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1.
Bioact Mater ; 19: 75-87, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35441117

RESUMO

Osteoporosis is one of the most disabling consequences of aging, osteoporotic fractures and higher risk of the subsequent fractures leading to substantial disability and deaths, indicating both local fractures healing and the early anti-osteoporosis therapy are of great significance. Teriparatide is strong bone formation promoter effective in treating osteoporosis, while side effects limit clinical applications. Traditional drug delivery is lack of sensitive and short-term release, finding a new non-invasive and easily controllable drug delivery to not only repair the local fractures but also improve total bone mass has remained a great challenge. Thus, bioinspired by the natural bone components, we develop appropriate interactions between inorganic biological scaffolds and organic drug molecules, achieving both loaded with the teriparatide in the scaffold and capable of releasing on demand. Herein, biomimetic bone microstructure of mesoporous bioglass, a near-infrared ray triggered switch, thermosensitive liposomes based on a valve, and polydopamine coated as a heater is developed rationally for osteoporotic bone regeneration. Teriparatide is pulsatile released from intelligent delivery, not only rejuvenating osteoporotic bone defect, but also presenting strong systemic anti-osteoporosis therapy. This biomimetic bone carrying novel drug delivery platform is well worth expecting to be a new promising strategy and clinically commercialized to help patients survive from the osteoporotic fracture.

2.
Bioact Mater ; 20: 663-676, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35891799

RESUMO

Cancer therapies based on energy conversion, such as photothermal therapy (PTT, light-to-thermal energy conversion) and photodynamic therapy (PDT, light-to-chemical energy conversion) have attracted extensive attention in preclinical research. However, the PTT-related hyperthermia damage to surrounding tissues and shallow penetration of PDT-applied light prevent further advanced clinical practices. Here, we developed a thermoelectric therapy (TET) based on thermoelectric materials constructed p-n heterojunction (SrTiO3/Cu2Se nanoplates) on the principle of light-thermal-electricity-chemical energy conversion. Upon irradiation and natural cooling-induced the temperature gradient (35-45 oC), a self-build-in electric field was constructed and thereby facilitated charges separation in bulk SrTiO3 and Cu2Se. Importantly, the contact between SrTiO3 (n type) and Cu2Se (p type) constructed another interfacial electric field, further guiding the separated charges to re-locate onto the surfaces of SrTiO3 and Cu2Se. The formation of two electric fields minimized probability of charges recombination. Of note, high-performance superoxide radicals and hydroxyl radicals' generation from O2 and H2O under catalyzation by separated electrons and holes, led to intracellular ROS burst and cancer cells apoptosis without apparent damage to surrounding tissues. Construction of bulk and interfacial electric fields in heterojunction for improving charges separation and transfer is also expected to provide a robust strategy for diverse applications.

3.
Gen Psychiatr ; 35(1): e100751, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372787

RESUMO

China's population has rapidly aged over the recent decades of social and economic development as neurodegenerative disorders have proliferated, especially Alzheimer's disease (AD) and related dementias (ADRD). AD's incidence rate, morbidity, and mortality have steadily increased to make it presently the fifth leading cause of death among urban and rural residents in China and magnify the resulting financial burdens on individuals, families and society. The 'Healthy China Action' plan of 2019-2030 promotes the transition from disease treatment to health maintenance for this expanding population with ADRD. This report describes related epidemiological trends, evaluates the economic burden of the disease, outlines current clinical diagnosis and treatment status and delineates existing available public health resources. More specifically, it examines the public health impact of ADRD, including prevalence, mortality, costs, usage of care, and the overall effect on caregivers and society. In addition, this special report presents technical guidance and supports for the prevention and treatment of AD, provides expertise to guide relevant governmental healthcare policy development and suggests an information platform for international exchange and cooperation.

