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1.
Medicine (Baltimore) ; 103(20): e38279, 2024 May 17.
Article En | MEDLINE | ID: mdl-38758867

To explore the influence of perinatal-related factors on meconium aspiration syndrome (MAS) in full-term neonates and construct a nomogram prediction model for risk stratification of neonatal MAS and adoption of preventive measures. A total of 424 newborns and their mothers who were regularly examined at our hospital between January 2020 and December 2023 who had meconium-contaminated amniotic fluid during delivery were retrospectively selected as participants. Neonates were divided into MAS and non-MAS groups based on whether MAS occurred within 3 days after birth. Data from the 2 groups were analyzed, and factors influencing MAS were screened using multivariate logistic regression analysis. The R3.4.3 software was used to construct a nomogram prediction model for neonatal MAS risk. Receiver operating characteristic (ROC) curve analysis and the Hosmer-Lemeshow goodness-of-fit test were used to evaluate the performance of the model, and its clinical effectiveness was evaluated using a decision curve. Among the 424 neonates with meconium-stained amniotic fluid, 51 developed MAS within 3 days of birth (12.03%). Multivariate logistic regression analysis showed that a low amniotic fluid index before delivery (OR = 2.862, P = .019), advanced gestational age (OR = 0.526, P = .034), cesarean section (OR = 2.650, P = .013), severe amniotic fluid contamination (OR = 4.199, P = .002), low umbilical cord blood pH (OR = 2.938, P = .011), and low neonatal Apgar 1-min score (OR = 3.133, P = .006) were influencing factors of MAS in full-term neonates. Based on the above indicators, a nomogram prediction model for MAS risk of full-term newborns was constructed. The area under the ROC curve of the model was 0.931. The model was also tested for goodness-of-fit deviation (χ2 = 3.465, P = .903). Decision curve analysis found that the model was clinically effective in predicting the net benefit of MAS risk in neonates with meconium-stained amniotic fluid. The construction of a column chart prediction model for neonatal MAS risk based on prenatal amniotic fluid index, gestational age, delivery method, amniotic fluid contamination level, newborn umbilical blood pH value, and Apgar 1-min score has a certain application value.


Amniotic Fluid , Meconium Aspiration Syndrome , Nomograms , Humans , Meconium Aspiration Syndrome/epidemiology , Infant, Newborn , Female , Retrospective Studies , Male , Pregnancy , Risk Assessment/methods , Risk Factors , ROC Curve , Gestational Age , Logistic Models , Apgar Score , Cesarean Section/statistics & numerical data , Meconium , Adult
2.
Sci Total Environ ; 921: 170975, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38360308

Studies on the dose effects of kidney impairment and metabolomes in co-exposure to polycyclic aromatic hydrocarbons (PAHs) and metals are limited. We aimed to identify overall associations and metabolic perturbations in 130 participants (53 petrochemical workers and 77 controls) exposed to a PAHs-metals mixture in Southern China. The urinary 7 hydroxylated PAHs and 15 metal(loid)s were determined, and serum creatinine, beta-2 microglobulin, and estimated glomerular filtration rate were health outcomes. The liquid chromatography-mass spectrometry-based method was applied to serum metabolomics. Generalized weighted quantile sum (gWQS) regressions were used to estimate the overall dose-response relationships, and pathway analysis, "meet-in-the-middle" approach, and mediation effect analyses were conducted to identify potential metabolites and biological mechanisms linking exposure with nephrotoxic effects. Our results indicated that renal function reduction was associated with a PAHs-metals mixture in a dose-dependent manner, and 1-hydroxynaphthalene and copper were the most predominant contributors among the two families of pollutants. Furthermore, the metabolic disruptions associated with the early onset of kidney impairment induced by the combination of PAHs and metals encompassed pathways such as phenylalanine-tyrosine-tryptophan biosynthesis, phenylalanine metabolism, and alpha-linolenic acid metabolism. In addition, the specifically identified metabolites demonstrated excellent potential as bridging biomarkers connecting the reduction in renal function with the mixture of PAHs and metals. These findings shed light on understanding the overall associations and metabolic mechanism of nephrotoxic effects of co-exposure to PAHs and metals.


