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1.
J Tradit Chin Med ; 44(3): 609-619, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38767646

ABSTRACT

OBJECTIVE: To assess the quality of Clinical practice guidelines (CPGs) in the context of diabetic kidney disease (DKD) and determine whether any factors affect the quality. METHODS: We searched eight databases along with five international and national organizations to develop or archive guidelines from their inception to July 2023, with an additional search of medlive.cn. And the authoritative organizations related to nephrology. CPGs and consensus statements created using direct differential diagnosis or therapy for DKD were included without language restrictions. Their quality was evaluated by four reviewers using the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) instrument. Along with the item and domain scores, the guideline was also allocated an overall quality score, which ranged from 1 (lowest possible quality) to 7 (highest possible quality). Moreover, an overall recommendation for use was also assigned ("recommended", "recommended with modifications" or "not recommended"). RESULTS: A total of 16 CPGs were included, of which 14 were from Asia and the remaining two from Europe. These two CPGs were updated in the third version. Six CPGs were recommended for use because their primary domains scored in the medium or high category. Furthermore, five CPGs were recommended with modifications as the stakeholder involvement, applicability, and editorial independence domains were evaluated as low categories. In all domains, the lowest average score was for rigour of development (33%), followed by application (36%), and stakeholder involvement (51%). The highest average score was for scope and purpose (79%), followed by clarity of presentation (75%). None of the CPGs considered the patient's viewpoint, and six of 16 CPGs did not use any grading system to translate the evidence into recommendations. Additionally, only three of 16 CPGs shared search strategy, and eight of 16 CPGs did not declare a funding source. CONCLUSIONS: According to the AGREE II evaluation, more than one in four CPGs for DKD had poor methodological quality. Enhanced efforts are needed to advance the rigour of development, application, and editorial independence of DKD guideline panels for most guidelines. Stakeholders, CPG developers, and CPG users should consider methodological quality while choosing CPGs, and interpret and implement their issued suggestions.


Subject(s)
Diabetic Nephropathies , Practice Guidelines as Topic , Humans , Diabetic Nephropathies/therapy , Diabetic Nephropathies/diagnosis
2.
Sci Rep ; 14(1): 11464, 2024 05 20.
Article in English | MEDLINE | ID: mdl-38769093

ABSTRACT

Long-term exposure to ambient air pollution raises the risk of deaths and morbidity worldwide. From 1990 to 2019, we observed the epidemiological trends and age-period-cohort effects on the cardiovascular diseases (CVD) burden attributable to ambient air pollution across Brazil, Russia, India, China, and South Africa (BRICS). The number of CVD deaths related to ambient particulate matter (PM) pollution increased nearly fivefold in China [5.0% (95% CI 4.7, 5.2)] and India [5.7% (95% CI 5.1, 6.3)] during the study period. The age-standardized CVD deaths and disability-adjusted life years (DALYs) due to ambient PM pollution significantly increased in India and China but decreased in Brazil and Russia. Due to air pollution, the relative risk (RR) of premature CVD mortality (< 70 years) was higher in Russia [RR 12.6 (95% CI 8.7, 17.30)] and India [RR 9.2 (95% CI 7.6, 11.20)]. A higher period risk (2015-2019) for CVD deaths was found in India [RR 1.4 (95% CI 1.4, 1.4)] followed by South Africa [RR 1.3 (95% CI 1.3, 1.3)]. Across the BRICS countries, the RR of CVD mortality markedly decreased from the old birth cohort to young birth cohorts. In conclusion, China and India showed an increasing trend of CVD mortality and morbidity due to ambient PM pollution and higher risk of premature CVD deaths were observed in Russia and India.