4.
Int Immunopharmacol ; 111: 109088, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35921779

RESUMO

OBJECTIVE: The aim of this study was to address the association between interstitial lung disease and the risk for severity and mortality among patients with coronavirus disease 2019 (COVID-19). METHODS: The electronic databases of PubMed, Web of Science and EMBASE were systematically searched. The pooled effect size with 95 % confidence interval (CI) was computed by a random-effects meta-analysis model. Heterogeneity test, sensitivity analysis, subgroup analysis, meta-regression analysis, Begg's test and Egger's test were performed. RESULTS: A total of sixteen eligible studies with 217,260 COVID-19 patients were enrolled in this meta-analysis. The findings based on adjusted effect estimates indicated that pre-existing interstitial lung disease was significantly associated with higher risk for COVID-19 severity (pooled effect = 1.34 [95 % CI: 1.16-1.55]) and mortality (pooled effect = 1.26 [95 % CI: 1.09-1.46]). Consistent results were observed in the subgroup analysis stratified by sample size, age, the percentage of male patients, study design, setting, the methods for adjustment and the factors for adjustment. The results of meta-regression demonstrated that sample size, age and region might be the potential sources of heterogeneity. Sensitivity analysis exhibited that our results were stable and robust. No publication bias was observed in Egger's test and Begg's test. CONCLUSION: This meta-analysis on the basis of adjusted effect estimates demonstrated that pre-existing interstitial lung disease was independently associated with significantly higher risk for COVID-19 severity and mortality.

5.
Cytokine ; 158: 155976, 2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-35921790

RESUMO

Long-standing inflammatory bowel disease predisposes to the development of colorectal cancer (CRC). Interleukin (IL) -6, a pivotal link between chronic inflammation and tumor progression, has recently been recognized as a potential therapeutic target. The effect of IL-6 on proliferation and metastasis of CRC by activating the STAT3 pathway has been widely demonstrated in recent years, but few on mediating tumor immune evasion. In this study, we found that IL-6 was remarkably overexpressed in CRC and its elevation was associated with a poor prognosis. We studied CRC tumorigenesis in vivo by inoculating MC38 tumors and induced-CRC model via AOM/DSS (azoxymethane/dextransulfate sodium) in IL-6 deficient (IL-6-/-) and wild-type (WT) mice and found that IL-6-/- mice were less susceptible to develop tumors, compared to WT mice. We detected CD8+ T cells via immunofluorescence and found they exhibit high expression in tumor of IL-6-/- mice. High level of IL-6 was found in colitis model, with down-regulation of MHC-I molecules. In in vitro experiments, we found that IL-6 may act as a negative regulator in IFNγ-STAT1-MHC-I signaling. In addition, vivo trials also confirmed that MHC-I mRNA level was negatively related to the existence of IL-6. Furthermore, the blockade of IL-6 also activated CD8+T-cell accumulation and led to the high PD-L1 expression in CRC, which can sensitize animals to anti-PD-1 therapy. Our study provides a research basis for the significant role of IL-6 in tumor evasion and highlights a novel target to improve the efficacy of immunotherapy.

6.
Environ Pollut ; 310: 119870, 2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-35921944

RESUMO

Irrational use of antibiotics produces a large number of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs). Wastewater treatment plants (WWTPs) act as important sources and sinks of ARGs, and play an important role in their generation, treatment, and dissemination. This study summarizes the types, concentrations, and factors of ARGs in WWTPs, investigates the sources of ARGs in wastewater, compares the removal efficiencies of different treatment processes on ARGs, and analyzes the potential risks of ARGs accumulation in effluent, sludge and their emission into the air. The results show that the main ARGs detected in the influent of WWTPs are the genes resistant to macrolides (ermB, ermF), tetracyclines (tetW, tetA, tetC), sulfonamides (sul1, sul2), and ß-lactams (blaOXA, blaTEM). The concentrations of ARGs in the influent of the WWTPs are 2.23 × 102-3.90 × 109 copies/mL. Wastewater quality and microbial community are the dominant factors that affect the distribution characteristics of ARGs. The accumulation of ARGs in effluent, sludge, and aerosols pose potential risks to the regional ecological environment and human health. Based on these results, research trends with respect to ARGs in WWTPs are also prospected.

