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1.
J Endocrinol Invest ; 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38795312

RESUMO

BACKGROUND: The prevalence of diabetic dyslipidemia has gradually increased worldwide and individuals with hypertriglyceridemia often have a high polygenic burden of triglyceride (TG)-increasing variants. However, the contribution of genetic variants to dyslipidemia in patients with type 2 diabetes (T2D) remains limited. Therefore, in this study, we aimed to investigate the genetic characteristics of longitudinal changes in TG levels among patients with T2D and summarize the genetic effects of polygenic risk score (PRS) on TG trajectory and risk of diabetic complications. METHODS: We conducted a case-control study. A total of 11,312 patients with T2D with longitudinal TG and genetic data were identified from a large hospital database in Taiwan. We then performed a genome-wide association study and calculated the relative PRS. RESULTS: In total, 21 single-nucleotide polymorphisms (SNPs) related to TG trajectory were identified and yielded an area under the receiver operating characteristic curve (ROC) of 0.712 for high TG trajectory risk among Taiwanese patients with T2D. A cumulative genetic effect was observed for high TG trajectory, even when considering the adherence of a lipid-lowering agent in stratified analysis. An increased PRS increases high TG trajectory risk in a logistic regression model (odds ratio = 1.55; 95% confidence interval [CI] = 1.31-1.83 in the validation cohort). The TG-specific PRS was associated with the risk of diabetic microvascular complications, including diabetic retinopathy and nephropathy (with hazard ratios of 1.11 [95% CI = 1.01-1.21, P = 0.027] and 1.05 [95% CI = 1.01-1.1, P = 0.018], respectively). CONCLUSIONS: This study may contribute to the identification of patients with T2D who are at risk of abnormal TG levels and diabetic microvascular complications using polygenic information.

2.
J Dairy Sci ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38825120

RESUMO

The widespread use of milk mid-infrared (MIR) spectroscopy for phenotype prediction has urged the application of prediction models across regions and countries. Spectra standardization is the most effective way to reduce the variability in the spectral signal provided by different instruments and labs. This study aimed to develop different standardization models for MIR spectra collected by multiple instruments, across 2 provinces of China, and investigate whether the standardization method (piecewise direct standardization, PDS, and direct standardization, DS), testing scenario (standardization of spectra collected on the same day or after 7 mo), infrared prediction model accuracy (high or low), and instrument (6 instruments from 2 brands) affect the performance of the standardization model. The results showed that the determination coefficient (R2) between absorbance values at each wavenumber provided by the primary and the secondary instruments increased from less than 0.90 to nearly 1.00 after standardization. Both PDS and DS successfully reduced spectra variation among instruments, and performed significantly better than non-standardization (P < 0.05). However, DS was more prone to overfitting than PDS. Standardization accuracy was higher when tested using spectra collected on the same time compared with those collected 7 mo after (P < 0.05), but great improvement in model transferability was obtained for both scenarios compared with the non-standardized spectra. The less accurate infrared prediction model (for C8:0 and C10:0 content) benefited the most (P < 0.05) from spectra standardization compared with the more accurate model (for total fat and protein content). For spectra collected after 7 mo from standardization, after PDS the RMSE between predictions obtained by different machines decreased on average by 86 and 94% compared with the values before standardization, for C8:0 and C10:0 respectively. The secondary instrument had no significant effect on the R2 between predictions (P > 0.05). The variation in the spectral signal provided by different instruments was successfully reduced by standardization across 2 provinces in China. This study lays the foundations for developing a national MIR spectra database to provide consistent predictions across provinces to be used in dairy farm management and breeding programs in China. Besides, this provides opportunities for data exchange and cooperation at international levels.

3.
Br Poult Sci ; : 1-11, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39345106

RESUMO

1. This study evaluated the effectiveness of different types of acidifiers on reproductive performance, body weight loss and plasma biochemical indices of breeding pigeons as well as on growth performance, carcass characteristics, meat quality and plasma biochemical indices of squabs.2. In a 45 d trial, 144 pairs of European white Mimas pigeons were selected and randomly divided into three experimental groups. Three groups of pigeons were fed plain pigeon grit (NC), pigeon grit supplemented with 5% single acidifier (SAG) and pigeon grit supplemented with 5% combined acidifiers (CAG).3. Supplementing with SAG and CAG significantly increased the weight gain in male pigeons from 1-12 d of incubation. However, SAG and CAG had no significant effect on the feed intake of breeding pigeons during incubation, but significantly increased total feed intake of breeding pigeons during the lactation period. Breeder pigeons fed SAG and CAG had significantly higher egg-laying rate at 40 d. In addition, feeding SAG and CAG significantly increased growth rate and slaughter weight of squabs, but SAG reduced the diameter of pectoral muscle fibres. Biochemical indices showed that feeding SAG and CAG improved metabolism and increased the liver function of breeder pigeons and squabs.4. In conclusion, supplementing pigeon grit with acidifiers increased feed intake of breeding pigeons during lactation, protected liver function, enhanced reproductive performance and promoted the growth and development of squabs.


