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1.
J Colloid Interface Sci ; 606(Pt 1): 748-757, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34418755

RESUMO

Although solar energy is promising for water purification, there is still a room for further improving the solar steam generation efficiency. Herein, an environmental energy-enhanced solar steam evaporator is fabricated by immersing a cellulose acetate fiber-based cigarette filter (CF) in an aqueous solution of polyvinyl alcohol (PVA) followed by freeze-drying and decorating with MXene sheets. The presence of MXene is to absorb solar light and convert solar energy to thermal energy for efficient water evaporation, while the porous PVA network generated inside the pores of the filter during the freeze-drying process accommodates the dispersed MXene sheets and interconnects the CF and MXene. Because of the constructed PVA/MXene network inside the CF porous architecture and the hydrophilic feature of both MXene and PVA, the resultant MXene/PVA modified CF (MPCF) is highly hydrophilic and competent for rapid upward transfer of water. Interestingly, in addition to the normal energy input by the incident solar light, the large-area sidewall of MPCF gains thermal energy from the environment in the forms of heat convection and heat radiation to enhance the solar steam generation efficiency, resulting in an ultrahigh water evaporation rate of 3.38 kg m-2 h-1 with an outstanding evaporation efficiency of 132.9%.


Assuntos
Vapor , Produtos do Tabaco , Celulose/análogos & derivados , Luz Solar
2.
Front Immunol ; 12: 744254, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721413

RESUMO

Patients with rheumatoid arthritis (RA) have a significantly high risk of atrial fibrillation (AF). This study aimed to compare the absolute and relative changes in peripheral T cells in patients with RA who were also affected with and without AF. To help make an early diagnosis and prevent the initiation and progression of AF, the changes in the lymphocyte subsets were assessed in RA patients with and without AF. A propensity score matching (PSM) system (1:3) was used to perform a matched case-control study with 40 RA-AF cases and 120 RA controls. Changes in the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-citrullinated peptide antibody (ACPA), and rheumatoid factor (RF) were examined. The percentage and absolute number of T, B, natural killer (NK), T helper (Th)1, Th2, Th17, and T-regulatory (Treg) cells in the peripheral blood of patients with and without RA-AF were determined using flow cytometry. Univariate and multivariate analyses were performed to determine the association between peripheral lymphocytes and RA-AF. Demographic data, ESR, CRP, ACPA, and the percentage, as well as the absolute value of B, NK, Th2, and Treg cells, showed no significant differences between the propensity score-matched groups of RA and RA-AF. Meanwhile, the absolute number and percentage of Th1 cells, the absolute number of Th17 cells, the ratio of Th1/Treg, Th17/Treg, and RF were significantly higher in patients with RA-AF than those in the control groups (P < 0.05). Univariate and multivariate logistic regression analyses also revealed that the percentage of Th1 cells, the absolute number of Th17 cells, and the ratio of Th1/Treg were associated with a significantly higher risk of AF. This PSM study demonstrated that the incidence of AF was higher in RA patients with Th cell immunological derangements.

3.
Front Genet ; 12: 771830, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721552

RESUMO

Background: In lung adenocarcinoma (LUAD), the predictive role of immune-related subgroup classification in immune checkpoint blockade (ICB) therapy remains largely incomplete. Methods: Transcriptomics analysis was performed to evaluate the association between immune landscape and ICB therapy in lung adenocarcinoma and the associated underlying mechanism. First, the least absolute shrinkage and selection operator (LASSO) algorithm and K-means algorithm were used to identify immune related subgroups for LUAD cohort from the Cancer Genome Atlas (TCGA) database (n = 572). Second, the immune associated signatures of the identified subgroups were characterized by evaluating the status of immune checkpoint associated genes and the immune cell infiltration. Then, potential responses to ICB therapy based on the aforementioned immune related subgroup classification were evaluated via tumor immune dysfunction and exclusion (TIDE) algorithm analysis, and survival analysis and further Cox proportional hazards regression analysis were also performed for LUAD. In the end, gene set enrichment analysis (GSEA) was performed to explore the metabolic mechanism potentially responsible for immune related subgroup clustering. Additionally, two LUAD cohorts from the Gene Expression Omnibus (GEO) database were used as validation cohort. Results: A total of three immune related subgroups with different immune-associated signatures were identified for LUAD. Among them, subgroup 1 with higher infiltration scores for effector immune cells and immune checkpoint associated genes exhibited a potential response to IBC therapy and a better survival, whereas subgroup 3 with lower scores for immune checkpoint associated genes but higher infiltration scores for suppressive immune cells tended to be insensitive to ICB therapy and have an unfavorable prognosis. GSEA revealed that the status of glucometabolic reprogramming in LUAD was potentially responsible for the immune-related subgroup classification. Conclusion: In summary, immune related subgroup clustering based on distinct immune associated signatures will enable us to screen potentially responsive LUAD patients for ICB therapy before treatment, and the discovery of metabolism associated mechanism is beneficial to comprehensive therapeutic strategies making involving ICB therapy in combination with metabolism intervention for LUAD.

