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1.
Opt Lett ; 47(15): 3888-3891, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35913339

RESUMO

This Letter proposes a holographic cylindrical vector beam converter (HCVBC) design that incorporates a continuously polarization-selective volume hologram circular-grating. A specially designed truncated cone prism is adopted for recording, which is conducted with a single incident, expanded, radially polarized beam. A prototype of this HCVBC was recorded and tested successfully. This design has the advantages of high diffraction efficiency, a narrow band, compactness, and planar configuration; thus, it is especially suitable for low-cost mass production and has high potential for application in related fields.

2.
Front Cell Infect Microbiol ; 12: 967493, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35923799

RESUMO

Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has posed a constant threat to human beings and the world economy for more than two years. Vaccination is the first choice to control and prevent the pandemic. However, an effective SARS-CoV-2 vaccine against the virus infection is still needed. This study designed and prepared four kinds of virus-like particles (VLPs) using an insect expression system. Two constructs encoded wild-type SARS-CoV-2 spike (S) fused with or without H5N1 matrix 1 (M1) (S and SM). The other two constructs contained a codon-optimized spike gene and/or M1 gene (mS and mSM) based on protein expression, stability, and ADE avoidance. The results showed that the VLP-based vaccine could induce high SARS-CoV-2 specific antibodies in mice, including specific IgG, IgG1, and IgG2a. Moreover, the mSM group has the most robust ability to stimulate humoral immunity and cellular immunity than the other VLPs, suggesting the mSM is the best immunogen. Further studies showed that the mSM combined with Al/CpG adjuvant could stimulate animals to produce sustained high-level antibodies and establish an effective protective barrier to protect mice from challenges with mouse-adapted strain. The vaccine based on mSM and Al/CpG adjuvant is a promising candidate vaccine to prevent the COVID-19 pandemic.


Assuntos
COVID-19 , Virus da Influenza A Subtipo H5N1 , Vacinas Virais , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/genética , Humanos , Imunoglobulina G , Camundongos , Camundongos Endogâmicos BALB C , Pandemias/prevenção & controle , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética
3.
Front Oncol ; 12: 848790, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35924158

RESUMO

Purpose: This study aimed to develop a deep convolutional neural network (DCNN) model to classify molecular subtypes of breast cancer from ultrasound (US) images together with clinical information. Methods: A total of 1,012 breast cancer patients with 2,284 US images (center 1) were collected as the main cohort for training and internal testing. Another cohort of 117 breast cancer cases with 153 US images (center 2) was used as the external testing cohort. Patients were grouped according to thresholds of nodule sizes of 20 mm and age of 50 years. The DCNN models were constructed based on US images and the clinical information to predict the molecular subtypes of breast cancer. A Breast Imaging-Reporting and Data System (BI-RADS) lexicon model was built on the same data based on morphological and clinical description parameters for diagnostic performance comparison. The diagnostic performance was assessed through the accuracy, sensitivity, specificity, Youden's index (YI), and area under the receiver operating characteristic curve (AUC). Results: Our DCNN model achieved better diagnostic performance than the BI-RADS lexicon model in differentiating molecular subtypes of breast cancer in both the main cohort and external testing cohort (all p < 0.001). In the main cohort, when classifying luminal A from non-luminal A subtypes, our model obtained an AUC of 0.776 (95% CI, 0.649-0.885) for patients older than 50 years and 0.818 (95% CI, 0.726-0.902) for those with tumor sizes ≤20 mm. For young patients ≤50 years, the AUC value of our model for detecting triple-negative breast cancer was 0.712 (95% CI, 0.538-0.874). In the external testing cohort, when classifying luminal A from non-luminal A subtypes for patients older than 50 years, our DCNN model achieved an AUC of 0.686 (95% CI, 0.567-0.806). Conclusions: We employed a DCNN model to predict the molecular subtypes of breast cancer based on US images. Our model can be valuable depending on the patient's age and nodule sizes.