Subject(s)
Air Pollution , Cardiovascular Diseases , Particulate Matter , Humans , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/mortality , Cardiovascular Diseases/etiology , Air Pollution/adverse effects , South Africa/epidemiology , China/epidemiology , Russia/epidemiology , Particulate Matter/adverse effects , Particulate Matter/analysis , Female , India/epidemiology , Male , Middle Aged , Aged , Brazil/epidemiology , Adult , Environmental Exposure/adverse effects , Disability-Adjusted Life Years , Air Pollutants/adverse effects , Cohort Studies
3.
Org Lett ; 26(18): 3727-3732, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38678575

ABSTRACT

Photoexcitation electron donor-acceptor (EDA) complexes provide an effective approach to produce radicals under mild conditions, while the catalytic version of EDA complex photoactivation remains scarce. Herein, we report a visible-light-induced organophotocatalytic pathway for the cyanoalkylation of azauracils using inexpensive and readily available 1,4-diazabicyclo[2.2.2]octane (DABCO) as a catalytic electron donor. This synthetic method exhibits exceptional compatibility with various functional groups and presents 34 examples in high yields. The efficient cyanoalkylation offers an environmentally friendly and sustainable route toward enhancing the structural and functional diversity of azauracils.

4.
Chem Commun (Camb) ; 60(31): 4230-4233, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38526583

ABSTRACT

Lead-free perovskite microcrystals (MCs) have been regarded as promising potential photocatalysts, owing to their high molar extinction coefficient, low economic cost, adjustable light absorption range, and ample surface-active sites. Herein, C-3 thio/selenocyanation of indoles is demonstrated in high selectivity and yield by using lead-free double perovskite Cs2AgBiBr6 MCs under visible light irradiation. Moreover, the photocatalyst can be recycled at least 5 times without a significant decrease in catalytic activity.

5.
Chem Commun (Camb) ; 60(21): 2958-2961, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38375889

ABSTRACT

Visible-light-induced EDA complex-promoted ring-opening of cycloketone oxime esters to synthesise various cyanoalkylated products with N-methacryloyl benzamides was developed. Various radical receptors were compatible with the current reaction system to furnish diverse heterocyclic compounds. Mechanistic analysis shows that the formation of an EDA complex was crucial to the photocatalytic strategy. Importantly, 4-cyanoalkyl isoquinoline-1,3-diones were obtained in high yields by using a catalytic amount of 1,4-diazabicyclo[2.2.2]octane (DABCO) through prolonging the reaction time, which provided a practical approach to give a variety of isoquinoline-1,3-dione derivatives.

6.
Chem Commun (Camb) ; 60(18): 2516-2519, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38324066

ABSTRACT

Allyl sulfones are important sulfur-containing compounds that have widespread applications in organic synthesis, medicinal chemistry and materials science. Herein, nickel-catalysed dehydrosulfonylation of unactivated allyl alcohols with aryl sulfonyl hydrazides without additional active agents under mild conditions was developed. A variety of functional allyl sulfones could be efficiently synthesized in the presence of air-stable Ni(acac)2 as the catalyst and 1,1'-bis(diphenylphosphino)ferrocene (DPPF) as the ligand.

7.
Org Biomol Chem ; 22(5): 965-969, 2024 Jan 31.
Article in English | MEDLINE | ID: mdl-38205855

ABSTRACT

A visible-light-induced decarboxylative cascade reaction of acryloylbenzamides with alkyl N-hydroxyphthalimide (NHP) esters for the synthesis of various 4-alkyl isoquinolinediones mediated by triphenylphosphine (PPh3) and sodium iodide (NaI) was developed. This operationally simple protocol proceeded via the photoactivation of electron donor-acceptor (EDA) complexes between N-hydroxyphthalimide esters and NaI/PPh3, resulting in multiple carbon-carbon bond formations without the use of precious metal complexes or synthetically elaborate organic dyes, which provided an alternative practical approach to synthesize diverse isoquinoline-1,3(2H,4H)-dione derivatives.

