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1.
Artigo em Inglês | MEDLINE | ID: mdl-36075228

RESUMO

PURPOSE: To investigate the clinical characteristics and associated factors of colonic polyps in patients with acromegaly. METHODS: Clinical characteristics and colonoscopy findings of 86 acromegaly patients who received treatment were retrospectively reviewed, and colonoscopy findings and the correlation with growth hormone (GH)-secreting pituitary adenoma (GHPA) volume and hormonal/metabolic levels were analyzed. RESULTS: The prevalence of colonic polyps in acromegaly patients was 40.7% and increased significantly with advanced age, especially in those ≥50 years. Multiple polyps (62.8%) and colonic polyps in the left colon (54.2%) were detected more frequently. Compared to acromegaly patients without polyps, those with polyps displayed higher insulin-like growth factor-1 × upper limit of normal (IGF-1×ULN) levels (P=0.03). IGF-1 levels and GHPA volumes in patients with polyps showed increasing trends, although the differences were not significant. GH levels were higher in patients with polyps of diameter ≤5 mm than those with polyps of diameter >5 mm (P=0.031). The univariate and multivariate logistic regression analysis revealed that GHPA volumes (OR: 1.09, 95% CI: 1.01-1.20; P=0.039) and IGF-1×ULN Q2 levels (OR: 6.51, 95% CI: 1.20-44.60; P=0.038) were independent factors for predicting the risk of colonic polyp occurrence in acromegaly patients. A nomogram was prepared to evaluate the risk of colonic polyps in acromegaly patients. CONCLUSION: The acromegalic patients are a population with a high prevalence of colonic polyps. GHPA volumes and IGF-1×ULN levels may be predictors of colonic polyp occurrence.

2.
World J Psychiatry ; 12(7): 999-1001, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-36051604

RESUMO

The article not only successfully evaluated regular physical activities can improve mental well-being during self-isolation and social distancing policies related to the coronavirus disease 2019 (COVID-19), but also concluded that the COVID-19 pandemic may lead to augmented levels of angiotensin-converting enzyme-2. By reading the article of Walid Kamal Abdelbasset, we have some questions and put forward some suggestions on the content of the article.

3.
Front Oncol ; 12: 905857, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052267

RESUMO

Leiomyosarcoma of the uterus (ULMS) is a rare malignant tumor originating from embryonic mesenchymal cells. ULMS tends to metastasize to the lungs, lymph nodes, liver, and bone. Computed tomography three-dimensional (CT 3D) imaging is an advanced diagnostic technique that can track the vessels and their relationships with tumors and reveal the invasion of vessels, including small vessels, around tumors in any slice. Here, we describe a case in which ULMS extended to the retrohepatic inferior vena cava. To date, no report has described resection of metastatic ULMS of the vena cava through supplemental CT 3D imaging. Our patient presented with right lumbar abdominal pain as the main symptom. After using CT 3D reconstruction to accurately assess the relationship between the tumor and the surrounding organs and blood vessels before the operation, the operation was successfully completed through multidisciplinary surgical collaboration.

4.
ACS Nano ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36094898

RESUMO

The construction of heterostructures is one of the most promising strategies for engineering interfaces of catalysts to perform high-efficiency oxygen evolution reaction (OER). However, accurately tuning heterostructures' interface during operation remains a challenge. Herein, we fabricated the needled-like heterostructure Co1-xS/Co(OH)F supported on flexible carbon fiber cloth via an atomic substitution strategy, in which sulfur atoms are simultaneously grafted into F vacancies after the partial removal of F atoms from Co(OH)F during the electrodeposition, thus achieving the growth of cobalt sulfide on the interface of Co(OH)F. This electrocatalyst with such design exhibits the following advantages: (1) The lattice distortion caused by atomic substitution leads to the increase of active sites; (2) Co1-xS constructed on the surface of Co(OH)F by the atomic replacement strategy optimizes the adsorption (OH-) and desorption (O2) energy in the OER process; (3) the needle-like structure possesses the tip-enhanced local electric field effect. As a result, the Co1-xS/Co(OH)F/CC catalyst exhibits very high OER catalytic performance with an overpotential of 269 mV at a current density of 10 mA cm-2 and a Tafel slope of 71 mV dec-1. The asymmetric electrode shows superior catalytic activity and stability in overall water splitting. The catalytic mechanism of these highly efficient Co1-xS/Co(OH)F/CC catalysts was investigated via DFT theoretical calculations and ex situ characterizations. This atomic substitution strategy displays universality for other transition metal sulfides (metal = Ni, Mn, Cu).