Supplementation with single acidifier and combined acidifier is healthy for both breeding pigeons and squabs.Supplementation with single acidifier and combined acidifier can improve the egg-laying rate of breeding pigeons.Supplementation with single acidifier and combined acidifier can improve the growth rate of squabs.Supplementation single acidifier and combined acidifier helps to protect the liver and reduce liver damage of breeding pigeons and squabs.

4.
Zhonghua Bing Li Xue Za Zhi ; 53(7): 716-721, 2024 Jul 08.
Artigo em Zh | MEDLINE | ID: mdl-38955704

RESUMO

Objectives: To investigate the mutation of PIK3CA in colorectal cancer and to analyze their clinicopathological features, and evaluate their role in clinical treatment and prognostication. Methods: A total of 128 paraffin-embbeded tissue samples of colorectal cancer from Shanxi Cancer Hospital from 2018 to 2021 were collected. DNA was extracted from the samples, and next-generation sequencing (NGS) was used to detect PIK3CA mutation. The relationship between PIK3CA mutation, their clinicopathological features, and prognosis were analyzed. Results: Among the 128 colorectal cancer samples, there were 75 males and 53 females; with aged range 32-86 years, median 61.5 years, 27 (21.09%) had PIK3CA mutations. Colorectal cancer with PIK3CA mutation was more likely to occur in male patients (P=0.007), which was related to tumor site (P=0.032), tumor size (P=0.029) and TP53 wild-type (P=0.001). The common site mutations of PIK3CA mostly occurred in tumors with tumor mutation burden≥10 Muts/Mb (P=0.031).PIK3CA mutation had no significant effect on the survival prognosis of patients, but the efficacy of anti-angiogenic therapy was poor in these patients. Conclusions: PIK3CA mutation is a common mutation in colorectal cancer and plays an important role in the occurrence and development of colorectal cancer. PIK3CA mutation may lead to resistance to anti-angiogenic drugs in colorectal cancer, but its impact on survival and prognosis to patients needs further study.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases , Neoplasias Colorretais , Sequenciamento de Nucleotídeos em Larga Escala , Mutação , Humanos , Classe I de Fosfatidilinositol 3-Quinases/genética , Masculino , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Pessoa de Meia-Idade , Idoso , Prognóstico , Adulto , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico
5.
Zhonghua Bing Li Xue Za Zhi ; 53(2): 149-154, 2024 Feb 08.
Artigo em Zh | MEDLINE | ID: mdl-38281782

RESUMO

Objective: To explore the correlation between MYB/NFIB gene fusion and clinicopathological features such as tumor grade and prognosis of head and neck adenoid cystic carcinoma (ACC), and to assess the concordant rate of fluorescent in situ hybridization (FISH) with MYB and NFIB immunohistochemistry. Methods: FISH detection of MYB/NFIB gene fusion was performed on 48 head and neck ACC cases and 15 non-ACC salivary gland tumors at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China during April 2014 and January 2020. ACC cases were divided into grade Ⅰ-Ⅱ, grade Ⅲ and high-grade transformation, according to pathological grading criteria. Prognosis, FISH results and other clinicopathological characteristics were analyzed. MYB and NFIB immunohistochemistry was performed on the 48 ACC and 15 non-ACC cases. The diagnostic accuracy of FISH and immunohistochemistry was compared. Results: FISH detected MYB/NFIB gene fusion in 41.7% (20/48) of the ACC. Its positive rate was inversely correlated with higher pathological grades (P=0.036). The higher histological grade was linked to worse progression-free survival (P=0.024), whereas there was no correlation between the status of gene fusion detected by FISH and progression-free survival (P=0.536). FISH didnot detect MYB/NFIB gene fusion in 15 non-ACC salivary gland tumors The specificity of diagnosing ACC is 100% for both FISH detection of gene fusion and immunohistochemical detection of MYB expression. However, the sensitivity for both methods was only about 41.7%, respectively. By combining FISH and MYB immunohistochemistry, the sensitivity for diagnosing ACC was increased to 66.7%. Conclusions: MYB/NFIB gene fusion has a lower detection rate in grade Ⅲ ACC and high-grade transformation ACC. Meanwhile gene fusion status is not correlated with prognosis. The sensitivity for diagnosing ACC can be improved by combining FISH and MYB immunohistochemistry.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias das Glândulas Salivares , Humanos , Carcinoma Adenoide Cístico/diagnóstico , Carcinoma Adenoide Cístico/genética , Hibridização in Situ Fluorescente , Proteínas de Fusão Oncogênica/genética , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/genética , Fusão Gênica , Prognóstico , Fatores de Transcrição NFI/genética
6.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(9): 801-806, 2024 Sep 12.
Artigo em Zh | MEDLINE | ID: mdl-39266477

