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Objective·To investigate the causal relationship between atrial fibrillation(AF)and cognitive impairment.Methods·A two-sample Mendelian randomization(TSMR)analysis was used to assess the potential causality of AF on cognitive dysfunction.Single nucleotide polymorphisms(SNPs)strongly associated with AF were extracted as instrumental variables by using a dataset of a large-scale genome-wide association study(GWAS)on AF.The associations of SNPs with Alzheimer's disease dementia,Parkinson's disease dementia,vascular dementia,Lewy body dementia,frontotemporal dementia,undefined dementia,and overall cognitive function assessment were extracted separately from publicly available GWAS data on cognitive dysfunction.The inverse variance-weighted(IVW)method was used for the main analysis,and sensitivity analyses were conducted by using Cochran's Q test,MR-Egger regression,and leave-one-out method.To verify the robustness of the results,replicate analyses and meta-analyses were performed by using different GWAS data.Results·In the initial analysis,101 SNPs were extracted as instrumental variables from a meta-analysis of a genome-wide association study involving up to 1 030 836 individuals.The IVW analysis showed no evidence for causal associations between AF and dementia[dementia(OR=1.032;95％CI 0.973-1.094;P=0.290),Parkinson's disease dementia(OR=1.004;95％CI 0.780-1.291;P=0.977),vascular dementia(OR=1.123;95％CI 0.969-1.301;P=0.125),or unspecified dementia(OR=1.013;95％CI 0.910-1.129;P=0.807)].In the replication analysis,27 SNPs were extracted as instrumental variables from the FinnGen AF GWAS data,and the 1VW analysis were consistent with the initial analysis[cognitive function(OR=0.999;95％CI 0.982-1.016;P=0.874),Alzheimer's disease dementia(OR=0.977;95％CI 0.943-1.012;P=0.193),Lewy body dementia(OR=1.014;95％CI 0.898-1.145;P=0.826),or frontotemporal dementia(OR=0.996;95％CI 0.745-1.333;P=0.980)].Both Mendelian randomization analyses and meta-analyses showed no evidence of an association between genetically predicted AF and different types of dementia or overall cognitive function assessment.MR-Egger regression suggested no horizontal pleiotropy and leave-one-out analysis showed stable results after individually removing each SNP.Conclusion·No evidence of a causal relationship between AF and cognitive impairment was found.The associations observed in observational studies can be partially attributed to confounding factors such as shared biology or co-morbidities.
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AIM: To investigate long-term efficacy and safety of patients after excimer laser in situ keratomileusis(LASIK)surgery in 20a.METHODS: A retrospective study.Patients who underwent LASIK in our hospital from January 1998 to December 2001 were recruited. The patients were notified by telephone to the outpatient for follow-up. The collected data included demographic characteristics(gender and age), preoperative uncorrected distance visual acuity(UCVA)and best corrected visual acuity(BCVA), preoperative diopter, intraoperative corneal flap thickness and corneal stromal residual thickness(RST). The main indicators were long-term efficacy index, safety index, UCVA, BCVA, corneal thickness and axial length. The slit lamp, fundus and optical coherence tomography(OCT)examination were performed at the same time.RESULTS: A total of 95 patients(190 eyes)were recruited. At the final postoperative visit, there were 71 patients(142 eyes, 74.7%)had UCVA≥1.0, and 82 patients(164 eyes, 86.3%)had BCVA≥1.0. There were 2 eyes among them had bad BCVA(≤0.6)due to macular retinoschisis and glaucoma, respectively, while other patients' BCVA was 0.8. There was no significant correlation between the UCVA and BCVA of patients after surgery in 20a and the factors such as age at surgery, preoperative diopter and corneal thickness(P>0.05), but there was a negative correlation with the increase of axis length(rs=-0.32, -0.31, all P<0.05). UCVA and BCVA were positively correlated with corneal stromal residual thickness at the last postoperative follow-up(P<0.05). The safety and efficacy indexes of LASIK after surgery in 20a were 1.00±0.10 and 0.83±0.27, respectively. During the follow-up, no patients were found to have corneal ectasia and complications related to corneal flap, and no patients underwent secondary surgery. No patients with corneal dryness were found after silt lamp examination.CONCLUSION: LASIK after surgery in 20a shows good safety and efficacy.
