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1.
Stem Cells ; 42(4): 385-401, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38206366

RESUMO

Pancreatic ductal progenitor cells have been proposed to contribute to adult tissue maintenance and regeneration after injury, but the identity of such ductal cells remains elusive. Here, from adult mice, we identify a near homogenous population of ductal progenitor-like clusters, with an average of 8 cells per cluster. They are a rare subpopulation, about 0.1% of the total pancreatic cells, and can be sorted using a fluorescence-activated cell sorter with the CD133highCD71lowFSCmid-high phenotype. They exhibit properties in self-renewal and tri-lineage differentiation (including endocrine-like cells) in a unique 3-dimensional colony assay system. An in vitro lineage tracing experiment, using a novel HprtDsRed/+ mouse model, demonstrates that a single cell from a cluster clonally gives rise to a colony. Droplet RNAseq analysis demonstrates that these ductal clusters express embryonic multipotent progenitor cell markers Sox9, Pdx1, and Nkx6-1, and genes involved in actin cytoskeleton regulation, inflammation responses, organ development, and cancer. Surprisingly, these ductal clusters resist prolonged trypsin digestion in vitro, preferentially survive in vivo after a severe acinar cell injury and become proliferative within 14 days post-injury. Thus, the ductal clusters are the fundamental units of progenitor-like cells in the adult murine pancreas with implications in diabetes treatment and tumorigenicity.


Assuntos
Células Acinares , Ductos Pancreáticos , Camundongos , Animais , Pâncreas , Células-Tronco , Diferenciação Celular
2.
Proc Natl Acad Sci U S A ; 119(12): e2114271119, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35286190

RESUMO

SignificanceOur study presents the largest whole-genome investigation of leadership phenotypes to date. We identified genome-wide significant loci for leadership phenotypes, which are overlapped with top hits for bipolar disorder, schizophrenia, and intelligence. Our study demonstrated the polygenetic nature of leadership, the positive genetic correlations between leadership traits and a broad range of well-being indicators, and the unique association of leadership with well-being after accounting for genetic influences related to other socioeconomic status measures. Our findings offer insights into the biological underpinnings of leadership.


Assuntos
Estudo de Associação Genômica Ampla , Esquizofrenia , Humanos , Liderança , Herança Multifatorial , Fenótipo , Esquizofrenia/genética
3.
J Org Chem ; 89(3): 1703-1708, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38227772

RESUMO

Visible-light-induced three-component 1,2-alkylpyridylation of alkenes with unactivated alkyl iodides and aryl cyanides is reported via a photocatalytic halogen-atom transfer (XAT) strategy. This metal-free protocol utilizes readily available tertiary alkylamine as the terminal reductant to smoothly convert alkyl iodides into the corresponding carbon radical species. The reaction features a broad substrate scope, excellent functional group tolerance, high efficiency, and mild reaction conditions. The practicability of this methodology is further demonstrated in the late-stage difunctionalization of bioactive molecules.

4.
J Stat Plan Inference ; 228: 34-45, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38264292

RESUMO

Expression quantitative trait locus (eQTL) analysis is a useful tool to identify genetic loci that are associated with gene expression levels. Large collaborative efforts such as the Genotype-Tissue Expression (GTEx) project provide valuable resources for eQTL analysis in different tissues. Most existing methods, however, either focus on one tissue at a time, or analyze multiple tissues to identify eQTLs jointly present in multiple tissues. There is a lack of powerful methods to identify eQTLs in a target tissue while effectively borrowing strength from auxiliary tissues. In this paper, we propose a novel statistical framework to improve the eQTL detection efficacy in the tissue of interest with auxiliary information from other tissues. This framework can enhance the power of the hypothesis test for eQTL effects by incorporating shared and specific effects from multiple tissues into the test statistics. We also devise data-driven and distributed computing approaches for efficient implementation of eQTL detection when the number of tissues is large. Numerical studies in simulation demonstrate the efficacy of the proposed method, and the real data analysis of the GTEx example provides novel insights into eQTL findings in different tissues.