5.
Echocardiography ; 39(9): 1252-1258, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36055800

RESUMO

BACKGROUND: There are differences between young and older patients diagnosed with acute aortic dissection. We aimed to explore the differences in echocardiographic and computed tomography angiography (CTA) characteristics between the young and the older patients diagnosed with acute aortic dissection. METHODS: The data from 1220 patients with aortic dissection were collected. They were divided into the young and the older groups with the age threshold set at 45 years old. The basic information and imaging data were collected and compared between the two groups. Univariate regression was used to find the risk factors for mortality in each group. RESULTS: Echocardiographic results showed the proportion of left ventricular enlargement (young vs older, 39.9% vs 26.9%, p-value <.001) and left ventricular dysfunction (22.3% vs 14.1%, p-value ​​smaller than .001) in the young group was significantly higher. Although there is no statistically significant difference in mortality within 60 days after admission (12.0% vs 15.1%, p-value equals to .164), the involvements of aortic branches were the risk factor for the mortality in the young group. For the older patients, the left ventricular remodeling detected by echocardiography (left atrial enlargement, ascending aortic dilation, aortic regurgitation) and decreased heart function were the risk factors for mortality. CONCLUSIONS: The mortality of the young and the older groups with acute aortic dissection are comparable. The involvements of aortic branches were the mortality risk factors in the young patients while the structural and functional change of the left ventricle detected by echocardiography was the mortality risk factor for the older patients.


Assuntos
Aneurisma Dissecante , Disfunção Ventricular Esquerda , Aneurisma Dissecante/diagnóstico por imagem , Ecocardiografia , Humanos , Hipertrofia Ventricular Esquerda , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento
6.
Sci Total Environ ; 853: 158437, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36057303

RESUMO

During the period of 2015-2018, Chinese government had made great efforts to mitigate air pollutants, such as air quality monitoring, energy structure adjustment, and pollutant emission reduction from industry, transportation and household sectors. With the special investment of 152 billion Chinese Yuan (CNY) in the Beijing-Tianjin-Hebei (BTH) and surrounding "2 + 26" regions, the annual local concentrations of PM2.5, PM10, SO2 and NO2 decreased from 77, 132, 38 and 46 µg/m3 to 60, 109, 20 and 43 µg/m3. It was estimated that the improvement in air quality avoided 27,021 (95 % CIs 12,548-39,738) premature deaths attributed to air pollution exposure based on an exposure-response function, including 45 %, 17 % and 15 % of cardiopulmonary, lung cancer and respiratory morality cases. Air pollution reduction was also effective in reducing work time loss, which reduced the total working time loss by 3.8 × 107 (95 % CIs 1.8 × 107-5.6 × 107) h, and the per capita working time loss by 0.28 (95 % CIs 0.13-0.41) h/capita by 2018. From the economic aspect, air pollution control actions in those regions saved 95.6 (95 % CIs 44.2-141) billion CNY economic loss by using the value of statistical life (VSL). The total benefit-cost ratio was 63.7 % (95 % CIs 29.4 %-93.7 %). The cost-effectiveness in Beijing and Tianjin were relatively low due to the regional contribution from other cities of the air pollution transmission channel. Despite the uncertainties, the results clearly show the significance of the environmental, health and economic benefits of actions in the BTH and surrounding "2 + 26" regions for combating air pollution.