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FGF21-164 is a fusion protein obtained by structural modification and coupling of endogenous FGF21. It is a candidate drug used in the treatment of glucose and lipid metabolic disorders caused by obesity. In this study, the candidate peptide mass spectrometry information of the protein hydrolyzed by trypsin was predicted by Skyline software and verified by high resolution mass spectrometry. The specific surrogate peptide (YLYTDDAQQTEAHLEIR) with the best mass response was selected after optimizing ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Under ESI positive ion mode, the parent ion m/z 689.3 with 3 charge and the product ion m/z 738.4 with single charge can be monitored. After dilution by PBS, the serum samples were denatured under 60 ℃ and alkylated to reduce the matrix effect, then incubated with trypsin at 37 ℃ for 2 h, to obtain the surrogate peptide. The chromatographic separation was carried out on an EclipsePlus C18 column (2.1 mm×50 mm, 1.8 μm) using aqueous solution containing 0.1% formic acid (phase A) and acetonitrile solution containing 0.1% formic acid (phase B). Finally, the concentration of FGF21-164 fusion protein in mouse serum was quantitatively analyzed by external standard method by monitoring the above ion pairs using triple quadrupole mass spectrometer. This method showed a good linearity in the range of 2.50-500 μg·mL-1 (r = 0.998 8), and was successfully applied to the pharmacokinetic study of FGF21-164 fusion protein in mice. This experiment was approved by the Experimental Animal Ethics Committee of Shanghai Institute of Materia Medica, Chinese Academy of Sciences (batch number: 20180004040450). Compared with the endogenous FGF21, the t1/2 of FGF21-164 fusion protein was prolonged from 0.5 h to 2.6 h, which is expected to prolong the therapeutic efficacy of this protein.
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Liquid chromatography-tandem mass spectrometry (LC-MS) is a promising alternative or complementary method for traditional ligand-binding assays (LBA) in antibody drug bioanalysis. However, issues related to method development, sample preparation, sensitivity and quantitative accuracy need to be addressed. This paper reviews progress in bioanalysis of antibody drugs by LC-MS methods, introduces the principle of the LC-MS method for the analysis of antibody drugs, and describes the challenges faced in quantitative antibody analysis by the LC-MS method. New strategies that can be used to deal with these challenges include: selection of surrogate peptides, purification and enrichment of samples, improvement in enzymatic digest efficiency, enrichment of peptides, and use of low rate LC. We review the application of LC-MS technology in the biological analysis of antibody drugs and discuss the prospect of using the LC-MS method for the analysis of antibody drugs.