5.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(2): 181-187, 2024 Feb 15.
Artigo em Zh | MEDLINE | ID: mdl-38436317

RESUMO

OBJECTIVES: To investigate the effects of α1-antitrypsin (AAT) on motor function in adult mice with immature brain white matter injury. METHODS: Five-day-old C57BL/6J mice were randomly assigned to the sham surgery group (n=27), hypoxia-ischemia (HI) + saline group (n=27), and HI+AAT group (n=27). The HI white matter injury mouse model was established using HI methods. The HI+AAT group received intraperitoneal injections of AAT (50 mg/kg) 24 hours before HI, immediately after HI, and 72 hours after HI; the HI+saline group received intraperitoneal injections of the same volume of saline at the corresponding time points. Brain T2-weighted magnetic resonance imaging scans were performed at 7 and 55 days after modeling. At 2 months of age, adult mice were evaluated for static, dynamic, and coordination parameters using the Catwalk gait analysis system. RESULTS: Compared to the sham surgery group, mice with HI injury showed high signal intensity on brain T2-weighted magnetic resonance imaging at 7 days after modeling, indicating significant white matter injury. The white matter injury persisted at 55 days after modeling. In comparison to the sham surgery group, the HI+saline group exhibited decreased paw print area, maximum contact area, average pressure, maximum pressure, paw print width, average velocity, body velocity, stride length, swing speed, percentage of gait pattern AA, and percentage of inter-limb coordination (left hind paw → left front paw) (P<0.05). The HI+saline group showed increased inter-paw distance, percentage of gait pattern AB, and percentage of phase lag (left front paw → left hind paw) compared to the sham surgery group (P<0.05). In comparison to the HI+saline group, the HI+AAT group showed increased average velocity, body velocity, stride length, and swing speed (right front paw) (P<0.05). CONCLUSIONS: The mice with immature brain white matter injury may exhibit significant motor dysfunction in adulthood, while the use of AAT can improve some aspects of their motor function.


Assuntos
Substância Branca , Animais , Camundongos , Camundongos Endogâmicos C57BL , Substância Branca/diagnóstico por imagem , Encéfalo , Modelos Animais de Doenças , Hipóxia
6.
Opt Express ; 31(12): 19990-20004, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37381403

RESUMO

Underwater wireless optical communication (UWOC) is a critical technology for underwater communication, providing high speed, low latency, and security advantages. However, the strong attenuation in the water channel still limits the UWOC systems and their performances require further improvement. In this study, an orbital angular momentum (OAM) multiplexing UWOC system that uses photon-counting detection is experimentally demonstrated. By employing a single-photon counting module to receive photon signals, we analyze the bit error rate (BER) and photon-counting statistics by building a theoretical model that fits the real system, and demodulate the OAM states in single photon level and implement signal processing using field programmable gate array (FPGA) programming. Based on these modules, a 2-OAM multiplexed UWOC link is established over a water channel of 9 m. By using on-off keying modulation and 2-pulse position modulation, we achieve a BER of 1.26×10-3 with data rate of 20Mbps and 3.17×10-4 with data rate of 10Mbps respectively, which below the forward error correction (FEC) threshold of 3.8×10-3. The total transmission loss is 37 dB under an emission power of 0.5 mW, which is equivalent to the attenuation of 283 m Jerlov I type seawater from the perspective of energy loss. Our verified communication scheme will benefit the development of long-range and high-capacity UWOC.