7.
Ann Palliat Med ; 11(7): 2464-2477, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35927780

RESUMO

BACKGROUND: Phase I clinical trials play an important role in the follow-up clinical trials and even the drug registration and marketing. However, the screening success ratio in phase I clinical trials is low, and the screening process of the trials consumes a significant amount of human and material resources, but the results are unsatisfactory. At present, there is no large sample data analysis for screening failure in phase I clinical trials. It is therefore urgent to find the reasons for screening failure in phase I clinical trials. METHODS: A total of 1,058 healthy volunteers who failed the screening in 11 phase I clinical trials were retrospectively collected from October 2018 to June 2021 in Cangzhou Central Hospital. Data on all participants who failed screening for the study were analyzed (descriptive analysis) and reasons for their non-randomization were classified, as well as the differences of main screening failures between four years. RESULTS: A total of 1,466 healthy volunteers were enrolled in the 11 trials, and among them 1,058 subjects failed the screening. The total screening success ratio of our study was only 27.8%, the highest being 38.5% and the lowest being 18.2%. The top 3 reasons for non-randomization were abnormalities in blood biochemistry tests (23.3%), vital sign examination (19.3%), and electrocardiogram (ECG) (16.6%). Abnormal blood biochemistry was the main reason between 2019 and 2021, except for 2018 in which it was the second reason. CONCLUSIONS: Screening failure is a burdensome issue which various clinical trial sites must contend with. Investigators can still take some effective measures by strengthening the in-depth understanding of informed consent, paying attention to the quality of test samples, a correcting definition of no clinical significance (NCS). Also, low-cost and non-invasive examinations can be arranged first to better protect the volunteers and reduce the screening costs of clinical trials. To our delight, we find people's attention to the annual physical examination may help to screen healthy volunteers. Overall, this study shows that it is crucial and professional to develop a screening plan to minimize the resultant impact on timelines and budgets of phase I clinical trials enrolling healthy volunteers.


Assuntos
Voluntários Saudáveis , Consentimento Livre e Esclarecido , Programas de Rastreamento , Ensaios Clínicos Fase I como Assunto , Humanos , Seleção de Pacientes , Estudos Retrospectivos
8.
BMC Musculoskelet Disord ; 23(1): 758, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941682

RESUMO

OBJECTIVES: To evaluate the oncologic and functional results of scapular reconstruction after partial or total scapulectomy for chondrosarcoma. MATERIALS AND METHODS: Twenty-one patients with chondrosarcoma who underwent partial or total scapulectomy between January 2005 and July 2019 were reviewed retrospectively. RESULTS: At a mean follow-up of 62.6 months (range, 13-123 months), four patients developed local recurrence, and three developed distant metastases, one of which developed both recurrence and metastasis. The overall survival rate of patients at 5 years was 84.6%, the disease-free survival rate was 69.3%, and the complication rate was 19% (4/21). The 1993 American Musculoskeletal Tumor Society (MSTS93) scores of patients in the partial scapulectomy group, total scapulectomy + humeral suspension group and prosthetic reconstruction group were 26.50 ± 1.38, 19.00 ± 2.58, and 21.38 ± 2.62, respectively. There was a statistically significant difference between the partial scapulectomy group and the total scapulectomy + humeral suspension or prosthetic reconstruction group ( P = 0.006 and 0.0336, respectively). The range of motion of the shoulder joint for forward flexion was 80.83° ± 11.14°, 51.25° ± 21.36°, and 52.50° ± 11.02°, respectively. The p-values for the comparison between the partial scapulectomy group and the total scapulectomy + humeral suspension or prosthetic reconstruction group were 0.0493 and 0.0174, respectively. And the range of motion of abduction was 75.00° ± 10.49°, 32.50° ± 11.90°, 41.88° ± 11.63°, respectively. Patients in the partial scapulectomy group had significantly better postoperative shoulder abduction function than the total scapulectomy + humeral suspension or prosthetic reconstruction group (P = 0.0035 and 0.0304, respectively). There was no significant difference in MSTS93 scores and flexion and abduction function of the shoulder joint in the upper extremity after total scapulectomy with humeral suspension or prosthetic reconstruction (P > 0.05). CONCLUSIONS: Surgical treatment of chondrosarcoma of the scapula can achieve a satisfactory prognosis and shoulder function. Total scapulectomy followed by prosthetic reconstruction or humeral suspension are both feasible treatments.