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Breast cancer is one of the common diseases among women. It is a malignant tumor with a variety of complex mechanisms. Its pathogenesis has not been clearly studied. Physical, chemical and surgical treatments often cause vomiting, nausea, dizziness and headache for women. As compared with traditional treatment, Chinese medicine is characterized by multiple targets, small side effect and good effect in treating breast cancer. In this paper, 85 kinds of Chinese herbal medicines that can treat breast cancer were included. Among them, 69 kinds of Chinese herbal medicines have been included in the 2015 edition of the Chinese Pharmacopoeia, and 16 kinds of Chinese herbal medicines have not been included. The main medicinal ingredients in these Chinese herbal medicines for treatment of breast cancer were alkaloids, glycosides, phenols, terpenes, carbohydrates, volatile oils, coumarins and so on. In addition, these herbal medicines were classified according to their effects in breast cancer. Then, combined with the recent studies at home and abroad, this paper summarized the effect of traditional Chinese medicine(TCM) on breast cancer, including the reversal of multi-drug resistance, the inhibition of metastasis and proliferation, the induction of tumor cell apoptosis, and the arrest of the cell cycle for breast cancer. This paper also explained three pathways for treating breast cancer by TCM, including intervening the tumor cell related apoptosis gene to inhibit breast cancer, inhibiting the expression of P-glycoprotein in the cell membrane to reverse the multi-drug resistance of breast cancer cells, and regulating the related epithelial mesenchymal transition signal pathway to prevent breast cancer cells metastasis and proliferation. In the end, it was concluded that Chinese medicine can reduce the drug resistance and metastasis of breast cancer cells, block the cell cycle of breast cancer cells, and also intervene the expression of apoptotic factors to promote the death of breast cancer cells. The inhibition of breast cancer by Chinese medicine was the result of the common effect of various ingredients. Therefore, Chinese medicine treatment for breast cancer has the unparalleled advantages as compared with chemical and surgical treatment. Chinese medicine is one of our important means to overcome breast cancer.
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?AlM: To investigate repeatability and accuracy of a latest Keratograph for evaluating the tear film stability and to compare its measurements with that of traditional examination methods. ?METHODS: The results of noninvasive tear film break-up time ( Nl-BUT ) including the first tear film break-up time ( BUT-f ) and the average tear film break-up time ( BUT - ave ) were measured by Keratograph. The repeatability of the measurements was evaluated by coefficient of variation ( CV ) and intraclass correlation coefficient ( lCC) . Wilcoxon Signed-Rank test was used to compare Nl-BUT with fluorescein tear film break-up time ( FBUT) to confirm the correlation between Nl-BUT and FBUT, Schirmer l test values. Bland-Altman analysis was used to evaluate consistency. ?RESULTS: The study recruited 48 subjects ( 48 eyes ) (mean age 38. 7±15. 2 years). The CV and lCC of BUT-f were respectively 12. 6% and 0. 95, those of BUT-ave were 9. 8% and 0. 96. The value of BUT-f was lower than that of FBUT. The difference had statistical significance ( 6. 16±2. 46s vs 7. 46±1. 92s, P ?CONCLUSlON: Keratograph can provide Nl-BUT data that has a better repeatability and reliability, which has great application prospects in diagnosis and treatment of dry eye and refractive corneal surgery.
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<p><b>OBJECTIVE</b>To assess the net health effect caused by the consumption of specific marine species based on Benefit-Risk Analysis for Foods (BRAFO)-tiered approach.</p><p><b>METHODS</b>Twenty species were collected from the Zhoushan Archipelago, China. Concentrations of n-3 long-chain polyunsaturated fatty acids, methyl mercury (MeHg), and dioxin-like compounds (DLCs) in the samples were analyzed for benefit risk assessment based on BRAFO-tiered approach.