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1.
Front Med (Lausanne) ; 8: 754944, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722591

RESUMO

Background: Bloodstream infections (BSIs) are recognized as important nosocomial infections. Klebsiella pneumoniae is one of the major causes of bacteremia. This retrospective study focused on drug susceptibility and molecular epidemiology of K. pneumoniae isolated from intensive care unit (ICU) patients with BSI in Shanghai, China. Methods: Consecutive K. pneumoniae isolates were collected from ICU patients. Antibiotic susceptibility testing was conducted by the broth microdilution method. PCR was performed to detect antimicrobial resistance genes. We also completed multilocus sequence typing (MLST) and GoeBURST was used to analyze the result of MLST. Results: A total of 78 K. pneumoniae isolates were enrolled. K. pneumoniae from ICU-BSIs were highly resistant to almost all common antibiotics. The most frequent resistance determinants responsible for extended-spectrum ß-lactamase (ESBL) producers were bla CTX-M-14, bla CTX-M-15, and bla CTX-M-55. KPC was the only enzyme, which was detected by the carbapenemase producers. The most principal sequence types (STs) were ST11, ST15, and ST23. Conclusion: This study presents for the first time the antibiotic resistance phenotype and molecular epidemiology of K. pneumoniae isolated from ICU patients with BSIs in Shanghai. ICU-BSI K. pneumoniae is characteristic of a high resistance rate. The occurrence of the KPC-2 enzyme may result from nosocomial clonal dissemination of ST11 K. pneumoniae.

2.
Front Vet Sci ; 8: 721102, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722696

RESUMO

Pigeon paramyxovirus type 1 (PPMV-1) is considered as an antigenic variant of Newcastle disease virus (NDV) which has an obvious host preference for pigeons and has caused significant economic losses to the global poultry industry. The evolutionary dynamics of PPMV-1 in China, however, are poorly understood. In this study, we characterized seven PPMV-1 isolates from diseased pigeons collected in Jiangsu, Anhui, and Henan provinces during 2020. Phylogenetic analysis revealed that seven isolates belonged to sub-genotype VI.2.1.1.2.2. Biological characterization indicated that seven isolates were mesogenic based on the mean death time (69.6-91.2 h) and intracerebral pathogenicity index (1.19-1.40) and had similar growth kinetics in chicken embryos and CEFs. Furthermore, the four representative viruses (AH/01/20/Pi, JS/06/20/Pi, HN/01/20/Pi, and HN/02/20/Pi) could result in marked cytopathic effects (CPE) in CEFs and induced syncytium formation in Vero cells. Our Bayesian phylogenetic analysis showed that PPMV-1 might first emerge in East China in 1974 and East China had the highest genotypic diversity of PPMV-1. Besides, phylogeographic analysis indicated that East China and South China were probably the major epicenters of dissemination of PPMV-1 in China. Selection pressure analysis and amino acid substitutions analysis revealed that the viral replication complex (NP, P, and L proteins) was likely related with the host preference of PPMV-1. Collectively, this study uncovered the epidemiology and evolutionary dynamics of PPMV-1 circulating in China, emphasizing the importance of strengthening the monitoring of PPMV-1 in East China and South China and providing significant clues for further studies on the molecular mechanism underlying host preference of PPMV-1.

3.
Thorac Cancer ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34730281

RESUMO

BACKGROUND: Esophageal cancer is currently the eighth most common tumor in the world and a leading cause of cancer death. SULT2B1 plays crucial roles in tumorigenesis. The purpose of this study is to explore the role of SULT2B1 in esophageal squamous cell carcinoma (ESCC). METHODS: The expression of SULT2B1 and its clinicopathological characteristics were evaluated in ESCC cohorts. Bisulfite genomic sequencing and methylation specific PCR were used to detect the promoter hypermethylation of the SULT2B1 gene. The effects of SULT2B1 on the biological characters of ESCC cells were identified on functional assays. Subcutaneous xenograft models revealed the role of SULT2B1 in vivo with tumor growth. RNA-Seq analysis and qRT-PCR were performed to recognize the targeted effect of SULT2B1 on PER1. RESULTS: SULT2B1 was not expressed or at a low level in most patients with ESCC or in ESCC cell lines, and this was accompanied by poor clinical prognosis. Furthermore, the downregulation of SULT2B1 occurred in promoter hypermethylation. According to the functional results, overexpression of SULT2B1 could inhibit tumoral proliferation in vitro and retard tumor growth in vivo, whereas SULT2B1 knockdown could accelerate ESCC progression. Mechanistically, SULT2B1 targeted PER1 at the mRNA level during post-transcriptional regulation. Finally, PER1 was verified as a suppressor and poor-prognosis factor in ESCC. CONCLUSIONS: SULT2B1 loss is a consequence owing to its ability to promote hypermethylation. In addition, it serves as a suppressor and poor-prognosis factor because of the post-transcriptional regulation of PER1 in ESCC.