4.
Food Funct ; 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34734623

RESUMO

Urolithin A (UroA) is a first-in-class natural compound derived from the gut microbiota-derived metabolites of ellagitannins. This research for the first time evaluates the mechanisms of UroA inhibiting advanced glycation end-product (AGE) formation by fluorescence spectroscopy, molecular docking, liquid chromatography (LC) and LC-Oribitrap tandem mass spectrometry. The results indicated that UroA exhibited a good suppression effect on the formation of AGEs in human serum albumin (HSA)-fructose and HSA-methylglyoxal (MGO) systems. Further mechanism analysis revealed that UroA alleviated AGE formation by changing the conformational structure of HSA, trapping reactive MGO to form mono-MGO-UroA complexes, promoting the exposure of chromophores to a more hydrophobic micro-environment, and forming stable UroA-HSA complexes. UroA bound with HSA in an equimolar manner, the binding was an exothermic spontaneous process, subdomain IIIA was the preferred binding pocket, and hydrogen bonding, hydrophobic interactions and van der Waals forces were the major interaction forces. The number of glycation sites detected in glycated HSA was reduced by 1 and 2, respectively, when 181.82 and 363.64 µM UroA was added. These could provide an insight into the mechanism of UroA inhibiting HSA glycation, and highlight its value as a promising glycation inhibitor in the prevention of diabetic complications.

5.
Mycopathologia ; 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34787839

RESUMO

PURPOSE: To observe clinical characteristics and treatment outcomes of fungal keratitis caused by Verticillium dahliae. METHODS: Clinical data of 7 patients diagnosed as fungal keratitis cause by Verticillium dahliae were retrospectively analyzed. The clinical manifestations, mycology, in vitro antifungal susceptibility, treatment regimens and prognoses of the patients were evaluated. RESULTS: All 7 patients were farm worker, of which 5 cases were caused by plant trauma. The corneal ulcer had a round shape and a relatively limited range with the diameters mainly in the range of 2-7 mm. The stromal infiltration was mild, and had no pseudopodia, mossiness or endothelial plaques. Intact hyphaes were detected in corneal scrapings and confocal microscopy, isolates were identified by morphology and by sequencing the internal transcribed spacer region of ribosomal DNA. In vitro antifungal susceptibility testing showed that the most sensitive antifungal drug was Amphotericin B. In the 6 patients with an ulcer less than 2/3 of the corneal thickness, the ulcer healed after 18 days of antifungal treatment only in one eye. The other five patients underwent corneal ulcer debridement or conjunctival flap covering surgery. The remaining one patient with ulcer depth more than 2/3 of the corneal thickness underwent lamellar keratoplasty. CONCLUSION: Fungal keratitis caused by Verticillium dahliae has typical signs of a mild inflammatory response, and is not sensitive to antifungal drugs. It is recommended that patients undergo corneal ulcer debridement as soon as possible to promote rapid healing of the ulcers.

6.
Plant Foods Hum Nutr ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34822099

RESUMO

Gut microbiota balance and metabolites have become a potentially mechanism in maintaining health. The specific aim of this study was to compare the modulation of puerarin and puerarin acid esters on gut microbial composition and metabolites. Male mice were fed a control diet or diets supplemented with puerarin, puerarin propanoate ester, puerarin hexanoate ester, puerarin myristate ester for 24 h, respectively. The result revealed that puerarin acid esters with different chain lengths showed different activities to create more own impacted bacterial. Puerarin propanoate and puerarin hexanoate ester significantly improved the diversity of microbiota and promoted the relative abundance of beneficial gut microbiota such as Lactobacillus, Barnesiella, Clostridium IV, Prevotella. Additionally, the puerarin propanoate ester group showed the capacity to deliver specific propionic acid to the colon. But esters with medium-long chain lengths had more opportunity to alter gut microbiota for enhancing the short chain fatty acids production. As a whole, puerarin acid esters with different chain lengths supplements shaped different gut microbial and short chain fatty acids metabolism, which could improve human health.