Assuntos
Neoplasias Ósseas , Condrossarcoma , Articulação do Ombro , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Condrossarcoma/diagnóstico por imagem , Condrossarcoma/patologia , Condrossarcoma/cirurgia , Seguimentos , Humanos , Amplitude de Movimento Articular , Estudos Retrospectivos , Escápula/patologia , Escápula/cirurgia , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/patologia , Articulação do Ombro/cirurgia
9.
Emerg Med Int ; 2022: 9621893, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35941961

RESUMO

Objective: To explore the diagnosis of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma (ICC) by cervical biopsy under colposcopy and analyze the factors influencing the detection. Methods: The clinical data of 134 CIN confirmed by colposcopy biopsy in our hospital from June 2018 to October 2019 and subsequent LEEP treatment were analyzed retrospectively. All patients were diagnosed pathologically after the operation. The diagnosis of CIN by cervical biopsy under colposcopy was observed. The influencing factors of CIN and ICC detected by colposcopy biopsy were analyzed by the pathological results of loop electrosurgical excision procedure (LEEP) as the gold standard. Results: After LEEP, the number of the no intraepithelial or malignant lesions (NILM) or ICC were higher than that of colposcopy biopsy, and CIN-III was lower than that of colposcopy biopsy, the differences were all statistically significant (P < 0.05). Among the 134 patients, the coincidence rate between colposcopy biopsy and LEEP examination results was 79.10% (106/134), and postoperative pathological findings showed that there were 13 cases (9.70%) with the pathological upgrade and 19 cases (14.18%) with pathological decrease. Multivariate logistic analysis showed that the image quality of colposcopy image, atypical blood vessels, biopsy sampling method, and visible lesion area of the cervix were the independent influencing factors for the detection of CIN and ICC by colposcopy biopsy (P < 0.05). Conclusion: CIN and ICC can be diagnosed by colposcopy cervical biopsy and postoperative histopathology. However, there are still some missed and misdiagnosed cervical biopsies under colposcopy, and the combined detection of the two can further ensure the diagnosis rate. The clinical registration number is E2018091.

10.
Anticancer Drugs ; 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35946506

RESUMO

Cisplatin (DDP) resistance limits therapeutic efficacy in patients diagnosed with ovarian cancer. Purvalanol A (Pur) is a novel cyclin-dependent kinase (CDK) inhibitor that has been demonstrated to induce apoptosis in various cancer cells. The present study investigated the effect of the combination treatment of Pur and DDP, and the potential anticancer mechanisms in epithelial ovarian cancer (EOC) cells in vitro and in vivo. We found that Pur enhanced the anti-tumor efficacy of cisplatin in EOC cells. The combination of Pur and DDP had more significant effects on apoptosis induction in EOC cells compared with the individual-treatment groups and the control group. We further demonstrated that the combination of Pur and DDP may trigger apoptosis and autophagy in EOC cells by inducing reactive oxygen species (ROS). And the ROS/Akt/mammalian target of rapamycin signaling pathway as a potential mechanism for the initiation of autophagy induced by combination therapy. Similar results were observed in vivo. These results demonstrated that Pur sensitized the response of EOC cells to cisplatin in vitro and in vivo, reversing the resistance to cisplatin in ovarian cancer.