4.
Foods ; 10(11)2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34828820

RESUMO

Salmonella typhimurium (S. typhimurium) is a foodborne pathogen that has caused numerous outbreaks worldwide, necessitating the development of on-site strategy to prevent early contamination. Here, we set up an enzyme-free strategy for aptamer-catalyzed hairpin assembly in which salt-induced aggregation of unmodified gold nanoparticles (AuNPs) served as a colorimetric signal output, allowing on-site detection of S. typhimurium in milk. The aptamer-functionalized magnetic beads were used as a vehicle of specifically enriching target bacteria which conjugated with target aptamer to trigger the "Y" shape catalytic hairpin assembly (Y-CHA) circuit. Due to the hairpins desorbing from the surface of AuNPs to the formation of a large amount of double-stranded DNA (dsDNA), AuNPs turned from dispersion to aggregation in the presence of S. typhimurium, resulting in a change of the colorimetric signal from red to blue-gray. The signal output showed a linear relationship for S. typhimurium over a concentration range of 102 to 106 CFU/mL, with a sensitivity of 2.4 × 102 CFU/mL under optimal conditions. The visual protocol has excellent selectivity even in the presence of other competitive bacteria and has been validated in real milk samples with a sensitivity of 2.8 × 103 CFU/mL.

5.
Small ; : e2105744, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34837337

RESUMO

For expanding the applications of 2D transition metal dichalcogenides (TMDCs), integrating functional devices with diverse conduction polarities in the same parent material is a very promising direction. Improving the contact issue at the metal-semiconductor interface also holds fundamental significance. To achieve these concurrently, step-like Cr2 S3 vertical stacks with varied thicknesses are achieved via a one-step chemical vapor deposition (CVD) method route. Various types of 2D Cr2 S3 lateral homojunctions are thus naturally evolved, that is, pm -ambipolar/n, p/ambipolar, ambipolar/n, and nm -ambipolar/n junctions, allowing the integration of diverse conduction polarities in single Cr2 S3 homojunctions. Significantly, on-state current density and field-effect mobility of the thinner 2D Cr2 S3 flakes stacked below are detected to be ≈5 and ≈6 times increased in the lateral homojunctions, respectively. This work should hereby provide insights for designing 2D functional devices with simpler structures, for example, multipolar field-effect transistors, photodetectors, and inverters, and provide fundamental references for optimizing the electrical performances of 2D materials related devices.

6.
Int J Mol Sci ; 22(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34769196

RESUMO

Flowering connects vegetative and generative developmental phases and plays a significant role in strawberry production. The mechanisms that regulate strawberry flowering time are unclear. B-box transcription factors (BBXs) play important roles in the flowering time regulation of plants. Nevertheless, BBXs in octoploid cultivated strawberry (Fragaria ananassa) and their functions in flowering time regulation have not been identified. Here, we identified 51 FaBBXs from cultivated strawberry and 16 FvBBXs from diploid wild strawberry (Fragaria vesca), which were classified into five groups according to phylogenetic analysis. Further evolutionary analysis showed that whole-genome duplication or segmental duplication is a crucial factor that leads to the expansion of the BBX gene family in two strawberry species. Moreover, some loss and acquisition events of FaBBX genes were identified in the genome of cultivated strawberry that could have affected traits of agronomic interest, such as fruit quality. The promoters of FaBBX genes showed an enrichment in light-responsive, cis-regulatory elements, with 16 of these genes showing changes in their transcriptional activity in response to blue light treatment. On the other hand, FaBBX28c1, whose transcriptional activity is reduced in response to blue light, showed a delay in flowering time in Arabidopsis transgenic lines, suggesting its role in the regulation of flowering time in cultivated strawberry. Our results provide new evolutionary insight into the BBX gene family in cultivated strawberry and clues regarding their function in flowering time regulation in plants.