7.
Front Bioeng Biotechnol ; 9: 778332, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805125

RESUMO

In this study, seven 316L stainless steel (316L SS) bulks with different angles (0°, 15°, 30°, 45°, 60°, 75°, and 90°) relative to a build substrate were built via selective laser melting (SLM). The influences of different angles on the metallography, microstructure evolution, tensile properties, and corrosion resistance of 316L SS were studied. The 0° sample showed the morphology of corrugated columnar grains, while the 90° sample exhibited equiaxed grains but with a strong <101> texture. The 60° sample had a good strength and plasticity: the tensile strength with 708 MPa, the yield strength with 588 MPa, and the elongation with 54.51%. The dislocation strengthening and grain refinement play a vital role in the mechanical properties for different anisotropy of the SLM-fabricated 316L SS. The 90° sample had greater toughness and corrosion resistance, owing to the higher volume fraction of low-angle grain boundaries and finer grains.

8.
Front Endocrinol (Lausanne) ; 12: 775233, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795643

RESUMO

Traditionally, the anteroventral periventricular (AVPV) nucleus has been the brain area associated with luteinizing hormone (LH) surge secretion in rodents. However, the role of the other population of hypothalamic kisspeptin neurons, in the arcuate nucleus (ARC), has been less well characterized with respect to surge generation. Previous experiments have demonstrated ARC kisspeptin knockdown reduced the amplitude of LH surges, indicating that they have a role in surge amplification. The present study used an optogenetic approach to selectively stimulate ARC kisspeptin neurons and examine the effect on LH surges in mice with different hormonal administrations. LH level was monitored from 13:00 to 21:00 h, at 30-minute intervals. Intact Kiss-Cre female mice showed increased LH secretion during the stimulation period in addition to displaying a spontaneous LH surge around the time of lights off. In ovariectomized Kiss-Cre mice, optogenetic stimulation was followed by a surge-like secretion of LH immediately after the stimulation period. Ovariectomized Kiss-Cre mice with a low dose of 17ß-estradiol (OVX+E) replacement displayed a surge-like increase in LH release during period of optic stimulation. No LH response to the optic stimulation was observed in OVX+E mice on the day of estradiol benzoate (EB) treatment (day 1). However, after administration of progesterone (day 2), all OVX+E+EB+P mice exhibited an LH surge during optic stimulation. A spontaneous LH surge also occurred in these mice at the expected time. Taken together, these results help to affirm the fact that ARC kisspeptin may have a novel amplificatory role in LH surge production, which is dependent on the gonadal steroid milieu.

9.
Dis Markers ; 2021: 5390195, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795806

RESUMO

Background: To investigate the association of long-term androgen deprivation therapy (ADT) with ocular surface characteristics in prostate cancer patients. Methods: A total of 30 male prostate cancer patients who received ADT were selected. All candidates were scored using the Ocular Surface Disease Index (OSDI) and subsequently divided into two groups containing 9 symptomatic patients (scores >12) and 21 asymptomatic patients (scores ≤ 12). Another 20 healthy age-matched males were selected as the control group. Each candidate was assessed with respect to eyelid margin abnormality, tear film break-up time (NI-BUT), tear meniscus height (TMH), meiboscore, meibum expressibility, and demodex infection. Results: The NI-BUT in the ADT group was significantly shorter than that in the control group. The scores for OSDI, eyelid margin abnormality, meibum expressibility, and meiboscores were significantly higher in the ADT group (P < 0.05). Moreover, the NI-BUT in the symptomatic ADT group was significantly shorter than that in the asymptomatic ADT group (P < 0.05). The meiboscores and meibum expressibility score in the symptomatic ADT group were significantly higher than those in the asymptomatic ADT group (P < 0.05). The presence of demodex in the symptomatic ADT group was also higher than that in the asymptomatic ADT group (P < 0.05).The length of time that patients had been taking ADT was positively correlated with meiboscores and negatively correlated with NI-BUT. Conclusion: Androgen levels were associated with significant changes in relative meibomian gland function. Subjective symptoms, such as dryness and foreign body sensation, were more obvious in prostate cancer patients receiving ADT, which may be caused by MGD and demodex infection. It's recommended that more attention be paid to the ocular surface in prostate cancer patients taking ADT by performing examination of NI-BUT and meibomian gland morphology and function with a view to providing more comprehensive prevention and treatment protocols.