4.
Acta Pharmacol Sin ; 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927312

RESUMO

As a breakthrough strategy for cancer treatment, immunotherapy mainly consists of immune checkpoint inhibitors (ICIs) and other immunomodulatory drugs that provide a durable protective antitumor response by stimulating the immune system to fight cancer. However, due to the low response rate and unique toxicity profiles of immunotherapy, the strategies of combining immunotherapy with other therapies have attracted enormous attention. These combinations are designed to exert potent antitumor effects by regulating different processes in the cancer-immunity cycle. To date, immune-based combination therapy has achieved encouraging results in numerous clinical trials and has received Food and Drug Administration (FDA) approval for certain cancers with more studies underway. This review summarizes the emerging strategies of immune-based combination therapy, including combinations with another immunotherapeutic strategy, radiotherapy, chemotherapy, anti-angiogenic therapy, targeted therapy, bacterial therapy, and stroma-targeted therapy. Here, we highlight the rationale of immune-based combination therapy, the biomarkers and the clinical progress for these immune-based combination therapies.

5.
J AOAC Int ; 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35924959

RESUMO

BACKGROUND: Fragrance allergens (FAs) refer to these volatile or semi-volatile fragrance compounds that can induce sensitization, and they are widely used in household goods. OBJECTIVE: In this work, a method combining solid-liquid extraction (SLE) and dispersive liquid-liquid microextraction (DLLME) with gas chromatography-mass spectrometry (GC-MS) has been developed and applied in the analysis of 19 FAs (including hydrocarbons, alcohols, aldehydes, esters and phenols) in paper household goods. METHOD: The samples (infant or personal paper hygiene products) were cut into small pieces, and underwent SLE with methanol as solvent. The supernatant was taken, and ultrapure water, sodium chloride and trichloromethane (extractant) were added, which was mixed with vortex. After centrifugation, the bottom chloroform layer was taken for GC-MS detection. RESULTS: Under optimized conditions, a good linearity was achieved (r ≥ 0.9985) in the range of 0.01-128.0 mg/kg with relative standard deviations lower than 15%. The method showed limits of detection (LODs) within the range of 0.96-12.0 µg/kg and recoveries from 70.6% to 128.9% except furfuryl alcohol with low recoveries (53.8-64.6%). Twenty kinds of paper household goods samples were analyzed by this method, nine FAs were detected. The linalool detected in one sample was more than 10 mg/kg, and the contents of other analytes in this sample and all analytes in other samples were less than 10 mg/kg. CONCLUSION: The performance evaluation of the method met the requirements of the analysis of trace components. The established method was successfully applied to the detection of FAs in paper household goods samples. The proposed method could provide a basis for the establishment of relevant detection standards in the future. HIGHLIGHTS: The LODs were found between 0.96-12.0 µg/kg. A simple, economical and sensitive method was established for the determination of 19 FAs in paper household goods.

6.
Artigo em Inglês | MEDLINE | ID: mdl-35925279

RESUMO

BACKGROUND: Sub-anesthetic ketamine has rapid-onset effects for the treatment of major depressive disorder (MDD). However, the mechanism underlying ketamine's antidepressant properties remains unclear. Recent studies have reported an interrelationship between autophagy and the inflammasome, both of which are involved in the pathophysiology of MDD. In this study, we assess whether ketamine exerts its antidepressant effects via an association with the autophagy-NLRP3 inflammasome pathway. METHODS: We established a depressive-like rat model by treating Wistar Kyoto rats with chronic restraint stress (CRS) for 28 days. Microglial cells from newborn Sprague-Dawley rats were used for in vitro experiments. RESULTS: We found sub-anesthetic ketamine treatment reversed depressive-like behavior in CRS rats. Ketamine triggered autophagy in the microglia of prefrontal cortex (PFC) and (hippocampus) HPC, with increased levels of LC3B, decreased levels of p62 protein, and elevated autophagosomes both in vivo and in vitro. Moreover, NLRP3 inflammasome activation was also inhibited by ketamine, with reduced expression of NLRP3-ASC-CASP1 assembly and decreased IL-1ß levels in cerebrospinal fluid (CSF) as well as in the serum. Increased BDNF levels and synaptophysin levels were detected in the ketamine-treated group. The rapid anti-depressive effects, elevation of autophagy, reduction in NLRP3, and neuroplasticity-related factors induced by ketamine could be significantly blocked by the autophagy inhibitor Baf A1 (0.1 mg/kg). CONCLUSIONS: Our findings demonstrate that sub-anesthetic doses of ketamine exert their antidepressant-like effects by inhibiting inflammation and initiating neuroprotection via autophagy activation. These data might help expand future investigations on the antidepressant properties of ketamine.