7.
Materials (Basel) ; 14(21)2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34771819

RESUMO

In this study, we measure the in-plane transport properties of high-quality Ba(Fe0.914Co0.086)2As2 single crystals. Signatures of vortex unbinding Berezinskii-Kosterlitz-Thouless (BKT) transition are shown from both the conventional approach and the Fisher-Fisher-Huse dynamic scaling analysis, in which a characteristic Nelson-Kosterlitz jump is demonstrated. We also observe a non-Hall transverse signal exactly at the superconducting transition, which is explained in terms of guided motion of unbound vortices.

8.
PLoS One ; 16(11): e0260028, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34780552

RESUMO

Hepatitis B is a leading cause of death worldwide. Here, we performed a large, population-based, cross-sectional study in Chongqing, China from 2011 to 2016 to assess the prevalence of HBsAg among couples of reproductive age, to predict subsequent trends, and to provide evidence for the WHO goal of "the elimination of viral hepatitis as a public health threat by 2030". A total of 386,286 couples aged 20 to 49 years were enrolled in the study. Approximately 14.35% of couples were HBsAg positive, including 95.00% with discordant HBsAg positivity. HBsAg prevalence was higher in men than in women. Among different occupations, the two categories of "houseworker" (female 6.73%, male 9.99%) and "unemployed" (female 6.64%, male 9.94%) showed the highest HBsAg positivity. In different regions, the lowest prevalence appeared in southeastern Chongqing (female 4.87%, male 7.71%). In 2030, the HBsAg positivity rate is expected to be 2.79%, 7.27% and 5.13% in females, males, and the whole population, respectively. According to the trends, this rate would drop to less than 2% in 2034, 2078 and 2051. In conclusion, the HBsAg prevalence in Chongqing is still relatively high compared with that in other parts of western China, especially among reproductive-age men. HBsAg-positive couples should be taken as an important unit of care. Vaccination is necessary before pregnancy if no antibody is found. More attention should be given to people without stable jobs. HBsAg-positive rate will decrease perceptibly by 2030 and will reach the level of low in epidemic areas by 2050.

9.
World J Clin Cases ; 9(30): 9269-9275, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34786413

RESUMO

BACKGROUND: Neonatal hepatic portal venous gas (HPVG) is associated with a high risk of necrotizing enterocolitis (NEC) and was previously believed to be associated with an increased risk of surgery. CASE SUMMARY: A 3-day-old full-term male infant was admitted to the pediatrics department after presenting with "low blood glucose for 10 min". Hypoglycemia was corrected by intravenous glucose administration and oral breast milk. On the 3rd d after admission, an ultrasound examination showed gas accumulation in the hepatic portal vein; this increased on the next day. Abdominal vertical radiograph showed intestinal pneumatosis. Routine blood examination showed that the total number of white blood cells was normal, but neutrophilia was related to age. There was a significant increase in C-reactive protein (CRP). The child was diagnosed with neonatal NEC (early-stage). With nil per os, rehydration, parenteral nutritional support, and anti-infection treatment with no sodium, his hepatic portal vein pneumatosis resolved. In addition, routine blood examination and CRP examination showed significant improvement and his symptoms resolved. The patient was given timely refeeding and gradually transitioned to full milk feeding and was subsequently discharged. Follow-up examination after discharge showed that the general condition of the patient was stable. CONCLUSION: The presence of HPVG in neonates indicates early NEC. Early active anti-infective treatment is effective in treating NEC, minimizes the risk of severe NEC, and reduces the need for surgery. The findings of this study imply that early examination of the liver by ultrasound in a sick neonate can help with the early diagnosis of conditions such as NEC.

11.
Nat Commun ; 12(1): 6538, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34764303

RESUMO

The Mizoroki-Heck reaction and its reductive analogue are staples of organic synthesis, but the ensuing products often lack a chemical handle for further transformation. Here we report an atom-economical cross-coupling of halopyridines and unactivated alkenes under photoredox catalysis to afford a series of alkene halopyridylation products. This protocol with mild and redox neutral conditions contributes broad substrate scope. As a complement to conventional Heck-type reaction, this radical process avoids the involvement of ß-H elimination and thus useful pyridyl and halide groups could be simultaneously and regioselectively incorporated onto alkenes. The success depends on TFA-promoted domino photocatalytic oxidative quenching activation and radical-polar crossover pathway. Plausible mechanism is proposed based on mechanistic investigations. Moreover, the reserved C - X bonds of these products are beneficial for performing further synthetic elaborations.