RESUMO

Objective: To study the impact of diabetes on bronchiectasis. Methods: From January 1 2017 to December 31 2021, data of 1 310 inpatients with bronchiectasis were retrospectively collected from Shanghai Pulmonary Hospital, Tongji University. This cohort inclueded 78 patients with bronchiectasis and diabetes (bronchiectasis-diabetes group) and 1 232 patients of bronchiectasis without diabetes (simple bronchiectasis group). To mitigate confounding variables, 269 patients with bronchiectasis but without diabetes (bronchiectasis non-diabetes group) were matched with 78 patients of bronchiectasis with diabetes (bronchiectasis-diabetes group) using the propensity score method in a 1∶4 ratio. A comparative analysis of clinical characteristics, laboratory test results, pathogenic infections, and disease severity was performed between the two groups. Analysis of continuous variables was performed using either a t-test or non-parametric test, while categorical data was assessed using the chi-square test. Results: The mean age of individuals in the bronchiectasis-diabetes group (62.99±8.09 years) was significantly higher than that of subjects in the simple bronchiectasis group (57.05±13.07 years) (t=-6.012, P<0.001). After propensity score matching, the pre-albumin level in the bronchiectasis-diabetes group (188.44±71.65 g/L) was found to be lower than in the bronchiectasis non-diabetes group (208.17±62.50 g/L) (t=2.023, P=0.044). In addition, the hospitalization cost for the bronchiectasis-diabetes group [1.59 (1.34, 2.15) Ten thousand yuan] was higher than that in the bronchiectasis non-diabetes group [1.39 (1.23, 1.62) Ten thousand yuan] (U=-3.744, P<0.001).The severity of mMRC in the bronchiectasis-diabetes group was significantly higher than that in the bronchiectasis non-diabetes group (χ2=25.392, P<0.001), and the frequency of previous hospitalization due to aggravation and acute exacerbation within the previous year were higher than in bronchiectasis non-diabetes group (χ2=34.031, 40.841, respectively, P<0.001). In additional, the BSI score was significantly increased in patients with bronchiectasis-diabetes compared to those with bronchiectasis non-diabetes (8.07±4.07 vs. 10.44±3.82) (P<0.001). Furthermore, fasting blood glucose concentration, urine glucose level, and BSI score exhibited positive correlations, whereas pre-albumin concentration showed a negative correlation with the BSI score (all P<0.05). Conclusion: Compared to those without diabetes, patients of bronchiectasis with diabetes have poorer nutritional status, more severe symptoms, increased risk of acute exacerbation, higher BSI score severity, and greater financial burden.


Assuntos
Bronquiectasia , Humanos , Bronquiectasia/etiologia , Bronquiectasia/fisiopatologia , Pessoa de Meia-Idade , Feminino , Masculino , Diabetes Mellitus , Idoso , Pontuação de Propensão , Complicações do Diabetes , Fatores de Risco
7.
Zhonghua Jie He He Hu Xi Za Zhi ; 47(5): 419-429, 2024 May 12.
Artigo em Zh | MEDLINE | ID: mdl-38706063

RESUMO

Objective: To assess the compliance with a lung protective ventilation strategy and to evaluate the relationship with prognosis in patients with acute respiratory distress syndrome (ARDS). Methods: In the prospective multicenter cohort study (CHARDS), patients with ARDS undergoing invasive mechanical ventilation were enrolled to collect essential information, mechanical ventilation data, and prognostic data. Compliance was operationally defined as tidal volume ≤7 ml/kg predicted body weight (PBW) or plateau pressure ≤30 cmH2O or driving pressure≤15 cmH2O. Tidal volume data collected 7 days prior to ventilation after ARDS diagnosis were categorized into four groups: standard group (Group A, 100% compliance), non-standard group (Group B, 50%-99% compliance, Group C,1%-49% compliance,and Group D,totally non-compliant). Plateau pressure and drive pressure measurements were recorded on the first day. Stepwise regression, specifically Logistics regression, was used to identify the factors influencing ICU survival. Results: A total of 449 ARDS patients with invasive mechanical ventilation were included; the proportion of mild, moderate, and severe patients was 71 (15.8%), 198 (44.1%) and 180 (40.1%), respectively. During the first 7 days, a total of 2880 tidal volume measurements were recorded with an average tidal volume of (6.89±1.93) ml/kg PBW. Of these measurements, 53.2% were found to be≤7 ml/kg PBW. The rates of compliance with lung protective mechanical ventilation were 29.8% (134/449), 24.5% (110/449), 23.6% (106/449), and 22% (99/449) in groups A, B, C, and D, respectively. In the standard group, the tidal volume for mild ARDS patients was 18.3%(13/71), while it was 81.7%(58/71)in the non-standard group. Similarly, in patients with moderate ARDS, the tidal volume was 25.8% (51/198) in the standard group, while it was 74.2% (147/198) in the non-standard group. Finally, in patients with severe ARDS, the tidal volume was 38.9% (70/180) in the standard group, while it was 61.1% (110/180) in the non-standard group. Notably, the compliance rate was higher in patients with moderate and severe ARDS in group A compared to patients with mild and moderate ARDS (18.3% vs. 25.8% vs. 38.9%, χ2=13.124, P=0.001). Plateau pressure was recorded in 221 patients, 95.9% (212/221) patients with plateau pressure≤30 cmH2O, and driving pressure was recorded in 207 patients, 77.8% (161/207) patients with a driving pressure ≤15 cmH2O.During the first 7 days, the mortality rate in the intensive care unit (ICU) was lower in the tidal volume standard group compared to the non-standard group (34.6% vs. 51.3%, χ2=10.464, P=0.001). In addition, the in-hospital mortality rate was lower in the standard group compared to the non-standard group (39.8% vs. 57%, χ2=11.016, P=0.001).The results of the subgroup analysis showed that the mortality rates of moderate and severe ARDS patients in the standard group were significantly lower than those in the non-standard group, both in the ICU and in the hospital (all P<0.05). However, there was no statistically significant difference in mortality among mild ARDS patients (all P>0.05). Conclusions: There was high compliance with recommended lung protective mechanical ventilation strategies in ARDS patients, with slightly lower compliance in patients with mild ARDS, and high compliance rates for plateau and drive pressures. The tidal volume full compliance group had a lower mortality than the non-compliance group, and showed a similar trend in the moderate-to-severe ARDS subgroup, but there was no significant correlation between compliance and prognosis in patients with mild ARDS subgroup.