7.
Cell Commun Signal ; 21(1): 319, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37946202

RESUMO

Deubiquitinases (DUBs) play important roles in various human cancers and targeting DUBs is considered as a novel anticancer therapeutic strategy. Overexpression of ubiquitin specific protease 7 and 22 (USP7 and USP22) are associated with malignancy, therapy resistance, and poor prognosis in many cancers. Although both DUBs are involved in the regulation of similar genes and signaling pathways, such as histone H2B monoubiquitination (H2Bub1), c-Myc, FOXP3, and p53, the interdependence of USP22 and USP7 expression has never been described. In the study, we found that targeting USP7 via either siRNA-mediated knockdown or pharmaceutical inhibitors dramatically upregulates USP22 in cancer cells. Mechanistically, the elevated USP22 occurs through a transcriptional pathway, possibly due to desuppression of the transcriptional activity of SP1 via promoting its degradation upon USP7 inhibition. Importantly, increased USP22 expression leads to significant activation of downstream signal pathways including H2Bub1 and c-Myc, which may potentially enhance cancer malignancy and counteract the anticancer efficacy of USP7 inhibition. Importantly, targeting USP7 further suppresses the in vitro proliferation of USP22-knockout (USP22-Ko) A549 and H1299 lung cancer cells and induces a stronger activation of p53 tumor suppressor signaling pathway. In addition, USP22-Ko cancer cells are more sensitive to a combination of cisplatin and USP7 inhibitor. USP7 inhibitor treatment further suppresses in vivo angiogenesis and tumor growth and induced more apoptosis in USP22-Ko cancer xenografts. Taken together, our findings demonstrate that USP7 inhibition can dramatically upregulate USP22 in cancer cells; and targeting USP7 and USP22 may represent a more effective approach for targeted cancer therapy, which warrants further study. Video Abstract.


Assuntos
Neoplasias Pulmonares , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/metabolismo , Peptidase 7 Específica de Ubiquitina/metabolismo , Ubiquitina Tiolesterase/metabolismo , Neoplasias Pulmonares/patologia , Histonas/metabolismo , Transdução de Sinais , Linhagem Celular Tumoral
8.
Catheter Cardiovasc Interv ; 101(4): 813-816, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36740232

RESUMO

A 67-year-old male patient was admitted with an enormous twisted thoracoabdominal aortic aneurysm (TAAA) with multiple branch arteries stenosis and occlusion. Three-dimensional (3D) printing technology combined with mechanics was used for developing a transparent model of lesion to simulate the segment of diseased aorta. A stent graft was deployed in the 3D model to make a physician-modified stent graft (PMSGs) on table. The locations of the opening of branches were marked twice during operation. The PMSG was successfully deployed during the surgery and repaired the TAAA, with no endoleak and all the branched arteries patency in follow-up. This technique could offer precision individualized therapy and could simplify the procedure process greatly.


Assuntos
Aneurisma da Aorta Torácica , Aneurisma da Aorta Toracoabdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Masculino , Humanos , Idoso , Prótese Vascular , Implante de Prótese Vascular/métodos , Stents , Aneurisma da Aorta Torácica/cirurgia , Constrição Patológica , Resultado do Tratamento , Desenho de Prótese , Impressão Tridimensional , Procedimentos Endovasculares/métodos , Estudos Retrospectivos
9.
J Endovasc Ther ; : 15266028231207023, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37902431