7.
Front Endocrinol (Lausanne) ; 13: 891313, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909545

RESUMO

Osteoporosis is a bone metabolic disorder characterized by decreased bone density and deteriorated microstructure, which increases the risk of fractures. The imbalance between bone formation and bone resorption results in the occurrence and progression of osteoporosis. Osteoblast-mediated bone formation, osteoclast-mediated bone resorption and macrophage-regulated inflammatory response play a central role in the process of bone remodeling, which together maintain the balance of the osteoblast-osteoclast-macrophage (OB-OC-MΦ) axis under physiological conditions. Bone formation and bone resorption disorders caused by the imbalance of OB-OC-MΦ axis contribute to osteoporosis. Many microRNAs are involved in the regulation of OB-OC-MΦ axis homeostasis, with microRNA-23a (miR-23a) being particularly crucial. MiR-23a is highly expressed in the pathological process of osteoporosis, which eventually leads to the occurrence and further progression of osteoporosis by inhibiting osteogenesis, promoting bone resorption and inflammatory polarization of macrophages. This review focuses on the role and mechanism of miR-23a in regulating the OB-OC-MΦ axis to provide new clinical strategies for the prevention and treatment of osteoporosis.


Assuntos
Reabsorção Óssea , MicroRNAs , Osteoporose , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Humanos , Macrófagos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteoporose/etiologia , Osteoporose/genética , Osteoporose/fisiopatologia , Osteoporose/terapia
8.
Ann Transl Med ; 10(9): 506, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35928745

RESUMO

Background: The proximal tubule is the sensing site of sodium and phosphate and the main place for the synthesis and metabolism of 1,25(OH)2D3. We aimed to investigate the effects of high sodium on the synthesis and function of active vitamin D and local phosphate regulation in proximal tubular epithelial cells. Methods: Human proximal tubule epithelial (HK-2) cells were treated with different concentrations of sodium/phosphate. The expression of 1α-OHase and 24-OHase was determined. Liquid chromatography/mass spectrometry (LC/MS) and enzyme-linked immunosorbent assay (ELISA) were used to detect the levels of 1,25(OH)2D3. RNA sequencing and bioinformatics analysis was used to probe into the possible pathways. Chromatin samples were immunoprecipitated with antibodies against parathyroid receptor 1 (PTH1R) and Klotho. Results: We found that high sodium decreased the expression of 1,25(OH)2D3 by reducing 1α-OHase and 24-OHase, reduced the expression of PTH1R and Klotho, and increased the intracellular calcium concentration. These effects were reversed by sodium phosphate transporter inhibitor, sodium hydrogen transporter inhibitor, and a chelator of the extracellular calcium, whereas enhanced by ouabain. Vitamin D receptor (VDR) agonists significantly increased the recruitment of VDR to the vitamin D response element (VDRE) of PTH1R and Klotho promoter, thus increasing the expression of PTH1R and Klotho. Conclusions: High sodium can decrease the synthesis of active vitamin D in the proximal tubules, affect the gene regulation of 1,25(OH)2D3/VDR, and significantly reduce the expression of PTH1R and Klotho. It revealed the influence of a high-sodium diet on mineral metabolism and the core role of vitamin D in kidney mineral metabolism.

