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1.
Biol Pharm Bull ; 46(1): 42-51, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36596525

RESUMO

Lung cancer is the leading cause of cancer-related deaths worldwide, synthesizing and screening of novel anti-cancer drugs provides an alternative therapeutic strategy for renewal of the chemotherapy regimens against lung cancer. To this end, several compounds were synthesized based on the modification of the original myricetin, and their anti-tumor activity against the human non-small cell lung cancer (NSCLC) A549 cells were measured. Among the myricetin derivatives, S4-10 has displayed the highest antitumor efficacy in dose-dependent manner. The proliferation of A549 cells were significantly attenuated by given 6 µM of S4-10 both in vitro and in vivo. Further, the treatment of S4-10 also results in the inhibition of cell migration and invasiveness and the induction of cell apoptosis and G2 cycle arrest of A549 cells. Moreover, we found that S4-10 inhibits the progression of A549 cells through the sterol biosynthetic-cell apoptosis axis. These findings shed the light of developing S4-10 as a promising treatment agent for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Células A549 , Pontos de Checagem do Ciclo Celular , Apoptose , Proliferação de Células , Linhagem Celular Tumoral , Ciclo Celular
2.
Diabetol Metab Syndr ; 15(1): 6, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36647090

RESUMO

BACKGROUND: Experimental and epidemiological studies have indicated an association between diabetes exposure and an increased risk of liver cancer due to nonalcoholic steatohepatitis (NASH). However, to date, no systematic study has specifically investigated the burden of NASH-related liver cancer due to exposure to high fasting plasma glucose (HFPG) levels worldwide. METHODS: The number and rate of deaths and disability-adjusted life years (DALYs) from HFPG-induced NASH-related liver cancer were estimated based on the results of the 2019 Global Burden of Disease Study. The estimated annual percentage changes (EAPCs) for age-standardized death or DALYs rates were calculated using a generalized linear model with a Gaussian distribution to quantify the temporal trends in the global burden of NASH-related liver cancer attributable to HFPG. The strength and direction of the association between the sociodemographic index (SDI) and death or DALY rate were measured using Spearman's rank-order correlation. RESULTS: Globally, approximately 7.59% of all DALY and 8.76% of all mortalities of NASH-related liver cancer in 2019 were due to HFPG. The age-standardized death and DALY rates of NASH-related liver cancer attributable to HFPG increased from 1990 to 2019. The corresponding EAPCs were 0.69 (95% UI 0.48-0.89), and 0.30 (95% UI 0.05-0.56), respectively. This increasing pattern was most obvious in the high- and low-SDI regions. The age-standardized mortality and DALYs rate of NASH-related liver cancer attributable to HFPG varies considerably worldwide, with the middle SDI region having the highest death and DALY rates in 2019 (DALY 0.96 [95% UI 0.23-2.18]; death 0.05 [95% UI 0.01-0.11]). CONCLUSION: The burden of NASH-related liver cancer attributable to HFPG has increased over the past three decades, particularly in regions with high and low SDI.

3.
Proc Natl Acad Sci U S A ; 120(1): e2215660120, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36574679

RESUMO

The aggregation of locusts from solitary to gregarious phases is crucial for the formation of devastating locust plagues. Locust management requires research on the prevention of aggregation or alternative and greener solutions to replace insecticide use, and insect-derived microRNAs (miRNAs) show the potential for application in pest control. Here, we performed a genome-wide screen of the differential expression of miRNAs between solitary and gregarious locusts and showed that miR-8-5p controls the γ-aminobutyric acid (GABA)/glutamate functional balance by directly targeting glutamate decarboxylase (Gad). Blocking glutamate-GABA neurotransmission by miR-8-5p overexpression or Gad RNAi in solitary locusts decreased GABA production, resulting in locust aggregation behavior. Conversely, activating this pathway by miR-8-5p knockdown in gregarious locusts induced GABA production to eliminate aggregation behavior. Further results demonstrated that ionotropic glutamate/GABA receptors tuned glutamate/GABA to trigger/hamper the aggregation behavior of locusts. Finally, we successfully established a transgenic rice line expressing the miR-8-5p inhibitor by short tandem target mimic (STTM). When locusts fed on transgenic rice plants, Gad transcript levels in the brain increased greatly, and aggregation behavior was lost. This study provided insights into different regulatory pathways in the phase change of locusts and a potential control approach through behavioral regulation in insect pests.


