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1.
Bioresour Technol ; 343: 126087, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34624467

RESUMO

To facilitate the lipid extraction from Nannochloropsis oceanica with thick cell wall using switchable hydrophilicity solvent, ultrasound-assisted N, N, N', N'-tetraethyl-1,3-propanediamine (TEPDA) was used to effectively destruct the cell wall. TEPDA cations were adsorbed on the cells via electrostatic force and formed the electron-donor-acceptor (EDA) complex with the hydroxyl groups in cellulose. This broke the hydrogen-bonding interactions between cellulose chains and stripped them from cell wall, thus reducing the cell wall thickness from 141 nm to 68.6 nm. Moreover, TEPDA cations neutralized the negatively charged phospholipid bilayers, decreasing the cell surface zeta potential from -27.5 eV to -14.1 eV. The local electrostatic equilibrium led to cell membrane leakage. The ultrasound promoted the stripping of the cellulose chains at a power intensity of 0.5 W/mL and frequency of 20 kHz, achieving the lipid extraction efficiency of 98.2% within 2 h at a volume ratio of 1:4 of wet microalgae to TEPDA.


Assuntos
Microalgas , Biocombustíveis , Biomassa , Interações Hidrofóbicas e Hidrofílicas , Lipídeos , Solventes
2.
Chin J Cancer Res ; 33(5): 574-582, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34815631

RESUMO

Curative therapy was not previously available for patients with advanced non-small cell lung cancer (NSCLC); thus, the concept of minimal/measurable (or molecular) residual disease (MRD) was not applicable to these patients. However, advances in targeted and immunotherapy have revolutionized the treatment landscape for patients with advanced NSCLC, with emerging evidence of long-term survival and even the hope of complete remission (CR) by imaging examination. The latest research shows that patients with oligometastatic lung cancer can benefit from local treatment. After removing the lesions, the choice of follow-up therapy and monitoring of the lesions could remain uncertain. MRD plays a role in identifying early-stage NSCLC patients with high risks of recurrence and determining adjuvant therapy after radical treatment. In recent years, evidence has been accumulating regarding the use of circulating cell-free tumor DNA (ctDNA) to assess MRD in solid tumors. This study discussed the possible applications of ctDNA-based MRD monitoring in advanced NSCLC and described the current challenges and unresolved problems in the application of MRD in advanced NSCLC.

3.
Biomark Med ; 15(17): 1599-1609, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34743548

RESUMO

Aim: WDR5 is a coactivator of transcription factor which promotes the progression of several cancer types, but its function in lung adenocarcinoma (AC) is unknown. Materials & methods: We detected WDR5 expression in lung AC with quantitative real-time polymerase chain reaction and immunohistochemistry. Results: WDR5 was significantly overexpressed in ACs compared with normal lung tissues. Moreover, WDR5 was an independent prognostic biomarker of lung AC. With clinical analyzation and in vitro experiments, we proved that SOX9 was a downstream effector of WDR5 in promoting A549 proliferation, and that SOX9 was also an unfavorable prognostic biomarker of lung AC. Conclusion: WDR5 and SOX9 are both prognostic biomarkers predicting poor outcome of lung AC. WDR5 could promote proliferation of lung AC by elevating SOX9 expression.