Environmental Pollutants , Polycyclic Aromatic Hydrocarbons , Humans , Polycyclic Aromatic Hydrocarbons/toxicity , Polycyclic Aromatic Hydrocarbons/analysis , Environmental Pollutants/toxicity , Environmental Pollutants/analysis , Metals , Biomarkers , Phenylalanine , Kidney/chemistry
3.
Saudi Med J ; 44(11): 1174-1179, 2023 Nov.
Article En | MEDLINE | ID: mdl-37926464

The incidence of malignant transformation in ectopic pancreas (EP), including adenocarcinoma, is extremely rare. Herein, we presented a single case with invasive adenocarcinoma caused by the EP in the stomach. The patient consulted our hospital due to abdominal discomfort with acid regurgitation. Computed tomography scan showed a pyloric obstruction and thickening of the gastric wall in the gastric antrum; a digestive endoscopic examination showed mucosal congestion, swelling in the anterior pyloric area, and pyloric canal stenosis. Next, the patient underwent gastrointestinal surgery, and the distal gastrectomy specimens revealed a deviation of 10 cm towards the lesser curvature and an extension of 22 cm towards the greater curvature. A 5.5 x 5.4 cm round-like mass was found during surgery. Pathological examination suggested invasive submucosal adenocarcinoma located under the gastric antrum mucosa. Our report provides additional clinical experience for diagnosing EP with canceration in the stomach.


Adenocarcinoma , Stomach Neoplasms , Humans , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/surgery , Pyloric Antrum/pathology , Pancreas/diagnostic imaging , Pancreas/pathology , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/surgery
4.
Front Psychiatry ; 14: 1281606, 2023.
Article En | MEDLINE | ID: mdl-37965365

Background: Several studies have investigated the link between post-traumatic stress disorder (PTSD) and cancer risk but reported mixed results. The objective of our study was to investigate the association between PTSD and cancer risk. Methods: Studies published in English about the relationship between PTSD and cancer incidence were systematically searched. We performed a meta-analysis to estimate the relative risks (RR) and 95% confidence intervals (CI) for cancer incidence. Result: A total of 3,129 articles were screened. Finally, 8 articles and 11 studies were included in the meta-analysis. We found that PTSD was not associated with cancer risk compared with controls. For site-specific cancer, our results showed that women with PTSD were associated with higher risk of ovarian cancer than controls. However, PTSD was not associated with the risk of gastrointestinal cancer, breast cancer and lung cancer. Conclusion: These analyzes based on studies published in English suggest that PTSD is associated with ovarian cancer risk, although the evidence base is very limited. Future studies are needed to investigate the mechanisms that PTSD diagnosis influenced cancer incidence depending on types of cancer.

5.
Arch Pharm (Weinheim) ; 356(12): e2300416, 2023 Dec.
Article En | MEDLINE | ID: mdl-37737557

In light of the cocrystal structure of ceritinib with anaplastic lymphoma kinase (ALK)WT protein, a series of novel 2,4-diarylaminopyrimidine analogs (L1-L25) bearing a typical piperidinyl-4-ol moiety were designed and synthesized with improved biological and physicochemical properties. Satisfyingly, most compounds demonstrated moderate to excellent antitumor effects with IC50 values below 5 µM on ALK-positive Karpas299 and H2228 cells. In particular, L6 bearing the 1-(6-methoxy-pyridin-2-yl)-4-(morpholinomethyl)piperidinyl-4-ol moiety was detected as the optimal compound against ALK-dependent cell lines of Karpas299 (0.017 µM) and H2228 cells (0.052 µM), in company with encouraging ALK enzyme inhibition (ALKWT , IC50 = 1.8 nM). In addition, L6 was also capable of inhibiting ALK-resistant mutations, including ALKL1196M (3.9 nM) and ALKG1202R (5.2 nM). Remarkably, L6 typically repressed colony formation and migration of H2228 cells in a dose-dependent manner. Meanwhile, acridine orange-ethidium bromide staining analysis indicated that the proapoptotic effect of L6 was better than that of ceritinib at the same concentration (50 nM). Ultimately, the binding patterns of L6 to ALKWT and ALKG1202R were ideally established, which further confirmed the structural basis in accordance with the structure-activity relationship analysis.