Assuntos
Gafanhotos , MicroRNAs , Animais , Gafanhotos/fisiologia , Ácido Glutâmico/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Interferência de RNA , Ácido gama-Aminobutírico/metabolismo
4.
Biochem Biophys Res Commun ; 642: 11-20, 2023 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-36543019

RESUMO

Endothelial progenitor cells (EPCs) are crucial for the maintenance of vascular homeostasis. The dysfunction of EPCs contributes to the endothelial damage in hypertension. Andrographolide (AGP) is a traditional Chinese patent medicine that has been reported to have protective effects on cardiovascular system. However, the effect of AGP on the function of EPCs in hypertension remains unknown. In this study, we aimed to elucidate the effect of AGP on EPCs and the underlying mechanisms. In vivo, the blood pressure and endothelial function (indicated by endothelial dependent vasodilation) of AGP-fed angiotensin II (Ang II)-infused hypertensive mice were examined. In vitro, the function of EPCs isolated from bone marrow were evaluated by tube formation, migration, and adhesion assay. Additionally, a silent information regulator 1 (SIRT1) inhibitor/agonist and a small interfering RNA (si-RNA) targeting SIRT1 were used to determine the pathway involved. The results showed that AGP not only reduced blood pressure, improved endothelial function in hypertensive mice but also restored the dysfunction of EPCs of hypertension in vitro. Mechanistically, AGP up-regulated SIRT1 expression, decreased the Bax/Bcl-2 ratio and the expression level of Cleaved caspase-3, thus inhibiting the apoptosis of Ang II induced EPCs. However, the beneficial effects of AGP on EPCs disappeared after the inhibition or the knockdown of SIRT1. To summarize, this study demonstrates for the first time that AGP improves the dysfunction of EPCs through SIRT1-mediated anti-apoptotic effects. Our findings might provide a novel therapeutic strategy for treating vascular damage in hypertension.


Assuntos
Células Progenitoras Endoteliais , Hipertensão , Camundongos , Animais , Células Progenitoras Endoteliais/metabolismo , Angiotensina II/farmacologia , Sirtuína 1/metabolismo , Células Cultivadas , Hipertensão/metabolismo
5.
Brain Res ; 1798: 148168, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36402179

RESUMO

General anesthesia is one of the most common clinical anesthesia methods. Many studies have suggested that 5-HT plays an important role in the mechanism of general anesthesia, but its basic principle is still unclear. The cerebrospinal fluid (CSF)-contacting nucleus, which we identified 30 years ago, contains a large number of 5-HT neurons. In the brain, many of the nuclei involved in regulating the effects of general anesthesia send projections to the CSF-contacting nucleus. Does the CSF-contacting nucleus and its 5-HT neurons participate in regulating the effect of general anesthesia? This is a new and interesting scientific question. To answer this question, rats underwent general anesthesia by intravenous injection of propofol. During the maintenance of and recovery from general anesthesia, the protein expression of c-Fos in the CSF-contacting nucleus was significantly increased. "Knockout" of this nucleus significantly increased the of number of low-frequency δ waves, which are indicative of deep anesthesia, during general anesthesia maintenance; however, the number of high-frequency ß waves, which indicate consciousness, was significantly decreased. During recovery from general anesthesia, the recovery of the righting reflex (RORR) time of rats with CSF-contacting nucleus ablation was significantly prolonged; activation of 5-HT neurons in the CSF-contacting nucleus promoted recovery from general anesthesia, while inhibition of 5-HT neurons in the CSF-contacting nucleus delayed recovery from general anesthesia. The above results suggest that the CSF-contacting nucleus and its 5-HT neurons play a key role in regulating the effect of intravenous anesthesia, especially during recovery from general anesthesia.


Assuntos
Anestesia Intravenosa , Propofol , Animais , Ratos , Serotonina , Anestésicos Intravenosos/farmacologia , Propofol/farmacologia , Núcleo Celular
6.
Ital J Pediatr ; 48(1): 191, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36461036