7.
J Mol Graph Model ; 117: 108325, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36088765

RESUMO

CRBN protein is an E3 ubiquitin ligase which plays an important role in the ubiquitin-proteasome system of eukaryotic cells. Small molecules can modulate CRBN and induce multiple target proteins to bind with CRBN, which contributes to ubiquitination and degradation of target proteins. Modulating the CRBN protein through small molecules provides a novel idea for treatment of tumors and immune system disease. Due to most of CRBN modulators containing glutarimide skeleton, we aimed to discover novel potent CRBN modulators. In this study, Lipinski's rule and Veber rule, pharmacophore based virtual screening, docking based virtual screening and ADMET screening methods were performed to discover potential CRBN modulators. The antitumor activity of 11 candidates were evaluated by MTS assay. AN7535 showed potent antitumor activity with IC50 = 0.72 µM against HL-60 and IC50 = 1.438 µM against SMMC-7721. AO6355 showed potent antitumor activity with IC50 = 7.469 µM against SMMC-7721. MD simulations and binding free energy calculations suggested that AN7535 and AO6355 could stabilize the CRBN protein and have favorable binding affinity with CRBN protein. Luciferase complementation assay suggested AN7535 could bind to CRBN with IC50 = 215.9 µM.

8.
Molecules ; 27(17)2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36080301

RESUMO

As a prevention tool for mosquito-borne diseases, mosquito repellents have received substantial attention. To make a convincing recommendation for repellent products to Chinese consumers, we compared the protection time (landing time and probing time) of the 26 best-selling commercial repellents in the Chinese market in a controlled laboratory environment. The data were analyzed by one-way ANOVA. Meanwhile, prices and favorable rates of repellents are also taken into consideration. In our study, N, N-diethyl-m-toluamide (DEET)-based products provided the longest protection time (0.5-3.88 h landing time and/or 1-5.63 h probing time) and lower prices (13.9-21.9 yuan) than other components (ethyl butylacetylaminopropionate (IR3535), picaridin, and botanical. Among the 26 selected products, only 17 repellents showed repellency, and the best repellent was Green Jungle (15% DEET), with a mean (±SD) landing and/or probing time of 3.88 ± 1.65 h and/or 5.63 ± 0.36 h. For botanicals, only ICE King, OMNIbaby, and Ren He showed a little repellency. Autan (20% picaridin) performed best in the picaridin group. Run Ben (7% IR3535) stood out from the IR3535 group. In conclusion, DEET repellent is highly recommended to consumers. The combination of botanicals and synthesized chemicals is a new prospect for eco-friendly repellents.


Assuntos
Repelentes de Insetos , Animais , China , DEET/farmacologia , Repelentes de Insetos/farmacologia , Masculino , Pele
9.
Eur Cytokine Netw ; 33(1): 13-24, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36102857

RESUMO

Background: Asthma is an airway disease characterized by airflow limitation and various additional clinical manifestations. Repeated inflammatory stimulation of the airways leads to epithelial-mesenchymal transition (EMT) which aggravates subepithelial fibrosis during the process of airway remodelling and enhances resistance to corticosteroids and bronchodilators in refractory asthma. There is growing evidence that IL-27 modulates airway remodelling, however, the molecular mechanisms involving IL-27 and EMT are poorly understood. The objective of this study was to investigate the effects of IL-27 on ovalbumin (OVA)-challenged asthmatic mice in vivo and TGF-ß1-induced EMT in 16HBE cells in vitro. Methods: Airway inflammation, mucus secretion, and collagen deposition were analysed by conventional pathological techniques. The ratio of Th17 and Th9 cells in the spleen of mice was measured using flow cytometry, ELISA was performed for cytokine analysis to identify EMT-related molecules and signalling pathways, and other molecular and cellular techniques were used to explore the functional mechanism involving IL-27 and EMT. Results: Airway inflammation in asthmatic mice was significantly alleviated by IL-27, with downregulation of RhoA and ROCK, upregulation of E-cadherin, and a decrease of vimentin and α-SMA expression, compared to asthmatic mice. Moreover, the frequency of Th17 and Th9 cells in the spleen of asthmatic mice decreased following treatment with IL-27. In TGF-ß1-induced 16HBE cells, the addition of IL-27 was shown to inhibit EMT, based on the expression of E-cadherin, vimentin, and α-SMA. Conclusion: Intranasal administration of IL-27 attenuates airway inflammation and EMT in a murine model of allergic asthma possibly by downregulating the RhoA/ROCK signalling pathway.