8.
Chinese Pharmacological Bulletin ; (12): 299-307, 2024.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1013590

ABSTRACT

Aim To explore the new mechanism of triptolide (TRI) inhibiting the progression of hepatocellular carcinoma (HCC) . Methods Different concentrations (0, 0 . 5, 2, and 8 jjunol • L~) of TRI were administered to act on liver cancer cells, and then the cell phenotypes and possible mechanisms were explored using experimental methods such as CCK-8, cell cloning, Transwell, and protein immunoblotting; siRNA was used to interfere with the target gene GSDME and its role was determined. Finally, the mechanism of TRI inhibiting the growth of HCC cells in vivo was validated using a transplanted tumor model. Results TRI could inhibit the proliferation, cloning, and invasion of HCC cells, and promote cell apoptosis. Immunoblotting results showed that the expression of GSDME was significantly upregulated in HepG2 or He-pal-6 hepatocellular carcinoma after TRI treatment, while the expression of cleaved caspase-3 and PARP also significantly increased. Knocking out GSDME could partially reverse TRI-induced cell apoptosis. At the same time, cells knocked down by GSDME had stronger cloning and migration abilities, and the apoptosis rate was reduced compared to the TRI treatment group alone. In vivo experiments showed that TRI inhibited HCC tumor growth, and the TRI + siGSDME group had a faster tumor growth rate than the TRI treatment group alone did. In addition, after TRI stimulation, p-eIF2a and ATF4 in HepG2 and Hepal-6 cells significantly increased. The immunofluorescence results showed a dose-dependent increase in the number of ATF4 positive cells in HepG2 and Hepal-6 cells after TRI stimulation. Conclusion The inhibitory effect of TRI on the growth and invasion of liver cancer cells may be related to its regulation of the ATF4/caspase-3/GSDME signaling pathway and promotion of liver cancer cell apoptosis.

9.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1006564

ABSTRACT

ObjectiveTo establish the clinical comprehensive evaluation index system for Chinese patent medicine(CPM) based on Evidence and Value:Impact on DEcisionMaking(EVIDEM) framework, so as to promote the scientific, systematic and standardized implementation of clinical comprehensive evaluation of CPM. MethodThe clinical comprehensive evaluation index system was determined through literature review, semi-structured interview and Delphi method, and the weights of each index were clarified by analytic hierarchy process(AHP). ResultThe recovery rates of both rounds of expert consultation were 100%, and the authority coefficient of experts was 0.90 and 0.905, respectively. Kendall's coordination coefficients(W) of the second- and third-level indicators in the first-round consultation were 0.320 and 0.283(P<0.001), and in the second round were 0.411 and 0.351, respectively(P<0.001). The finally constructed clinical comprehensive evaluation index system for CPM included 6 first-level indicators, 13 second-level indicators and 28 third-level indicators. Among the first-level indicators, the weights of effectiveness, safety, economy, innovation, suitability and accessibility were 37.34%, 32.68%, 11.85%, 5.87%, 5.79% and 6.47%, respectively. ConclusionThis study has constructed a universal clinical comprehensive evaluation index system for CPM, and the domain and criteria are introduced and interpreted in detail, which can provide reference and information for carrying out the clinical comprehensive evaluation of CPM, but it needs to be refined and improved in combination with the clinical practice of CPM for specialized diseases.