RESUMO

BACKGROUND: Renovascular hypertension (RVH) is one of the main causes of hypertensive crisis (HTN-C). It is characterized by acute onset and severe disease, and early diagnosis and treatment are difficult. The objective was to describe the characteristics of RVH and factors associated with RVH leading to HTN-C in children. At present, there are few clinical studies on RVH in children with large cases in China. METHODS: This study retrospectively analyzed the clinical data of inpatient children with RVH. Patients were divided into non-hypertensive crisis (non-HTN-C) group, and HTN-C group according to the first symptoms and blood pressure. Further, HTN-C were classified as hypertensive urgency (HTN-U) or hypertensive emergency (HTN-E). RESULTS: Fifty-four pediatric cases (41 boys and 13 girls) were included. 83.3% of the RVH cases were ≥ 6 years old. Three cases were classified into the non-HTN-C group. Of the 51 HTN-C cases, 18 cases were grouped as HTN-U and 33 as HTN-E. The HTN-U group were mainly asymptomatic (50.0%, 9/18) while the HTN-E group mainly presented with neurological symptoms (72.7%, 24/33). The number of unknown etiology children was 32 (59.2%). The top three known etiologies were Takayasu's arteritis (50.0%, 11/22), congenital renal dysplasia (27.3%, 6/22) and fibromuscular dysplasia (13.6%, 3/22). As for the target organ damage of RVH, patients had a higher prevalence of left ventricular hypertrophy (71.4%, 35/49) and retinopathy (77.8%, 21/27). CONCLUSIONS: Most RVH patients with HTN-C as the first symptoms, especially for males over 6 years old, should be assessed for RVH even if they were asymptomatic. Most asymptomatic patients with RVH already had target organ damage, and symptomatic patients even developed life-threatening complications. As preventive measures, routine monitoring of BP during children's physical examinations is advised.


Assuntos
Hipertensão Renovascular , Masculino , Feminino , Humanos , Criança , Hipertensão Renovascular/diagnóstico , Hipertensão Renovascular/epidemiologia , Hipertensão Renovascular/etiologia , Estudos Retrospectivos , Pressão Sanguínea , China/epidemiologia , Pacientes Internados
7.
PLoS One ; 17(12): e0278415, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36454926

RESUMO

BACKGROUND: The latest guidance on chronic fatigue syndrome (CFS) recommends exercise therapy. Tai Chi, an exercise method in traditional Chinese medicine, is reportedly helpful for CFS. However, the mechanism remains unclear. The present longitudinal study aimed to detect the influence of Tai Chi on functional brain connectivity in CFS. METHODS: The study recruited 20 CFS patients and 20 healthy controls to receive eight sessions of Tai Chi exercise over a period of one month. Before the Tai Chi exercise, an abnormal functional brain connectivity for recognizing CFS was generated by a linear support vector model. The prediction ability of the structure was validated with a random forest classification under a permutation test. Then, the functional connections (FCs) of the structure were analyzed in the large-scale brain network after Tai Chi exercise while taking the changes in the Fatigue Scale-14, Pittsburgh Sleep Quality Index (PSQI), and the 36-item short-form health survey (SF-36) as clinical effectiveness evaluation. The registration number is ChiCTR2000032577 in the Chinese Clinical Trial Registry. RESULTS: 1) The score of the Fatigue Scale-14 decreased significantly in the CFS patients, and the scores of the PSQI and SF-36 changed significantly both in CFS patients and healthy controls. 2) Sixty FCs were considered significant to discriminate CFS (P = 0.000, best accuracy 90%), with 80.5% ± 9% average accuracy. 3) The FCs that were majorly related to the left frontoparietal network (FPN) and default mode network (DMN) significantly increased (P = 0.0032 and P = 0.001) in CFS patients after Tai Chi exercise. 4) The change of FCs in the left FPN and DMN were positively correlated (r = 0.40, P = 0.012). CONCLUSION: These results demonstrated that the 60 FCs we found using machine learning could be neural biomarkers to discriminate between CFS patients and healthy controls. Tai Chi exercise may improve CFS patients' fatigue syndrome, sleep quality, and body health statement by strengthening the functional connectivity of the left FPN and DMN under these FCs. The findings promote our understanding of Tai Chi exercise's value in treating CFS.


Assuntos
Síndrome de Fadiga Crônica , Tai Chi Chuan , Humanos , Síndrome de Fadiga Crônica/diagnóstico por imagem , Síndrome de Fadiga Crônica/terapia , Imageamento por Ressonância Magnética , Projetos Piloto , Estudos Longitudinais , Aprendizado de Máquina
8.
Front Endocrinol (Lausanne) ; 13: 1054046, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36568093