</p><p><b>RESULTS</b>Based on the BRAFO-tiered approach, reference scenario (no intake) and alternative scenario (intake of specific species of 200 g/week) were determined. The exposure to MeHg/DLCs via alternative scenario of all studied species did not exceed provisional tolerable weekly/monthly intake. However, the adult population with high DLCs exposure in China would significantly exceed the upper limit of DLCs via an additional alternative scenario of some species such as Auxis thazard. The results of deterministic computation showed that alternative scenario of all studied species generated clear net beneficial effects on death prevention and child IQ gain.</p><p><b>CONCLUSION</b>The alternative scenario of all studied species could be recommended to population with average DLCs exposure, and the reference scenario of species with relatively high DLCs concentration could be recommended to population exposed to high DLCs.</p>
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Animais , Humanos , China , Dioxinas , Poluentes Ambientais , Ácidos Graxos Ômega-3 , Peixes , Compostos de Metilmercúrio , Medição de Risco , Alimentos Marinhos , Especificidade da EspécieRESUMO
<p><b>OBJECTIVE</b>To observe the effect of Tangke Decoction (TD) on the expression of TGF-beta1/Smad4 of rats with early diabetes and to explore the effect and mechanism of TD against the renal injury induced by diabetes.</p><p><b>METHODS</b>SD rats were randomly divided into the normal control group (n = 12), the model group (n = 10), the Chinese herbs prevented group (n =10), the Chinese herbs treated group (n = 10), and the Western medicine control group (n = 10). TD (18 mg/kg) was given by gastrogavage to rats in the Chinese herbs prevented group immediately after successful modeling for 12 weeks, once daily. At the 4th week of successful modeling, rats in the rest 4 groups were administered by gastrogavage. Equal volume of normal saline was given to rats in the model group and the normal control group. Benazepril suspension (1 mg/kg) was administered by gastrogavage to rats in the Western medicine control group for 8 weeks, once daily. TD (18 mg/kg) was given by gastrogavage to rats in the Chinese herbs treated group for 8 weeks, once daily. The body weight, kidney weight, index of kidney weight, fasting blood sugar, 24 h urinary albumin excretion rate were examined after experiment. The pathological changes of the renal tissue were observed by HE staining, Masson staining, and electron microscope. The expression of renal transforming growth factor-beta1, (TGF-beta1) and Smad4 were detected using immunohistochemical assay.</p><p><b>RESULTS</b>Compared with the normal control group, the body weight of rats decreased significantly; the kidney weight, index of kidney weight, blood sugar, 24 h urinary protein excretion, the urinary albumin excretion rate,TGF-beta1 and Smad4 expression increased significantly in the model group (all P < 0.01). Compared with the model group, the aforesaid indices were improved in each treatment group with statistical difference (P < 0.05, P < 0.01). Compared with the Western medicine control group, the kidney weight, index of kidney weight, blood sugar, 24 h urinary protein excretion, and the urinary albumin excretion rate were obviously improved in the Chinese herbs prevented group (P < 0.01). The renal pathological changes were most obvious in the model group significantly, but they were improved in all treatment groups.</p><p><b>CONCLUSION</b>TD could obviously improve the symptoms of diabetes and down-regulate the expression of renal TGF-beta1 and Smad4 of early diabetic nephropathy rats, which suggested that TD had certain preventive effect on early diabetic nephropathy.</p>
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Animais , Masculino , Ratos , Diabetes Mellitus Experimental , Tratamento Farmacológico , Metabolismo , Medicamentos de Ervas Chinesas , Usos Terapêuticos , Rim , Metabolismo , Ratos Wistar , Proteína Smad4 , Metabolismo , Fator de Crescimento Transformador beta1 , MetabolismoRESUMO
