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1.
J Acoust Soc Am ; 152(3): 1416, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36182274

RESUMO

The NiMnGa alloy is a typical magnetic shape memory alloy with up to 6% immense strain, high energy density, and low effective elastic modulus. These comprehensive characteristics make it possible to realize a low-frequency underwater acoustic transducer. To describe the field-induced dynamic strain, an equivalent circuit model (ECM) of a longitudinal NiMnGa transducer is presented as a lumped parameter model, which couples magnetics, mechanics, and acoustics. In this paper, we focus on the piezomagnetic equations as the constitutive relationship of the NiMnGa element with a dynamic magnetic field. Furthermore, combined with the dynamic kinetic equation, the equivalent circuit is derived, and it has the advantage of containing acoustical terminals. The proposed model can predict the resonance frequency, effective stiffness, and input impedance of the NiMnGa transducer. Finally, a finite element model (FEM) is developed to verify the lumped parameter model. The results indicate that the spring's stiffness increases the resonance frequency, while the mass load is on the contrary, and they both agree well with the results of ECM. In addition, the FEM and ECM can also predict the dynamic responses, which provide a guideline for the design of longitudinal NiMnGa transducers.

2.
J Immunol Res ; 2022: 8689777, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189146

RESUMO

Background: Vitamin D deficiency is common in patients with systemic lupus erythematosus (SLE). Observational studies have reported that it is associated with SLE. In this bidirectional Mendelian randomization (MR) study, we explored the genetic association between serum vitamin D (VD) levels and SLE using two models. Methods: Genetic variants associated with vitamin D (n = 304,181), 25-hydroxyvitamin D levels (n = 401,460), and SLE (n = 213,683) at genome-wide significance (P < 5∗10-8) derived from large-scale publicly available GWAS data were used as instrumental variables. Bidirectional two-sample MR analyses were performed using the inverse variance weighted method (IVW, random, or fixed effect model). Sensitivity analyses including maximum likelihood, MR-Egger method, penalized weighted median method, MR-PRESSO, MR-RAPS, and MR-radial method were conducted. Results: The findings showed that genetically predicted SLE using the IVW method had a negative effect on the vitamin D and 25-hydroxyvitamin D levels in the two models. The results of sensitivity analyses of different analytical approaches were consistent. Conclusions: These findings indicated that genetically determined SLE had a negative effect on the vitamin D and 25-hydroxyvitamin D levels. Future studies, including random controlled clinical trials, should evaluate the association and mechanisms between serum VD levels and SLE.


Assuntos
Lúpus Eritematoso Sistêmico , Deficiência de Vitamina D , Estudo de Associação Genômica Ampla/métodos , Humanos , Análise da Randomização Mendeliana/métodos , Polimorfismo de Nucleotídeo Único , Vitamina D , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/genética , Vitaminas
3.
Eur Radiol ; 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36197579

RESUMO

OBJECTIVES: To compare image quality between a deep learning image reconstruction (DLIR) algorithm and conventional iterative reconstruction (IR) algorithms in dual-energy CT (DECT) and to assess the impact of these algorithms on radiomics robustness. METHODS: A phantom with clinical-relevant densities was imaged on seven DECT scanners with the same voxel size using typical abdominal-pelvis examination protocols. On one DECT scanner, raw data were reconstructed using both conventional IR (adaptive statistical iterative reconstruction-V, ASIR-V) and DLIR. Nine sets of corresponding images were generated on other six DECT scanners using scanner-equipped conventional IR. Regions of interest were delineated through rigid registrations. Image quality was compared. Pyradiomics platform was used for radiomics feature extraction. Test-retest repeatability was assessed by Bland-Altman analysis for repeated scans. Inter-reconstruction algorithm reproducibility between conventional IR and DLIR was tested by intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC). Inter-scanner reproducibility was evaluated by coefficient of variation (CV) and quartile coefficient of dispersion (QCD). Robust features were identified. RESULTS: DLIR significantly improved image quality. Ninety-four radiomics features were extracted and nine features were considered as robust. 93.87% features were repeatable between repeated scans. ASIR-V images showed higher reproducibility to other conventional IR than DLIR (ICC mean, 0.603 vs 0.558, p = 0.001; CCC mean, 0.554 vs 0.510, p = 0.004). 7.45% and 26.83% features were reproducible among scanners evaluated by CV and QCD, respectively. CONCLUSIONS: DLIR improves quality of DECT images but may alter radiomics features compared to conventional IR. Nine robust DECT radiomics features were identified. KEY POINTS: • DLIR improves DECT image quality in terms of signal-to-noise ratio and contrast-to-noise ratio compared with ASIR-V and showed the highest noise reduction rate and lowest peak frequency shift. • Most of radiomics features are repeatable between repeated DECT scans, while inter-reconstruction algorithm reproducibility between conventional IR and DLIR, and inter-scanner reproducibility, are low. • Although DLIR may alter radiomics features compared to IR algorithms, nine radiomics features survived repeatability and reproducibility analysis among DECT scanners and reconstruction algorithms, which allows further validation and clinical-relevant analysis.