10.
Cell Death Discov ; 7(1): 348, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34759295

RESUMO

Spermiogenesis is a complex process depending on the sophisticated coordination of a myriad of testis-enriched gene regulations. The regulatory pathways that coordinate this process are not well understood, and we demonstrate here that AXDND1, as a novel testis-enriched gene is essential for spermiogenesis and male fertility. AXDND1 is exclusively expressed in the round and elongating spermatids in humans and mice. We identified two potentially deleterious mutations of AXDND1 unique to non-obstructive azoospermia (NOA) patients through selected exonic sequencing. Importantly, Axdnd1 knockout males are sterile with reduced testis size caused by increased germ cell apoptosis and sloughing, exhibiting phenotypes consistent with oligoasthenoteratozoospermia. Axdnd1 mutated late spermatids showed head deformation, outer doublet microtubules deficiency in the axoneme, and loss of corresponding accessory structures, including outer dense fiber (ODF) and mitochondria sheath. These phenotypes were probably due to the perturbed behavior of the manchette, a dynamic structure where AXDND1 was localized. Our findings establish AXDND1 as a novel testis-enrich gene essential for spermiogenesis and male fertility probably by regulating the manchette dynamics, spermatid head shaping, sperm flagellum assembly.

11.
BMC Pediatr ; 21(1): 483, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34719383

RESUMO

BACKGROUND: Minerals play an important role in children's growth and cognition. In this study, our aim was to establish reference intervals of mineral level in Children of Liaoning province (China) and provide a reliable basis for future preventive healthcare guidelines. METHODS: Random samples of 2217 healthy children aged 0-15 years who were referred for routine hospital laboratory examinations in the cities of Shenyang, Fushun, Fuxin, Benxi, Chaoyang and Lingyuan were invited to participate in the study. Serum levels of Calcium (Ca), Iron (Fe), Zinc (Zn), Magnesium (Mg), Copper (Cu), Manganese (Mn), Selenium (Se), Mercury (Hg), Nickel (Ni), Cobalt (Co), and Lithium (Li) were determined by inductively coupled plasma mass spectrometer(ICP-MS). RESULTS: Sex-related significant differences in the serum concentrations of the Mg and Cu (P < 0.05). Age-related significant differences were found in serum levels of Ca, Fe, Zn, Mg, Cu and Mn (P < 0.05) and the concentrations of 9 minerals (Ca, Mg, Cu, Mn,Se,Hg,Ni,Co and Li in serum varied from season to season (P < 0.05). The Spearman correlation matrix of 11 minerals was shown as a heat map, the correlations between Ca-Zn, Ca-Mg, Fe-Zn, Fe-Se, Mn-Ni, Se-Hg, Se-Ni, Hg-Ni, and Ni-Co, Ni-Li were the strongest compared with others. CONCLUSIONS: The reference intervals of serum 11 minerals for children should considering the sex, age and season, which may be useful for decisive diagnoses of abnormality of the 11minerals and the related diseases.

12.
Crit Rev Food Sci Nutr ; : 1-22, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34755571

RESUMO

Sand rice (Agriophyllum squarrosum) is prized for its well-balanced nutritional properties, broad adaptability in Central Asia and highly therapeutic potentials. It has been considered as a potential climate-resilient crop. Its seed has comparable metabolite profile with Chenopodium quinoa and is rich in proteins, essential amino acids, minerals, polyunsaturated fatty acids, and phenolics, but low in carbohydrates. Phenolics like protocatechuic acid and quercetins have been characterized with biological functions on regulation of lipid and glucose metabolism in addition to anti-inflammatory and antioxidant activities. Sand rice is thus an important source for developing functional and nutraceutical products. Though historical consumption has been over 1300 years, sand rice has undergone few agronomic improvements until recently. Breeding by individual selection has been performed and yield of the best genotype can reach up to 1295.5 kg/ha. Furthermore, chemical mutagenesis has been used to modify the undesirable traits and a case study of a dwarf line (dwarf1), which showed the Green Revolution-like phenotypes, is presented. Utilization of both breeding methodologies will accelerate its domestication process. As a novel crop, sand rice research is rather limited compared with quinoa. More scientific input is urgently required if the nutritional and commercial potentials are to be fully realized.