13.
Micron ; 152: 103176, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34763214

RESUMO

The fine structure of the larval eyes of the hangingfly Terrobittacus implicatus (Huang & Hua) was investigated using scanning and transmission electron microscopy. The results show that the larval eyes of T. implicatus each consist of seven spaced ommatidia. Each ommatidium is composed of a corneal lens with about 45 lamellae, a tetrapartite eucone type of crystalline cone, eight retinula cells, two primary pigment cells, and an undetermined number of secondary pigment cells. The rhabdomeres of eight retinula cells effectively fuse into a centrally-fused, tiered funnel-shaped rhabdom extending from the base of the crystalline cone deeply into the ommatidium. In light of different positions in the ommatidium, the retinula cells can be divided into four distal and four proximal retinula cells. Pigment cells envelop the entire ommatidium. Electron-lucent vesicles are abundant throughout the cytoplasm of the eight retinula cells. The larval ommatidia of T. implicatus are similar to those of the Panorpidae, except for the distal retinula cells that also participate in the formation of the proximal rhabdom. In this case, the larval eyes of T. implicatus may lie in the transitional stage during the larval eye evolution of insects from ommatidia to stemmata.

14.
Sci Total Environ ; : 151410, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34742958

RESUMO

Marine pollution caused by the substandard discharge of domestic sewage from ships has received considerable attention in recent years. Thus, the research and application of efficient treatment and supervision system of domestic ship sewage are matters of considerable interest in marine pollution prevention. The environmental impacts of black and grey water on marine and river environments were reviewed to emphasize the urgency and importance of sewage treatment. Development and changes of emission indexes revealed the emphasis on marine environmental protection and domestic sewage discharge. Based on summarizing the difficulties of high salinity, high organic load and poor stability in ship sewage treatment, the technologies of physical-, chemical- and biochemical-based processing were reviewed. Case study of online monitoring system was displayed to provide research trends. The challenges and future perspectives were also provided to promote supervision and disposal of domestic sewage from ships.

15.
Ann Transl Med ; 9(19): 1498, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34805360

RESUMO

Background: To investigate the protective effect of resolvin D1 (RvD1) on aortic dissection (AD) in mice and explore the related mechanisms. Methods: Mice were randomly divided into a blank group, model group, and RvD1 group. The RvD1 and model groups were administered 0.4% ß-aminopropionitrile (BAPN) solution, while the blank group was administered distilled water. When the experiment began, whether mice had AD was determined by echocardiogram. The RvD1 group was also administered RvD1 (30 µg/kg), while the model and blank groups were administered saline intraperitoneally. After 21 d, body weight trend and survival rate in the three groups were compared. The diameter of the ascending aorta of mice was detected by echocardiography. Then, the mice were sacrificed, and histopathological staining procedures were performed. Enzyme-linked immunosorbent assay (ELISA) was used to detect cytokines and chemokines in blood and tissue, respectively. Results: At 21 d, there was no statistically significant difference in body weight between three groups (P>0.05). The survival rate showed a significant difference between the RvD1 and model group (P<0.05). Echocardiography revealed that compared with the RvD1 and blank groups, aortic dilatation was significant in the model group. Pathological staining showed that the destruction of the aortic wall structure and inflammatory cell infiltration were more noticeable in the model group than in the RvD1 group. A slight disintegration of elastic fibers and collagen in the aorta was observed in the RvD1 group, and the aortic structure was clear. The results of ELISA showed that the inflammatory factors levels in the RvD1 group, although higher than those in blank group, were significantly decreased compared with the model group. The ELISA results of AD tissue showed that at 21 d, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in the aorta were significantly decreased in the RvD1 group compared with the model group (P<0.05). Conclusions: Administration of RvD1 significantly delayed aortic dilation and disintegration and inhibited local macrophage and neutrophil infiltration in the early stages of aortic injury. Moreover, RvD1 significantly downregulated the expression of cytokines and chemokines in aortic tissues and serum and improved aortic remodeling.