4.
Am J Transl Res ; 14(8): 5491-5500, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105022

RESUMO

OBJECTIVE: To analyze the effect of comprehensive traditional Chinese medicine (TCM) care on the clinical efficacy and psychological improvement of elderly patients with knee arthritis. METHODS: Retrospective analysis was conducted on 114 patients with knee osteoarthritis who underwent arthroscopic minimally invasive surgery in our hospital from January 2018 to January 2022. Among them, 55 patients received routine nursing served as the control group (CG), and the remaining 59 patients received comprehensive TCM care as the observation group (OG). Patients were re-examined two weeks after discharge from the hospital, and the knee joint function recovery effect, pain score, nursing satisfaction, as well as the changes in adverse mood, hospitalization expenses and length of hospitalization during the treatment were compared between two groups. Logistic regression analysis was used to identify factors affecting the curative effect of patients. RESULTS: Compared with the CG, the OG held a significantly better clinical efficacy and lower knee joint score and visual analogue scale (VAS) score (P<0.05). After intervention, the OG showed markedly higher SF-36 score as well as notably declined scores of anxiety and depression than the CG (P<0.05). Quadriceps peak torque ratio (H/Q), as well as satisfaction of patients on nursing in the OG was comparatively better than those of the CG (P<0.05). For hospitalization costs and length of stay, the OG has proven to be more economical and effective with lower cost in both two indexes (P<0.05). Age, course of disease, and nursing program were risk factors affecting the efficacy of treatment in patients (P<0.05). CONCLUSION: Comprehensive TCM care markedly improved the clinical efficacy of the elderly with knee arthritis, relieved patients' pain, and improved knee function and quality of life, as well as reduced patients' anxiety and economic pressure.

5.
Front Surg ; 9: 903334, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090339

RESUMO

Aim: To analyze clinical associations between Guillain-Barré syndrome (GBS) and trauma. Material and Methods: We retrospectively reviewed the data of eight patients with post-traumatic GBS between July 2011 and December 2018 at the Second Xiangya Hospital, China, and analyzed the triggers, clinical manifestation, examination results, treatment, prognosis, and potential mechanism related to post-traumatic GBS. Results: The included patients had GBS preceded by no risk factors other than trauma. Their age ranged from 15 to 60 years (the median age was 52 years), and six patients were males. The potential traumatic triggers included spinal surgery (n = 2), high-intensity exercise (n = 2), traumatic brain injury (n = 1), excessive fatigue (n = 1), ischemic stroke (n = 1), and cardiopulmonary resuscitation (n = 1). The major manifestation was symmetrical limb weakness and/or numbness in all patients. The diagnosis of GBS was based on the results of electromyography, albumino-cytological dissociation, or antiganglioside antibody in cerebrospinal fluid, and other diseases were excluded. Immunotherapy improved symptoms, except in one patient who died. Conclusions: Trauma is a probable risk factor for GBS that is very easily overlooked, thereby leading to misdiagnosis in clinical practice. We emphasize a new concept of post-traumatic GBS to promote doctors' awareness when they meet people with weakness and sensory deficits after trauma, which benefit early diagnosis, timely treatment, and reduced mortality rate of GBS.