RESUMO

OBJECTIVE: This study aimed to evaluate the outcomes of physician-modified endografts (PMEGs) for the treatment of thoracic aortic pathologies involving the aortic arch. METHODS: A retrospective single-center study was performed on consecutive patients with thoracic aortic pathologies treated by PMEGs between February 2018 and May 2022. Data on baseline characteristics, operative procedure, and follow-up information were collected. The endpoints included technical success, complications, mortality, overall survival, re-intervention, and target vessel instability. RESULTS: This study comprised 173 patients (mean age=58±13, range=28-83, 148 men) with thoracic aortic pathologies, including 44 thoracic aortic aneurysms, 113 aortic dissections (9 type A, 4 residual type A, 75 type B, 32 non-A non-B), 3 aortic intramural hematomas, and 13 penetrating aortic ulcers. Thirty-five of the patients had PMEGs with 3 fenestrations, 32 had 2 fenestrations, and 106 had 1 single fenestration. Technical success was 98% (170/173), and the 30-day mortality was 2% (3/173). Perioperative complications included stroke (n=3, 2%), retrograde type A dissection (RTAD; n=3, 2%) and renal injury (n=3, 2%). Seven deaths (4%) were noted during a median follow-up of 11 (range=1-52) months. Eleven cases of re-intervention were stent-related. There were 5 type Ia endoleaks (3%), 2 type III endoleaks (1%) from the innominate artery (IA), and 3 type Ic endoleaks (2%) from the left subclavian arteries. One case of IA stent-graft (SG) stenosis was noted because of mural thrombus. Estimate rates of overall survival, freedom from secondary intervention, and freedom from target vessel instability at 2 years were 93.4% (95% confidence interval [CI]=88.7%-98.1%), 80.7% (95% CI=73.3%-88.1%), and 89.0% (95% CI=80.4%-97.6%), respectively. CONCLUSIONS: Physician-modified endografts showed promising immediate therapeutic results in the treatment of thoracic aortic pathologies involving the aortic arch. Our study demonstrates that the technique is feasible and produces acceptable results. Long-term outcomes are required for further refinement of this technical approach to confirm technical success and durability over time as a valuable option for endovascular aortic arch repair in specialized centers. CLINICAL IMPACT: Our short- and mid-term outcomes of physician-modified endografts in 173 patients showed promising results compared to other branched/fenestrated techniques and backed up the endovascular repair of the aortic arch. Meanwhile, the technical expertise pointed out in our manuscript, including preloaded guidewire, diameter-reducing wire and inner mini-cuffs, provided reference and technical guidance for our peers. Most importantly, it demonstrated that the PMEG, as a device whose components were all commercially available, might be a better option for emergency surgery and for centers who had no access to custom-made devices.

10.
J Endovasc Ther ; : 15266028231161244, 2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36942654

RESUMO

PURPOSE: To summarize experience with and the efficacy of fenestrated/branched thoracic endovascular repair (F/B-TEVAR) using physician-modified stent-grafts (PMSGs) under 3D printing guidance in triple aortic arch branch reconstruction. MATERIALS AND METHODS: From February 2018 to April 2022, 14 cases of aortic arch aneurysms and 30 cases of aortic arch dissection (22 acute aortic arch dissection and 8 long-term aortic arch dissection)were treated by F/B-TEVAR in our department, including 34 males and 10 females, with an average age of 59.84 ± 11.72 years. Three aortic arch branches were affected in all patients. A 3D-printed model was made according to computed tomography angiography images and used to guide the fabrication of PMSGs. All patients were followed up. RESULTS: A total of 132 branches were successfully reconstructed with no case of conversion to open surgery. The average operation time was 4.97 ± 1.40 hours, including a mean 44.05 ± 7.72 minutes for stent-graft customization, the mean postoperative hospitalization duration was 9.91 ± 4.47 days, the average intraoperative blood loss was 480.91 mL (100-2810 mL), and the mean postoperative intensive care unit monitoring duration was 1.02 days (0-5 days). No deaths occurred within 30 days of surgery. Postoperative neurological complications occurred in 1 case (2.3%), and retrograde type A dissection occurred in 1 case (2.3%). CONCLUSION: Compared with conventional surgery, triple aortic arch branch reconstruction under the guidance of 3D printing is a minimally invasive treatment method with the advantages of accurate positioning, rapid postoperative recovery, few complications, and reliable short- to mid-term effects. CLINICAL IMPACT: At present the PMSG usually depend on imaging data and software calculation. With the guidance of 3D printing technology, image data could be transformed into 3D model, which has improved the accuracy of the positioning of the fenestrations. The diameter reduction technique and the internal mini cuff technique have made a complement to the slimed-down fenestration selection process and the low rate of endoleak. As reproducible study, our results may provide reference for TEVAR in different cases.