13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(10): 1007-1011, 2021 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-34625943

RESUMO

OBJECTIVE: To study rare para-Bombay blood type Bmh and to investigate the molecular genetic basis of para-Bombay phenotype in a Chinese family. METHODS: ABO and H phenotype of the proband and her pedigree were determined with serological methods. The ABO genotype was analyzed by polymerase chain reaction-sequence specific primer(PCR-SSP). The full coding region of alpha-l,2 fucosyltransferase (FUT1) gene of the pedigree was analyzed by polymerase chain reaction and direct sequencing of the amplified fragments. The haplotype of the FUT1 gene were analyzed by cloning sequencing. RESULTS: The rare para-Bombay blood type Bmh was identified in the proband, with ABO*B.01/ABO*O.01.01 genotype. Two variants of FUT1 gene, c.508dupT and c.787A>C, were found in the proband. The cloning sequencing revealed that the two variants were on different alleles, and the haplotype of FUT1 gene was h508dupT/h787C. Both of the two variants were predicted to cause inactivation of the enzyme, which is consistent with the result of serological techniques. CONCLUSION: Two new alleles of FUT1 gene (h508dupT and h787C), which were associated with para-Bombay phenotype, were identified in the Chinese pedigree.


Assuntos
Sistema ABO de Grupos Sanguíneos , Fucosiltransferases , Sistema ABO de Grupos Sanguíneos/genética , China , Feminino , Fucosiltransferases/genética , Genótipo , Humanos , Fenótipo
14.
Artigo em Inglês | MEDLINE | ID: mdl-34632492

RESUMO

OBJECTIVES: Vascular rings are rare anomalies of congenital heart disease that cause respiratory and gastrointestinal symptoms. This study assessed the long-term outcomes of patients with vascular ring division. METHODS: A multi-institution retrospective review of 371 patients with vascular rings undergoing surgical division at 3 paediatric cardiac institutions between November 2007 and October 2019 was performed. RESULTS: The complete vascular rings consisted of a double aortic arch (24.5%), right aortic arch with left ligamentum arteriosum (36.7%) and left aortic arch, with right ligamentum arteriosum (0.5%). The incomplete vascular rings consisted of a pulmonary artery sling (22.9%), left aortic arch with aberrant right subclavian artery (15.1%) and innominate artery compression syndrome (0.3%). Respiratory symptoms included stridor (71.4%), wheezing (49.1%), coughing (31.5%), gastrointestinal symptoms included choking (12.4%), dysphagia (3.2%) and emesis (1.9%). Only one patient died after discharge, yielding a late mortality rate of 0.3% (1/360). The 10-year overall survival rate was 96.8%. Postoperative complications were reported in 51 patients, 15 of whom required reoperation. The 10-year freedom from reoperation rate was 95.9%. Follow-up was completed in 95.4% (354/371) of patients, with a mean follow-up time of 4.3 ± 2.9 years (range from 1 to 13 years). Twenty patients (5.6%) experienced residual symptoms during long-term follow-up. CONCLUSIONS: The outcomes of vascular ring division are excellent. A Kommerell diverticulum >1.5 times the aberrant left subclavian artery origin is an operative indication for primary resection. Tracheomalacia is a risk factor for reoperation and residual symptoms, and preoperative fibrobronchoscopy is important for evaluation.