6.
Diabetes Metab Syndr Obes ; 15: 2725-2732, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091484

RESUMO

Aim: Dickkopf-1 (DKK-1) is a major inhibitor of Wingless protein signaling pathway, which is involved in glucose metabolism and cardiovascular diseases. The aim of the study was to investigate the changes of serum DKK-1 levels after hypoglycemic treatments and the relationship between DKK-1 and clinical parameters. Materials and Methods: The study was a sub-study of a previously published clinical trial (the effect of Acarbose on glycemic variability in patients with type 2 diabetes mellitus using premixed insulin compared to metformin). All subjects underwent anthropometric and biochemical assessments at baseline and endpoint. Serum DKK-1 levels of 92 subjects were measured at baseline and after 12-week hypoglycemic treatment. Results: DKK-1 levels were significantly decreased after hypoglycemic treatment for 12 weeks (P < 0.001). ΔDKK-1 levels were not correlated with improvement of metabolic parameters (all P > 0.05) but were negatively correlated with baseline DKK-1 levels (r = -0.263, P = 0.011). Spearman correlation showed that baseline DKK-1 levels were positively related to baseline total cholesterol (r = 0.226, P = 0.030) and low-density lipoprotein cholesterol (LDL-C) (r = 0.277, P = 0.007). Compared with the higher baseline DKK-1 group (≥3700 pg/mL), subjects in the lower baseline DKK-1 group (<3700 pg/mL) had significantly lower baseline glycated hemoglobin A1c levels (P = 0.008) and LDL-C levels (P = 0.048). Systolic and diastolic pressure were decreased more significantly in the lower baseline DKK-1 group than that in the higher baseline DKK-1 group (both P < 0.05). Conclusion: Serum DKK-1 levels were decreased after hypoglycemic treatments. Patients with lower baseline DKK-1 levels were featured by more favorable cardiometabolic factors.

7.
Risk Manag Healthc Policy ; 15: 1659-1669, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092550

RESUMO

Purpose: Based on the diagnosis-related groups payment, China developed an innovative episode-based payment scheme, called "payment method by disease types with point counting", to control health expenditures inflation. This study aimed to investigate the impacts of this new payment method on volume, expenditures, and efficiency in Chinese public hospitals. Methods: The study sample consisted of 7 tertiary hospitals and 14 secondary hospitals in Jinhua (intervention group) and 4 tertiary hospitals and 14 secondary hospitals in Taizhou (control group). Monthly data points were collected for each sampled hospital from June 2016 to June 2019 using a self-administered questionnaire with impact evaluation indicators. Controlled interrupted time-series analysis was employed to estimate the effect of the new payment method. Results: The significant slowing trends in inpatient expenditures per visit (tertiary hospitals: ß7=-123.16, p=0.042; secondary hospitals: ß7=-89.24, p=0.021) and out-of-pocket payments (tertiary hospitals: ß7=-4.18, p=0.027; secondary hospitals: ß7=-4.87, p=0.019) were observed after policy intervention. However, outpatient expenditures per visit in tertiary (ß7=1.67, p=0.018) and secondary hospitals (ß7=1.24, p=0.003) rose faster with the new payment method. Additionally, payment reform also caused an increase in the number of inpatient visits (ß7=100.01, p=0.038) and reduced the length of stay (ß7=-0.10, p=0.036) in tertiary hospitals. Conclusion: The introduction of payment method by disease types with point counting causes the cost containment for inpatient care, whereas the increase in outpatient expenditures. The findings suggest this new payment scheme has the potential for rollout in other areas, but the cost-shifting from the inpatient to outpatient setting should be prevented.