4.
Orthop Surg ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34651434

RESUMO

OBJECTIVE: To explore the main causes of hypertrophied ligamentum flavum (HLF) and the possibility of using bipedal standing mouse model to simulate the pathological changes in human HLF. METHODS: Thirty-two 8-week-old C57BL/6 male mice were randomly assigned to the experimental group (n = 16) and control group (n = 16). In the experimental group, mice were induced to adopt a bipedal standing posture by their hydrophobia. The experimental mice were maintained bipedal standing for 8 h a day with an interval of 2 h to consume food and water. The control mice were placed in a similar environment without bipedal standing. Eight 18-month-old C57BL/6 male mice were compared to evaluate the LF degeneration due to aging factor. Three-dimensional (3D) reconstruction and finite element models were carried out to analyze the stress and strain distribution of the mouse LF in sprawling and bipedal standing postures. Hematoxylin and Eosin (HE), Verhoeff-Van Gieson (VVG), and immunohistochemistry (IHC) staining were used to evaluate the LF degeneration of mice and humans. RT-qPCR and immunofluorescence analysis were used to evaluate the expressions of fibrosis-related factors and inflammatory cytokines of COL1A1, COL3A1, α-SMA, MMP2, IL-1ß, and COX-2. RESULTS: The von Mises stress (8.85 × 10-2 MPa) and maximum principal strain (6.64 × 10-1 ) in LF were increased 4944 and 7703 times, respectively, in bipedal standing mice. HE staining showed that the mouse LF area was greater in the bipedal standing 10-week-old group ([10.01 ± 2.93] × 104 µm2 ) than that in the control group ([3.76 ± 1.87] × 104 µm2 ) and 18-month-old aged group ([6.09 ± 2.70] × 104 µm2 ). VVG staining showed that the HLF of mice (3.23 ± 0.58) and humans (2.23 ± 0.31) had a similar loss of elastic fibers and an increase in collagen fibers. The cell density was higher during the process of HLF in mice (39.63 ± 4.81) and humans (23.25 ± 2.05). IHC staining showed that the number of α-SMA positive cells were significantly increased in HLF of mice (1.63 ± 0.74) and humans (3.50 ± 1.85). The expressions of inflammatory cytokines and fibrosis-related factors of COL1A1, COL3A1, α-SMA, MMP2, IL-1ß, and COX-2 were consistently higher in bipedal standing group than the control group. CONCLUSION: Our study suggests that 3D finite element models can help analyze the abnormal stress and strain distributions of LF in modeling mice. Mechanical stress is the main cause of hypertrophied ligamentum flavum compared to aging. The bipedal standing mice model can reflect the pathological characteristics of human HLF. The bipedal standing mice model can provide a standardized condition to elucidate the molecular mechanisms of mechanical stress-induced HLF in vivo.

5.
MMWR Morb Mortal Wkly Rep ; 70(43): 1520-1524, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34710075

RESUMO

By September 21, 2021, an estimated 182 million persons in the United States were fully vaccinated against COVID-19.* Clinical trials indicate that Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), and Janssen (Johnson & Johnson; Ad.26.COV2.S) vaccines are effective and generally well tolerated (1-3). However, daily vaccination rates have declined approximately 78% since April 13, 2021†; vaccine safety concerns have contributed to vaccine hesitancy (4). A cohort study of 19,625 nursing home residents found that those who received an mRNA vaccine (Pfizer-BioNTech or Moderna) had lower all-cause mortality than did unvaccinated residents (5), but no studies comparing mortality rates within the general population of vaccinated and unvaccinated persons have been conducted. To assess mortality not associated with COVID-19 (non-COVID-19 mortality) after COVID-19 vaccination in a general population setting, a cohort study was conducted during December 2020-July 2021 among approximately 11 million persons enrolled in seven Vaccine Safety Datalink (VSD) sites.§ After standardizing mortality rates by age and sex, this study found that COVID-19 vaccine recipients had lower non-COVID-19 mortality than did unvaccinated persons. After adjusting for demographic characteristics and VSD site, this study found that adjusted relative risk (aRR) of non-COVID-19 mortality for the Pfizer-BioNTech vaccine was 0.41 (95% confidence interval [CI] = 0.38-0.44) after dose 1 and 0.34 (95% CI = 0.33-0.36) after dose 2. The aRRs of non-COVID-19 mortality for the Moderna vaccine were 0.34 (95% CI = 0.32-0.37) after dose 1 and 0.31 (95% CI = 0.30-0.33) after dose 2. The aRR after receipt of the Janssen vaccine was 0.54 (95% CI = 0.49-0.59). There is no increased risk for mortality among COVID-19 vaccine recipients. This finding reinforces the safety profile of currently approved COVID-19 vaccines in the United States.