Assuntos
Respiração Artificial , Síndrome do Desconforto Respiratório , Humanos , Síndrome do Desconforto Respiratório/terapia , Respiração Artificial/métodos , Estudos Prospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Unidades de Terapia Intensiva , Prognóstico , Adulto , Fidelidade a Diretrizes/estatística & dados numéricos , Complacência Pulmonar
8.
Zhonghua Wai Ke Za Zhi ; 62(10): 924-929, 2024 Aug 26.
Artigo em Zh | MEDLINE | ID: mdl-39183017

RESUMO

Objective: To summarize the experience of robot-assisted enucleation of tumors located in uncinate process of pancreas. Methods: This is a retrospective case series study. The clinical data of patients with robot-assisted enucleation of tumors located in the uncinate process of pancreas at the Department of Gastroenterology and Pancreatic Surgery,Zhejiang Provincial People's Hospital from June 2019 to December 2023 were retrospectively analyzed. A total of 16 cases were enrolled,including 10 males and 6 females,with an age(M(IQR)) of 56(21)years (range: 28 to 77 years),and body mass index of 22.4(2.3)kg/m2 (range:19.8 to 25.6 kg/m2). Follow-up was asked every 6 to 12 months after the first 3-month postoperative follow-up through out-patient service or via telephone. Results: In total 16 cases,there were 11 cases with pancreatic enucleation,and 5 cases with resection of the uninate process. The operation time was 70(60) minutes (range: 40 to 165 minutes),and the blood loss was 30(13)ml (range: 10 to 80 ml). The rate of pancreatic fistula was 5/16. The length of stay were 8(6)days (range: 5 to 33 days). The pathological finding included non-functional neuroendocrine tumor(n=3),insulinoma(n=2),introductal papillary mucinous neoplasm (n=5),solid pseudopapillary neoplasm (n=2),mucinous cystadenoma (n=1),serous cystadenoma (n=2),pseudocyst (n=1). Follow-up as of March 12, 2024, the follow-up time was 16(12)months (range: 3 to 41 months). All patients had no new onset diabetes and no dyspepsia. Conclusion: Robot-assisted surgical system can be used for local resection of uncinate process tumors of pancreas,and the quality of life of patients can be improved.

9.
Zhonghua Yan Ke Za Zhi ; 60(1): 43-48, 2024 Jan 11.
Artigo em Zh | MEDLINE | ID: mdl-38199767

RESUMO

Objective: To describe clinical characteristics and surgical outcomes of pediatric epiretinal membranes (ERMs) without specific etiologies. Methods: Medical data of a cohort of pediatric patients (≤14 years) who had ERMs without specific etiologies, underwent surgical removal from January 2019 to September 2021, and were followed up for at least 12 months were retrospectively reviewed. Age at presentation, chief complaints, color fundus photographs, optical coherence tomographic images, preoperative and postoperative visual acuities, anatomical changes, and postoperative complications were assessed. Results: There were 14 patients (17 eyes), including 5 females (6 eyes) and 9 males (11 eyes). The mean age at surgery was 6.31±2.91 years, and the follow-up duration was 17.3±9.5 months. Eight patients were found to have low vision in the school physical examination. Fifteen eyes had an appearance of cellophane macular reflex on fundus images. On optical coherence tomographic images, 10 eyes had"taco"folds, and 7 eyes had"ripple"folds. Five eyes had ellipsoid zone disruptions, while 12 eyes had ellipsoid zone integrity. The preoperative and postoperative best-corrected visual acuities in logMAR were 0.532±0.302 and 0.340±0.298. One patient suffered traumatic cataract and secondary retinal detachment postoperatively, and after further vitrectomy, the retina became attached. Conclusion: Pediatric ERMs without specific etiologies were mostly found in school-age children with cellophane macular reflex and"taco"folds. Vitrectomy may result in both potential visual acuity and macular anatomical improvements.