8.
Front Cell Dev Biol ; 10: 925835, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092711

RESUMO

Glaucoma is the most common cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) and relative hypoxia in the retina stimulate the production of reactive oxygen species (ROS), which, in turn, puts the retina and optic nerve under chronic oxidative stress. Emerging evidence has shown that oxidative stress can trigger PARP-1 overactivation, mitochondrial-associated endoplasmic reticulum membrane (MAM) dysregulation, and NLRP3 activation. Oxidative damage can trigger inflammasome activation, and NLRP3 is the only inflammasome associated with MAM dysregulation. In addition, multiple transcription factors are located on the MAM. This study aimed to investigate the protective effects and underlying mechanisms of a PARP-1 inhibitor (olaparib) against chronic ocular hypertension-associated retinal cell damage. We also mimicked hypoxic stimulation of a retinal precursor cell line by exposing the cells to 0.2% O2 in vitro. We discovered that chronic ocular hypertension (COH) induces oxidative damage and MAM dysregulation in the retinal ganglion cells (RGCs). The protein levels of cleaved-PARP and NLRP3 were upregulated in the retinas of the COH rats. Olaparib, a PARP-1 inhibitor, alleviated COH-induced RGC loss, retinal morphological alterations, and photopic negative response amplitude reduction. Olaparib also relieved hypoxic stimulation-induced loss of cell viability and MAM dysregulation. Additionally, some indicators of mitochondrial performance, such as reactive oxygen species accumulation, mitochondrial Ca2+ influx, and mitochondrial membrane potential collapse, decreased after olaparib treatment. Olaparib attenuated the hypoxia-induced upregulation of NLRP3 protein levels as well as the phosphorylation of ERK1/2 and histone H2A.X. These results suggest that olaparib protects RGCs from chronic intraocular pressure elevation in vivo and alleviates the abnormal MAM dysregulation and mitochondrial dysfunction caused by hypoxia in vitro. This protection may be achieved by inhibiting PARP-1 overactivation, NLRP3 upregulation, and phosphorylation of ERK1/2.

10.
Chin Med J (Engl) ; 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36070458

RESUMO

BACKGROUND: Corneal confocal microscopy (CCM) is a noninvasive technique to detect early nerve damage of diabetic sensorimotor polyneuropathy (DSPN). Time in range (TIR) is an emerging metric of glycemic control which was reported to be associated with diabetic complications. We sought to explore the relationship between TIR and corneal nerve parameters in asymptomatic patients with type 2 diabetes (T2DM). METHODS: In this cross-sectional study, 206 asymptomatic inpatients with T2DM were recruited. After 7 days of continuous glucose monitoring, the TIR was calculated as the percentage of time in the glucose range of 3.9 to 10.0 mmol/L. CCM was performed to determine corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length (CNFL). Abnormal CNFL was defined as ≤15.30 mm/mm2. RESULTS: Abnormal CNFL was found in 30.6% of asymptomatic subjects. Linear regression analyses revealed that TIR was positively correlated with CCM parameters both in the crude and adjusted models (all P  < 0.05). Each 10% increase in TIR was associated with a 28.2% (95% CI: 0.595-0.866, P = 0.001) decreased risk of abnormal CNFL after adjusting for covariates. With the increase of TIR quartiles, corneal nerve fiber parameters increased significantly (all P for trend <0.01). The receiver operating characteristic curve indicated that the optimal cutoff point of TIR was 77.5% for predicting abnormal CNFL in asymptomatic patients. CONCLUSIONS: There is a significant independent correlation between TIR and corneal nerve fiber loss in asymptomatic T2DM patients. TIR may be a useful surrogate marker for early diagnosis of DSPN.