Antineoplastic Agents , Pyrimidines , Structure-Activity Relationship , Cell Proliferation , Pyrimidines/pharmacology , Pyrimidines/chemistry , Sulfones/pharmacology , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Mutation , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry
6.
Heliyon ; 9(8): e18501, 2023 Aug.
Article En | MEDLINE | ID: mdl-37600416

ARHGEF6, a member of the Dbl-related guanylate exchanger (GEF) family, is highly expressed in gastric cancer and glioma. However, scientists still do not know whether it plays a pivotal role in the pathogenesis of lung adenocarcinoma(LUAD). The prognostic significance of ARHGEF6 expression was assessed by TCGA data. This paper focuses on the level of immune infiltration associated with ARHGEF6 and explored the relationship of this gene with the tumor mutational burden (TMB), immune checkpoints, and drug sensitivity. The results showed that the high expression of ARHGEF6 was associated with a good prognosis in LUAD patients, and positively correlated with a variety of immune cells and drugs. Meanwhile, ARHGEF6 was found to be negatively correlated with TMB. In conclusion, the results of this study suggest that ARHGEF6 is a protective gene in LUAD patients. A combination of ARHGEF6 and TMB could be used as a potential biomarker in the screening of immunotherapy regimens, which are provided to patients with LUAD.

7.
Front Psychiatry ; 14: 1198734, 2023.
Article En | MEDLINE | ID: mdl-37398592

Background: There are bidirectional associations between immunological dysfunction and psychiatric symptoms. However, the associations between the levels of immune cells in the peripheral blood and psychiatric symptoms remain unclear. The present study aimed to evaluate levels of immune cells in peripheral blood in people with positive psychiatric symptoms. Methods: This retrospective study analyzed data from routine blood tests and psychopathology and sleep quality assessments. Data were compared between a group of 45 patients with de novo psychological symptoms and 225 matched controls. Results: Patients with psychiatric symptoms had higher white blood cell and neutrophil counts compared with controls. However, in a subgroup analysis, neutrophil counts were significantly higher than in controls only in patients with multiple psychiatric symptoms. Furthermore, monocyte counts were significantly higher in patients with multiple psychiatric symptoms than in controls. Further, sleep quality was lower in patients with psychiatric symptoms than in controls. Conclusion: White blood cell and neutrophil counts in the peripheral blood of patients with psychiatric symptoms were significantly higher and sleep quality was significantly lower than in controls. Participants with multiple psychiatric symptoms showed more significant differences in peripheral blood immune cell counts than other subgroups. These results provided evidence for the relationship between psychiatric symptoms, immunity, and sleep.

8.
Nano Lett ; 23(14): 6330-6336, 2023 07 26.
Article En | MEDLINE | ID: mdl-37440701

Membrane morphology and its dynamic adaptation regulate many cellular functions, which are often mediated by membrane proteins. Advances in DNA nanotechnology have enabled the realization of various protein-inspired structures and functions with precise control at the nanometer level, suggesting a viable tool to artificially engineer membrane morphology. In this work, we demonstrate a DNA origami cross (DOC) structure that can be anchored onto giant unilamellar vesicles (GUVs) and subsequently polymerized into micrometer-scale reconfigurable one-dimensional (1D) chains or two-dimensional (2D) lattices. Such DNA origami-based networks can be switched between left-handed (LH) and right-handed (RH) conformations by DNA fuels and exhibit potent efficacy in remodeling the membrane curvatures of GUVs. This work sheds light on designing hierarchically assembled dynamic DNA systems for the programmable modulation of synthetic cells for useful applications.


