corneal morphogenesis, we deleted Cited2 in surface ectoderm derived ocular structures including cornea by crossing Cited2-floxed mice with Le-Cre transgenic mice. Cited2(flox/flox);Le-Cre(+) eyes invariably displayed corneal opacity and developed spontaneous corneal neovascularization at older age. Fewer layers of corneal epithelial cells and the absence of cytokeratin 12 (K12) expression featured Cited2 deficient postnatal and adult eyes. Cited2 deficient cornea exhibited impaired healing in response to corneal epithelial debridement by manifesting abnormal histology, lack of K12 expression and corneal neovascularization. Moreover, mechanistic studies suggest that Cited2 may play a role in corneal morphogenesis in part through modulating the expression of Pax6 and Klf4. Collectively, these findings demonstrate a novel function of Cited2 in postnatal corneal morphogenesis and maintenance. Our study will help better understand the molecular mechanisms involved in corneal biology, and more importantly, it may provide a valuable animal model for testing therapeutics in the treatment of corneal disorders, especially blindness as a result of corneal epithelial cell deficiency.

Early ultrasound diagnosis of conjoined twins at eight weeks of pregnancy: A case report.

BACKGROUND: Conjoined twins are a rare occurrence, and the majority of these malformations are detected during second trimester screening. CASE SUMMARY: Herein we report a case of conjoined twins, which was diagnosed by ultrasound at 8 wk gestation and was normal at 7 wk gestation. The two fetuses shared one heart and were diagnosed as thoracopagus twins. This is the first report of conjoined twins diagnosed at 8 wk gestation. The pregnancy was terminated electively at 9 wk gestation. Because some congenital malformations can be diagnosed earlier, a prenatal ultrasound examination at an early gestational stage cannot be dismissed. CONCLUSION: This case demonstrates that a 7-8 wk gestation might be the earliest period when conjoined twins can be diagnosed by ultrasound.

Encapsulation of phycocyanin by prebiotics and polysaccharides-based electrospun fibers and improved colon cancer prevention effects.

To preserve bioactivity and achieve colon targeted release of phycocyanin (PC), the polysaccharides-based electrospun fiber mat (EFM) containing PC and prebiotics was prepared and characterized. In vitro release tests confirmed the colon targeting behavior of PC, in particular, faster release of PC was achieved due to the addition of prebiotics. Ritger-Peppas model confirmed that the release of PC in simulated colon fluids follows a mechanism of anomalous transport (non-Fickian). CCK-8 results showed that the combination of PC and prebiotics exerted a significant anti-proliferative effect on HCT116 cells with an IC50 values of 22.31, 17.12 and 11.63 mg/mL after 24, 48, and 72 h, respectively. Furthermore, the cell cycle and apoptosis analysis revealed that the inhibition activity on HCT116 cells was caused by arresting cell cycle at G0/G1 phase that is relevant to the inhibition of cyclin D1 and CDK4 and the up-regulation of p21 expression, and inducing cell apoptosis by mediating the mitochondrial pathway as well, in which the decrease of Bcl-2/Bax, activation of caspase 3 and release of cytochrome c were included. This study suggests that the PC-loaded EFM with GOS holds a great potential as an effective formulation for colon cancer prevention.

Zwitterionic-to-cationic charge conversion polyprodrug nanomedicine for enhanced drug delivery.

Zwitterionic surface modification is a promising strategy for nanomedicines to achieve prolonged circulation time and thus effective tumor accumulation. However, zwitterion modified nanoparticles suffer from reduced cellular internalization efficiency. Methods: A polyprodrug-based nanomedicine with zwitterionic-to-cationic charge conversion ability (denoted as ZTC-NMs) was developed for enhanced chemotherapeutic drug delivery. The polyprodrug consists of pH-responsive poly(carboxybetaine)-like zwitterionic segment and glutathione-responsive camptothecin prodrug segment. Results: The ZTC-NMs combine the advantages of zwitterionic surface and polyprodrug. Compared with conventional zwitterionic surface, the ZTC-NMs can respond to tumor microenvironment and realize ZTC surface charge conversion, thus improve cellular internalization efficiency of the nanomedicines. Conclusions: This ZTC method offers a strategy to promote the drug delivery efficiency and therapeutic efficacy, which is promising for the development of cancer nanomedicines.

Altered Functional Connectivity in the Motor and Prefrontal Cortex for Children With Down's Syndrome: An fNIRS Study.

Children with Down's syndrome (DS) might exhibit disrupted brain functional connectivity in the motor and prefrontal cortex. To inspect the alterations in brain activation and functional connectivity for children with DS, the functional near-infrared spectroscopy (fNIRS) method was applied to examine the brain activation difference in the motor and prefrontal cortex between the DS and typically developing (TD) groups during a fine motor task. In addition, small-world analysis based on graph theory was also carried out to characterize the topological organization of functional brain networks. Interestingly, behavior data demonstrated that the DS group showed significantly long reaction time and low accuracy as compared to the TD group (p < 0.05). More importantly, significantly reduced brain activations in the frontopolar area, the pre-motor, and the supplementary motor cortex (p < 0.05) were identified in the DS group compared with the TD group. Meanwhile, significantly high global efficiency (E g ) and short average path length (L p ) were also detected for the DS group. This pilot study illustrated that the disrupted connectivity of frontopolar area, pre-motor, and supplementary motor cortex might be one of the core mechanisms associated with motor and cognitive impairments for children with DS. Therefore, the combination of the fNIRS technique with functional network analysis may pave a new avenue for improving our understanding of the neural mechanisms of DS.