11.
Vascular ; : 17085381231154354, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37526208

RESUMO

OBJECTIVES: To evaluate the efficacy and clinical outcomes of accurate embolization of endoleaks after fenestrated thoracic endovascular aortic repair (F-TEVAR) for thoracic aortic dissections. METHODS: Twenty patients with endoleaks (17 type I and 3 type II) after fenestrated thoracic endovascular aortic repair (F-TEVAR) were embolized using detachable and ordinary coils. We assessed the success rate and complications of the operation, and its effects, through clinical and CT follow-up. RESULTS: The mean clinical follow-up duration was 25.68 ± 11.07 months (3-44 months). During follow-up, all endoleaks were completely embolized and aortic remodeling was improved. Secondary endoleaks occurred in four patients who were embolized twice. No other complications or death were reported. CONCLUSION: Embolization using detachable and ordinary coils is effective and safe for the treatment of endoleaks after fenestrated thoracic endovascular aortic repair.

12.
Parasitol Res ; 122(5): 1107-1126, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36933066

RESUMO

The identification of additional Echinococcus granulosus sensu lato (s.l.) complex species/genotypes in recent years raises the possibility that there might be more variation among this species in China than is currently understood. The aim of this study was to explore intra- and inter-species variation and population structure of Echinococcus species isolated from sheep in three areas of Western China. Of the isolates, 317, 322, and 326 were successfully amplified and sequenced for cox1, nad1, and nad5 genes, respectively. BLAST analysis revealed that the majority of the isolates were E. granulosus s.s., and using the cox1, nad1, and nad5 genes, respectively, 17, 14, and 11 isolates corresponded to Elodea canadensis (genotype G6/G7). In the three study areas, G1 genotypes were the most prevalent. There were 233 mutation sites along with 129 parsimony informative sites. A transition/transversion ratio of 7.5, 8, and 3.25, respectively, for cox1, nad1, and nad5 genes was obtained. Every mitochondrial gene had intraspecific variations, which were represented in a star-like network with a major haplotype with observable mutations from other distant and minor haplotypes. The Tajima's D value was significantly negative in all populations, indicating a substantial divergence from neutrality and supporting the demographic expansion of E. granulosus s.s. in the study areas. The phylogeny inferred by the maximum likelihood (ML) method using nucleotide sequences of cox1-nad1-nad5 further confirmed their identity. The nodes assigned to the G1, G3, and G6 clades as well as the reference sequences utilized had maximal posterior probability values (1.00). In conclusion, our study confirms the existence of a significant major haplotype of E. granulosus s.s. where G1 is the predominant genotype causing of CE in both livestock and humans in China.


Assuntos
Equinococose , Echinococcus granulosus , Animais , Humanos , Ovinos , Echinococcus granulosus/genética , Tibet , Equinococose/epidemiologia , Equinococose/veterinária , China , Genótipo , Haplótipos , Mutação , Filogenia , Variação Genética
13.
Zhongguo Zhong Yao Za Zhi ; 48(18): 5068-5077, 2023 Sep.
Artigo em Zh | MEDLINE | ID: mdl-37802849

RESUMO

This study investigated the drug delivery performance of oral co-loaded puerarin(PUE) and daidzein(DAZ) mixed micelles(PUE/DAZ-FS/PMMs) from the perspectives of pharmacokinetics, pharmacodynamics, and tissue distribution. The changes in PUE plasma concentration in rats were evaluated based on PUE suspension, single drug-loaded micelles(PUE-FS/PMMs), and co-loaded micelles(PUE/DAZ-FS/PMMs). Spontaneously hypertensive rats(SHR) were used to monitor systolic blood pressure, diastolic blood pressure, and mean arterial pressure for 10 weeks after administration by tail volume manometry. The content of PUE in the heart, liver, spleen, lung, kidney, brain, and testes was determined using LC-MS/MS. The results showed that compared with PUE suspension and PUE-FS/PMMs, PUE/DAZ-FS/PMMs significantly increased C_(max) in rats(P<0.01) and had a relative bioavailability of 122%. The C_(max), AUC_(0-t), AUC_(0-∞), t_(1/2), and MRT of PUE/DAZ-FS/PMMs were 1.77, 1.22, 1.22, 1.17, and 1.13 times higher than those of PUE suspension, and 1.76, 1.16, 1.08, 0.84, and 0.78 times higher than those of PUE-FS/PMMs, respectively. Compared with the model control group, PUE/DAZ-FS/PMMs significantly reduced systolic blood pressure, diastolic blood pressure, and mean arterial pressure in SHR rats(P<0.05). The antihypertensive effect of PUE/DAZ-FS/PMMs was greater than that of PUE suspension, and even greater than that of PUE-FS/PMMs at high doses. Additionally, the distribution of PMMs in various tissues showed dose dependency. The distribution of PMMs in the kidney and liver, which are metabolically related tissues, was lower than that in the suspension group, while the distribution in the brain was higher than that in the conventional dose group. In conclusion, PUE/DAZ-FS/PMMs not only improved the bioavailability of PUE and synergistically enhanced its therapeutic effect but also prolonged the elimination of the drug to some extent. Furthermore, the micelles facilitated drug penetration through the blood-brain barrier. This study provides a foundation for the development of co-loaded mixed micelles containing homologous components.