Nanostructures , Nanostructures/chemistry , Nucleic Acid Conformation , Nanotechnology/methods , DNA/chemistry , Unilamellar Liposomes , Lipids
9.
Clin Breast Cancer ; 23(6): 664-671.e21, 2023 08.
Article En | MEDLINE | ID: mdl-37353431

Several studies have investigated the link between beta blockers (BB) and breast cancer outcomes but have reported mixed results. Our aim was to investigate the relationship between BB and breast cancer outcomes. Literatures investigating the relationship between BB and breast cancer outcomes were searched through PubMed and Embase. A total 43 articles were included by meta-analysis. We found BB increased breast cancer risk (n = 22, RR: 1.169, 95% CI: 1.063-1.285). We also found BB were associated with a lower overall survival (OS, n = 19, RR: 1.125, 95% CI: 1.078-1.173) and a higher recurrence risk (n = 8, RR: 1.130, 95% CI: 1.040-1.227) for breast cancer. Interestingly, subgroup analyses found only selective BB increased breast cancer risk (n = 5, RR: 1.766, 95% CI: 1.148-2.718) and recurrence risk (n = 2, RR: 1.168 -, 95% CI: 1.026-1.328) while only nonselective BB were associated with a lower OS (n = 4, RR: 1.135, 95% CI: 1.073-1.202) for breast cancer. Moreover, we found BB were associated with a significantly lower OS (n = 3, RR: 2.751, 95% CI: 1.213-6.238) and higher recurrence (n = 2, RR: 1.284, 95% CI: 1.102-1.497) only in luminal breast cancer while with a higher PFS (n = 2, RR: 0.585, 95% CI: 0.343-0.997) in Her2+ breast cancer. No significant differences in terms of CSM (n = 19, RR: 1.009, 95% CI: 0.947-1.077), PFS (n = 4, RR: 0.932, 95% CI: 0.616-1.305), and DFS (n = 2, RR: 0.776, 95% CI: 0.512-1.176) were observed. Our results provide evidence of the relationship between BB and breast cancer incidence and prognosis.


Breast Neoplasms , Humans , Female , Breast Neoplasms/epidemiology , Incidence , Prognosis
10.
Transl Pediatr ; 12(3): 354-363, 2023 Mar 31.
Article En | MEDLINE | ID: mdl-37035407

Background: Double filtration plasmapheresis (DFPP) was initially used to facilitate the conduction of ABO-incompatible renal transplantation. The applicability of DFPP has recently expanded to cover the removal of various antibodies in adults with immune-mediated diseases. However, DFPP is seldom used in children, with few reports addressing its efficacy and safety in this population. This study aimed to explore the efficacy and adverse effects of DFPP for pediatric patients with renal indications. Methods: Children who received DFPP between December 2017 and December 2020 at Tongji Hospital were retrospectively studied, and sub-grouped for analysis according to the types of disease. All children received 3 to 6 DFPP sessions within 2 to 3 weeks, and were assessed for clinical outcomes according to glomerular filtration rate, proteinuria and extra-renal symptoms. Pre- and post-DFPP plasma were collected to measure the levels of pathogenic autoantibodies, immunoglobulins, fibrinogen, albumin, calcium, etc. In-hospital complications were also recorded. Results: Totally there were 10 children receiving 44 sessions of DFPP, including 2 males and 8 females, with a median age of 11.2 years old (5-13 years) and a median weight of 42.1 kg (20-59 kg). Five patients were treated for systemic lupus erythematosus (SLE), three patients for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), one for C3 glomerulopathy and one for ABO-incompatible renal transplantation. Plasma autoantibodies decreased substantially by 93% and 89% in those with SLE and AAV after the last session, respectively. Complete or partial responses were achieved in 80%, 33.3%, 100% and 100% of patients with SLE, AAV, C3 glomerulopathy, and ABO-incompatible renal transplantation, respectively. The proportion of cumulative IgG, fibrinogen, and albumin removal at the end of the last sessions were 58.8%, 67.69%, and 14.05% respectively. The removal of calcium, potassium and creatinine were not statistically significant. A few episodes (4.55%) of hypotension were observed when fresh frozen plasma was used as the replacement fluid, and no bleeding nor severe anaphylaxis was noted. Conclusions: The efficacy and safety of DFPP treatment in children with SLE, AAV, C3 glomerulopathy and ABO-incompatible renal transplantation were described in the present study. DFPP is proven to be a safe apheresis method for children weighing more than 20 kg.