13.
Chiropr Man Therap ; 30(1): 34, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050701

RESUMO

BACKGROUND: Myofascial pain syndrome (MPS) is a condition with local and referred pain characterized by trigger points (taut bands within the muscle). Ischemic compression is a noninvasive manual therapy technique that has been employed for the treatment of MPS in past decades. However, little attention has been devoted to this topic. OBJECTIVES: The present review was designed to explore the efficacy of ischemic compression for myofascial pain syndrome by performing a descriptive systematic review and a meta-analysis to estimate the effect of ischemic compression on MPS. METHODS: A systematic review and meta-analysis concerning randomized controlled trials (RCTs) with myofascial pain subjects who received ischemic compression versus placebo, sham, or usual interventions. Five databases (PubMed, The Cochrane Library, Embase, Web of Science, Ovid) were searched from the earliest data available to 2022.1.2. The standardized mean difference (SMD) and the 95% confidence interval (CI) were used for statistics. Version 2 of the Cochrane risk of tool 2 (RoB 2) was used to assess the quality of the included RCTs. RESULTS: Seventeen studies were included in the systematic review, and 15 studies were included in the meta-analysis. For the pressure pain threshold (PPT) index, 11 studies and 427 subjects demonstrated statistically significant differences compared with the control at posttreatment (SMD = 0.67, 95% CI [0.35, 0.98], P < 0.0001, I2 = 59%). For visual analog scale (VAS) or numeric rating scale (NRS) indices, 7 studies and 251 subjects demonstrated that there was no significant difference between ischemic compression and controls posttreatment (SMD = - 0.22, 95% CI [- 0.53, 0.09], P = 0.16, I2 = 33%). CONCLUSION: Ischemic compression, as a conservative and noninvasive therapy, only enhanced tolerance to pain in MPS subjects compared with inactive control. Furthermore, there was no evidence of benefit for self-reported pain. The number of currently included subjects was relatively small, so the conclusion may be changed by future studies. Big scale RCTs with more subjects will be critical in future.


Assuntos
Síndromes da Dor Miofascial , Humanos , Síndromes da Dor Miofascial/tratamento farmacológico , Dor , Medição da Dor/métodos , Limiar da Dor
14.
J Med Virol ; 2022 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-36089764

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused extensive loss of life worldwide. Further, the COVID-19 and influenza mix-infection had caused great distress to the diagnosis of the disease. To control illness progression and limit viral spread within the population, a real-time reverse-transcription PCR (RT-PCR) assay for early diagnosis of COVID-19 was developed, but detection was time-consuming (4-6 h). To improve the diagnosis of COVID-19 and influenza, we herein developed a recombinase polymerase amplification (RPA) method for simple and rapid amplification of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19 and Influenza A (H1N1, H3N2) and B (influenza B). Genes encoding the matrix protein (M) for H1N1, and the hemagglutinin (HA) for H3N2, and the polymerase A (PA) for Influenza B, and the nucleocapsid protein (N), the RNA-dependent-RNA polymerase (RdRP) in the open reading frame 1ab (ORF1ab) region, and the envelope protein (E) for SARS-CoV-2 were selected, and specific primers were designed. We validated our method using SARS-CoV-2, H1N1, H3N2 and influenza B plasmid standards and RNA samples extracted from COVID-19 and Influenza A/B (RT-PCR-verified) positive patients. The method could detect SARS-CoV-2 plasmid standard DNA quantitatively between 102 and 105 copies/ml with a log linearity of 0.99 in 22 min. And this method also be very effective in simultaneous detection of H1N1, H3N2 and influenza B. Clinical validation of 100 cases revealed a sensitivity of 100% for differentiating COVID-19 patients from healthy controls when the specificity was set at 90%. These results demonstrate that this nucleic acid testing method is advantageous compared with traditional PCR and other isothermal nucleic acid amplification methods in terms of time and portability. This method could potentially be used for detection of SARS-CoV-2, H1N1, H3N2 and influenza B, and adapted for point-of-care (POC) detection of a broad range of infectious pathogens in resource-limited settings.

15.
Clin Neurophysiol ; 143: 56-66, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36116424

RESUMO

OBJECTIVE: Preferential wasting of the thenar muscles, the split-hand sign, may be used for early diagnosis of amyotrophic lateral sclerosis (ALS). METHODS: Electronic databases were searched for studies assessing the split-hand index (SHI) and the compound muscle action potential (CMAP) amplitudes of abductor pollicis brevis (APB), first dorsal interosseous (FDI), and abductor digiti minimi (ADM). The SHI was obtained by multiplying CMAP amplitudes of APB and FDI and dividing the product by the CMAP amplitude of ADM. The Bayesian analysis was used for validation. RESULTS: In total, 17 studies and 1635 patients were included. Our meta-analysis revealed that ALS patients had significantly decreased SHI (standardized mean difference [SMD], -1.60, P < 0.001), CMAP of the APB (SMD, -1.67, P < 0.001), FDI (SMD, -1.12, P < 0.001), and ADM (SMD, -1.09, P < 0.001). The binormal receiver operating characteristic curve analysis showed a threshold of < 7.4 for SHI, and cutoff values of < 6.4 mV for APB and < 8.4 mV for FDI, respectively. The Bayesian analysis validated decreased SHI in ALS patients (posterior mean difference of - 5.91). CONCLUSIONS: An SHI of < 7.4 can be used facilitating earlier diagnosis of ALS. SIGNIFICANCE: SHI can be used as a standard neurophysiological biomarker for early diagnosis.