11.
Chin J Integr Med ; 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35947230

RESUMO

OBJECTIVE: To investigate the effects of Pien Tze Huang (PZH) on the migration and invasion of HCC cells and underlying molecular mechanism. METHODS: Cell counting kit-8 (CCK-8) was applied to evaluate the cell viabilities of SMMC-7721, SK-Hep-1, C3A and HL-7702 (6 × 103 cells/well) co-incubated with different concentrations of PZH (0, 0.2, 0.4, 0.6, 0.8 mg/mL) for 24 h. Transwell, wound healing assay, CCK-8 and Annexin V-FITC/PI staining were conducted to investigate the effects of PZH on the migration, invasion, proliferation and apoptosis of SK-Hep-1 and SMMC-7721 cells (650 µ g/mL for SK-Hep-1 cells and 330 µ g/mL for SMMC-7721 cells), respectively. In vivo, lung metastasis mouse model constructed by tail vein injection of HCC cells was used for evaluating the anti-metastasis function of PZH. SK-Hep-1 cells (106 cells/200 µ L per mice) were injected into B-NDG mice via tail vein. Totally 8 mice were randomly divided into PZH and control groups, 4 mice in each group. After 2-d inoculation, mice in the PZH group were administered with PZH (250 mg/kg, daily) and mice in the control group received only vehicle (PBS) from the 2nd day after xenograft to day 17. Transcriptome analysis based on RNA-seq was subsequently used for deciphering anti-tumor mechanism of PZH. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were applied to verify RNA-seq results. Luciferase reporter assay was performed to examine the transcriptional activity of yes-associated protein (YAP). RESULTS: PZH treatment significantly inhibited the migration, invasion, proliferation and promoted the apoptosis of HCC cells in vitro and in vivo (P<0.01). Transcriptome analysis indicated that Hippo signaling pathway was associated with anti-metastasis function of PZH. Mechanical study showed PZH significantly inhibited the expressions of platelet derived growth factor receptor beta (PDGFRB), YAP, connective tissue growth factor (CCN2), N-cadherin, vimentin and matrix metallopeptidase 2 (MMP2, P<0.01). Meanwhile, the phosphorylation of YAP was also enhanced by PZH treatment in vitro and in vivo. Furthermore, PZH played roles in inhibiting the transcriptional activity of YAP. CONCLUSION: PZH restrained migration, invasion and epithelial-mesenchymal transition of HCC cells through repressing PDGFRB/YAP/CCN2 axis.

12.
J Phys Chem Lett ; : 7541-7546, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35947432

RESUMO

Single-walled carbon nanotube (SWNT)-based devices are expected to play an important role in the next generation of electronic integrated circuits. As an important structural unit for SWNT-based electronics, the Schottky junction has a series of functions such as rectification, photoelectric detection, switching, etc. Here, we demonstrate a well-controlled localized radical reaction method to prepare an intramolecular SWNT Schottky junction with a closed edge. This junction exhibits strong gate-dependent rectifying behavior and a high rectification ratio of 962. Furthermore, the semiconducting part on the junction side could be effectively tuned from p-type doping to n-type doping, resulting in reversible rectifying behavior. Our work paves a new avenue for the design and synthesis of an SWNT Schottky junction, which is very important to future applications for carbon-based nanoelectronic devices.

13.
Mitochondrial DNA B Resour ; 7(8): 1421-1423, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937903

RESUMO

Carex laevissima Nakai 1914 (Cyperaceae) is vital for ecological conservation and land virescence, and has high ornamental value. Here the chloroplast genome of Carex laevissima was assembled and systematically analyzed for further genetic research of Carex plants. The chloroplast sequence of Carex laevissima was 188,029 bp in length, including two inverted repeat (IR) regions of 36,699 bp each, a large single-copy (LSC) region of 106,171 bp and a small single-copy region (SSC) of 8460 bp. The overall GC content is 34.0%. It contains 133 genes, including 89 protein-coding, 36 tRNA, and eight rRNA genes. Phylogenetic analysis showed that Carex laevissima is most closely related to Carex neurocarpa.