Assuntos
Vacinas contra COVID-19/administração & dosagem , Mortalidade/tendências , Vacinação/estatística & dados numéricos , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/prevenção & controle , Criança , Prestação Integrada de Cuidados de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Estados Unidos/epidemiologia , Adulto Jovem
6.
JAMA Pediatr ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34617975

RESUMO

Importance: The COVID-19 pandemic has affected routine vaccine delivery in the US and globally. The magnitude of these disruptions and their association with childhood vaccination coverage are unclear. Objectives: To compare trends in pediatric vaccination before and during the pandemic and to evaluate the proportion of children up to date (UTD) with vaccinations by age, race, and ethnicity. Design, Setting, and Participants: This surveillance study used a prepandemic-postpandemic control design with data from 8 health systems in California, Oregon, Washington, Colorado, Minnesota, and Wisconsin in the Vaccine Safety Datalink. Children from age groups younger than 24 months and 4 to 6, 11 to 13, and 16 to 18 years were included if they had at least 1 week of health system enrollment from January 5, 2020, through October 3, 2020, over periods before the US COVID-19 pandemic (January 5, 2020, through March 14, 2020), during age-limited preventive care (March 15, 2020, through May 16, 2020), and during expanded primary care (May 17, 2020, through October 3, 2020). These individuals were compared with those enrolled during analogous weeks in 2019. Exposures: This study evaluated UTD status among children reaching specific ages in February, May, and September 2020, compared with those reaching these ages in 2019. Main Outcomes and Measures: Weekly vaccination rates for routine age-specific vaccines and the proportion of children UTD for all age-specific recommended vaccines. Results: Of 1 399 708 children in 2019 and 1 402 227 in 2020, 1 371 718 were female (49.0%) and 1 429 979 were male (51.0%); 334 216 Asian individuals (11.9%), 900 226 were Hispanic individuals (32.1%), and 201 619 non-Hispanic Black individuals (7.2%). Compared with the prepandemic period and 2019, the age-limited preventive care period was associated with lower weekly vaccination rates, with ratios of rate ratios of 0.82 (95% CI, 0.80-0.85) among those younger than 24 months, 0.18 (95% CI, 0.16-0.20) among those aged 4 to 6 years, 0.16 (95% CI, 0.14-0.17) among those aged 11 to 13 years, and 0.10 (95% CI, 0.08-0.13) among those aged 16 to 18 years. Vaccination rates during expanded primary care remained lower for most ages (ratios of rate ratios: <24 months, 0.96 [95% CI, 0.93-0.98]; 11-13 years, 0.81 [95% CI, 0.76-0.86]; 16-18 years, 0.57 [95% CI, 0.51-0.63]). In September 2020, 74% (95% CI, 73%-76%) of infants aged 7 months and 57% (95% CI, 56%-58%) of infants aged 18 months were UTD vs 81% (95% CI, 80%-82%) and 61% (95% CI, 60%-62%), respectively, in September 2019. The proportion UTD was lowest in non-Hispanic Black children across most age groups, both during and prior to the COVID-19 pandemic (eg, in May 2019, 70% [95% CI, 64%-75%] of non-Hispanic Black infants aged 7 months were UTD vs 82% [95% CI, 81%-83%] in all infants aged 7 months combined). Conclusions and Relevance: As of September 2020, childhood vaccination rates and the proportion who were UTD remained lower than 2019 levels. Interventions are needed to promote catch-up vaccination, particularly in populations at risk for underimmunization.

7.
MMWR Morb Mortal Wkly Rep ; 70(40): 1415-1419, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34618801

RESUMO

Data from observational studies demonstrate that variants of SARS-CoV-2, the virus that causes COVID-19, have evolved rapidly across many countries (1,2). The SARS-CoV-2 B.1.617.2 (Delta) variant of concern is more transmissible than previously identified variants,* and as of September 2021, is the predominant variant in the United States.† Studies characterizing the distribution and severity of illness caused by SARS-CoV-2 variants, particularly the Delta variant, are limited in the United States (3), and are subject to limitations related to study setting, specimen collection, study population, or study period (4-7). This study used whole genome sequencing (WGS) data on SARS-CoV-2-positive specimens collected across Kaiser Permanente Southern California (KPSC), a large integrated health care system, to describe the distribution and risk of hospitalization associated with SARS-CoV-2 variants during March 4-July 21, 2021, by patient vaccination status. Among 13,039 SARS-CoV-2-positive specimens identified from KPSC patients during this period, 6,798 (52%) were sequenced and included in this report. Of these, 5,994 (88%) were collected from unvaccinated persons, 648 (10%) from fully vaccinated persons, and 156 (2%) from partially vaccinated persons. Among all sequenced specimens, the weekly percentage of B.1.1.7 (Alpha) variant infections increased from 20% to 67% during March 4-May 19, 2021. During April 15-July 21, 2021, the weekly percentage of Delta variant infections increased from 0% to 95%. During March 4-July 21, 2021, the weekly percentage of variants was similar among fully vaccinated and unvaccinated persons, but the Delta variant was more commonly identified among vaccinated persons then unvaccinated persons overall, relative to other variants. The Delta variant was more prevalent among younger persons, with the highest percentage (55%) identified among persons aged 18-44 years. Infections attributed to the Delta variant were also more commonly identified among non-Hispanic Black persons, relative to other variants. These findings reinforce the importance of continued monitoring of SARS-CoV-2 variants and implementing multiple COVID-19 prevention strategies, particularly during the current period in which Delta is the predominant variant circulating in the United States.