Assuntos
Isoflavonas , Micelas , Ratos , Animais , Distribuição Tecidual , Cromatografia Líquida , Espectrometria de Massas em Tandem , Ratos Endogâmicos SHR , Isoflavonas/farmacologia
14.
BMC Genomics ; 23(1): 571, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35948880

RESUMO

BACKGROUND: Skeletal muscle tissue is among the largest organ systems in mammals, essential for survival and movement. Embryonic muscle development determines the quantity and quality of muscles after the birth of an individual. MicroRNAs (miRNAs) are a significant class of non-coding RNAs that bind to the 3'UTR region of mRNA to regulate gene function. Total RNA was extracted from the leg muscles of chicken embryos in different developmental stages of Chengkou Mountain Chicken and used to generate 171,407,341 clean small RNA reads. Target prediction, GO, and KEGG enrichment analyses determined the significantly enriched genes and pathways. Differential analysis determined the significantly different miRNAs between chicken embryo leg muscles at different developmental stages. Meanwhile, the weighted correlation network analysis (WGCNA) identified key modules in different developmental stages, and the hub miRNAs were screened following the KME value. RESULTS: The clean reads contained 2047 miRNAs, including 721 existing miRNAs, 1059 known miRNAs, and 267 novel miRNAs. Many genes and pathways related to muscle development were identified, including ERBB4, MEF2C, FZD4, the Wnt, Notch, and MAPK signaling pathways. The WGCNA established the greenyellow module and gga-miR-130b-5p for E12, magenta module and gga-miR-1643-5p for E16, purple module and gga-miR-12218-5p for E19, cyan module and gga-miR-132b-5p for E21. CONCLUSION: These results lay a foundation for further research on the molecular regulatory mechanism of embryonic muscle development in Chengkou mountain chicken and provide a reference for other poultry and livestock muscle development studies.


Assuntos
Galinhas , MicroRNAs , Regiões 3' não Traduzidas , Animais , Embrião de Galinha , Galinhas/genética , Galinhas/metabolismo , Perfilação da Expressão Gênica , Mamíferos/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Desenvolvimento Muscular/genética , RNA Mensageiro
15.
Opt Express ; 30(24): 43301-43316, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36523031

RESUMO

Wireless optical communication is a crucial direction for improving the data transmission rate in underwater environments. In order to improve the communication performance over the water channel, this paper studies underwater wireless optical communication (UWOC) employing polarization multiplexing modulation and photon counting detection. The improvements in bit error rates and communication capacities are analyzed theoretically by constructing the communication model of polarization multiplexing modulation UWOC based on photon counting. Under specific conditions, the polarization maintenance characteristics of photons over water channels are demonstrated by measuring the Mueller matrix, the fidelity of quantum states, depolarization ratio, and calculating the ratios of ballistic photons. Based on these results, by designing and developing the experimental system of UWOC with the polarization multiplexing modulation and photon counting detection, the data transmission rates of 14.58Mbps and 7.29Mbps are realized over a water channel of 92 m by using polarization on-off keying multiplexing modulation and polarization 2-pulse-position multiplexing modulation, respectively.