16.
JAMA Netw Open ; 5(9): e2232133, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36129711

RESUMO

Importance: One of the ordinary manifestations of Parkinson disease (PD) is anxiety, which remains untreated. Anxiety is closely associated with the accelerated progression of PD. Efficacy of acupuncture for anxiety has been reported. However, to date, there are no data on acupuncture's effectiveness on anxiety for patients with PD. Objective: To investigate the effect of acupuncture vs sham acupuncture for treating anxiety in patients with PD. Design, Setting, and Participants: This is randomized, double-blinded, clinical trial enrolled patients between June 20, 2021, and February 26, 2022. Final follow-up was April 15, 2022. Patients with Parkinson disease and anxiety were allocated randomly (1:1) to receive acupuncture or sham acupuncture for 8 weeks. Acupuncture operators, outcome measures evaluators, and statistical analysts were blinded to the grouping of patients. Patients were blinded to their own grouping during the study. This study took place in the Parkinson clinic of a hospital in China. Interventions: Real acupuncture or sham acupuncture for 8 weeks. Main Outcomes and Measures: Primary outcome was Hamilton Anxiety Scale (HAM-A) score. Secondary outcomes were scores on the Unified Parkinson Disease Rating Scale (UPDRS), 39-item Parkinson Disease Questionnaire (PDQ-39), and serum levels of the adrenocorticotropic hormone (ACTH) and cortisol (CORT). Results: Seventy eligible patients were enrolled, including 34 women (48.5%) and 36 men (51.4%). Sixty-four patients (91%) completed the intervention and the 8-week follow-up, including 30 women (46.9%) and 34 men (53.1%) with a mean (SD) age of 61.84 (8.47) years. At the end of treatment, the variation of HAM-A score was 0.22 (95% CI, -0.63 to 1.07; P = .62) between the real acupuncture and sham acupuncture groups. At the end of follow-up, the real acupuncture group had a significant 7.03-point greater (95% CI, 6.18 to 7.88; P < .001) reduction in HAM-A score compared with the sham acupuncture group. Four mild adverse reactions occurred during the study. Conclusions and Relevance: This study found acupuncture to be an effective treatment for anxiety in patients with PD. These findings suggest that acupuncture may enhance the wellbeing of patients who have Parkinson disease and anxiety. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2100047253.


Assuntos
Terapia por Acupuntura , Doença de Parkinson , Hormônio Adrenocorticotrópico , Ansiedade/terapia , Feminino , Humanos , Hidrocortisona , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Salicilamidas
17.
Eur J Med Chem ; 243: 114786, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36170799

RESUMO

Proteolysis targeting chimera (PROTAC) technology has received widespread attention in recent years as a promising strategy for drug development. Herein, we report a series of novel Wee1 degraders, which were designed and synthesized based on PROTAC technology by linking AZD1775 with CRBN ligands through linkers of different lengths and types. All degraders could effectively and completely degrade cellular Wee1 protein in MV-4-11 cell line at IC50 concentrations. Preliminary assessments identified 42a as the most active degrader, which possessed potent antiproliferative activity and induced CRBN- and proteasome-dependent degradation of Wee1. Moreover, 42a also exhibited a time- and concentration-dependent depletion manner and inducing cell cycle arrest in G0/G1 phase and cancer cell apoptosis. More importantly, 42a showed acceptable in vitro and in vivo pharmacokinetic properties and displayed rapid and sustained Wee1 degradation ability in vivo. Taken together, these findings contribute to understanding the development of PROTACs and demonstrate that our Wee1-targeting PROTAC strategy has potential novel applications in cancer therapy.