Assuntos
Asma , Interleucina-27 , Remodelação das Vias Aéreas , Animais , Asma/tratamento farmacológico , Caderinas/metabolismo , Caderinas/farmacologia , Caderinas/uso terapêutico , Transição Epitelial-Mesenquimal/fisiologia , Inflamação/tratamento farmacológico , Camundongos , Fator de Crescimento Transformador beta1/metabolismo , Vimentina/farmacologia , Vimentina/uso terapêutico
10.
Mycoses ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36111370

RESUMO

BACKGROUND: Cryptococcal meningitis (CM) is increasingly recognized in human immunodeficiency virus (HIV)-uninfected patients with high mortality. The efficacy and safety profiles of induction therapy with high dose fluconazole plus flucytosine remain unclear. METHODS: HIV-uninfected CM patients who received high dose fluconazole (800mg/d) for initial therapy in Huashan Hospital were included in this retrospective study from January 2013 to December 2018. Efficacy and safety of initial therapy, clinical outcomes and risk factors were evaluated. RESULTS: Twenty-seven (71.1%) patients who received high dose fluconazole with flucytosine combination therapy and 11 (28.9%) having fluconazole alone for induction therapy were included. With a median duration of 42 days (IQR, 28-86), the successful response rate of initial therapy was 76.3% (29/38), while adverse drug reactions occurred in 14 patients (36.8%). The rate of persistently positive cerebrospinal fluid (CSF) culture results was 30.6% at 2 weeks, which was significantly associated with CSF CrAg titer > 1:1280 (OR 9.56; 95% CI 1.40 - 103.65; P = .010) and CSF culture of Cryptococcus > 3.9 log10 CFU/ml (OR 19.20; 95% CI 1.60 - 920.54; P = .011), and decreased to 8.6% at 4 weeks. One-year mortality rate was 15.8% (6/38), the independent risk factor associated with which was low serum albumin (< 35g/L) in multivariate analysis (HR 6.31; 95% CI 1.150 - 34.632; P = .034). CONCLUSIONS: Induction therapy with high dose fluconazole (800mg/d), combined with flucytosine, effectively treated HIV-uninfected CM and was well tolerated. Long-term fluconazole treatment with continued monitoring is beneficial for patients with persistent infection.

11.
Nanomaterials (Basel) ; 12(16)2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-36014646

RESUMO

Carbon fiber reinforced plastic (CFRP) is the main material of aircraft skin. Preparing superhydrophobic anti-icing/deicing surface on the CFRP is of great importance for aircraft flight safety. In this work, a variety of multi-scale micro-nano structures were imprinted on CFRP by femtosecond laser processing, and a transition from hydrophilic to superhydrophobic CFRP was realized. After being optimized by different geometries and laser conditions, the water contact angle, which is tested at 24.3 °C and 34% humidity, increased from 88 ± 2° (pristine) to 149 ± 3° (100 µm groove) and 153 ± 3° (80 µm grid). A further anti-icing test at -10 °C (measured on the cooling platform) and 28% humidity showed that the freezing time was increased from 78 ± 10 s (pristine) to 282 ± 25 s (80 µm grid). Most importantly, the tensile tests showed that the femtosecond laser processing method did not deteriorate the mechanical properties of CFRP. This work provides great significance for aircraft passive deicing technology.

12.
Pharmaceuticals (Basel) ; 15(8)2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36015161

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disease, and there is still no cure for it. PD is characterized by the degeneration of dopaminergic neurons, and oxidative stress has been considered an important pathological mechanism. Therefore, the discovery of antioxidants to alleviate the oxidative damage of dopaminergic neurons is a promising therapeutic strategy for PD. First, a network pharmacology approach was used, and nine common core targets of galangin and PD were screened, mainly involving cell aging, apoptosis, and cellular responses to hydrogen peroxide and hypoxia. In addition, the Gene Ontology (GO) function and pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) identified apoptosis, PI3K/Akt, and HIF-1 signaling pathways. Furthermore, the molecular docking results revealed a strong affinity between galangin and the NFE2L2/Nrf2 protein. To validate the above predictions, we employed 6-hydroxydopamine (6-OHDA) to induce neuronal death in HT22 cells and Caenorhabditis elegans (C. elegans). MTT, cell morphology observation, and Hoechst 33342-PI staining results showed that galangin significantly increased the viability of 6-OHDA-treated HT22 cells. In addition, galangin inhibited 6-OHDA-induced ROS generation and apoptosis in HT22 cells. Mechanistic studies demonstrated that galangin activates the Nrf2/Keap1 signaling pathway, as evidenced by the decreased protein expression of Keap1 and increased protein expression of Nrf2 and HO-1. In the 6-OHDA-induced PD model of C. elegans, galangin indeed inhibited the degeneration of dopaminergic neurons, improved behavioral ability, and decreased ROS generation. In conclusion, the current study is the first to show that galangin has the capacity to inhibit neuronal degeneration via the Nrf2/Keap1 pathway, suggesting that galangin is a possible PD treatment.