Assuntos
COVID-19/diagnóstico , COVID-19/virologia , Prestação Integrada de Cuidados de Saúde , SARS-CoV-2/isolamento & purificação , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , California/epidemiologia , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Transl Lung Cancer Res ; 10(8): 3594-3607, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34584859

RESUMO

Background: Currently, there is no standard context that conforms to the Chinese national framework for evaluating medical decisions regarding the treatment of lung cancer. Methods: This draft was formulated after a systematic review and a focus group discussion among 20 experts, who were senior physicians with extensive clinical experience from the Chinese Thoracic Oncology Group (CTONG) task force. Subsequently, a draft and a five-point Likert scale were sent to 300 CTONG working group members. These were modified according to feedback from a four-round modified Delphi approach. Hence, the first version of the 'Therapeutic option of lung cancer: CTONG scoring system' was formulated. Afterward, a corresponding questionnaire was designed to collect opinions on the weight allocation of various indicators. This was issued through the WeChat platform, "Oncology News" application and e-mails from October 23, 2020, to November 25, 2020. Participants from numerous occupations in cancer-related fields from various regions of China were included in the study. Overall and subgroup analyses regarding weight allocations were performed. The differences between participant-allocated and reference weights were considered to adjust the framework. Results: The framework contained four aspects and six indicators, including efficacy [progression-free survival (PFS)/overall survival (OS) and subsequent treatment], safety [treatment-related severe adverse event (SAE), dose adjustment], quality of life (Qol), and compensation. The reference weights were 50%, 5%, 10%, 5%, 10%, and 20% for each indicator. By November 25, 2020, 1,043 valid questionnaires had been obtained. The majority of the questionnaires were completed by physicians (86.5%). Subgroup analysis among the various groups showed an overall consistent trend. Besides, significant differences between the participant-allocated and reference weights were found among PFS/OS (difference: -11.5%), compensation (difference: -10.1%), and subsequent treatment (difference: 9.7%) indicators. After discussion, the final weight allocations were set at 45%, 10%, 15%, 5%, 10%, and 15% for PFS/OS, subsequent treatment, treatment-related SAE, dose adjustment, Qol, and compensation, respectively. Conclusions: The CTONG scoring system, as an objective evaluation model that involves multiple parameters, is a breakthrough method for evaluating the therapeutic value of lung cancer treatment options in China, which is worthy of further verification in future clinical practice.

9.
Pest Manag Sci ; 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480397

RESUMO

BACKGROUND: Elevated CO2 can directly affect the toxicity of insecticides to insects and the physiological response of insects to insecticides. Frankliniella occidentalis and F. intonsa are highly destructive pests that target horticultural crops. Spinetoram is an effective pesticide against thrips. This study sought to explore the effect of elevated CO2 on efficacy of spinetoram against F. occidentalis and F. intonsa and effect of the spinetoram on activities of protective and detoxifying enzymes under elevated CO2 . Notably, these enzymes can be exploited in further studies to develop interventions for thrips resistance management. RESULTS: Toxicity bioassay showed that the LC50 values of F. occidentalis and F. intonsa exposed to spinetoram at elevated CO2 (800 µL L-1 concentration) for 48 h was 0.08 and 0.006 mg L-1 , respectively, which is 0.62 and 0.75 times of the values at ambient CO2 (400 µL L-1 concentration). The findings showed that elevated CO2 decreased activities of the superoxide dismutase and acetylcholinesterase in thrips, while increasing the activities of carboxylesterase and glutathione S-transferase. However, spinetoram increased activities of protective and detoxifying enzymes in both thrips under the two CO2 levels. Elevated CO2 and spinetoram affect the physiological enzyme activity in thrips synergistically, and the activities of analyzed enzymes were generally higher in F. occidentalis than in F. intonsa. CONCLUSION: Elevated CO2 amplifies the efficacy of spinetoram on thrips, F. intonsa is more susceptibility to spinetoram than F. occidentalis and the latter showed better adaptation to adverse conditions than the former.