Assuntos
Membrana Epirretiniana , Feminino , Masculino , Humanos , Criança , Membrana Epirretiniana/cirurgia , Celofane , Estudos Retrospectivos , Retina , Resultado do Tratamento
10.
J Endocrinol Invest ; 46(9): 1815-1824, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36856982

RESUMO

AIM: To explore the specific association between sarcopenia and prediabetes based on large population samples. METHODS: A total of 16,116 U.S. adults aged 20-59 with dual energy X-ray absorptiometry (DXA) was identified from the National Health and Nutrition Examination Surveys (NHANES). Sarcopenia was defined according to appendicular skeletal muscle mass (ASM) adjusted for body mass index (BMI). Multivariable binary logistic regression models were used to ascertain odds ratios (ORs) for developing prediabetes. Stratified analyses were also performed. RESULTS: Prevalence of prediabetes was higher in the sarcopenia group (n = 1055) compared with the non-sarcopenia group (n = 15,061) (45.50% vs 28.74%, P < 0.001). Sarcopenia was strongly associated with an increased risk of prediabetes after full adjustment (OR = 1.21, 95CI%: 1.05, 1.39, P = 0.009). In the stratified analysis, this association remained significant independent of obesity, triglycerides, and low-density lipoprotein cholesterol levels. When sarcopenia subjects combined with obesity especially central obesity, the risk of prediabetes was the highest (OR = 2.63, 95CI%: 2.22, 3.11, P < 0.001). Furthermore, a greater proportion of any of impaired glucose tolerance (IGT) individuals was observed in the sarcopenia group compared to the non-sarcopenia group among prediabetes population (41.72% vs 24.06%, P < 0.001). CONCLUSIONS: Sarcopenia was positively associated with prevalent prediabetes especially IGT in the non-elderly. Moreover, synergistic interactions between the sarcopenia and obesity could greatly increase the risk of prediabetes.


Assuntos
Intolerância à Glucose , Estado Pré-Diabético , Sarcopenia , Adulto , Humanos , Pessoa de Meia-Idade , Estado Pré-Diabético/complicações , Estado Pré-Diabético/epidemiologia , Inquéritos Nutricionais , Sarcopenia/complicações , Sarcopenia/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/diagnóstico , Absorciometria de Fóton , Intolerância à Glucose/complicações , Índice de Massa Corporal , Prevalência , Músculo Esquelético
11.
J Endocrinol Invest ; 46(5): 869-882, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36282471

RESUMO

PURPOSE: Type 2 diabetes mellitus (T2DM) with distal symmetric polyneuropathy (DSPN) is a disease involving the nervous system caused by metabolic disorder, while the metabolic spectrum and key metabolites remain poorly defined. METHODS: Plasma samples of 30 healthy controls, 30 T2DM patients, and 60 DSPN patients were subjected to nontargeted metabolomics. Potential biomarkers of DSPN were screened based on univariate and multivariate statistical analyses, ROC curve analysis, and logistic regression. Finally, another 22 patients with T2DM who developed DSPN after follow-up were selected for validation of the new biomarker based on target metabolomics. RESULTS: Compared with the control group and the T2DM group, 6 metabolites showed differences in the DSPN group (P < 0.05; FDR < 0.1; VIP > 1) and a rising step trend was observed. Among them, phenylacetylglutamine (PAG) and sorbitol displayed an excellent discriminatory ability and associated with disease severity. The verification results demonstrated that when T2DM progressed to DSPN, the phenylacetylglutamine content increased significantly (P = 0.004). CONCLUSION: The discovered and verified endogenous metabolite PAG may be a novel potential biomarker of DSPN and involved in the disease pathogenesis.


Assuntos
Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Polineuropatias , Humanos , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/etiologia , Polineuropatias/complicações , Biomarcadores , Metabolômica
12.
Adv Exp Med Biol ; 1398: 267-279, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36717500

RESUMO

Disruption of water and electrolyte balance is frequently encountered in clinical medicine. Regulating water metabolism is critically important. Diabetes insipidus (DI) presented with excessive water loss from the kidney is a major disorder of water metabolism. To understanding the molecular and cellular mechanisms and pathophysiology of DI and rationales of clinical management of DI is important for both research and clinical practice. This chapter will first review various forms of DI focusing on central diabetes insipidus (CDI) and nephrogenic diabetes insipidus (NDI). This is followed by a discussion of regulatory mechanisms underlying CDI and NDI, with a focus on the regulatory axis of vasopressin, vasopressin receptor 2 (V2R) and the water channel molecule, aquaporin 2 (AQP2). The clinical manifestation, diagnosis, and management of various forms of DI will also be discussed with highlights of some of the latest therapeutic strategies that are developed from in vitro experiments and animal studies.