10.
Front Endocrinol (Lausanne) ; 14: 1267338, 2023.
Article in English | MEDLINE | ID: mdl-38098860

ABSTRACT

Background: Gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) are the predominant pregnancy complications among singleton and twin pregnancies worldwide. Our primary objective was to explore the adverse effect of GDM and HDP on maternal-perinatal outcomes compared with non-GDM and non-HDP in singleton and twin pregnancies. The secondary objective was to find the risk of adverse maternal-perinatal outcomes in twin pregnancies compared with singleton pregnancies complicated with GDM and HDP in Hubei, China. Methods: A tertiary hospital-based retrospective study was conducted at Wuhan University Renmin Hospital, Hubei Province, China, from 2011 to 2019. A chi-square test was used to determine the difference in adverse maternal-perinatal outcomes between singleton and twin pregnancies. A multiple binary logistic regression model and a joinpoint regression model were used to determine the association of GDM and HDP with adverse maternal-perinatal outcomes and GDM and HDP temporal trend among singleton and twin pregnancies. Results: The trend of HDP [average annual percentage change (AAPC) 15.1% (95% confidence interval (95%CI): 5.3, 25.7)] among singleton pregnancies and GDM [AAPC 50.4% (95%CI: 19.9, 88.7)] among twin pregnancies significantly increased from 2011 to 2019. After adjusting for confounding factors, GDM is associated with an increased risk of C-section (adjusted odds ratio (aOR), 1.5; 95%CI: 1.3, 1.6) and macrosomia (aOR, 1.3; 95%CI: 1.1, 1.6) in singleton and preterm birth (PTB) (aOR, 2.1; 95%CI: 1.2, 3.3) in twin pregnancies compared with non-GDM. HDP was associated with a higher risk of C-section, PTB, perinatal mortality, and low birth weight (LBW) in both singleton and twin pregnancies compared with the non-HDP. Compared with singleton pregnancies complicated with GDM and HDP, twin pregnancies showed higher odds of C-section [(aOR, 1.7; 95%CI: 1.1, 2.7), (aOR, 4.6; 95%CI: 2.5, 8.7), respectively], PTB [(aOR, 22.9; 95%CI: 14.1, 37.3), (aOR, 8.1; 95%CI: 5.3, 12.3), respectively], LBW [(aOR, 12.1; 95%CI: 8.2, 18.1), (aOR, 5.1; 95%CI: 3.6, 7.4), respectively], and low Apgar score [(aOR, 8.2; 95%CI: 4.4, 15.1), (aOR, 3.8; 95%CI: 2.4, 5.8), respectively] complicated with GDM and HDP. Conclusion: In conclusion, GDM showed an increased risk of a few adverse maternal-perinatal outcomes and HDP is associated with a higher risk of several adverse maternal-perinatal outcomes in singleton and twin pregnancies compared to non-GDM and non-HDP. Moreover, twin pregnancies complicated with GDM and HDP showed higher odds of adverse maternal-neonatal outcomes compared with singleton pregnancies complicated with GDM and HDP.


Subject(s)
Diabetes, Gestational , Drug-Related Side Effects and Adverse Reactions , Hypertension, Pregnancy-Induced , Infant, Newborn, Diseases , Pre-Eclampsia , Premature Birth , Pregnancy , Female , Humans , Infant, Newborn , Diabetes, Gestational/epidemiology , Pregnancy, Twin , Retrospective Studies , Pregnancy Outcome/epidemiology , Hypertension, Pregnancy-Induced/epidemiology , Hypertension, Pregnancy-Induced/etiology , Premature Birth/epidemiology , Premature Birth/etiology
11.
Chem Commun (Camb) ; 60(1): 106-109, 2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38032358

ABSTRACT

Organophotocatalytic cascade cross-dehydrogenative-coupling/cyclization reaction of o-hydroxyarylenaminones with α-amino acid derivatives for the construction of α-chromone substituted α-amino acid derivatives was developed. Various N-arylglycine esters, amides and dipeptides underwent the cascade cyclization reaction well with o-hydroxyarylenaminones to afford the corresponding 3-aminoalkyl chromones in good to excellent yields. This approach consists of visible-light-promoted oxidation of α-amino acid derivatives, the Mannich reaction, and intramolecular nucleophilic cyclization under acidic conditions, and features a wide reaction scope, a simple operation and mild reaction conditions, which may have the potential to be used for the synthesis of bioactive molecules.

12.
Nutrients ; 15(17)2023 Aug 28.
Article in English | MEDLINE | ID: mdl-37686788

ABSTRACT

BRICS-Plus countries (Brazil, Russia, India, China, South Africa, and 30 other countries) is a group of 35 countries with emerging economies making up more than half of the world's population. We explored epidemiological trends of cardiovascular disease (CVD) mortality attributable to modifiable risk factors and its association with period and birth cohort effects and sociodemographic index (SDI) across BRICS-Plus countries by using joinpoint regression and age-period-cohort modeling from 1990 to 2019. Between 1990 and 2019, the all-ages CVD deaths increased by 85.2% (6.1 million to 11.3 million) across BRICS-Plus countries. The CVD age-standardized mortality rate attributable to dietary risks and smoking significantly decreased across BRICS-Plus countries, with some exceptions. However, four-fifths of BRICS-Plus countries observed a remarkable increasing trend of high body mass-index (BMI)-related CVD deaths, in particular, among younger adults (25-49 years). Early birth cohorts and individuals aged greater than 50 years showed a higher risk of CVD mortality. Both the China-ASEAN FTA and Mercosur regions stand out for their successful sociodemographic transition, with a significant reduction in CVD mortality over the study period. Singapore and Brazil achieved great progress in CVD mortality reduction and the other BRICS-Plus countries should follow their lead in adopting public health policies and initiatives into practice.