16.
Ann Transl Med ; 9(18): 1448, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34734000

RESUMO

Background: Stanford type A aortic dissection (TAAD) has a sudden onset and high mortality, and emergency total aortic arch replacement (TAAR) is the main treatment option for TAAD. The mortality rate of patients with postoperative acute kidney injury (AKI) combined with continuous renal replacement therapy (CRRT) is remarkable higher than that of patients without AKI. However, incidence of AKI and risk factors for CRRT following TAAR isn't entirely understood. Methods: From October 2018 to March 2021, all patients with Stanford type A dissection who underwent total arch replacement surgery under MHCA were enrolled. According to whether CRRT treatment was performed, participants were divided into a CRRT group (n=49) and control group (n=72). Both groups incorporated the brain protection strategy of moderate hypothermia, and the left common carotid artery and the innominate artery were perfused anteriorly. Relevant medical data was collected. Results: Age, gender, and a history of smoking and drinking were not significantly different between the 2 groups (P>0.1). There were statistical differences between the 2 groups in aortic sinus diameter and Bentall procedure (P≤0.05). Univariate analysis revealed that fresh frozen plasma was a protective factor (P<0.05) and the intraoperative transfusion volume of red blood cells, platelets, fresh frozen plasma, autologous blood used for intraoperative bleeding, aortic sinus diameter, and Bentall procedure were risk factors (P<0.1). Multivariate analysis showed that the Bentall procedure and intraoperative bleeding were risk factors for CRRT (P<0.05), and the aortic sinus diameter and intraoperative transfusion score were also risk factors for CRRT (P<0.05). Receiver operating characteristic (ROC) analysis demonstrated that the model of aortic sinus diameter and intraoperative transfusion score had more significantly different discriminatory powers. Conclusions: The Bentall procedure, intraoperative bleeding, aortic sinus diameter, and intraoperative transfusion score were risk factors for postoperative CRRT. The model of aortic sinus diameter and intraoperative transfusion score had more significantly different discriminatory powers.

17.
J Transl Med ; 19(1): 455, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732216

RESUMO

BACKGROUND: Circular RNAs (circRNAs) are pivotal regulators of various human cancers and circ-ERBB2 is abnormally expressed in breast cancer cells. However, the role and mechanism of circ-ERBB2 in HER2-positive breast cancer are still unknown. METHODS: The circ-ERBB2 expressions in the tumor tissues of HER2-positive breast cancer patients were tested using quantitative real-time PCR. The circ-ERBB2 function was investigated by cell counting kit 8 assay, Transwell, flow cytometry and Western blot. Mechanistically, fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull-down and dual-luciferase reporter gene assays were conducted to confirm the interaction between circ-ERBB2 and miR-136-5p or miR-198 in HER2-positive breast cancer cells. RESULTS: Circ-ERBB2 was elevated in the tumor tissues of HER2-positive breast cancer patients. Functionally, the interference with circ-ERBB2 repressed HER2-positive breast cancer cell proliferation, migration, invasion and accelerated cell apoptosis. Furthermore, the mechanistic analysis corroborated that circ-ERBB2 acted as a competing endogenous RNA for miR-136-5p or miR-198 to relieve the repressive influence of miR-136-5p or miR-198 on its target transcription factor activator protein 2C (TFAP2C). Meanwhile, in vivo assays further corroborated the oncogenic function of circ-ERBB2 in HER2-positive breast cancer. CONCLUSIONS: Circ-ERBB2 accelerated HER2-positive breast cancer progression through the circ-ERBB2/miR-136-5p/TFAP2C axis or the circ-ERBB2/miR-198/TFAP2C axis.

18.
Dalton Trans ; 50(44): 16273-16280, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34730150

RESUMO

With the aim of gaining new insight into the underlying apoptosis mechanisms and in vivo efficacy of cyclometalated Ir(III) complexes as metalodrugs, six new cyclometalated Ir(III)-quinoline complexes, [Ir(1a)(2pq)2] (2a), [Ir(1b)(2pq)2] (2b), [Ir(1c)(2pq)2] (2c), [Ir(1d)(2pq)2] (2d), [Ir(1e)(2pq)2] (2e), and [Ir(1f)(2pq)2] (2f) (2pq = 2-phenylisoquinoline), have been synthesized using 5,7-dihalo-8-hydroxylquinoline ligands (1a-1f) and [Ir(2pq)2Cl]2 precursors and characterized. Complexes 2a-2f have shown potent anticancer activity against cisplatin-resistant SK-OV-3/DDP and A549/DDP cells (IC50 = 0.11-1.83 µM), following the order 2e > 2f > 2b > 2c > 2d > 2a. Confocal microscopy images suggest that 2e and 2b could act as red-color probes for specific cell imaging and efficiently initiate apoptosis and autophagy in the mitochondria, cell cytosol, and nucleus. Overexpression of beclin1, caspase-9, cytochrome c, LC3II, and apaf-1; inhibition of p62, cyclin D1, cyclin A2, and CDK2; and a substantial rapid accumulation suggest a paraptotic mode of cell death induced by autophagy, DNA damage, and mitochondrial stress. In addition, the inhibitory rate of 2e on A549/DDP tumor growth was 64.1% at a concentration of 10.0 mg kg-1, which is clearly higher than that of cisplatin. According to the biological assay, the cyclometalated Ir(III)-quinoline complex 2e exhibited a higher anticancer effect than 2b, which may be associated with the electronic effect of the methyl group of the 1e ligand of 2e playing a key role in the mechanism.