11.
Front Genet ; 14: 1002157, 2023.
Article En | MEDLINE | ID: mdl-36936412

Background: Breast cancer has the highest incidence among malignant tumors in women, and its prevalence ranks first in global cancer morbidity. Aim: This study aimed to explore the feasibility of a prognostic model for patients with breast cancer based on the differential expression of genes related to fatty acid metabolism. Methods: The mRNA expression matrix of breast cancer and paracancer tissues was downloaded from The Cancer Genome Atlas database. The differentially expressed genes related to fatty acid metabolism were screened in R language. The TRRUST database was used to predict transcriptional regulators related to hub genes and construct an mRNA-transcription factor interaction network. A consensus clustering approach was used to identify different fatty acid regulatory patterns. In combination with patient survival data, Lasso and multivariate Cox proportional risk regression models were used to establish polygenic prognostic models based on fatty acid metabolism. The median risk score was used to categorize patients into high- and low-risk groups. Kaplan-Meier survival curves were used to analyze the survival differences between both groups. The Cox regression analysis included risk score and clinicopathological factors to determine whether risk score was an independent risk factor. Models based on genes associated with fatty acid metabolism were evaluated using receiver operating characteristic curves. A comparison was made between risk score levels and the fatty acid metabolism-associated genes in different subtypes of breast cancer. The differential gene sets of the Kyoto Encyclopedia of Genes and Genomes for screening high- and low-risk populations were compared using a gene set enrichment analysis. Furthermore, we utilized CIBERSORT to examine the abundance of immune cells in breast cancer in different clustering models. Results: High expression levels of ALDH1A1 and UBE2L6 prevented breast cancer, whereas high RDH16 expression levels increased its risk. Our comprehensive assessment of the association between prognostic risk scoring models and tumor microenvironment characteristics showed significant differences in the abundance of various immune cells between high- and low-risk breast cancer patients. Conclusions: By assessing fatty acid metabolism patterns, we gained a better understanding of the infiltration characteristics of the tumor microenvironment. Our findings are valuable for prognosis prediction and treatment of patients with breast cancer based on their clinicopathological characteristics.

12.
Am J Transl Res ; 15(1): 582-595, 2023.
Article En | MEDLINE | ID: mdl-36777863

This study presents an in-depth analysis on a machine-designed computational web-based information system, which was used to conduct nasal mucosal care before and after nasal endoscopic surgery for chronic sinusitis. The system was developed and implemented using the mainstream B/S structure model with a Java development framework and MySQL database. Sinus irrigation solution has been shown to be effective for postoperative flushing after nasal endoscopy, by eliminating mucosal edema and promoting mucosal epithelialization at the operative cavity, and it is currently a desirable method that deserves promotion. By comparing the time required for surgical cavity cleaning, the rinsing solution was shown to be key of the physical flushing effect in the initial period after nasal endoscopy. It could remove blood cemented and surgical cavity surface cemented skin and secretions. In addition, the sinus irrigation solution can accelerate the mucosal epithelialization of the operative cavity more effectively than compounded saline. It could effectively eliminate mucosal edema, restore its protective and defensive functions, and help local blood circulation, secretion absorption, mucosal growth, mucosal regeneration and repair, and mucus cilia removal.

13.
Drug Resist Updat ; 68: 100951, 2023 05.
Article En | MEDLINE | ID: mdl-36841134

AIMS: Microtubule inhibitors are widely used in first line cancer therapy, though drug resistance often develops and causes treatment failure. Colchicine binds to tubulins and inhibits tumor growth, but is not approved for cancer therapy due to systemic toxicity. In this study, we aim to improve the therapeutic index of colchicine through structural modification. METHODS: The methoxyl group of the tropolonic ring in colchicine was replaced with amino groups. The cross-resistance of the derivatives with paclitaxel and vincristine was tested. Antitumor effects of target compounds were tested in vivo in A549 and paclitaxel-resistant A549/T xenografts. The interaction of target compounds with tubulins was measured using biological and chemical methods. RESULTS: Methylamino replacement of the tropolonic methoxyl group of colchicine increases, while demethylation loses, selective tubulin binding affinity, G2/M arrest and antiproliferation activity. Methylaminocolchicine is more potent than paclitaxel and vincristine to inhibit tumor growth in vitro and in vivo without showing cross-resistance to paclitaxel. Methylaminocolchicine binds to tubulins in unique patterns and inhibits P-gp with a stable pharmacokinetic profile. CONCLUSION: Methylanimo replacement of the tropolonic methoxyl group of colchicine increases antitumor activity with improved therapeutic index. Methylaminocolchicine represents a new type of mitotic inhibitor with the ability of overcoming paclitaxel and vincristine resistance.