Subject(s)
Cardiovascular Diseases , Cardiovascular System , Adult , Humans , Aged , Risk Factors , Smoking , Birth Cohort
13.
Chem Commun (Camb) ; 59(8): 1050-1053, 2023 Jan 24.
Article in English | MEDLINE | ID: mdl-36602378

ABSTRACT

An efficient nickel-catalyzed cross-coupling for the synthesis of 2-sulfonylthiazoles from readily available 2-chlorobenzothiazoles and sodium sulfinates has been developed. A variety of 2-chlorobenzothiazoles and sulfinates having a diverse range of substitution patterns can undergo the coupling process successfully at room temperature. Avoiding the use of precious catalysts and sensitive ligands, moderate to excellent yields of various 2-sulfonylthiazoles were observed.


Subject(s)
Nickel , Sodium , Temperature , Catalysis , Ligands
14.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1015598

ABSTRACT

N6-adenosine methylation, a form of methylation of the adenosine N6 site, is often found in eukaryotic mRNA and is one of the most common forms of internal RNA modification. Studies have shown that m6A affects cellular biological processes by regulating gene expression; also the regulators of m6A play a key role in the occurrence and development of various cancers. Prostate Cancer (PCa) is a common malignant tumor in men, and the risk of the disease in men over 60 years of age is increasing year by year. With the aging population, the number of PCa can be expected to continue to rise. In recent years, the role of m6A in tumorigenesis has received widespread attention, but studies on m6A methylation modification in PCa are still limited; therefore, it is particularly important to further explore the relationship between m6A methylation and PCa. In this paper, we review the recent research progress on the role, mechanism, and application of m6A methylation modification in PCa, especially the detailed review of the mechanism of METTL3, FTO, YTHDF2, three classical m6A-related regulatory proteins in PCa; and the potential application of m6A in advanced PCa (e. g., destructive resistant prostate cancer, bone metastatic prostate cancer). From the perspective of methylation modification, this paper may provide some clues to find effective therapeutic strategies for early diagnosis, treatment, and prognosis of PCa, and more theoretical references to achieve individualized treatment.

15.
Chinese Pharmacological Bulletin ; (12): 1210-1212, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1013751

ABSTRACT

Glucagon-like peptide-1 (GLP-1) is a major hormone of incretin hormone and gut-brain axis, which is related to the control of energy homeostasis and the occurrence of obesity. In addition to suppressing appetite, GLP-1 has neuroprotective effects by acting on areas of the brain involved in stress response and mood regulation. Depression is a common mental disease, and GLP-1 is closely related to depression. This article reviews the role and mechanism of GLP-1 in depression.

16.
Chinese Journal of Hematology ; (12): 900-905, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1012254

ABSTRACT

Objective: To investigate the clinical features of coronavirus disease 2019 (COVID-19) in patients with aplastic anemia (AA) undergoing immunosuppressive therapy (IST) . Methods: In this prospective cohort study, we collected the demographic and clinical data of patients with AA and COVID-19 from December 1, 2022, to January 31, 2023. We described the clinical features of COVID-19 among patients with AA and evaluated the effects of IST on the signs and severity of COVID-19. Results: A total of 170 patients with AA and COVID-19 were included. The common early symptoms, including fever, dizziness or headache, muscle or body aches, and sore throat, disappeared within 1-2 weeks. Approximately 25% of the patients had persistent fatigue within 2 weeks. Many patients experienced cough after an initial 1-3 days of infection, which lasted for more than 2 weeks. There were no differences in the duration of total fever episodes and maximum body temperature when patients were stratified according to whether or not they underwent IST, by IST duration, or by use of anti-lymphocyte globulin (ALG) (P>0.05). No differences were observed in the occurrence of symptoms in either the early or recovery stages when patients with AA were stratified according to whether or not they underwent IST, or by IST duration (P>0.05). However, patients who received ALG had fewer fever episodes within 1 week after infection (P=0.035) and more sore throat episodes within 2 weeks after infection (P=0.015). There were no other significant differences in clinical symptoms between patients who did and patients who did not receive ALG (P>0.05) . Conclusion: The majority of patients with AA and COVID-19 recovered within 2 weeks of noticing symptoms when treated with IST.