9.
Brain Res Bull ; 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35931406

RESUMO

Mounting evidence indicates that histone modifications are involved in aging-associated cognitive decline (AACD) and can be transmitted to offspring over multiple generations under conditions of stress. Here, we investigated the effects of maternal sub-chronic inflammation caused by lipopolysaccharide (LPS) on AACD and histone modifications in the F1 and F2 generations of experimental mice as well as the potential sex specificity of intergenerational effects. In brief, F0-generation CD-1 dams were exposed to LPS (50µg/kg) or saline (CON) during late pregnancy. Subsequently, F1 males and females (at 2 months-of-age) from the LPS treatment group were mated with non-littermates from the LPS group or wild-type mice to produce F2 generations of parental- (F2-LPS2), paternal- (F2M-LPS1) and maternal-origin (F2F-LPS1) mice. Then, CON-F1 males and females were mated with wild-type mice to generate F2 generations of paternal- (F2M-CON1) and maternal-origin (F2F-CON1). Next, we evaluated the cognitive ability and levels of hippocampal H4K12ac and H3K9me3 in the F1 and F2 offspring at 3- and 13 months-of-age. Overall, F1 male and female LPS groups presented with elevated corticosterone (P < 0.001, P = 0.036, P = 0.025, 0.012, respectively) and cytokine responses, poorer cognitive performance (all P < 0.05) and H3K9 hypermethylation and H4K12 hypoacetylation in the dorsal hippocampus (all P < 0.05); these issues were carried over to the F2 generation via the parents, predominantly in the paternal lineage. Moreover, the levels of H3K9me3 and H4K12ac were significant correlated with cognitive performance (all P < 0.05), regardless of whether inflammatory insults had been incurred directly or indirectly. These findings indicated that gestational inflammatory insults in the F0 generation accelerated AACD in the F2 generation, along with H3K9 hypermethylation and H4K12 hypoacetylation in the hippocampus, and that these issues were derived from the F1 parents, especially from the F1 fathers. AVAILABILITY OF DATA AND MATERIALS: The datasets supporting the conclusions of this article are included within.

11.
Front Pediatr ; 10: 896824, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911838

RESUMO

An 11-year-old girl presented with frequent chest pain, fever, and a cough that she had had for more than 13 months, as well as pleural effusion and large pericardial effusion. She was misdiagnosed with tuberculosis and received anti-tuberculosis drugs for 6 months. Within the past year, she also underwent two more thoracotomies and a thoracoscopic partial pericardiectomy. The final diagnosis of pulmonary paragonimiasis was established once it was known that she had eosinophilia, always drank stream water, and tested positive for antibodies against Paragonimus. Since antiparasitic praziquantel therapy was effective, paragonimiasis should be considered as a possibility in the differential diagnosis of tuberculosis in children.

12.
Front Mol Biosci ; 9: 919274, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911954

RESUMO

Senescence is a double-edged sword in tumorigenesis and affects the immunotherapy response through the modulation of the host's immune system. However, there is currently a lack of comprehensive analysis of the senescence-related genes (SRGs) in human cancers, and the predictive role of senescence in cancer immunotherapy response has not been explored. The multi-omics approaches were performed in this article to conduct a systematic pan-cancer genomic analysis of SRGs in cancer. In addition, we calculated the generic senescence score (SS) to quantify the senescence levels in cancers and explored the correlations of SS with cancer prognosis, biological processes, and tumor microenvironment (TME). The gene signatures were deregulated in multiple cancers and indicated a context-dependent correlation with prognosis, tumor-immune evasion, and response to therapy across various tumor types. Further analysis disclosed that SS was positively associated with the infiltration levels of immune suppressive cells, including induced Tregs (iTregs), central memory Ts (Tcms), and natural Tregs (nTregs), and negatively associated with immune killer cells, including natural killers (NKs) and mucosal-associated invariant Ts (MAITs). Moreover, the SS was significantly correlated with tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), immune-related genes, and immune checkpoints and had a predictive value of immunotherapy response. Thus, the expression of SRGs was involved in resistance to several anticancer drugs. Our work illustrates the characterization of senescence across various malignancies and highlights the potential of senescence as a biomarker of the response to immunotherapy.