Assuntos
Aquaporinas , Diabetes Insípido Nefrogênico , Diabetes Insípido , Diabetes Mellitus , Animais , Aquaporina 2/genética , Aquaporina 2/metabolismo , Diabetes Insípido Nefrogênico/genética , Diabetes Insípido Nefrogênico/metabolismo , Diabetes Insípido/diagnóstico , Diabetes Insípido/genética , Aquaporinas/genética , Aquaporinas/metabolismo , Rim/metabolismo , Água/metabolismo , Mutação , Receptores de Vasopressinas/genética , Receptores de Vasopressinas/metabolismo
13.
J Integr Neurosci ; 22(6): 145, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-38176940

RESUMO

Fluctuations in mechanical force vectors within living cells can substantially influence the behavior and functions of proteins. Tau protein can spontaneously be raptured and entangled in refolding under picoNewton compressive forces that are biologically available in a living cell: a hidden aggregation pathway due to stress and crowding. Our findings were achieved through a customized modification of atomic force microscopy (AFM) for single-molecule manipulation. This previously hidden phenomenon of proteins rupturing collectively while subsequently and spontaneously refolding into a complex entangled conformation, distinct from the Tau protein's folded or unfolded states, could potentially explain the early-event initiation of the aggregation of the Tau protein seen in various neurodegenerative diseases. This article introduces our recent discovery of the missing Tau protein property that is of significant relevance to the Tau protein and neurodegenerative disease research and medical treatment, aiming to stimulate the collective observation and a new perspective on the Tau aggregation mechanism and disease mechanism studies.


Assuntos
Doenças Neurodegenerativas , Proteínas tau , Humanos , Proteínas tau/metabolismo , Agregados Proteicos , Proteínas
14.
Br Poult Sci ; 64(1): 74-80, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36069737

RESUMO

1. Methyltransferase-like 21C (METTL21C) and insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) play important roles in the proliferation of chicken myoblasts. However, it remains unclear whether there is protein-protein interaction between METTL21C and IGF2BP1 to regulate proliferation of chicken myoblasts.2. In this study, the Igf2bp1 gene was amplified from cDNA of liver tissue of Lueyang black-bone chicken to construct the overexpression vector HA-Igf2bp1. The HA-Igf2bp1 and Flag-Mettl21c vectors were individually transfected and co-transfected into HEK293T, respectively. Co-immunoprecipitation (Co-IP) assay indicated a protein-protein interaction between METTL21C and IGF2BP1.3. Using the Western blotting and LC-MS/MS, it was found that METTL21C could mediate the lysine methylation modification of IGF2BP1. Furthermore, the His-tagged overexpression vector HA-Igf2bp1-His was constructed, transfected and co-transfected with Flag-Mettl21c into HEK293T. His-tagged IGF2BP1 was purified by nickel ion affinity chromatography. Western blotting revealed that IGF2BP1 was successfully purified, and the trimethylation modification level of co-transfection group was significantly elevated compared with the single-transfection Igf2bp1 group.4. Mettl21c and Igf2bp1 overexpression vectors were transfected and co-transfected into primary chicken myoblasts, respectively. The results of 5-ethynyl-2'-deoxyuridine assay and the expression level of Pax7 and MyoD indicated that overexpression of Igf2bp1 alone inhibited the chicken myoblast proliferation, whereas co-expression of Mettl21c and Igf2bp1 eliminated the inhibitory effects of Igf2bp1, thereby favouring cell proliferation and differentiation.5. The results, for the first time, revealed that METTL21C mediated the lysine trimethylation modification of IGF2BP1 to regulate the proliferation of chicken myoblasts, which provided a new insight into in-depth analysis of the molecular mechanism of METTL21C methylation involved in regulating the growth and development of skeletal muscle in Lueyang black-bone chicken.


Assuntos
Galinhas , Lisina , Animais , Humanos , Galinhas/genética , Lisina/metabolismo , Lisina/farmacologia , Cromatografia Líquida/veterinária , Células HEK293 , Espectrometria de Massas em Tandem/veterinária , Mioblastos/fisiologia , Proliferação de Células/genética
15.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(4): 702-707, 2023 Aug 18.
Artigo em Zh | MEDLINE | ID: mdl-37534655

RESUMO

OBJECTIVE: To define the clinical factors that influence local recurrence and survival in patients with lower gingival squamous cell carcinoma (LGSCC) and determine whether bone invasion is an independent prognostic factor for them. METHODS: A total of 104 patients with LGSCC hospitalized in Peking University Stomatology Hospital from June 2013 to December 2015 were enrolled in this retrospective study.All the patients were followed-up for more than 3 years.The degree of bone invasion was assessed using preoperative imaging data (CT and panoramic radiograph).The degree of bone invasion was divi-ded into four categories: no bone invasion, invasion of cortical bone, invasion of bone marrow cavity, and invasion of the mandibular canal.According to the central position of tumor, it was divided into two types: anterior mandibular invasion (anterior region of the mental foramen) and posterior mandibular invasion (posterior region of the mental foramen). RESULTS: of different invasion depth groups were compared using Mann-Whitney U test.P value < 0.05 was considered to be statistically significant.Kaplan-Meier survival analysis method was used to draw survival curve, and COX regression was used to explore the risk ratio (HR) and 95% confidence interval (CI) of prognostic factors of LGSCC. RESULTS: The follow-up results showed that the 1-, 3-, and 5-year survival rates of LGSCC in this group were 91%, 84%, 82%, respectively.32.7%(34/104) of patients had cervical lymph node metastasis.The cervical lymph node metastasis rate of the anterior segment of the mandible was 12.5%(2/16), and 36.4%(32/88) for the posterior segment of the mandible (P < 0.05).Univariate and multivariate COX analysis showed that the N stage and local recurrence were the prognostic factors of LGSCC patients (P < 0.05). CONCLUSION: As the degree of mandibular invasion increases, the prognosis of patients with mandibular gum cancer becomes worse.N stage and local recurrence are prognostic risk factors for LGSCC.The incidence of cervical lymph node metastasis for LGSCC is related to the primary tumor location.It is concluded that tumors located at the posterior of the mandible might be more prone to cervical lymph node metastasis than the anterior of the mandible.Thus various levels of cervical lymph node dissection strategies should be adopted for different sites of LGSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Gengivais , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Gengivais/patologia , Estudos Retrospectivos , Prognóstico , Metástase Linfática
16.
Acta Orthop Belg ; 89(1): 51-58, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37294985