19.
Front Mol Neurosci ; 14: 739526, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790095

RESUMO

This research aimed to investigate the role of glyoxalase 1 (Glo-1) polymorphisms in the susceptibility of schizophrenia. Using the real-time polymerase chain reaction (PCR) and spectrophotometric assays technology, significant differences in Glo-1 messenger ribonucleic acid (mRNA) expression (P = 3.98 × 10-5) and enzymatic activity (P = 1.40 × 10-6) were found in peripheral blood of first-onset antipsychotic-naïve patients with schizophrenia and controls. The following receiver operating characteristic (ROC) curves analysis showed that Glo-1 could predict the schizophrenia risk (P = 4.75 × 10-6 in mRNA, P = 1.43 × 10-7 in enzymatic activity, respectively). To identify the genetic source of Glo-1 risk in schizophrenia, Glo-1 polymorphisms (rs1781735, rs1130534, rs4746, and rs9470916) were genotyped with SNaPshot technology in 1,069 patients with schizophrenia and 1,023 healthy individuals. Then, the impact of risk polymorphism on the promoter activity, mRNA expression, and enzymatic activity was analyzed. The results revealed significant differences in the distributions of genotype (P = 0.020, false discovery rate (FDR) correction) and allele (P = 0.020, FDR correction) in rs1781735, in which G > T mutation significantly showed reduction in the promoter activity (P = 0.016), mRNA expression, and enzymatic activity (P = 0.001 and P = 0.015, respectively, GG vs. TT, in peripheral blood of patients with schizophrenia) of Glo-1. The expression quantitative trait locus (eQTL) findings were followed up with the resting-state functional magnetic resonance imaging (fMRI) analysis. The TT genotype of rs1781735, associated with lower RNA expression in the brain (P < 0.05), showed decreased neuronal activation in the left middle frontal gyrus in schizophrenia (P < 0.001). In aggregate, this study for the first time demonstrates how the genetic and biochemical basis of Glo-1 polymorphism culminates in the brain function changes associated with increased schizophrenia risk. Thus, establishing a combination of multiple levels of changes ranging from genetic variants, transcription, protein function, and brain function changes is a better predictor of schizophrenia risk.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34797416

RESUMO

PURPOSE: The objective of this study was to evaluate the safety and efficacy of immune checkpoint inhibitor (ICI) plus anlotinib as third-line treatment in extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 120 patients with ES-SCLC who were admitted to Shandong Cancer Hospital between January 2019 and December 2020 were retrospectively analyzed. They were divided into the observation group (n = 62) and the control group (n = 58) according to their different treatment plans. The observation group was given ICI plus anlotinib, while the control group was given anlotinib alone. The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR) and disease control rate (DCR). An efficacy evaluation was carried out every 6 weeks. Univariate and multivariate analyses were performed to identify the prognostic factors. The main treatment-related adverse events were evaluated according to the Common Terminology Criteria for Adverse Events version 5.0. RESULTS: In the observation group and the control group, the DCRs were 87.1% and 72.4% (p = 0.044), and the ORRs were 19.4% and 6.9% (p = 0.045), respectively. The median PFS was longer in the observation group (7.5 months) than in the control group (4.6 months) (p = 0.0033). In Cox regression analysis, the Eastern Cooperative Oncology Group performance status score, brain metastases and metastatic sites were prognostic factors of ICI plus anlotinib. Compared with the control group, grade 1-2 immune-related pneumonia and hypothyroidism of patients in the observation group were significantly increased (p < 0.05), but grade 3-4 treatment-related adverse reactions were not significantly increased (p > 0.05). CONCLUSION: ICI plus anlotinib showed promising efficacy and manageable toxicity in third-line treatment of ES-SCLC.

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