16.
BMC Cancer ; 22(1): 750, 2022 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-35810271

RESUMO

OBJECTIVE: To describe and analyze the predictive models of the prognosis of patients with hepatocellular carcinoma (HCC) undergoing systemic treatment. DESIGN: Systematic review. DATA SOURCES: PubMed and Embase until December 2020 and manually searched references from eligible articles. ELIGIBILITY CRITERIA FOR STUDY SELECTION: The development, validation, or updating of prognostic models of patients with HCC after systemic treatment. RESULTS: The systematic search yielded 42 eligible articles: 28 articles described the development of 28 prognostic models of patients with HCC treated with systemic therapy, and 14 articles described the external validation of 32 existing prognostic models of patients with HCC undergoing systemic treatment. Among the 28 prognostic models, six were developed based on genes, of which five were expressed in full equations; the other 22 prognostic models were developed based on common clinical factors. Of the 28 prognostic models, 11 were validated both internally and externally, nine were validated only internally, two were validated only externally, and the remaining six models did not undergo any type of validation. Among the 28 prognostic models, the most common systemic treatment was sorafenib (n = 19); the most prevalent endpoint was overall survival (n = 28); and the most commonly used predictors were alpha-fetoprotein (n = 15), bilirubin (n = 8), albumin (n = 8), Child-Pugh score (n = 8), extrahepatic metastasis (n = 7), and tumor size (n = 7). Further, among 32 externally validated prognostic models, 12 were externally validated > 3 times. CONCLUSIONS: This study describes and analyzes the prognostic models developed and validated for patients with HCC who have undergone systemic treatment. The results show that there are some methodological flaws in the model development process, and that external validation is rarely performed. Future research should focus on validating and updating existing models, and evaluating the effects of these models in clinical practice. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020200187 .


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Bilirrubina , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Prognóstico , Sorafenibe/uso terapêutico
17.
Cell Commun Signal ; 20(1): 147, 2022 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123698

RESUMO

BACKGROUND: Ubiquitin-specific protease 22 (USP22), a putative cancer stem cell marker, is frequently upregulated in cancers, and USP22 overexpression is associated with aggressive growth, metastasis, and therapy resistance in various human cancers including lung cancer. However, USP22 gene amplification seldom occurs, and the mechanism underlying USP22 upregulation in human cancers remains largely unknown. METHODS: A luciferase reporter driven by a promoter region of USP22 gene was selectively constructed to screen against a customized siRNA library targeting 89 selected transcription factors to identify potential transcription factors (TFs) that regulate USP22 expression in human non-small cell lung cancers (NSCLC). Association of identified TFs with USP22 and potential role of the TFs were validated and explored in NSCLC by biological assays and immunohistochemistry analysis. RESULTS: Luciferase reporter assays revealed that SP1 and activating transcription factor 3 (ATF3) inhibit USP22 transcription, while transcription factor AP-2 Alpha/Beta (TFAP2A/2B) and c-Myc promote USP22 transcription. Binding site-directed mutagenesis and chromosome immunoprecipitation (ChIP) assays validated AP2α and AP2ß are novel TFs of USP22. Furthermore, overexpression of AP2A and AP2B significantly upregulates USP22 expression, and its target: Cyclin D1, concurrently enhances the proliferation, migration, and invasion of NSCLC A549 and H1299 cells in a partially USP22-dependent manner. Moreover, AP2 protein level correlated with USP22 protein in human NSCLC tissues. CONCLUSION: Our findings indicate AP2α and AP2ß are important transcription factors driving USP22 gene expression to promote the progression of NSCLC, and further support USP22 as a potential biomarker and therapeutic target for lung cancer. Video Abstract.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Fator de Transcrição AP-2/metabolismo , Fator 3 Ativador da Transcrição/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Ciclina D1/metabolismo , Expressão Gênica , Humanos , Luciferases/genética , Luciferases/metabolismo , Neoplasias Pulmonares/patologia , RNA Interferente Pequeno , Tioléster Hidrolases/genética , Tioléster Hidrolases/metabolismo , Fator de Transcrição AP-2/genética , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Proteases Específicas de Ubiquitina/genética , Proteases Específicas de Ubiquitina/metabolismo , Regulação para Cima/genética
18.
Appl Opt ; 61(14): 4113-4119, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-36256087