13.
Front Public Health ; 10: 871306, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35991042

RESUMO

Peer support for physical exercise is defined as behaviors such as mutual or one-way provision of material help and/or emotional care and companionship between peers in the physical environment and/or physical behavior. The assessment of peer support is complex and based on reasoning. Trustworthy assessment processes need to provide sufficient evidence of validity. The purpose of this study was to organize, collect, and use Kane's validity framework to provide validity evidence for the identification of peer support for physical exercise among college students. The article describes the experience of using the framework in this study, considers data related to the four inferences (scoring, generalization, extrapolation, and implication) that emerge from the assessment process. The findings of the study are then interpreted through the four inferences to determine whether this evidence supports the purpose of this study. Based on Kane's framework to explain the validity process of this study, the study concludes that the evidence in terms of scoring, generalization, extrapolation, and implication supports the use of the PEPSQ for the identification of physical exercise peer support among college students.


Assuntos
Competência Clínica , Avaliação Educacional , Exercício Físico , Humanos , Reprodutibilidade dos Testes , Estudantes , Inquéritos e Questionários
14.
Front Immunol ; 13: 993495, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36032125

RESUMO

The cerebrospinal fluid (CSF) immune responses in HIV-uninfected cryptococcal meningitis (CM) have not been well studied. In this study, we aimed to explore the phenotype of CSF immune response during the course of disease and to examine relationships between phenotypes and disease severity. We profiled the CSF immune response in 128 HIV-uninfected CM and 30 pulmonary cryptococcosis patients using a 27-plex Luminex cytokine kit. Principal component analyses (PCA) and logistic regression model were performed. Concentrations of 23 out of 27 cytokines and chemokines in baseline CSF were significantly elevated in CM patients compared with pulmonary cryptococcosis cases. In CM patients with Cryptococcus neoformans infection, IL-1ra, IL-9, and VEGF were significantly elevated in immunocompetent cases. Cytokine levels usually reached peaks within the first 2 weeks of antifungal treatment and gradually decreased over time. PCA demonstrated a co-correlated CSF cytokine and chemokine response consisting of Th1, Th2, and Th17 type cytokines. Prognostic analysis showed that higher scores for the PCs loading pro-inflammatory cytokines, IFN-γ, TNF-α, and IL-12; and anti-inflammatory cytokine, IL-4; and chemokines, Eotaxin, FGF-basis, and PDGF-bb; as well as lower scores for the PCs loading RANTES were associated with disease severity, as defined by a Glasgow Coma Scale of <15 or death. In conclusion, combined inflammatory responses in CSF involving both pro- and anti-inflammatory cytokines and chemokines are upregulated in HIV-uninfected CM, and associated with disease severity.


Assuntos
Criptococose , Infecções por HIV , Meningite Criptocócica , Quimiocinas , Citocinas , Humanos , Prognóstico
15.
Acta Pharmacol Sin ; 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35948752