RESUMO

Background: Physical activity (PA) has been associated with decreased incidence of diabetes. However, few studies have evaluated the influence of occupational and domestic PA on the risk of diabetes with a long-term follow-up. We aimed to examine the association between occupational and domestic PA and the risk of diabetes in a long-term prospective cohort of Chinese adults. Methods: A total of 10,343 adults who were followed up in the China Health and Nutrition Survey from 1997 to 2015 were included in our analysis. Occupational and domestical PA were collected with detailed seven-day data and were converted into metabolic equivalents values. Total PA included occupational, domestic, transportation, and leisure time PA. Diabetes cases were identified by self-reported doctor/health professional diagnosis of diabetes, fasting blood glucose ≥7.0 mmol/L, and glycosylated hemoglobin (HbA1c) ≥6.5%. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results: During up to 18 years of follow-up (median 10 years), there were 575 diabetes cases documented. Occupational PA accounted for the majority of total PA (68%) in Chinese population, followed by domestic PA (25%). With adjustments for possible covariates, the highest quartiles of total PA (HR, 0.728 [95% CI, 0.570-0.929]) and occupational PA (HR, 0.765 [95% CI, 0.596-0.982]) were significantly associated with a lower risk of diabetes compared with lowest quartiles. The association between domestic PA and the risk of diabetes was insignificant (P >0.05). Conclusion: Higher levels of occupational PA were associated with a decreased risk of diabetes risk in the Chinese population. Domestic PA was not associated with the incidence of diabetes.


Assuntos
Diabetes Mellitus , Exercício Físico , Humanos , Adulto , Seguimentos , Estudos Prospectivos , Atividade Motora , Diabetes Mellitus/epidemiologia
9.
Front Surg ; 9: 1047975, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36582965

RESUMO

Purpose: Bilateral Wilms tumor (BWT) with renal sinus invasion requires extremely difficult surgical care. This study presents an alternative strategy for tumor removal while at the same time preserving the renal parenchyma. Materials and methods: In total, 9 cases of synchronous BWT were admitted to our hospital between May 2016 to Aug 2020. We retrospectively reviewed the clinical data, surgical technique, and functional and oncological outcomes of these cases. Results: The 9 cases included 3 males and 6 females, with a median age of 12 months at surgery (range 7-40). A total of 14 kidney units had renal sinus invasion (77.8%), whereas multifocal neoplasms were observed in 7 units (38.9%). The local stage distribution revealed 1 kidney with stage I, 10 kidneys with stage II, and 7 kidneys with stage III. Nephron-sparing surgery was performed on 15 kidney units (83.3%), among which 13 (72.2%) underwent bench surgery with autotransplantation (BS-AT), whereas 2 (11.1%) were subjected to tumor enucleation in vivo. Urinary leakage was the most prevalent postoperative complication. We observed negative margins. During the mean follow-up of 28.4 months, 2 patients (22.2%) succumbed from sepsis and renal failure, respectively, whereas the other 7 (77.8%) survived without recurrence. Survivors experienced an estimated glomerular filtration rate of 81 ± 15.4 ml/(min × 1.73 m2). The endpoint renal volume of 9 renal units receiving BS-AT significantly increased (P = 0.02). Conclusions: In summary, the surgical management of bilateral Wilms tumor requires meticulous operative approach and technique. Besides, BS-AT provides a viable alternative to nephron-sparing surgery for BWT patients with renal sinus invasion.

10.
J Pain Res ; 15: 3931-3939, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36540574

RESUMO

Objective: To assess the receptors of TRPV1 and GABAB1 receptors that were colocalized in cerebrospinal fluid contacting nucleus (CSF-contact nucleus) of chronic inflammatory pain (CIP) rats bringing inspiration for reducing chronic pain. Methods: A rat model of CIP was constructed by plantar injection of complete Freund's adjuvant (CFA), and the paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured 1, 3, 5, 7, 10, and 14 days after plantar injection. In the first part of the experiment, rats with CIP were divided into the immunofluorescence group and the coimmunoprecipitation (Co-IP) group (n = 6). Rats in the immunofluorescence group were injected with the retrograde tracer CB conjugated with Alexa Fluor 594 into the lateral ventricle two days before the injection of CFA into the plantar surface of the left paw. Three days later, rats that exhibited hyperalgesia were perfused, and their brains were extracted and used for double immunofluorescence staining of the CSF-contacting nucleus. Rats in the Co-IP group were anesthetized and dissected 3 days after CFA injection, and fresh brain segments containing the CSF-contacting nucleus were collected for Co-IP to assess the colocalization of TRPV1 and GABAB1 in the CSF-contacting nucleus (n = 6). In the second part of the experiment, SD rats were divided into the normal saline group (control group) and the CFA group. Fresh CSF-contacting nucleus-containing tissues were collected for Western blot analysis 3 days after plantar injection to observe the changes in TRPV1 and GABAB1 expression in the CSF-contacting nucleus. Results: TRPV1 and GABAB1 were co-expressed in the CSF-contacting nucleus in rats with CIP, and their expression was upregulated. Conclusion: TRPV1 and GABAB1 in the CSF-contacting nucleus are jointly involved in CIP in rats, and there is a direct or indirect link between TRPV1 and GABAB1.