10.
Cancer Biol Med ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34570442

RESUMO

Cytokine release syndrome (CRS) is a major obstacle to the widespread clinical application of chimeric antigen receptor (CAR) T cell therapies. CRS can also be induced by infections (such as SARS-CoV-2), drugs (such as therapeutic antibodies), and some autoimmune diseases. Myeloid-derived macrophages play key roles in the pathogenesis of CRS, and participate in the production and release of the core CRS cytokines, including interleukin (IL)-1, IL-6, and interferon-γ. In this review, we summarize the roles of macrophages in CRS and discuss new developments in macrophage activation and the related mechanisms of cytokine regulation in CRS.

11.
Front Immunol ; 12: 730070, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552592

RESUMO

Background: Inflammation may trigger skeletal muscle atrophy induced by cancer cachexia. As a pro-inflammatory factor, interleukin-6 may cause skeletal muscle atrophy, but the underlying molecular mechanisms have not been explored. Methods: In this experimental study, we used adult male ICR mice, weighing 25 ± 2 g, and the continuous infusion of interleukin-6 into the tibialis anterior muscle to construct a skeletal muscle atrophy model (experimental group). A control group received a saline infusion. RNA-sequencing was used to analyze the differentially expressed genes in tissue samples after one and three days. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis were applied to define the function of these genes, and protein-protein interaction analysis was performed to identify potential transcription factors. Fluorescence microscopy was used to determine the muscle fiber cross-sectional area after 14 days. Results: Continuous infusion of interleukin-6 for 14 days caused significant muscle atrophy. RNA-sequencing found 359 differentially expressed genes in the 1- and 3-day tissue samples and 1748 differentially expressed genes only in the 3-day samples. Functional analysis showed that the differentially expressed genes found in both the 1- and 3-day samples were associated with immune receptor activation, whereas the differentially expressed genes found only in the 3-day sample were associated with reduced energy metabolism. The expression of multiple genes in the oxidative phosphorylation and tricarboxylic acid cycle pathways was down-regulated. Furthermore, differentially expressed transcription factors were identified, and their interaction with interleukin-6 and the differentially expressed genes was predicted, which indicated that STAT3, NF-κB, TP53 and MyoG may play an important role in the process of interleukin-6-induced muscle atrophy. Conclusions: This study found that interleukin-6 caused skeletal muscle atrophy through immune receptor activation and a reduction of the energy metabolism. Several transcription factors downstream of IL-6 have the potential to become new regulators of skeletal muscle atrophy. This study not only enriches the molecular regulation mechanism of muscle atrophy, but also provides a potential target for targeted therapy of muscle atrophy.