Antineoplastic Agents , Neoplasms , Humans , Paclitaxel/pharmacology , Paclitaxel/chemistry , Paclitaxel/therapeutic use , Colchicine/pharmacology , Colchicine/chemistry , Colchicine/metabolism , Tubulin , Vincristine/pharmacology , Vincristine/therapeutic use , Neoplasms/drug therapy , Cell Line, Tumor , Antineoplastic Agents/therapeutic use
14.
Entropy (Basel) ; 24(12)2022 Dec 01.
Article En | MEDLINE | ID: mdl-36554169

Congestive heart failure (CHF) is a chronic heart condition associated with debilitating symptoms that can lead to mortality. The electrocardiogram (ECG) is a noninvasive and simple diagnostic method that can show detectable changes in CHF. However, manual diagnosis of ECG signals is often erroneous due to the small amplitude and duration of the ECG signals. This paper presents a CHF diagnosis method based on generalized multiscale entropy (MSE)-wavelet leaders (WL) and extreme learning machine (ELM). Firstly, ECG signals from normal sinus rhythm (NSR) and congestive heart failure (CHF) patients are pre-processed. Then, parameters such as segmentation time and scale factor are chosen, and the multifractal spectrum features and number of ELM hidden layer nodes are determined. Two different data sets (A, B) were used for training and testing. In both sets, the balanced data set (B) had the highest accuracy of 99.72%, precision, sensitivity, specificity, and F1 score of 99.46%, 100%, 99.44%, and 99.73%, respectively. The unbalanced data set (A) attained an accuracy of 99.56%, precision of 99.44%, sensitivity of 99.81%, specificity of 99.17%, and F1 score of 99.62%. Finally, increasing the number of ECG segments and different algorithms validated the probability of detection of the unbalanced data set. The results indicate that our proposed method requires a lower number of ECG segments and does not require the detection of R waves. Moreover, the method can improve the probability of detection of unbalanced data sets and provide diagnostic assistance to cardiologists by providing a more objective and faster interpretation of ECG signals.

15.
Front Psychiatry ; 13: 997593, 2022.
Article En | MEDLINE | ID: mdl-36353572

Background and aims: Depression often triggers addictive behaviors such as Internet addiction. In this network analysis study, we assessed the association between Internet addiction and residual depressive symptoms in patients suffering from clinically stable recurrent depressive disorder (depression hereafter). Materials and methods: In total, 1,267 depressed patients were included. Internet addiction and residual depressive symptoms were measured using the Internet Addiction Test (IAT) and the two-item Patient Health Questionnaire (PHQ-2), respectively. Central symptoms and bridge symptoms were identified via centrality indices. Network stability was examined using the case-dropping procedure. Results: The prevalence of IA within this sample was 27.2% (95% CI: 24.7-29.6%) based on the IAT cutoff of 50. IAT15 ("Preoccupation with the Internet"), IAT13 ("Snap or act annoyed if bothered without being online") and IAT2 ("Neglect chores to spend more time online") were the most central nodes in the network model. Additionally, bridge symptoms included the node PHQ1 ("Anhedonia"), followed by PHQ2 ("Sad mood") and IAT3 ("Prefer the excitement online to the time with others"). There was no gender difference in the network structure. Conclusion: Both key central and bridge symptoms found in the network analysis could be potentially targeted in prevention and treatment for depressed patients with comorbid Internet addiction and residual depressive symptoms.