Subject(s)
Humans , Anemia, Aplastic , COVID-19 , Prospective Studies , Fever , Immunosuppression Therapy , Pharyngitis
17.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-989116

ABSTRACT

Pyrethroids, a broad class of synthetic organic insecticides applied in daily life, are highly toxic in the water environment and can cause organisms to develop symptoms of neurotoxicity.Environmental exposure has become one of the important factors explored during child growth and development in recent years, and the exposure of pyrethroids in the environment has gradually increased, making their effects on child growth and development also highly valued.A large number of studies at home and abroad have found that pyrethroids have effects on multi system development: exposure during pregnancy can lead to intrauterine growth restriction, malformations, etc.Postnatal exposure can lead to cognitive retardation, abnormal pubertal development, and may also increase the risk of allergic diseases, wheeze, cough, and acute lymphoblastic leukemia.This article provides a review of the effects of pyrethroid exposure on growth and developmental processes in children.

18.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-980180

ABSTRACT

In order to evaluate the efficacy and safety of Hexue Mingmu tablets in the treatment of diabetic retinopathy(DR) and retinal vein obstruction(RVO), and to provide a basis for the clinical treatment of ophthalmic diseases, this paper obtained randomized controlled trials(RCTs) of Hexue Mingmu tablets in the treatment of DR and RVO by searching Chinese and English electronic databases and trial registration platforms(up to September 13, 2022). The risk of bias in the included studies was assessed using RoB2.0, and Meta-analysis was performed using RevMan5.4. A total of 35 RCTs involving a total sample size of 3 261 patients were included. Meta-analysis results showed that compared with conventional western medical treatment alone, the combination of Hexue Mingmu tablets with conventional western medical treatment improved patients' macular thickness{mean difference(MD) =-39.83, 95% confidence interval(CI) [-51.60, -28.06], P<0.000 01}, improved corrected visual acuity{risk ratio(RR)dichotomous=1.09, 95% CI [1.00, 1.18], P=0.04; MDcontinuous variable=0.15, 95% CI [0.13, 0.17], P<0.000 01}, increased effective rate of fundus symptom improvement(RR=1.26, 95% CI [1.22, 1.30], P<0.000 01), improved hemorheology index{standard mean difference(SMD)=-1.53, 95% CI [-2.04, -1.01], P<0.000 01}, shortened improvement time of fundus symptoms(MD=-5.53, 95% CI [-5.96, -5.09], P<0.000 01), and there was no significant difference on adverse events between the two groups. The results show that treatment of DR and RVO with Hexue Mingmu tablets may improve the macular thickness and hemorheology index of patients, which can significantly enhance the effect of corrected visual acuity and clinical efficiency, and shorten the time to symptom improvement. However, the original literature is of low quality and the pooled results have some limitations. Subsequent studies should try to use uniform standard assessment criteria and testing methods, focus on the rigor of study design and implementation, and pay attention to the key outcomes of this disease and the clinical safety of medication, so as to provide more reliable evidence to support this kind of clinical problems.