Update on thyroid ultrasound: a narrative review from diagnostic criteria to artificial intelligence techniques.

OBJECTIVE: Ultrasound imaging is well known to play an important role in the detection of thyroid disease, but the management of thyroid ultrasound remains inconsistent. Both standardized diagnostic criteria and new ultrasound technologies are essential for improving the accuracy of thyroid ultrasound. This study reviewed the global guidelines of thyroid ultrasound and analyzed their common characteristics for basic clinical screening. Advances in the application of a combination of thyroid ultrasound and artificial intelligence (AI) were also presented. DATA SOURCES: An extensive search of the PubMed database was undertaken, focusing on research published after 2001 with keywords including thyroid ultrasound, guideline, AI, segmentation, image classification, and deep learning. STUDY SELECTION: Several types of articles, including original studies and literature reviews, were identified and reviewed to summarize the importance of standardization and new technology in thyroid ultrasound diagnosis. RESULTS: Ultrasound has become an important diagnostic technique in thyroid nodules. Both standardized diagnostic criteria and new ultrasound technologies are essential for improving the accuracy of thyroid ultrasound. In the standardization, since there are no global consensus exists, common characteristics such as a multi-feature diagnosis, the performance of lymph nodes, explicit indications of fine needle aspiration, and the diagnosis of special populations should be focused on. Besides, evidence suggests that AI technique has a good effect on the unavoidable limitations of traditional ultrasound, and the combination of diagnostic criteria and AI may lead to a great promotion in thyroid diagnosis. CONCLUSION: Standardization and development of novel techniques are key factors to improving thyroid ultrasound, and both should be considered in normal clinical use.

Tumor-Specific Drug Release and Reactive Oxygen Species Generation for Cancer Chemo/Chemodynamic Combination Therapy.

The combination of chemotherapeutic drugs and reactive oxygen species (ROS) is a promising strategy to achieve improved anticancer effect. Herein, a nanomedicine (LaCIONPs) that can achieve tumor-specific chemotherapeutic drug release and ROS generation is developed for cancer chemo/chemodynamic combination therapy. The LaCIONPs are constructed by encapsulation of iron oxide nanoparticles (IONPs) and ß-lapachone (La) in nanostructure assembled by hydrogen peroxide (H2O2)-responsive polyprodrug and pH-responsive polymer. Through the enhanced permeability and retention effect, the nanosized LaCIONPs can accumulate in tumor tissue. After the LaCIONPs are internalized by tumor cells, the structure of LaCIONPs is disintegrated in acidic intracellular environment, leading to rapid release of La and iron ions. Then the released La generates massive H2O2 through tumor specific catalysis. On the one hand, H2O2 further reacts with iron ions to produce highly toxic hydroxyl radicals for chemodynamic therapy. On the other hand, H2O2 also activates the release of camptothecin from the polyprodrug for chemotherapy. The potent antitumor effect of the LaCIONPs is demonstrated by both in vitro and in vivo results. Therefore, the LaCIONP is a promising nanomedicine for tumor-specific chemo/chemodynamic combination therapy.

Cooperation of endogenous and exogenous reactive oxygen species induced by zinc peroxide nanoparticles to enhance oxidative stress-based cancer therapy.

Reactive oxygen species (ROS)-generating anticancer agents can act through two different mechanisms: (i) elevation of endogenous ROS production in mitochondria, or (ii) formation/delivery of exogenous ROS within cells. However, there is a lack of research on the development of ROS-generating nanosystems that combine endogenous and exogenous ROS to enhance oxidative stress-mediated cancer cell death. Methods: A ROS-generating agent based on polymer-modified zinc peroxide nanoparticles (ZnO2 NPs) was presented, which simultaneously delivered exogenous H2O2 and Zn2+ capable of amplifying endogenous ROS production for synergistic cancer therapy. Results: After internalization into tumor cells, ZnO2 NPs underwent decomposition in response to mild acidic pH, resulting in controlled release of H2O2 and Zn2+. Intriguingly, Zn2+ could increase the production of mitochondrial O2·- and H2O2 by inhibiting the electron transport chain, and thus exerted anticancer effect in a synergistic manner with the exogenously released H2O2 to promote cancer cell killing. Furthermore, ZnO2 NPs were doped with manganese via cation exchange, making them an activatable magnetic resonance imaging contrast agent. Conclusion: This study establishes a ZnO2-based theranostic nanoplatform which achieves enhanced oxidative damage to cancer cells by a two-pronged approach of combining endogenous and exogenous ROS.