13.
Front Oncol ; 12: 881829, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912184

RESUMO

Helicobacter pylori (H. pylori)-derived vacuolating cytotoxin A (VacA) causes damage to various organelles, including mitochondria, and induces autophagy and cell death. However, it is unknown whether VacA-induced mitochondrial damage can develop into mitophagy. In this study, we found that H. pylori, H. pylori culture filtrate (HPCF), and VacA could activate autophagy in a gastric epithelial cell line (GES-1). VacA-caused mitochondrial depolarization retards the import of PINK1 into the damaged mitochondria and evokes mitophagy. And, among mass spectrometry (LC-MS/MS) identified 25 mitochondrial proteins bound with VacA, Tom20, Tom40, and Tom70, TOM complexes responsible for PINK1 import, were further identified as having the ability to bind VacA in vitro using pull-down assay, co-immunoprecipitation, and protein-protein docking. Additionally, we found that the cell membrane protein STOM and the mitochondrial inner membrane protein PGAM5 also interacted with VacA. These findings suggest that VacA captured by STOM forms endosomes to enter cells and target mitochondria. Then, VacA is transported into the mitochondrial membrane space through the TOM complexes, and PGAM5 aids in inserting VacA into the inner mitochondrial membrane to destroy the membrane potential, which promotes PINK1 accumulation and Parkin recruitment to induce mitophagy. This study helps us understand VacA entering mitochondria to induce the mitophagy process.

14.
Front Oncol ; 12: 947810, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912235

RESUMO

Background: Endoscopic forceps biopsy (EFB) lacks precision in diagnosing indeterminate tumors. When the presence of early gastric cancer (EGC) is macroscopically suspected, but biopsy pathology fails to give a diagnosis of neoplasia, it causes problems in clinical management. The purpose of this study was to discuss the outcome of gastric indeterminate tumors and the clinical factors associated with predicting EGC. Methods: The medical records of 209 patients diagnosed with gastric indeterminate neoplasia by biopsy forceps were retrospectively studied. Initial endoscopic findings were analyzed and predictors of EGC were evaluated. Results: The final pathological diagnosis in 209 patients included adenocarcinoma (n = 7), high-grade intraepithelial neoplasia (n = 11), low-grade intraepithelial neoplasia (n = 21), and non-neoplastic lesion (n = 170). Multivariate analysis showed that older age (OR = 1.78; 95% CI = 1.17-2.71; p = 0.008), patients undergoing narrow band imaging (NBI) (OR = 3.40; 95% CI = 1.37-8.43; p = 0.008), and surface erosion (OR = 3.53; 95% CI = 1.41-8.84; p = 0.007) were associated with the upgraded group, and were significantly associated with risk. Univariate logistic regression analysis showed that among patients with NBI, the presence of demarcation line (DL) (OR = 24.00; 95% CI = 4.99-115.36; p < 0.0001), microvascular (MV) pattern irregularity (OR = 9.129; 95% CI = 2.36-35.34; p = 0.001), and the presence of white opaque substance (WOS) (OR = 10.77; 95% CI = 1.14-101.72; p = 0.038) were significant risk factors. Conclusions: For gastric indeterminate tumors, older patient age, lesion surface with erosion, clear DL visible under NBI observation, presence of WOS, and irregular MV pattern are suggestive of the high possibility of neoplasia and need to be focused on and may benefit more from endoscopic resection treatment as opposed to simple endoscopic follow-up.