<p><b>OBJECTIVE</b>To analyze the main fatty acids in edible marine fish from Zhoushan, Zhejiang province.</p><p><b>METHODS</b>From September to October 2011, a total of 186 edible marine fish (31 species,6 individual fishes/species) were collected in local markets. Total lipids of edible part were extracted by Folch's method and fatty acids were separated and quantified by gas chromatographic after the homogenization of edible part. The differences of composition of n-6 polyunsaturated fatty acid (n-6 PUFA), n-3 polyunsaturated fatty acid (n-3 PUFA),saturated fatty acid (SFA) and monounsaturated fatty acid (MUFA) among fishes were analyzed.</p><p><b>RESULTS</b>Among the 31 fishes, total lipids were highest in Auxis thazard ((13.2 ± 1.2)g/100 g edible part) and lowest in Thamnaconus modestus ((0.6 ± 0.1)g/100 g edible part). Total n-6 PUFA were highest in Mugil cephalus ((875.7 ± 506.4)mg/100 g edible part) and lowest in Seriola quinqueradiata((2.1 ± 1.9)mg/100 g edible part). Total n-3 PUFA were highest in Auxis thazard ((2623.8 ± 426.1)mg/100 g edible part) and lowest in Scoliodon sorrakowah ((82.0 ± 13.9)mg/100 g edible part). SFA were highest in Trachinotus ovatus((3014.9 ± 379.0)mg/100 g edible part) and lowest in Seriola quinqueradiata ((89.7 ± 5.8)mg/100 g edible part). MUFA were highest in Coilia nasus ((3335.7 ± 383.5)mg/100 g edible part) and lowest in Thamnaconus modestus ((32.1 ± 16.9)mg/100 g edible part).</p><p><b>CONCLUSION</b>There were significant differences of composition of total lipids and of fatty acids among 31 edible marine fish species from Zhoushan.</p>
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Animais , China , Ácidos Graxos , Ácidos Graxos Insaturados , Peixes , Alimentos MarinhosRESUMO
<p><b>OBJECTIVE</b>To assess the distribution frequency of Gly82Ser polymorphism of receptor for advanced glycation end products (RAGR) gene and investigate its association with type 2 diabetic Chinese patients.</p><p><b>METHODS</b>The allele frequencies and genotype distribution of Gly82Ser polymorphism of RAGE gene were compared in a case-control study of 194 type 2 diabetic and 546 non-diabetic subjects. PCR-restriction fragment length polymorphism (PCR-RFLP) was used for detection of the genotype variants.</p><p><b>RESULTS</b>In general Chinese population and type 2 diabetic Chinese patients, the most frequent genotype and allele of RAGR gene Gly82Ser polymorphism were genotype GG and allele G, whose frequency distribution were significantly higher than those in other countries (P<0.01). No significantly difference in the genotype frequencies or allele frequencies of Gly82Ser polymorphism were found between the diabetic patients and non-diabetic subjects (P>0.05).</p><p><b>CONCLUSION</b>Gly82Ser polymorphism of RAGE gene does not demonstrate any association with type 2 diabetes in Chinese patients, but high genotype and allele frequencies of Gly82Ser polymorphism occur in Chinese population and type 2 diabetic Chinese patients.</p>
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Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Substituição de Aminoácidos , Povo Asiático , Genética , China , Diabetes Mellitus Tipo 2 , Etnologia , Genética , Frequência do Gene , Genótipo , Glicina , Genética , Reação em Cadeia da Polimerase , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos , Genética , Serina , GenéticaRESUMO
<p><b>OBJECTIVE</b>To investigate effects of the furosemide, antisterone and hydrochlorothiazide on expression of kidney aquaporin-2 (AQP(2)) gene and urine aquaporin-2 excretion in rats.</p><p><b>METHODS</b>Forty SD rats were randomized into 4 groups, namely the control group, furosemide group, antisterone group and hydrochlorothiazide group with corresponding treatment. Blood and urine samples were collected from the rats for measurement of serum Na(+), urine volume and urine osmolality during medication. Semi-quantitative RT-PCR was performed to measure kidney inner medullary AQP(2) and vasopressin V(2)-R mRNA. Western blotting was employed to detect kidney inner medullary AQP(2) protein expression. Urine AQP(2) concentration was measured by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULT</b>Urine volume and urinary AQP(2) excretion were both increased in rats treated with the 3 drugs as compared with that of the control group. However, urine osmolality was lower in furosemide group but higher inhydrochlorothiazide and antisterone groups than in the control group (P<0.05). The kidney inner medullary AQP(2) mRNA, V(2)-R mRNA and AQP(2) protein expression of furosemide group increased in comparison with that of the control group (Plt;0.05). In hydrochlorothiazide group, however, the above parameters were all decreased (Plt;0.05).</p><p><b>CONCLUSION</b>The three classes of diuretics can all increase the excretion of the urinary AQP(2) but have different effects on the inner medullary AQP(2) mRNA and protein expression in normal rats. Hydrochlorothiazide reduces kidney AQP(2) mRNA and protein expression, while furosemide increased kidney AQP(2) gene expression.</p>