16.
Adv Drug Deliv Rev ; 190: 114525, 2022 11.
Article En | MEDLINE | ID: mdl-36100142

Nanomedicines for cancer treatment have been studied extensively over the last few decades. Yet, only five anticancer nanomedicines have received approvals from the United States Food and Drug Administration (FDA) for treating solid tumors. This drastic mismatch between effort and return calls into question the basic understanding of this field. Various viewpoints on nanomedicines have been presented regarding their potentials and inefficiencies. However, the underlying logics of nanomedicine research and its inadequate translation to the successful use in the clinic have not been thoroughly examined. Tumor-targeted drug delivery was used to understand the shortfalls of the nanomedicine field in general. The concept of tumor-targeted drug delivery by nanomedicine has been based on two conjectures: (i) increased drug delivery to tumors provides better efficacy, and (ii) decreased drug delivery to healthy organs results in fewer side effects. The clinical evidence gathered from the literature indicates that nanomedicines bearing classic chemotherapeutic drugs, such as Dox, cis-Pt, CPT and PTX, have already reached the maximum drug delivery limit to solid tumors in humans. Still, the anticancer efficacy and safety remain unchanged despite the increased tumor accumulation. Thus, it is understandable to see few nanomedicine-based formulations approved by the FDA. The examination of FDA-approved nanomedicine formulations indicates that their approvals were not based on the improved delivery to tumors but mostly on changes in dose-limiting toxicity unique to each drug. This comprehensive analysis of the fundamentals of anticancer nanomedicines is designed to provide an accurate picture of the field's underlying false conjectures, hopefully, thereby accelerating the future clinical translations of many formulations under research.


Antineoplastic Agents , Nanoparticles , Neoplasms , Antineoplastic Agents/therapeutic use , Drug Delivery Systems/methods , Humans , Nanomedicine/methods , Neoplasms/therapy , United States
17.
Bioorg Med Chem ; 72: 116995, 2022 10 15.
Article En | MEDLINE | ID: mdl-36095945

Aiming to develop novel tropomyosin receptor kinase A (TrkA) inhibitors, a scaffold hopping strategy was utilized by transforming the fused indazole of Entrectinib to phenyl triazole/thiazole skeleton to obtain compounds 7a-7 h and 13a-13 h. In the light of MTT assay, phenyl triazole derivatives 7a-7 h exhibited moderate anti-proliferative activities against KM-12 cells with the IC50 values of 1.78-17.51 µM, while phenyl thiazole derivatives 13a-13 h showed the weaker efficacy. Further structure-guided optimizations by combining the phenyl triazole skeleton with 3,5­difluorophenyl and 3-carbamoyl-4-piperazinylaniline moiety led to compounds 19a-19d and 20. Eventually, 19c bearing (2-(4-methylpiperazin-1-yl)phenyl)(morpholino)methanone moiety exhibited excellent anti-proliferative activity on TrkA-positive KM-12 cells with IC50 value of 0.17 µM. Meanwhile, compound 19c showed the inhibitory potency on TrkA with IC50 value of 1.6 nM, and displayed higher selectivity on TrkA over TrkB (IC50 = 12.3 nM) and TrkC (IC50 = 18.4 nM). The dedicated wound healing and colony formation assay indicated that the optimal compound 19c could suppress migration and significantly inhibit KM-12 cell colony formation in a dose-dependent manner. In addition, 19c could weakly induce apoptosis of KM-12 cell in immunofluorescent staining analysis. Taken together, the above results suggest 19c as a novel TrkA inhibitor worthy of further profiling.


Antineoplastic Agents , Thiazoles , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation , Drug Design , Drug Screening Assays, Antitumor , Indazoles/pharmacology , Molecular Structure , Morpholinos/pharmacology , Protein Kinase Inhibitors/pharmacology , Structure-Activity Relationship , Thiazoles/pharmacology , Triazoles/pharmacology , Tropomyosin/pharmacology
18.
Transl Psychiatry ; 12(1): 303, 2022 07 29.
Article En | MEDLINE | ID: mdl-35906234

The coronavirus disease 2019 (COVID-19) pandemic has a disproportionate impact on vulnerable subpopulations, including those with severe mental illness (SMI). This study examined the one-year prevalence of suicidal ideation (SI), suicide plans (SP), and suicide attempts (SA) in bipolar disorder (BD) and schizophrenia (SCZ) patients during the pandemic. Prevalence rates were compared between the two disorders and associated factors were examined. A survey was conducted in six tertiary psychiatric hospitals and psychiatric units. People with a diagnosis of BD or SCZ were invited to participate. SI, SP, and SA (suicidality for short) were assessed and associated factors were examined using binary logistical regression. The 1-year prevalence of SI, SP and SA in BD patients were 58.3%, (95% CI: 54.1-62.6%), 38.4% (95% CI: 34.3-42.6%) and 38.6% (95% CI: 34.5-42.8%), respectively, which were higher than the corresponding figures in SCZ patients (SI: 33.2%, 95% CI: 28.6-37.8%; SP: 16.8%, 95% CI: 13.2-20.5%; SA: 19.4%, 95% CI: 15.5-23.3%). Patients with younger age, experience of cyberbullying, a history of SA among family or friends, a higher fatigue and physical pain score, inpatient status, and severe depressive symptoms were more likely to have suicidality. The COVID-19 pandemic was associated with increased risk of suicidality, particularly in BD patients. It is of importance to regularly screen suicidality in BD and SCZ patients during the pandemic even if they are clinically stable.