15.
Eur J Pharm Biopharm ; 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35932965

RESUMO

Co-amorphous strategy has been extensively investigated to improve the dissolution of hydrophobic drugs. Here, epigallocatechin-3-gallate (EGCG) was exploited as a co-former in co-amorphous systems based on its unique structure including phenyl rings, phenolic hydroxyl groups and the galloyl moiety. Two model BCS class II drugs, simvastatin (SIM) and nifedipine (NIF), were selected to be co-amorphized with EGCG. All drug-EGCG systems at three molar ratios became amorphous by the means of spray drying and showed high physically stable either under dry condition and 75% RH at 40 °C or under dry conditions at 25 °C. The optimal feed molar ratios of both EGCG based co-amorphous systems fabricated were determined to be three, under which the significant increases were obtained in the maximum apparent concentrations of 4.90-fold for SIM at 1 h and 106.03-fold for NIF at 0.25 h compared to crystalline drugs by non-sink dissolution studies. The underlying molecular mechanisms of two co-amorphous systems formation were involved in molecular miscibility, hydrogen bonds and π-π stacking interactions unraveled by means of DSC, FTIR and molecular dynamics simulations. More to the point, oral pharmacokinetic studies in rats demonstrated that co-amorphous SIM-EGCG and NIF-EGCG systems at 1:3 have a significant increase in Cmax of 1.81- and 5.69-fold, and AUC 0-24 h of 1.62- and 4.57-fold compared with those of corresponding crystalline drugs, respectively. In conclusion, EGCG is proved to be a promising co-former in co-amorphous systems.

16.
Phytomedicine ; 105: 154342, 2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-35914360

RESUMO

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been regarded as an effective and exciting target in the treatment of atherosclerotic cardiovascular disease since 2003. Only two monoclonal antibodies have been approved in the market which, however, were also criticized for their high cost to $9000 per dose and delivery route. Exploration of natural new effective and cheaper small molecule alternatives with effective PCSK9 inhibition is feasible and desired. PURPOSE: The aim of the study was to explore natural small molecules with anti-hyperlipidemia activity through PCSK9 from Alisma plantago-aquatica. METHOD: A targeted isolation of triterpenoids from A. plantago-aquatica by LC-Orbitrap-QDa was conducted. The isolates were evaluated for their DiI-LDL uptake promoting activity with fluorescence intensity assayed in High-content Imaging System and PCSK9 inhibitory activity by Human PCSK9 Kit or western blot. The LDL uptake and PCSK9 level of target component in different concentrations and their mRNA level were further verified by corresponding kit, qPCR and western blot. RESULTS: Six novel triterpenoids, including three unusual nor-triterpenoids (1-3) and three protostane-type triterpenoids (4-6), along with thirty-four known ones, were isolated from A. plantago-aquatica. Compound 2 had the lowest number of carbon atoms than previous reported nor-PTs in this plant. The 17 triterpenoids showed relatively remarkable activities in promoting LDL uptake with relevant structure-activity relationships. And 6 triterpenoids may improve LDL uptake in HepG2 cells by inhibiting PCSK9, especially for alisol G (28) with PCSK9 inhibition reaching to 55.6%, which demonstrated to increase LDLR mRNA or protein, and simultaneously reduce PCSK9 mRNA or protein significantly. CONCLUSION: The protostane triterpenoids may serve as a new source for PCSK9 inhibitors.

17.
Comput Math Methods Med ; 2022: 1557861, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928975

RESUMO

Objective: To study the effects of modified Lamaze breathing on abdominal pain experienced during colonoscopy. Methods: Eighty-five patients who underwent common colonoscopy at our hospital between March 2021 and May 2021 were selected and randomly divided into the Lamaze group (n = 40) and a control group (n = 45). Their basic clinical information was collected, and the bowel cleanliness, the time for the endoscope to reach the ileocecal junction, and the degree of abdominal pain of the two groups were compared. Results: No significant difference was observed in age, gender, bowel cleanliness, and time of endoscope to reach the ileocecal junction between the two groups. However, the degree of abdominal pain (anal region, descending sigmoid colon junction, splenic flexure, and hepatic flexure) was significantly lower in the Lamaze group compared with the control group. Conclusion: Modified Lamaze breathing demonstrated promising effectiveness in reducing abdominal pain during colonoscopy and improving the quality of the examination.