14.
Am J Surg Pathol ; 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35939829

RESUMO

The prognosis of prostate cancers exhibiting extraprostatic extension [other than bladder or seminal vesicle invasion (EPE)] and/or microscopic bladder neck invasion (mBNI) is variable, and further risk stratification is required. We herein assessed radical prostatectomy findings and long-term oncologic outcomes in consecutive 957 patients with pT3a disease. The patient cohort was divided into 4 groups, focal EPE (F-EPE) only (n=177; 18.5%), nonfocal/established (E-EPE) only (n=634; 66.2%), mBNI only (n=51; 5.3%). The rate of positive surgical margin and estimated volume of tumor were significantly higher in patients with both EPE and mBNI than in those with either. In addition, compared with F-EPE or mBNI only, E-EPE only was significantly associated with higher Grade Group, lymph node metastasis, and larger tumor volume. Kaplan-Meier analysis revealed a comparable prognosis after prostatectomy between those showing F-EPE only versus mBNI only (P=0.986), and these 2 cohorts were combined for further analysis. Then, patients showing E-EPE only had a significantly higher or lower risk of progression compared with those showing F-EPE or mBNI only (P<0.001) or both EPE and mBNI (P<0.001), respectively. These significant differences in progression-free survival were also seen in subgroups, including those with or without undergoing adjuvant therapy before recurrence and those showing no lymph node metastasis. In multivariate analysis, F-EPE or mBNI only (hazard ratio=0.524, P=0.003) or both EPE and mBNI (hazard ratio=1.465, P=0.039) (vs. E-EPE only) showed significance for progression. Based on these findings, we propose a novel pT3a subclassification, pT3a1 (F-EPE or mBNI alone), pT3a2 (E-EPE alone), and pT3a3 (both EPE and mBNI).

15.
ISME J ; 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941172

RESUMO

Studying the microbial symbionts of eukaryotic hosts has revealed a range of interactions that benefit host biology. Most eukaryotes are also infected by parasites that adversely affect host biology for their own benefit. However, it is largely unclear whether the ability of parasites to develop in hosts also depends on host-associated symbionts, e.g., the gut microbiota. Here, we studied the parasitic wasp Leptopilina boulardi (Lb) and its host Drosophila melanogaster. Results showed that Lb successfully develops in conventional hosts (CN) with a gut microbiota but fails to develop in axenic hosts (AX) without a gut microbiota. We determined that developing Lb larvae consume fat body cells that store lipids. We also determined that much larger amounts of lipid accumulate in fat body cells of parasitized CN hosts than parasitized AX hosts. CN hosts parasitized by Lb exhibited large increases in the abundance of the bacterium Acetobacter pomorum in the gut, but did not affect the abundance of Lactobacillus fructivorans which is another common member of the host gut microbiota. However, AX hosts inoculated with A. pomorum and/or L. fructivorans did not rescue development of Lb. In contrast, AX larvae inoculated with A. pomorum plus other identified gut community members including a Bacillus sp. substantially rescued Lb development. Rescue was further associated with increased lipid accumulation in host fat body cells. Insulin-like peptides increased in brain neurosecretory cells of parasitized CN larvae. Lipid accumulation in the fat body of CN hosts was further associated with reduced Bmm lipase activity mediated by insulin/insulin-like growth factor signaling (IIS). Altogether, our results identify a previously unknown role for the gut microbiota in defining host permissiveness for a parasite. Our findings also identify a new paradigm for parasite manipulation of host metabolism that depends on insulin signaling and the gut microbiota.