RESUMO

Sensitization of central pain and inflammatory pathways play essential roles in migraine, a primary neurobiological headache disorder. Since hypoxia-inducible factor-1α (HIF-1α) is implicated in neuroprotection and inflammation inhibition, herein we investigated the role of HIF-1α in migraine. A chronic migraine model was established in mice by repeated injection of nitroglycerin (10 mg/kg, i.p.) every other day for 5 total injections. In the prevention and acute experiments, roxadustat, a HIF-1α stabilizer, was orally administered starting before or after nitroglycerin injection, respectively. Pressure application measurement, and tail flick and light-aversive behaviour tests were performed to determine the pressure pain threshold, thermal nociceptive sensitivity and migraine-related light sensitivity. At the end of experiments, mouse serum samples and brain tissues were collected for analyses. We showed that roxadustat administration significantly attenuated nitroglycerin-induced basal hypersensitivity and acute hyperalgesia by improving central sensitization. Roxadustat administration also decreased inflammatory cytokine levels in serum and trigeminal nucleus caudalis (TNC) through NF-κB pathway. Consistent with the in vivo results showing that roxadustat inhibited microglia activation, roxadustat (2, 10, and 20 µM) dose-dependently reduced ROS generation and inflammation in LPS-stimulated BV-2 cells, a mouse microglia cell line, by inhibiting HIF-1α/NF-κB pathway. Taken together, this study demonstrates that roxadustat administration ameliorates migraine-like behaviours and inhibits central pain sensitization in nitroglycerin-injected mice, which is mainly mediated by HIF-1α/NF-κB/inflammation pathway, suggesting the potential of HIF-1α activators as therapeutics for migraine.

16.
Front Microbiol ; 13: 932197, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35958122

RESUMO

Background: Gut microbiota is a complex ecosystem that is vital for the development and function of the immune system, is closely associated with host immunity, and affects human health and disease. Therefore, the current progress and trends in this field must be explored. Purpose: No bibliometric analysis has been conducted on gut microbiota and host immune response. This study aimed to analyze the current progress and developing trends in this field through bibliometric and visual analysis. Methods: Global publications on gut microbiota and host immune response from January 2011 to December 2021 were extracted from the Web of Science (WOS) collection database. GraphPad Prism, VOSviewer software, and CiteSpace were employed to perform a bibliometric and visual study. Results: The number of publications has rapidly increased in the last decade but has declined in the most recent year. The Cooperation network shows that the United States, Harvard Medical School, and Frontiers in Immunology were the most active country, institute, and journal in this field, respectively. Co-occurrence analysis divided all keywords into four clusters: people, animals, cells, and diseases. The latest keyword within all clusters was "COVID," and the most frequently occurring keyword was "SCFA." Conclusion: Gut microbiota and host immune response remain a research hotspot, and their relation to cancer, CNS disorders, and autoimmune disease has been explored. However, additional studies on gut microbiota must be performed, particularly its association with bacterial strain screening and personalized therapy.

17.
Cancer Res ; 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35969151

RESUMO

High-grade serous cancer (HGSC) is the most common subtype of ovarian cancer. HGSC is highly aggressive with poor patient outcomes, and a deeper understanding of HGSC tumorigenesis could help guide future treatment development. To systematically characterize the underlying pathological mechanisms and intratumoral heterogeneity in human HGSC, we used an optimized single-cell multiomics sequencing technology to simultaneously analyze somatic copy number alterations (SCNA), DNA methylation, chromatin accessibility, and transcription in individual cancer cells. Genes associated with interferon (IFN) signaling, metallothioneins, and metabolism were commonly upregulated in ovarian cancer cells. Integrated multiomics analyses revealed that upregulation of IFN signaling and metallothioneins was influenced by both demethylation of their promoters and hypomethylation of satellites and LINE1, and potential key transcription factors regulating glycolysis using chromatin accessibility data were uncovered. Additionally, gene expression and DNA methylation displayed similar patterns in matched primary and metastatic tumor cells of the same genetic lineage, suggesting that metastatic cells potentially preexist in subclones of primary tumors. Finally, the lineages of cancer cells with higher residual DNA methylation levels and upregulated expression of CCN1 and HSP90AA1 presented greater metastatic potential. This study characterizes the critical genetic, epigenetic, and transcriptomic features and their mutual regulatory relationships in ovarian cancer, providing valuable resources for identifying new molecular mechanisms and potential therapeutic targets for HGSC.