Assuntos
Dor Abdominal , Colonoscopia , Dor Abdominal/etiologia , Humanos
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(8): 829-835, 2022 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-35929931

RESUMO

OBJECTIVE: To analyze the characteristics of lysosomal enzymes in mucolipidosis (ML) type II α/ß and type III α/ß for the choice of enzyme evaluating indicators. METHODS: Multiple lysosomal enzymes including α-iduronidase (IDUA), α -N-acetylglucosaminidase (NAGLU), ß-galactosidase-1 (GLB1), ß-glucuronidase (GUSB), α-galactosidase A (GLA), glucocerebrosidase (GBA) and arylsulphatase A (ASA) in plasma and leukocyte of two Chinese pedigrees with ML type II α/ß and type III α/ß and healthy controls were determined. Previous publications on ML type II α/ß and type III α/ß during the last five years were retrieved from PubMed, CNKI and WanFang databases by using "mucolipidosis" as key word. RESULTS: The activities of several lysosomal enzymes were increased in the plasma of both patients: ASA, IDUA (20-fold) > GUSB (10-fold) > GLB1, GLA (5-fold) > NAGLU (2-fold), whilst there was no significant change in GBA. The activities of several lysosomal enzymes in the leukocyte of the two patients were normal. 15 lysosomal enzymes have been used in 22 previous studies, the most frequently used were hexosaminidase A and B (Hex A+B) (12 papers), α-mannosidase (α-man) (11 papers) and GUSB (10 papers). The degree of Hex A+B and α-man elevation was most obvious (24.4-fold and 24.7-fold on average respectively), followed by ASA (22.4-fold on average), GUSB is 18.8-fold on average. CONCLUSION: Based on the lysosomal enzyme analysis of the two cases and literature review, ASA, GUSB, Hex A+B and α-man are recommended as the evaluating indicators for lysosomal enzyme analysis of ML type II α/ß and type III α/ß.

19.
Nat Commun ; 13(1): 4565, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931700

RESUMO

Reactions that lead to destruction of aromatic ring systems often require harsh conditions and, thus, take place with poor selectivities. Selective partial dearomatization of fused arenes is even more challenging but can be a strategic approach to creating versatile, complex polycyclic frameworks. Herein we describe a general organophotoredox approach for the chemo- and regioselective dearomatization of structurally diverse polycyclic aromatics, including quinolines, isoquinolines, quinoxalines, naphthalenes, anthracenes and phenanthrenes. The success of the method for chemoselective oxidative rupture of aromatic moieties relies on precise manipulation of the electronic nature of the fused polycyclic arenes. Mechanistic studies show that the addition of a hydrogen atom transfer (HAT) agent helps favor the dearomatization pathway over the more thermodynamically downhill aromatization pathway. We show that this strategy can be applied to rapid synthesis of biologically valued targets and late-stage skeletal remodeling en route to complex structures.

20.
BMC Cancer ; 22(1): 858, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35932022

RESUMO

BACKGROUND: Inflammatory parameters and Epstein-Barr virus (EBV) DNA status have been confirmed to be associated with prognosis in nasopharyngeal carcinoma (NPC) patients. However, there are few in-depth studies on the prognosis of NPC patients with negative EBV DNA. Our study aimed to look for inflammatory biomarkers that can identify disease progression in NPC patients with negative EBV DNA. METHODS: A total of 795 NPC patients were recruited, and ultimately 325 NPC patients with negative EBV DNA were included in this study (170 in training cohort and 155 in validation cohort). Kaplan-Meier method and log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). The multivariate analysis of Cox proportional hazards regression model was used to determine the independent prognostic factors. Receiver operating characteristic (ROC) curves were used to assess prognostic value. The logistic regression was used to evaluate the relationship between EBV DNA status and inflammatory parameters. The correlation between clinical characteristics was analyzed by the chi-squared test or the Fisher's exact test. RESULTS: The optimal cutoff point for the SIRI was 1.12. The EBV DNA-negative NPC patients with high SIRI level had worse PFS and OS (all p < 0.001). In multivariate Cox proportional hazard models analysis, SIRI was an independent prognostic factor for PFS and OS (all p < 0.05), and had higher prognostic value than other indicators. Above results were found in the training cohort and confirmed in the validation cohort. In addition, EBV DNA status was not associated with any inflammatory parameters. CONCLUSIONS: The SIRI can provide more accurate risk stratification and better prognostic prediction for NPC patients with negative EBV DNA.

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