15.
Pharm Biol ; 59(1): 1388-1401, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34663173

RESUMO

CONTEXT: Genistein (Gen) has shown protective effects against ageing process. OBJECTIVE: To explore the role of Gen on the senescence of H2O2-induced human umbilical vein endothelial cells (HUVECs) and investigate the possible mechanism. MATERIALS AND METHODS: HUVECs were treated with different concentrations of H2O2 (50, 100, 200 and 400 µmol/L) for 1 h or Gen administration (20, 40, 80 and 160 µg/mL) for 24 h. Functional experiments (cell counting kit-8, ß-galactosidase staining and flow cytometry) were used to detect the effect of Gen on H2O2-induced HUVECs. After HUVECs were transfected with TXNIP overexpression plasmids, the expression of p16, p21, thioredoxin-interacting protein (TXNIP), nucleotide-binding and oligomerization domain-like receptor 3 (NLRP3), cleaved caspase-3 and cleaved caspase-1 in HUVECs were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. RESULTS: H2O2 (200 and 400 µmol/L) inhibited the proliferation of HUVECs. At concentrations of >50 µmol/L, H2O2 induced the cell cycle progression arrests in G1 phase and promoted cell senescence of HUVECs. Gen had no obvious cytotoxicity to HUVECs below 160 µg/mL. H2O2-induced HUVEC senescence and the expression of TXNIP and NLRP3 in HUVECs were down-regulated by Gen (40 and 80 µg/mL). Expressions of TXNIP and NLRP3 in HUVECs were up-regulated by H2O2 but down-regulated by Gen. Overexpressed TXNIP partially reversed the suppressive effect of Gen on H2O2-induced senescence and apoptosis of HUVECs. Expressions of p16, p21, TXNIP, NLRP3, cleaved caspase-3 and cleaved caspase-1 in H2O2-treated HUVECs were inhibited by Gen, while the inhibition as such was partially reversed by overexpressed TXNIP. DISCUSSION AND CONCLUSIONS: H2O2-induced HUVEC senescence was alleviated by Gen via suppressing the TXNIP/NLRP3 axis, which may offer a potential therapeutic approach for improving HUVEC senescence and provide a new direction for the treatment of cardiovascular disease.

16.
Thorac Cancer ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34651449

RESUMO

BACKGROUND: For lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) sensitive mutation and synchronous brain metastasis (syn-BM), when and how to apply radiotherapy (RT) during first-line tyrosine kinase inhibitor (TKI) treatment remains debatable. METHODS: From a real-world multicenter database, EGFR-mutant patients with syn-BM diagnosed between 2010-2020 and treated with first-line TKIs were enrolled and divided into upfront TKI + RT and upfront TKI groups. Median intracranial progression-free survival (mIC-PFS), median overall survival (mOS), and their risk factors were estimated. RESULTS: There were 60 and 186 patients in the upfront TKI + RT group and upfront TKI group, respectively. Their mIC-PFS were 28.9 months (m) and 17.5 m (p = 0.023), and mOS were 42.7 m and 40.1 m (p = 0.51). Upfront brain RT improved mIC-PFS in patients ≤60-year-old (p = 0.035), with symptomatic BM (p = 0.002), and treated with first-generation TKIs (p = 0.012). There was no significant difference in mOS in any subgroup. Upfront brain stereotactic radiosurgery (SRS) showed a trend of better mIC-PFS and mOS. mIC-PFS was independently correlated with symptomatic BM (HR = 1.54, p = 0.030), EGFR L858R mutation (HR = 1.57, p = 0.019), and upfront brain RT (HR = 0.47, p = 0.001). mOS was independently correlated with being female (HR = 0.54, p = 0.007), ECOG 3-4 (HR = 10.47, p < 0.001), BM number>3 (HR = 2.19, p = 0.002), and third-generation TKI (HR = 0.54, p = 0.044) or antiangiogenic drugs (HR = 0.11, p = 0.005) as first/second-line therapy. CONCLUSIONS: Upfront brain RT based on first-line EGFR-TKI might improve IC-PFS but not OS in EGFR-mutant lung adenocarcinoma patients, indicating potential survival benefit from brain SRS and early application of drugs with higher intracranial activity.

17.
Natl Sci Rev ; 8(3): nwaa297, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34676096

RESUMO

Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2. Halting these steps can cure COVID-19. Here we have identified and characterized a potent human monoclonal antibody, HB27, that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations. Remarkably, HB27 can also prevent SARS-CoV-2 membrane fusion. Consequently, a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse models. Rhesus macaques showed no obvious adverse events when administrated with 10 times the effective dose of HB27. Cryo-EM studies on complex of SARS-CoV-2 trimeric S with HB27 Fab reveal that three Fab fragments work synergistically to occlude SARS-CoV-2 from binding to the ACE2 receptor. Binding of the antibody also restrains any further conformational changes of the receptor binding domain, possibly interfering with progression from the prefusion to the postfusion stage. These results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19.