12.
J Gen Intern Med ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34379280

RESUMO

BACKGROUND: Influenza infection can result in decompensation or exacerbation of heart failure (HF) symptoms, hospitalization, and death. OBJECTIVE: To examine the association of influenza vaccination with mortality and hospitalization during influenza and non-influenza seasons between 2009 and 2018. DESIGN, SETTING, AND PARTICIPANTS: In this prospective, observational cohort study, we included Kaiser Permanente Southern California members with a HF diagnosis prior to September 1 each year from 2009 to 2017. EXPOSURE: The first influenza vaccination in each season (September 1 to May 31) was recorded. Vaccinated/unvaccinated patients were matched 1:1 on age, sex, and ejection fraction at the vaccination date (n-total = 74,870). MAIN OUTCOMES: Patients were followed through the end of each influenza season for all-cause mortality. Secondary outcomes included cardiovascular mortality and all-cause hospitalization. In a sensitivity analysis, we examined mortality in the non-influenza season. RESULTS: Influenza vaccinated vs unvaccinated patients had more comorbidities and higher healthcare utilization. After multivariable adjustment for utilization, sociodemographics, comorbidities, and medications, influenza vaccinated vs unvaccinated patients had a lower risk of all-cause mortality and cardiovascular mortality during the influenza season (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.63, 0.70 and HR 0.68, 95% CI 0.63, 0.74, respectively) but a higher risk of all-cause hospitalization (HR 1.27, 95% CI 1.21, 1.31). There was no association between influenza vaccination and all-cause or cardiovascular mortality during the non-influenza season (HR 0.99, 95% CI 0.89, 1.09 and HR 1.00, 95% CI 0.84, 1.21, respectively). CONCLUSIONS: Influenza vaccination in HF patients was associated with a lower risk of mortality during the influenza season. Our findings provide support for recommendations of universal influenza vaccination in patients with HF.

13.
J Med Internet Res ; 23(9): e29959, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34351865

RESUMO

BACKGROUND: Dramatic decreases in outpatient visits and sudden increases in telehealth visits were observed during the COVID-19 pandemic, but it was unclear whether these changes differed by patient demographics and socioeconomic status. OBJECTIVE: This study aimed to assess the impact of the pandemic on in-person outpatient and telehealth visits (telephone and video) by demographic characteristics and household income in a diverse population. METHODS: We calculated weekly rates of outpatient and telehealth visits by age, sex, race/ethnicity, and neighborhood-level median household income among members of Kaiser Permanente Southern California (KPSC) from January 5, 2020, to October 31, 2020, and the corresponding period in 2019. We estimated the percentage change in visit rates during the early pandemic period (March 22 to April 25, 2020) and the late pandemic period (October 4 to October 31, 2020) from the prepandemic period (January 5 to March 7, 2020) in Poisson regression models for each subgroup while adjusting for seasonality using 2019 data. We examined if the changes in visit rates differed by subgroups statistically by comparing their 95% CIs. RESULTS: Among 4.56 million KPSC members enrolled in January 2020, 15.0% (n=682,947) were ≥65 years old, 51.5% (n=2,345,020) were female, 39.4% (n=1,795,994) were Hispanic, and 7.7% (n=350,721) lived in an area of median household income

Assuntos
COVID-19 , Telemedicina , Idoso , Atenção à Saúde , Feminino , Humanos , Pacientes Ambulatoriais , Pandemias , Estudos Retrospectivos , SARS-CoV-2
14.
EClinicalMedicine ; 39: 101088, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34430840

RESUMO

Background: IBI362 (LY3305677) is a novel weekly-dose glucagon-like peptide-1 and glucagon receptor dual agonist being developed for the treatment of obesity and type 2 diabetes. The aim of this randomised, placebo-controlled, multiple ascending dose phase 1b study was to evaluate the safety, tolerability, pharmacokinetics and efficacy of IBI362 in Chinese adults with overweight or obesity. Methods: This study enrolled adults with overweight (body mass index [BMI]≥24 kg/m2) accompanied by hyperphagia and/or at least one comorbidity or obesity (BMI≥28 kg/m2) from six study centres in China. Eligible participants were randomised 2:1 to receive once-weekly subcutaneous injection of IBI362 or placebo in each of the three ascending dose cohorts for 12 weeks with additional 8 weeks of safety follow-up. The dose-escalation regimens were: 3.0 mg cohort (1.0 mg weeks 1-4; 2.0 mg weeks 5-8; 3.0 mg weeks 9-12); 4.5 mg cohort (1.5 mg weeks 1-4; 3.0 mg weeks 5-8; 4.5 mg weeks 9-12); 6.0 mg cohort (2.0 mg weeks 1-4; 4.0 mg weeks 5-8; 6.0 mg weeks 9-12). The participants, investigators and study site personnel involved in treating and assessing participants within each cohort were masked to treatment allocation. The primary endpoints were safety and tolerability of IBI362. This study is registered with ClinicalTrials.gov, number NCT04440345. Findings: Between June 15th, 2020 and January 15th, 2021, 12 participants were enrolled and randomised in each cohort. Throughout the study, no participant discontinued the treatment due to safety reason and no serious adverse event was reported. Gastrointestinal adverse events and decreased appetite were the most common adverse events and mostly mild in severity. Three participants receiving IBI362 reported mild and asymptomatic cardiac disorders revealed by electrocardiogram. Estimated percent changes in mean body weight from baseline to week 12 were -4.81% (95%CI -6.61 to -3.02), -6.40% (-8.23 to -4.58) and -6.05% (-7.91 to -4.18) for participants receiving IBI362 in the 3.0 mg, 4.5 mg and 6.0 mg cohort, respectively, compared with 0.60% (-0.86 to 2.07) for those receiving placebo. Interpretation: IBI362 was well tolerated and showed a body weight-lowering effect in Chinese adults with overweight or obesity. Funding: Innovent Biologics.