Bipolar Disorder , COVID-19 , Schizophrenia , Suicide , Bipolar Disorder/epidemiology , Bipolar Disorder/psychology , Humans , Pandemics , Risk Factors , Schizophrenia/epidemiology , Suicidal Ideation
19.
J Affect Disord ; 314: 112-116, 2022 10 01.
Article En | MEDLINE | ID: mdl-35777497

BACKGROUND: Internet addiction (IA) is associated with mental health problems but its impact on quality of life (QOL) is understudied. We examined the prevalence of IA and its association with QOL in clinically stable patients with major depressive disorder (MDD). METHODS: In a cross-sectional survey between September 2020 and July 2021, the Young's Internet Addiction Test (IAT), the Patient Health Questionnaire-2 (PHQ-2) and the World Health Organization Quality of Life Brief version scale (WHOQOL-BREF) were administered to 1267 patients with MDD. Logistic regression was used to examine the correlates of IA, while analysis of covariance (ANCOVA) was used to examine the association between IA and QOL." RESULTS: The prevalence of IA (IAT total scores ≥50) was 27.2 % (95 % CI: 24.7 %-29.6 %) in MDD patients. Compared to patients without IA, those with IA had lower QOL (F(1, 1267) = 19.1, P < 0.001). Logistic regression revealed that higher education (senior high school and above; OR = 1.85, 95 % CI: 1.13-3.03), family history of psychiatric disorders (OR = 1.72, 95 % CI: 1.08-2.73), and higher PHQ-2 total score (OR = 1.23, 95 % CI: 1.14-1.32) were positively associated with IA while older age (OR = 0.93, 95 % CI: 0.91-0.96) was inversely related to IA. CONCLUSION: IA is much more common in clinically stable patients with MDD compared to the reported figures in the general population. It would be prudent to screen and monitor internet use in MDD patients and treat those with IA.


Behavior, Addictive , Depressive Disorder, Major , Behavior, Addictive/epidemiology , Behavior, Addictive/psychology , Cross-Sectional Studies , Depressive Disorder, Major/epidemiology , Depressive Disorder, Major/psychology , Humans , Internet , Internet Addiction Disorder , Prevalence , Quality of Life/psychology , Surveys and Questionnaires
20.
Comput Math Methods Med ; 2022: 2096583, 2022.
Article En | MEDLINE | ID: mdl-35720040

Higher education has always been the top priority of the country and society. With the gradual completion of the Chinese curriculum system, in addition to some subject knowledge, the education on ideology, morality, and quality has also become more and more perfect. Moral education in colleges and universities is an example of this. However, current moral education instruction in colleges and universities is still based on examination-oriented education, and students have not been exposed to the culture deeply. As a result, the goal of this study is to strengthen traditional culture's function in moral education instruction in colleges and universities, as well as conduct research on its application value. In response to this, this paper designs an embedded moral education network teaching platform, which focuses on increasing the importance of the role of administrators, and is responsible for collecting statistics of traditional culture resources and applying them to teaching. The education for traditional culture also traces its origins and provides suggestions for the new era with reference to historical moral education research. The results of this paper believe that, for the response time of the system, in the campus network environment, the response time is about 3 s, the minimum value is 2.8 s, and the maximum value is also 3.2 s. In an ordinary network environment, the response time is also within 3.8 s. This demonstrates that the approach proposed in this research is efficient and capable of meeting the needs of moral education instruction in colleges and universities.


Curriculum , Students , Educational Status , Humans , Morals , Universities
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