RESUMO

Elderly individuals are often affected by osteoporosis and have poor stability after fracture reduction. Moreover, there is still controversy regarding the clinical effects of the treatment for unstable intertrochanteric fractures in the elderly. The Cochrane, Embase, PubMed, and other databases were searched, and a meta-analysis of the literature on the treatment of unstable intertrochanteric fractures of the elderly with InterTan, PFNA, and PFNA-II was conducted. Seven studies were screened, with a total of 1236 patients. Our meta-analysis results show that InterTan is not significantly different from PFNA in terms of operation and fluoroscopy times, but it takes longer than PFNA-II. In terms of postoperative screw cut, pain, femoral shaft fracture, and secondary operations, InterTan is superior to PFNA and PFNA-II. Conversely, in terms of intraoperative blood loss, hospital stay, and postoperative Harris score, there is no significant difference between InterTan and PFNA and PFNA-II. Compared to PFNA and PFNA-II, InterTan internal fixation has advantages in the treatment of unstable intertrochanteric fractures in elderly individuals in terms of screw cutting, femoral shaft fractures, and secondary operations. However, InterTan operation and fluoroscopy times take longer than PFNA and PFNA-II.


Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Fraturas do Quadril , Humanos , Idoso , Pinos Ortopédicos , Fraturas do Quadril/cirurgia , Fixação Interna de Fraturas/métodos , Fraturas do Fêmur/cirurgia , Parafusos Ósseos , Resultado do Tratamento , Fixação Intramedular de Fraturas/métodos , Estudos Retrospectivos
17.
Zhonghua Jie He He Hu Xi Za Zhi ; 46(7): 697-699, 2023 Jul 12.
Artigo em Zh | MEDLINE | ID: mdl-37402660

RESUMO

Some patients who present with a "fever" may only have a localized increase in body surface temperature, while their core body temperature remains normal. This phenomenon is commonly referred to as pseudo fever. A retrospective analysis of clinical data from January 2013 to January 2020 at our fever clinic showed that 66 adolescents were diagnosed with pseudo fever. These patients typically showed a gradual increase in axillary temperature after their cold symptoms had disappeared. Most patients reported no significant complaints other than mild dizziness. Laboratory tests showed no significant abnormalities, and antipyretics were ineffective in lowering their body temperature. Pseudo fever is a relatively independent clinical phenomenon that is distinct from functional fever or simulated fever, and its underlying mechanism remains to be studied.


Assuntos
Antipiréticos , Febre , Humanos , Adolescente , Estudos Retrospectivos , Febre/diagnóstico , Temperatura Corporal
18.
Artigo em Zh | MEDLINE | ID: mdl-37667155

RESUMO

Objective: To analyze the change trends and risk factors of mesothelioma disease burden in Jiangsu Province from 1990 to 2019. Methods: In January 2022, using the 2019 Global Burden of Disease Study Data, the Joinpoint regression model was used to analyze the change trends of incidence, mortality, disable-adjusted life years (DALY) and premature mortality of mesothelioma residents in Jiangsu Province from 1990 to 2019, and the attribution level of mesothelioma risk factors was estimated by population attributing fraction. Results: The standardized incidence rates of mesothelioma in Jiangsu Province from 1990 to 2019 ranged from 0.07/10(5) to 0.09/10(5), with an average annual percentage change (AAPC) of -1.1% (t=-13.56, P<0.001). AAPCs in males and females were -0.3% (t=-2.18, P=0.029) and -1.6% (t=-11.39, P<0.001), respectively. The standardized mortality rates of mesothelioma ranged from 0.07/10(5) to 0.09/10(5), the AAPC was -1.1% (t=-12.23, P<0.001), AAPC was -1.6% (t=-14.09, P<0.001) for females, and there was no significant change in males (t=-1.83, P=0.068). The premature mortality was 0.004%-0.006%, the AAPC was -1.0% (t=-4.40, P<0.001), AAPC was -1.7% (t=-13.72, P<0.001) for females, and there was no significant change in males (t=-0.68, P=0.495). The standardized DALY rates ranged from 1.86/10(5) to 2.32/10(5), the AAPC was -0.9% (t=-11.08, P<0.001), AAPC was -1.6% (t=-11.05, P<0.001) for females, and there was no significant change in males (t=-0.95, P=0.343). Both the standardized years of life lost (YLL) rate and the standardized years lived with disability (YLD) rate showed a decreasing trend, and the AAPCs were -0.9% (t=-7.66, P<0.001) and -1.0% (t=-12.88, P<0.001), respectively. The proportion of YLL in DALY was more than 98.5%. Among the risk factors for mesothelioma burden attribution, the AAPC attributed to occupational asbestos exposure of DALY was 1.4% (t=3.43, P=0.001). The AAPC of DALY rate of standardized attribution was -1.7% (t=-12.11, P<0.001) . Conclusion: The overall burden of mesothelioma in Jiangsu Province is decreasing, occupational asbestos exposure is still the main risk factor of mesothelioma in Jiangsu Province, and early diagnosis and treatment should be strengthened.