18.
Angew Chem Int Ed Engl ; : e202208174, 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-35960211

RESUMO

Here we report a new type of chiral all-carbon tetrasubstituted VQMs generated via chiral phosphoric acids catalyzed nucleophilic addition of 2-alkynylnaphthols to o-quinone methides or imines, which can be captured intramolecularly as a result of cycloaddition reaction. A new class of naphthyl-2H-chromenes bearing axially and centrally chiral elements and axially chiral quinone-naphthols were prepared efficiently with good to excellent yields, diastereoselectivities and enantioselectivities. Noteworthy, the enantioselective cycloaddition of alkynylnaphthols with o-quinone methides proceeded via a [2+2] cycloaddition, followed by a retro-4π-electrocyclization and a 6π re-cyclization. While the cycloaddition of alkynylnaphthols with imines proceeded via a sequential [2+4] cycloaddition and an auto oxidation reaction. Moreover, the obtained axially chiral naphthols can be converted into valuable phosphine ligands and other functional molecules.

19.
Infect Drug Resist ; 15: 4137-4147, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937782

RESUMO

Purpose: The emergence of drug-resistant tuberculosis (DR-TB) represents a threat to the control of tuberculosis. This study aimed to estimate the patterns and trends of DR-TB in patients with suspected DR-TB. In addition, risk factors for multidrug-resistant tuberculosis (MDR-TB) were identified among suspected DR-TB patients in Dalian, China. Patients and Methods: A total of 5661 patients with suspected DR-TB from Jan 1, 2013 to Dec 31, 2020 were included in the final analysis. The resistance pattern of all resistant strains was determined by drug susceptibility testing (DST) using the conventional Lowenstein-Jensen Proportion Method (LJ). DR-TB trends were estimated from 2013 to 2020. During the research period, the chi-square test was employed to analyze the significance of linear drug-resistance trends across time. Bivariate and multivariate logistic regression were performed to assess factors associated with MDR-TB. Results: From 2013 to 2020, the resistance rates of rifampicin (RFP) and isoniazid (INH) decreased significantly, whereas the resistance rates of ethambutol (EMB) and streptomycin (SM) increased in patients with suspected DR-TB. From 2013 to 2020, the prevalence of DR-TB decreased in all patients from 34.71% to 28.01% with an average annual decrease of 3.02%. Among new cases, from 2013 to 2020, the prevalence of DR-TB (from 26.67% to 24.75%), RFP-resistant TB (RR-TB) (from 15.09% to 3.00%) and MDR-TB (from 6.08% to 2.62%) showed a significant downward trend. Among patients with a previous treatment history, DR-TB (from 54.70% to 37.50%), RR-TB (from 44.16% to 11.49%) and MDR-TB (from 26.90% to 10.34%) showed a significant downward trend from 2013 to 2020. Males (AOR 1.28, 95% CI 1.035-1.585), patients 45 to 64 years of age (AOR 1.75, 95% CI 1.342-2.284), patients 65 years and older (AOR 1.65, 95% CI 1.293-2.104), rural residents (AOR 1.24, 95% CI 1.014-1.519) and a previous treatment history (AOR 3.94, 95% CI 3.275-4.741) were risk factors for MDR-TB. Conclusion: The prevalence of DR-TB, RR-TB and MDR-TB was significantly reduced from 2013 to 2020. Considerable progress has been made in the prevention and treatment of DR-TB during this period. However, the increasing rate of drug resistance in EMB and SM should be taken seriously. Suspected DR-TB patients who are male, older than 45 years of age, live in rural areas, and have a history of TB treatment should be given priority by health care providers.

20.
Biometrics ; 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35894546

RESUMO

The existing methods for subgroup analysis can be roughly divided into two categories: finite mixture models (FMM) and regularization methods with an ℓ1 -type penalty. In this paper, by introducing the group centers and ℓ2 -type penalty in the loss function, we propose a novel center-augmented regularization (CAR) method; this method can be regarded as a unification of the regularization method and FMM and hence exhibits higher efficiency and robustness and simpler computations than the existing methods. In particular, its computational complexity is reduced from the O ( n 2 ) $O(n^2)$ of the conventional pairwise-penalty method to only O ( n K ) $O(nK)$ , where n is the sample size and K is the number of subgroups. The asymptotic normality of CAR is established, and the convergence of the algorithm is proven. CAR is applied to a dataset from a multicenter clinical trial, Buprenorphine in the Treatment of Opiate Dependence; a larger R2 is produced and three additional significant variables are identified compared to those of the existing methods.

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