15.
Am J Transl Res ; 13(7): 8214-8220, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34377308

RESUMO

OBJECTIVE: To investigate the effects of Roy's adaptation model combined with the forgetting curve in the clinical instruction of operating room nursing interns. METHODS: 115 nursing students in our hospital were randomized and allocated into two groups: the observation group (n=60) and the control group (n=55). The control group underwent the traditional nursing instruction method, and the observation group underwent a new instruction mode guided by Roy's adaptation model combined with the forgetting curve method. The learning effects of the two groups of nursing students and their satisfaction with the nursing instruction were compared. RESULTS: The observation group's theoretical examination score was (96.18±3.94) points, and the group's skill examination score was (83.78±5.19) points, which were higher than the corresponding scores in the control group (83.78±5.19) and (81.32±3.66), with statistical significance (all P<0.05). The operating doctors' scores on the operating room nursing students' psychological adaptability in the operating room, their proficiency in common operation cooperation, their aseptic concepts, their ability to prepare and dispose of instruments and articles, and their work and learning initiatives were significantly higher than they were in the control group, and the differences were statistically significant (P<0.05). The nursing students' professional level, interpersonal communication ability, and teaching ability scores and their total score in the observation group were significantly higher than they were in the control group (P<0.05). CONCLUSION: The new instruction method which combines Roy's adaptation model with the forgetting curve can not only effectively improve the nursing students' learning abilities and adaptability, but it also has an important significance in improving the relationship between doctors and nurses, the instruction relationship, and in improving the quality of the nursing instruction and the comprehensive ability of the nursing staff in the operating room.

16.
Front Endocrinol (Lausanne) ; 12: 704620, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335475

RESUMO

Hydrogen sulfide (H2S), as one of the three known gaseous signal transduction molecules in organisms, has attracted a surging amount of attention. H2S is involved in a variety of physiological and pathological processes in the body, such as dilating blood vessels (regulating blood pressure), protecting tissue from ischemia-reperfusion injury, anti-inflammation, carcinogenesis, or inhibition of cancer, as well as acting on the hypothalamus and pancreas to regulate hormonal metabolism. The change of H2S concentration is related to a variety of endocrine disorders, and the change of hormone concentration also affects the synthesis of H2S. Understanding the effect of biosynthesis and the concentration of H2S on the endocrine system is useful to develop drugs for the treatment of hypertension, diabetes, and other diseases.

17.
Pak J Pharm Sci ; 34(1(Special)): 381-386, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34275783

RESUMO

To investigate the effects of hydralazine combined with nitrate on serum levels of Adropin and brain natriuretic peptide (BNP), left ventricular remodeling and prognosis in patients with chronic heart failure (CHF). 126 CHF patients were divided into control group (n=13, sodium nitroprusside) and combined treatment group (n=63, sodium nitroprusside ± hydralazine). Serum Adropin and BNP levels and left ventricular mass index (LVMI) of patients before treatment and 10 days after treatment were recorded, so did patient's end-point events. It was found that compared with those before treatment, the serum levels of Adropin, BNP, and LVMI in combined group and control group after 10 days of treatment were lower (P<0.05). The end-point event rate in the combined group was 19.05% (12/63). The serum levels of Adropin, BNP, and LVMI in the combined group with end-point events were higher than those of patients without end-point events (P<0.05). Spearman correlation analysis showed that serum levels of Adropin and BNP were positively correlated with LVMI and the end-point events rate (P<0.05). To sum up, hydralazine combined with sodium nitroprusside treatment can effectively reduce serum Adropin and BNP levels, and the risk of left ventricular remodeling and poor prognosis in patients with CHF.