Assuntos
Mesotelioma Maligno , Mesotelioma , Exposição Ocupacional , Feminino , Masculino , Humanos , Mesotelioma/epidemiologia , Fatores de Risco , Efeitos Psicossociais da Doença
19.
Osteoporos Int ; 33(10): 2137-2153, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35687123

RESUMO

This systematic review and meta-analysis estimated the global, regional prevalence, and risk factors of osteoporosis. Prevalence varied greatly according to countries (from 4.1% in Netherlands to 52.0% in Turkey) and continents (from 8.0% in Oceania to 26.9% in Africa). Osteoporosis is a common metabolic bone disorder in the elderly, usually resulting in bone pain and an increased risk of fragility fracture, but few summarized studies have guided global strategies for the disease. Therefore, we pooled the epidemiologic data to estimate the global, regional prevalence, and potential risk factors of osteoporosis. We conducted a comprehensive literature search through PubMed, EMBASE, Web of Science, and Scopus, to identify population-based studies that reported the prevalence of osteoporosis based on the World Health Organization (WHO) criteria. Meta-regression and subgroup analyses were used to explore the sources of heterogeneity. The study was registered in the PROSPERO database (CRD42021285555). Of the 57,933 citations evaluated, 108 individual studies containing 343,704 subjects were included. The global prevalence of osteoporosis and osteopenia was 19.7% (95%CI, 18.0%-21.4%) and 40.4% (95%CI, 36.9%-43.8%). Prevalence varied greatly according to countries (from 4.1% in Netherlands to 52.0% in Turkey) and continents (from Oceania 8.0% to 26.9% in Africa). The prevalence was higher in developing countries (22.1%, 95%CI, 20.1%-24.1%) than in developed countries (14.5%, 95%CI, 11.5%-17.7%). Our study indicates a considerable prevalence of osteoporosis among the general population based on WHO criteria, and the prevalence varies substantially between countries and regions. Future studies with robust evidence are required to explore risk factors to provide effective preventive strategies for the disease.


Assuntos
Doenças Ósseas Metabólicas , Osteoporose , Idoso , Doenças Ósseas Metabólicas/etiologia , Saúde Global , Humanos , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Osteoporose/etiologia , Prevalência , Fatores de Risco , Organização Mundial da Saúde
20.
J Chem Phys ; 156(5): 055102, 2022 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-35135261

RESUMO

Conformational dynamics play a crucial role in protein functions. A molecular-level understanding of the conformational transition dynamics of proteins is fundamental for studying protein functions. Here, we report a study of real-time conformational dynamic interaction between calcium-activated calmodulin (CaM) and C28W peptide using single-molecule fluorescence resonance energy transfer (FRET) spectroscopy and imaging. Plasma membrane Ca-ATPase protein interacts with CaM by its peptide segment that contains 28 amino acids (C28W). The interaction between CaM and the Ca-ATPase is essential for cell signaling. However, details about its dynamic interaction are still not clear. In our current study, we used Cyanine3 labeled CaM (N-domain) and Dylight 649 labeled C28W peptide (N-domain) to study the conformational dynamics during their interaction. In this study, the FRET can be measured when the CaM-C28W complex is formed and only be observed when such a complex is formed. By using single-molecule FRET efficiency trajectory and unique statistical approaches, we were able to observe multiple binding steps with detailed dynamic features of loosely bound and tightly bound state fluctuations. The C-domain of CaM tends to bind with C28W first with a higher affinity, followed by the binding of the CaM N-domain. Due to the comparatively high flexibility and low affinity of the N-domain and the presence of multiple anchor hydrophobic residues on the peptide, the N-domain binding may switch between selective and non-selective binding states, while the C-domain remains strongly bound with C28W. The results provide a mechanistic understanding of the CaM signaling interaction and activation of the Ca-ATPase through multiple-state binding to the C28W. The new single-molecule spectroscopic analyses demonstrated in this work can be applied for broad studies of protein functional conformation fluctuation and protein-protein interaction dynamics.


Assuntos
Calmodulina , Transferência Ressonante de Energia de Fluorescência , Sítios de Ligação , Cálcio/metabolismo , Calmodulina/química , Ligação Proteica , Conformação Proteica , Análise Espectral
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