16.
Stroke ; : 101161STROKEAHA122039082, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35942881

RESUMO

BACKGROUND: The utility of magnetic resonance imaging (MRI) brain in patients with transient or minor neurological symptoms is uncertain. We sought to determine the proportion of participants with transient or minor neurological symptoms who had MRI evidence of acute ischemia at different clinical probabilities of transient ischemic attack (TIA) or minor stroke. METHODS: Cohort of participants with transient or minor neurological symptoms from emergency and outpatient settings. Clinicians at different levels of training gave each participant a diagnostic probability (probable when TIA/stroke was the most likely differential diagnosis; possible when TIA/stroke was not the most likely differential diagnosis; or uncertain when diagnostic probability could not be given) before 1.5 or 3T brain MRI ≤5 days from onset. Post hoc, each clinical syndrome was defined blind to MRI findings as National Institute of Neurological Disorders and Stroke criteria TIA/stroke; International Headache Society criteria migraine aura; non-TIA focal symptoms; or nonfocal symptoms. MRI evidence of acute ischemia was defined by 2 reads of MRI. Stroke was ascertained for at least 90 days and up to 18 months after recruitment. RESULTS: Two hundred seventy-two participated (47% female, mean age 60, SD 14), 58% with MRI ≤2 days of onset. Most (92%) reported focal symptoms. MR evidence of acute ischemia was found, for stroke/TIA clinical probabilities of probable 23 out of 75 (31% [95% CI, 21%-42%]); possible 26 out of 151 (17% [12%-24%]); and uncertain 9 out of 43, (20% [10%-36%]). MRI evidence of acute ischemia was found in National Institute of Neurological Disorders and Stroke criteria TIA/stroke 40 out of 95 (42% [32%-53%]); migraine aura 4 out of 38 (11% [3%-25%]); non-TIA focal symptoms 16 out of 99 (16% [10%-25%]); and no focal features 1 out of 29 (3% [0%-18%]). After MRI, a further 14 (5% [95% CI, 3-8]) would be treated with an antiplatelet drug compared with treatment plan before MRI. By 18 months, a new ischemic stroke occurred in 9 out of 61 (18%) patients with MRI evidence of acute ischemia and 2 out of 211 (1%) without (age-adjusted hazard ratio, 13 [95% CI, 3-62]; P<0.0001). CONCLUSIONS: MRI evidence of acute brain ischemia was found in about 1 in 6 transient or minor neurological symptoms patients with a nonstroke/TIA initial diagnosis or uncertain diagnosis. Methods to determine the clinical and cost-effectiveness of MRI are needed in this population.

17.
Artigo em Inglês | MEDLINE | ID: mdl-35942908

RESUMO

Isolated nocturnal hypertension (INH) is a special type of out-of-office hypertension. Its determinants and pathophysiology remain unclear. In a nested case-control study, we intend to investigate the host, environmental, and genetic factors in relation to INH. Among 2030 outpatients screened from December 2008 till June 2015, 128 patients with INH were identified, and then 128 normotensives were matched according to sex and age. INH was an elevated nocturnal blood pressure (BP ≥120/70 mmHg) in the presence of a normal daytime BP (< 135/85 mmHg). Host factors included age, sex, body mass index, smoking and drinking, sleep time and duration, heart rate, serum lipids, and serum creatinine. Environmental cues encompassed season, ambient temperature, atmospheric pressure, humidity, and wind speed, and genetic cues 29 single-nucleotide polymorphisms (SNPs) in 12 clock genes. Daytime and nighttime BPs averaged 124.9/80.7  and 114.5/73.7 mmHg, respectively, in the INH patients and 121.0/76.5 and 101.8/63.3 mmHg in the normotensive controls. Stepwise logistic regression analyses revealed that INH was associated with nighttime heart rate (P = .0018), sleep duration (P = .0499), and relative humidity (P = .0747). The odds ratios (95% CI) for each 10 beats/min faster nighttime heart rate and 10% lower relative humidity were 1.82 (1.25-2.65) and 0.82 (0.67-1.00), respectively. Irrespective of the genetic models, no significant association was observed between INH and the SNPs (P ≥ .054). In conclusion, INH was associated with host and environmental factors rather than genetic markers.

18.
Clin Transl Immunology ; 11(7): e1406, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910005

RESUMO

Objectives: Despite remarkable advances in the treatment of non-small cell lung cancer (NSCLC) with anti-programmed death (PD)-1 therapy; only a fraction of patients derives durable clinical benefit. In this study, we investigated whether the differentiation status of systemic CD8+ T cells predicts the outcome of PD-1 blockade in NSCLC. Methods: We carried out a prospective study on a total of 77 NSCLC patients receiving anti-PD-1 blockers, among which 47 patients were assigned as a discovery cohort and 30 patients as a validation cohort. Peripheral blood samples were obtained at baseline and upon multiple therapy cycles and analyzed by multi-parameter flow cytometry. Results: We found that a higher baseline ratio of PD-1+ early effector memory CD8+ T cells (CD28+CD27-CD45RO+, TEEM) to PD-1+ effector CD8+ T cells (CD28-CD27-CD45RO-, TE) delineated responders to PD-1 blockade from progressors and was associated with prolonged progression-free survival (PFS) and durable clinical benefit. Moreover, PD-1+CD8 TEEM cells exhibited early responses after anti-PD-1 therapy and was the major fraction of cycling PD-1+Ki67+CD8+ T cells to expand specifically with positive impact on PFS. Conclusion: These findings provide insights into how the baseline differentiation status of the peripheral immune system determines responses to PD-1-targeted therapies.