18.
Thorac Cancer ; 13(19): 2751-2758, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36065806

RESUMO

BACKGROUND: To investigate the independent risk factors of poor short-term outcomes in patients with lung cancer-associated acute ischemic stroke (LCAIS) and use them to develop an index of prognosis LCAIS (pLCAIS) which could help clinicians identify patients at high risk for poor short-term outcomes. METHODS: We retrospectively enrolled patients with lung cancer-associated acute ischemic stroke and employed the 90D modified Rankin cale (mRS) to divide them into two groups: good outcomes (score 0-2) and poor outcomes (score 3-6). Propensity score matching (PSM) was used to remove confounding factors, and multivariable logistic regression analysis was used to analyze the independent risk factors of pLCAIS. The receiver operating characteristic (ROC) and area under the ROC curve (AUC) developed a multiple model combining the independent risk factors of pLCAIS. RESULTS: A total of 172 patients were included: 67 (38.9%) with good outcomes and 105 (61.1%) with poor outcomes. After using PSM, there were 33 cases in each group. The results showed that patients with poor short-term outcomes were significantly higher in D-dimer (OR = 1.001, 95% CI: 1.000-1.002, p = 0.048), CRP (OR = 1.078, 95% CI: 1.008-1.153, p = 0.028), and neutrophil count (OR = 14.673, 95% CI: 1.802-19.500, p = 0.012). The ROC curve, used to assess the diagnostic ability of binary classifiers, showed that the product of these three independent risk factors showed high sensitivity and specificity. CONCLUSION: In this study, we have identified three independent risk factors associated with poor short-term outcomes in pLCAIS: higher NC, CRP, and D-dimer levels. These findings may be helpful for clinicians in identifying poor short-term outcomes patients.


Assuntos
AVC Isquêmico , Neoplasias Pulmonares , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/complicações , Neoplasias Pulmonares/complicações , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia
19.
J Mol Diagn ; 2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36162759

RESUMO

Shwachman-Diamond syndrome (SDS) is the second most common cause of exocrine pancreatic insufficiency, and 90% of patients carry mutations in the SBDS gene, the most common being the c.183_184delinsCT and c.258+2T>C variants. However, precise detection of these most contributory variants by conventional short-read next-generation sequencing data analysis is limited because of the SBDS/SBDSP1 highly homologous sequences. In this study, an efficient approach was established to infer the haplotype of SBDS based on the expectation-maximization algorithm. The workflow was retrospectively applied to detect the two most common SBDS variants in a Chinese SDS high-risk cohort, and a systematic comparison of variant detection results was performed between the workflow and conventional next-generation sequencing analysis based on Sanger sequencing validation. Among the Chinese SDS high-risk cohort (n = 47) and their available parents (n = 64), the established workflow improved the diagnostic rate for these two variants by 27.7% (95% CI, 15.6%-42.6%) compared with conventional analysis. For overall variant detection, the established workflow achieved 100% (95% CI, 92.5%-100%) concordance with Sanger sequencing, whereas conventional analysis showed only 65.8% accuracy; these results included 25.2% with missed variant calls, 7.2% with diagnosed but inaccurate variant calls, and 1.8% with false-positive calls. With its favorable result in both SDS patient diagnosis and carrier detection performance, the provided workflow showed its potential in clinical application for SDS molecular diagnosis.

20.
J Comp Eff Res ; 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36148921

RESUMO

Aim: To explore the effectiveness of home-based exercise programs with e-devices (HEPEs) on falls among community-dwelling older adults. Methods: Twelve randomized controlled trials were included in the meta-analysis considering four fall-related outcomes. Results: HEPEs significantly reduced the rate of falls (risk ratio: 0.82; 95% CI: 0.72-0.95; p = 0.006) and improved lower extremity strength (mean difference: -0.94; 95% CI: -1.71 to -0.47; p < 0.001). There was a significant improvement favoring HEPEs on balance if the participants were aged >75 years (mean difference: -0.55; 95% CI: -1.05 to -0.05; p = 0.03), or the intervention duration was at least 16 weeks (mean difference: -0.81; 95% CI: -1.58 to -0.05; p = 0.04). Conclusion: HEPEs demonstrated an overall positive effect on falls among community-dwelling older adults.

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