19.
Neuroscience Bulletin ; (6): 881-892, 2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-982411

ABSTRACT

Mutations in genes encoding amyloid precursor protein (APP) and presenilins (PSs) cause familial forms of Alzheimer's disease (AD), a neurodegenerative disorder strongly associated with aging. It is currently unknown whether and how AD risks affect early brain development, and to what extent subtle synaptic pathology may occur prior to overt hallmark AD pathology. Transgenic mutant APP/PS1 over-expression mouse lines are key tools for studying the molecular mechanisms of AD pathogenesis. Among these lines, the 5XFAD mice rapidly develop key features of AD pathology and have proven utility in studying amyloid plaque formation and amyloid β (Aβ)-induced neurodegeneration. We reasoned that transgenic mutant APP/PS1 over-expression in 5XFAD mice may lead to neurodevelopmental defects in early cortical neurons, and performed detailed synaptic physiological characterization of layer 5 (L5) neurons from the prefrontal cortex (PFC) of 5XFAD and wild-type littermate controls. L5 PFC neurons from 5XFAD mice show early APP/Aβ immunolabeling. Whole-cell patch-clamp recording at an early post-weaning age (P22-30) revealed functional impairments; although 5XFAD PFC-L5 neurons exhibited similar membrane properties, they were intrinsically less excitable. In addition, these neurons received smaller amplitude and frequency of miniature excitatory synaptic inputs. These functional disturbances were further corroborated by decreased dendritic spine density and spine head volumes that indicated impaired synapse maturation. Slice biotinylation followed by Western blot analysis of PFC-L5 tissue revealed that 5XFAD mice showed reduced synaptic AMPA receptor subunit GluA1 and decreased synaptic NMDA receptor subunit GluN2A. Consistent with this, patch-clamp recording of the evoked L23>L5 synaptic responses revealed a reduced AMPA/NMDA receptor current ratio, and an increased level of AMPAR-lacking silent synapses. These results suggest that transgenic mutant forms of APP/PS1 overexpression in 5XFAD mice leads to early developmental defects of cortical circuits, which could contribute to the age-dependent synaptic pathology and neurodegeneration later in life.


Subject(s)
Mice , Animals , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Amyloid beta-Protein Precursor/metabolism , Mice, Transgenic , Neurons/metabolism , Receptors, AMPA/metabolism , Disease Models, Animal
20.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-981415

ABSTRACT

This study systematically evaluated the clinical efficacy and safety of Fengliao Changweikang prescription for treating acute gastroenteritis(AGE). The databases of CNKI, Wanfang, VIP, SinoMed, Medline, Cochrane Library and two clinical trial registration platforms were retrieved from inception to August 30, 2022, to collect randomized controlled trial(RCT) on Fengliao Changweikang prescription treating AGE. Two researchers independently conducted literature screening, data extraction, and risk of bias assessment according to pre-established inclusion and exclusion criteria. RevMan 5.4.1 was used for data analysis. Finally, 18 RCTs were included, involving 3 489 patients. Meta-analysis showed that compared with conventional western medicine, Fengliao Changweikang prescription improved the relief rate of abdominal pain(RR=1.27, 95%CI[1.17, 1.38],P<0.000 01); Fengliao Changweikang prescription + conventional western medicine increased the cure rate(RR=1.43, 95%CI[1.12, 1.82], P=0.004), shortened the duration of diarrhoea(RR=-1.65, 95%CI[-2.44,-0.86], P<0.000 1), abdominal pain(RR=-1.46, 95%CI[-2.00,-0.92], P<0.000 01), vomiting(RR=-2.16, 95%CI[-2.51,-1.81], P<0.000 01) and fever(RR=-2.61, 95%CI[-4.00,-1.23], P=0.000 2), down-regulated the level of interleukin-8(IL-8)(RR=-1.07, 95%CI[-1.26,-0.88], P<0.000 01), IL-6(RR=-8.24, 95%CI[-8.99,-7.49], P<0.000 01) and hypersensitive C-reactive protein(hs-CRP)(RR=-3.04, 95%CI[-3.40,-2.69], P<0.000 01) and recurrence of AGE(RR=0.20, 95%CI[0.05, 0.90], P<0.04). In conclusion, Fengliao Changweikang prescription was safe in clinical application. It was beneficial to alleviate the clinical symptoms of diarrhea, abdominal pain, vomiting, and fever, and down-regulate the levels of some serum inflammatory factors in AGE patients. However, considering that few high-quality studies have evaluated the efficacy and safety of Fengliao Changweikang prescription in treatment of AGE, further evidence is needed in the future.


Subject(s)
Humans , Drugs, Chinese Herbal/adverse effects , Treatment Outcome , Gastroenteritis/drug therapy , Prescriptions
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