19.
Front Pharmacol ; 13: 919269, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910355

RESUMO

Improving healthy life expectancy by targeting aging-related pathological changes has been the spotlight of geroscience. Scorpions have been used in traditional medicine in Asia and Africa for a long time. We have isolated heat-resistant peptides from scorpion venom of Buthusmartensii Karsch (SVHRP) and found that SVHRP can attenuate microglia activation and protect Caenorhabditis elegans (C. elegans) against ß-amyloid toxicity. Based on the amino acid sequence of these peptides, scorpion venom heat-resistant synthesized peptide (SVHRSP) was prepared using polypeptide synthesis technology. In the present study, we used C. elegans as a model organism to assess the longevity-related effects and underlying molecular mechanisms of SVHRSP in vivo. The results showed that SVHRSP could prolong the lifespan of worms and significantly improve the age-related physiological functions of worms. SVHRSP increases the survival rate of larvae under oxidative and heat stress and decreases the level of reactive oxygen species and fat accumulation in vivo. Using gene-specific mutation of C. elegans, we found that SVHRSP-mediated prolongation of life depends on Daf-2, Daf-16, Skn-1, and Hsf-1 genes. These results indicate that the antiaging mechanism of SVHRSP in nematodes might be mediated by the insulin/insulin-like growth factor-1 signaling pathway. Meanwhile, SVHRSP could also up-regulate the expression of stress-inducing genes Hsp-16.2, Sod-3, Gei-7, and Ctl-1 associated with aging. In general, our study may have important implications for SVHRSP to promote healthy aging and provide strategies for research and development of drugs to treat age-related diseases.

20.
Artigo em Inglês | MEDLINE | ID: mdl-35911140

RESUMO

Type 2 diabetes mellitus (T2DM), a common disease with a complex etiology in the world, is an important risk factor for severe cardiovascular and cerebrovascular diseases. However, treatments of T2DM are mainly based on Western medicine, whose severe side effects make traditional Chinese medicine (TCM) therapy more appealing to patients and clinicians. The overall clinical evidence for different TCM therapies in the treatment of T2DM is still unclear. This study aimed to adopt the evidence-mapping method and integrate the evidence from various researches on this topic, to depict the whole picture of TCM therapies for T2DM. This review included searches of PubMed, Embase, Web of Science, and three major Chinese literature databases (CNKI, VIP, and Wanfang) from inception to November 18, 2021. Two independent reviewers screened the literature, extracted information, and evaluated the quality of all included studies. A systematic review was subsequently performed. In total, 47 studies were reviewed, of which 46 studies (97.9%) were from China and 1 (2.1%) was from Canada. The evidence map was conducted according to different TCM therapies, including herbs or herbal extracts, compounds, powders, decoctions, pills, external treatment, basic theories and treatment principles of TCM, proprietary Chinese medicines, and unspecified TCM integrated therapies. According to the AMSTAR-2 scoring results, 4 papers were rated as high quality, 11 were low quality, and 32 were very low quality. Outcome indicators mainly focused on FBG, HbA1c, 2-h PBG, TC, TG, LDL-C, etc. The results showed that different types of TCM treatment had different improvement effects on the outcome indicators of T2DM. More consistent benefits were observed in the improvement of FBG, HbA1c, and 2-h PBG with treatment regimens based on basic theories and treatment principles of TCM, decoctions and pills, and unspecified TCM integrated therapies. Among herbs, ginger and Coptis root showed more improvement in all outcomes. Compounds, powders, and external treatment showed relatively consistent beneficial effects on the improvement of FBG. No serious adverse events were reported. Overall, the current evidence map provided an intuitive overview of the beneficial effects of TCM therapies in the treatment of type 2 diabetes. This study can be used as a reference for the clinical application of traditional Chinese medicine in T2DM, but due to the low-quality level of the included studies, it should be treated with caution in clinical practices.

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