RESUMO

We study the influence rules of the speckle size of a light source on ghost imaging, and propose a type of speckle pattern to improve the quality of ghost imaging. The results show that image quality will first increase and then decrease with the increase in speckle size, and there is an optimal speckle size for a specific object. At the same time, by using a random distribution of speckle positions, a type of displacement speckle pattern is designed, and the imaging quality is better than that of random speckle patterns. These results are of great significance for finding the best speckle patterns suitable for detecting targets, which further promotes practical applications of ghost imaging.

19.
Appl Opt ; 61(15): 4471-4477, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-36256286

RESUMO

Polarization encoding quantum key distribution has been proven to be a reliable method to build a secure communication system. It has already been used in an inter-city fiber channel and near-Earth atmosphere channel, leaving an underwater channel the last barrier to conquer. Here we demonstrate a decoy-state BB84 quantum key distribution system over a water channel with a compact system design for future experiments in the ocean. In the system, a multiple-intensity modulated laser module is designed to produce the light pulses of quantum states, including signal state, decoy state, and vacuum state. Classical communication and synchronization are realized by wireless optical transmission. Multiple filtering techniques and wavelength division multiplexing are further used to avoid cross talk of different lights. We test the performance of the system and obtain a final key rate of 245.6 bps with an average quantum bit error rate of 1.91% over a 2.4 m water channel, in which the channel attenuation is 16.35 dB. Numerical simulation shows that the system can tolerate up to 21.7 dB total channel loss and can still generate secure keys in 277.9 m Jerlov type I ocean channel.

20.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(6): 654-661, 2022 Jun 15.
Artigo em Zh | MEDLINE | ID: mdl-35762432

RESUMO

OBJECTIVES: To establish a nomogram model for predicting the risk of death of very preterm infants during hospitalization. METHODS: A retrospective analysis was performed on the medical data of 1 714 very preterm infants who were admitted to the Department of Neonatology, the Third Affiliated Hospital of Zhengzhou University, from January 2015 to December 2019. These infants were randomly divided into a training cohort (1 179 infants) and a validation cohort (535 infants) at a ratio of 7∶3. The logistic regression analysis was used to screen out independent predictive factors and establish a nomogram model, and the feasibility of the nomogram model was assessed by the validation set. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to assess the discriminatory ability, accuracy, and clinical applicability of the model. RESULTS: Among the 1 714 very preterm infants, 260 died and 1 454 survived during hospitalization. By the multivariate logistic regression analysis of the training set, 8 variables including gestational age <28 weeks, birth weight <1 000 g, severe asphyxia, severe intraventricular hemorrhage (IVH), grade III-IV respiratory distress syndrome (RDS), and sepsis, cesarean section, and use of prenatal glucocorticoids were selected and a nomogram model for predicting the risk of death during hospitalization was established. In the training cohort, the nomogram model had an AUC of 0.790 (95%CI: 0.751-0.828) in predicting the death of very preterm infants during hospitalization, while in the validation cohort, it had an AUC of 0.808 (95%CI: 0.754-0.861). The Hosmer-Lemeshow goodness-of-fit test showed a good fit (P>0.05). DCA results showed a high net benefit of clinical intervention in very preterm infants when the threshold probability was 10%-60% for the training cohort and 10%-70% for the validation cohort. CONCLUSIONS: A nomogram model for predicting the risk of death during hospitalization has been established and validated in very preterm infants, which can help clinicians predict the probability of death during hospitalization in these infants.


Assuntos
Doenças do Prematuro , Nomogramas , Cesárea , Feminino , Retardo do Crescimento Fetal , Hospitalização , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Gravidez , Estudos Retrospectivos
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