18.
Front Microbiol ; 12: 759208, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34691010

RESUMO

Tigecycline serves as one of the last-resort antibiotics to treat severe infections caused by carbapenem-resistant Enterobacterales. Recently, a novel plasmid-mediated resistance-nodulation-division (RND)-type efflux pump gene cluster, TmexCD1-ToprJ1, and its variants, TmexCD2-ToprJ2 and TmexCD3-ToprJ3, encoding tetracyclines and tigecycline resistance, were revealed. In this study, we reported three TmexCD2-ToprJ2-harboring Klebsiella species strains, collected from two teaching tertiary hospitals in China, including one K. quasipneumoniae, one K. variicola, and one K. michiganensis. The three strains were characterized by antimicrobial susceptibility testing (AST), conjugation assay, WGS, and bioinformatics analysis. AST showed that K. variicola and K. quasipneumoniae strains were resistant to tigecycline with MIC values of 4µg/ml, whereas the K. michiganensis was susceptible to tigecycline with an MIC value of 1µg/ml. The TmexCD2-ToprJ2 clusters were located on three similar IncHI1B plasmids, of which two co-harbored the metallo-ß-lactamase gene bla NDM-1. Conjugation experiments showed that all three plasmids were capable of self-transfer via conjugation. Our results showed, for the first time, that this novel plasmid-mediated tigecycline resistance mechanism TmexCD2-ToprJ2 has spread into different Klebsiella species, and clinical susceptibility testing may fail to detect. The co-occurrence of bla NDM-1 and TmexCD2-ToprJ2 in the same plasmid is of particular public health concern as the convergence of "mosaic" plasmids can confer both tigecycline and carbapenem resistance. Its further spread into other clinical high-risk Klebsiella clones will likely exacerbate the antimicrobial resistance crisis. A close monitoring of the dissemination of TmexCD-ToprJ encoding resistance should be considered.

19.
Zhen Ci Yan Jiu ; 46(10): 893-900, 2021 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-34698466

RESUMO

In this paper, the articles of auricular acupuncture in recent 20 years are sorted out and analyzed, and the theory and mechanism of auricular acupuncture in different schools are summarized and compared. Eight theories are included totally, i.e. meridian-collateral theory and zangfu theory of classic TCM, as well as neurodoctrine, neurohumoral theory, embryology theory, holography theory, biological cybernetics and chronobiology theory in modern times. Each of them has its own rationality.Hereafter, through more rigour scientific deign and in accordance with clinical and experimental studies, auricular acupuncture theory should be explored more scientifically and universally so as to provide the theoretic guidance and evidences for clinical treatment with auricular acupuncture, and then to improve the clinical therapeutic effect and promote the application of auricular acupuncture.


Assuntos
Acupuntura Auricular , Meridianos , Pontos de Acupuntura
20.
Clin Rheumatol ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34709497

RESUMO

OBJECTIVE: The equivalence of the biosimilar HS016 to adalimumab (Humira) for the treatment of active ankylosing spondylitis (AS) patients has been previously validated. The aim was to compare the efficacy of HS016 and adalimumab in stratified subgroups at different time points using Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) and short form 36 (SF-36) questionnaires. METHODS: We carried out a multicenter, randomized, double-blind, parallel, positive control, phase 3 trial of patients with active AS. They were selected randomly to be subcutaneously administered 40 mg HS016 or adalimumab every 2 weeks for a total treatment period of 24 weeks in a 2:1 ratio. A health surveys were used to assess mental and physical improvements of patients as well as other factors. RESULTS: HAQ-S revealed that changes in scores from baseline in both groups were time dependent until 14 weeks and that during the first 4 weeks of treatment the changes declined rapidly. The SF-36 health survey revealed that both HS016 and adalimumab produced rapid beneficial effects against AS during the first 2 weeks of therapy, which gradually declined between 2 and 12 weeks and flattened out after 12 weeks until 24 weeks. CONCLUSION: This trial demonstrated that both HS016 and adalimumab produced rapid improvements in symptoms during the first 2 weeks of treatment. These findings suggest that HS016 is an alternative economical treatment for Chinese AS patients producing a rapid amelioration of symptoms, aiding them to recover their lifestyle satisfaction. TRIAL REGISTRATION: http://www.chictr.org.cn/enindex.aspx , ChiCTR1900022520, retrospectively registered. Key points • HS016 and adalimumab produced rapid AS symptom improvements during the first 2 weeks followed by a slowdown of improvements until week 4 with afterwards few improvements evaluated by HAQ-S • The improvements according to the short form of the 36 (SF-36) questionnaires revealed similar trends as for HAQ-S • There was no significant difference in HAQ-S and SF-36 scores between HS016 and adalimumab.

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