18.
Vaccine X ; 8: 100101, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34195599

RESUMO

Post-licensure vaccine safety studies are essential to identify adverse events that may not have been detected in pre-licensure clinical trials and to address questions that arose during the pre-licensure phase. These studies are increasingly conducted using real-world data collected as part of routine health care delivery. However, design of post-licensure vaccine safety studies involves many pragmatic and scientific decisions, which must be made while balancing diverse stakeholder opinions. Challenges include selecting exposure and comparison groups, deciding on the most appropriate outcome, determining sample size and length of follow-up time, and other analytic considerations. As an example of this process and to inform other post-licensure vaccine safety studies in real-world settings, we discuss our experience with design of an FDA-required Phase 4 post-licensure safety study of a hepatitis B vaccine in a large integrated health care organization in the United States.

19.
J Neurochem ; 158(6): 1292-1306, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34109634

RESUMO

Cholinergic basal forebrain (cBF) neurons are particularly vulnerable to degeneration following trauma and in neurodegenerative conditions. One reason for this is their characteristic expression of the p75 neurotrophin receptor (p75NTR ), which is up-regulated and mediates neuronal death in a range of neurological and neurodegenerative conditions, including dementia, stroke and ischaemia. The signalling pathway by which p75NTR signals cell death is incompletely characterised, but typically involves activation by neurotrophic ligands and signalling through c-Jun kinase, resulting in caspase activation via mitochondrial apoptotic signalling pathways. Less well appreciated is the link between conditions of oxidative stress and p75NTR death signalling. Here, we review the literature describing what is currently known regarding p75NTR death signalling in environments of oxidative stress and hypoxia to highlight the overlap in signalling pathways and the implications for p75NTR signalling in cBF neurons. We propose that there is a causal relationship and define key questions to test this assertion.


Assuntos
Neurônios Colinérgicos/metabolismo , Hipóxia/metabolismo , Degeneração Neural/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Estresse Oxidativo/fisiologia , Receptores de Fator de Crescimento Neural/metabolismo , Animais , Prosencéfalo Basal/metabolismo , Prosencéfalo Basal/patologia , Morte Celular/fisiologia , Neurônios Colinérgicos/patologia , Humanos , Hipóxia/patologia , Degeneração Neural/patologia
20.
J Colloid Interface Sci ; 602: 355-366, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34139533

RESUMO

Simple preparation, favorable price and environmental protection have been a long-term challenge in the field of electrochemistry. Herein, we studied and prepared a bifunctional Mo-doped Co3O4 ultrathin nanosheets, which has been validated as an effective binder-free electrode material for electrocatalytic water splitting and supercapacitors. The material has a large specific surface area, high electrical conductivity and exposure to more active sites, breaking down the limited performance and range of use of transition metal oxides. Benefiting from intriguing ultrathin property and conductivity, OER and HER process of 0.4Mo-Co3O4 have a small Tafel slope of 83.7 and 98 mV dec-1, respectively. The current density at 10 mA cm-2 show a low overpotential of 315 and 79 mV and significant stability. The water electrolytic device requires a potential of 1.64 V to reach 10 mA cm-2, and the potential change is negligible after 12 h of continuous electrolysis. In addition, the manifest improved electrochemical performance of 0.3Mo-Co3O4 as supercapacitor electrode material shows high areal capacitance 2815 mF cm-2 at 1 mA cm-2, excellent rate performance (85% at 10 mA cm-2) and retains 90% of the initial capacitance by cycling 5000 at a current density of 10 mA cm-2. Moreover, 0.3Mo-Co3O4||0.3Mo-Co3O4 symmetrical supercapacitor has a maximum volumetric energy density of 1.25 mW h cm-3 at a power density of 7.1 mW cm-3 and superior cycle life. The influence of doping on electrochemical performance was studied by changing the content of doped metal ions, which is of great significance for the exploration of supercapacitor and electrocatalytic hydrolysis of bifunctional electrode materials.

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