11.
Front Oncol ; 12: 1022290, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387184

RESUMO

Solid pseudopapillary neoplasm (SPN) of the pancreas is rare relatively low-grade malignant neoplasm and metastasis rarely. Surgical resection is the primary treatment option for primary and metastatic lesions of SPN, and chemotherapy is often ineffective in non-operable SPNs. SPNs are characterized by the presence of somatic CTNNB1 exon 3 mutations, leading to the activation of Wnt/ß-catenin/Cox-2 signal pathway. Here, we firstly report that a refractory liver metastatic pancreatic SPN patient after the failure of multi-line chemotherapies benefited from the Cox-2 selective inhibitor (Celecoxib) based on CTNNB1 D32V mutation detected by next-generation sequencing (NGS), achieving a more than 22-month progression-free survival without any adverse events. Our case provides a potential treatment option for liver metastatic SPN patients with CTNNB1 mutations and highlights the application of NGS for the better treatment decision making.

12.
Diabetes Res Clin Pract ; 194: 110154, 2022 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-36379413

RESUMO

OBJECTIVE: The aim is to assess the relationship between the hemoglobin glycation index(HGI) and dietary patterns, and investigates whether inflammation and oxidative stress mediate the relationship. METHODS: Cross-sectional data were collected from 453 dwellers in a Chinese rural community. Diet was assessed using 24 h food recalls. Based on the energy intake ratio from three macronutrients, dietary patterns were identified by cluster analysis. The HGI was defined as the observed HbA1c minus predicted HbA1c. Indicators of inflammation and oxidative stress were assessed. RESULT: 3 dietary patterns were clustered, namely "fat(n = 100)", "balance(n = 186)" and "carbohydrate(n = 167)". The fat dietary patterns had lower HGI than the other two dietary patterns. TNFα was higher in the carbohydrate dietary pattern. Linear regression analysis suggested that the carbohydrate dietary pattern was correlated with higher HGI levels(ß = 0.204,95 %CI(0.071,0.338)), compared with the fat dietary pattern. The relationship disappeared after accounting for biomarkers of inflammation and oxidative stress. Mediation analyses indicated that TNFα might explain for 19.15 % effects of the carbohydrate dietary pattern on HGI, compared with the fat dietary pattern. CONCLUSION: The carbohydrate dietary pattern had positive associations with HGI and TNFα. TNFα partly mediated the relationship between dietary patterns and HGI.

13.
Cell Rep ; 41(8): 111709, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36417884

RESUMO

The function of fibroblasts in intracerebral hemorrhage (ICH) remains elusive. By targeting Col1α1, a fibroblast-specific marker, we generate mice with ablated Col1α1+ fibroblasts. These mutants show exacerbated blood-brain barrier (BBB) damage, enlarged injury volume, and worse neurological function, highlighting a beneficial role of Col1α1+ fibroblasts in ICH. Echoing these findings, fibroblasts significantly decrease endothelial permeability in an in vitro ICH model. Next, we demonstrate that fibroblasts promote BBB integrity in ICH mainly via up-regulating tight junction proteins without affecting transcytosis-associated proteins, indicating a paracellular rather than transcellular mechanism. A subsequent mechanistic study reveals that the BBB-protective effect of fibroblasts is partially mediated by TIMP metallopeptidase inhibitor 2 (TIMP2). Furthermore, we find that exogenous TIMP2 attenuates BBB disruption in these mutants after ICH. These results suggest that Col1α1+ fibroblasts repair BBB damage in ICH via the paracellular pathway in a TIMP2-dependent manner, and that Col1α1+ fibroblasts and TIMP2 may be targeted in ICH treatment.


Assuntos
Barreira Hematoencefálica , Lesões Encefálicas , Animais , Camundongos , Barreira Hematoencefálica/metabolismo , Hemorragia Cerebral/metabolismo , Transporte Biológico , Fibroblastos/metabolismo
14.
Sci Total Environ ; 859(Pt 1): 160210, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36395845

RESUMO

Formaldehyde (HCHO) is a vital reactive carbonyl compound, which plays an important role in the photochemical process and atmospheric oxidation capacity. However, the current studies on the quantification of HCHO impacts on atmospheric photochemistry in southeast coastal areas of China with an obvious upward trend of ozone remain scarce and unclear, thus limiting the full understanding of formation mechanism and control strategy of photochemical pollution. Here, systematic field campaigns were conducted at a typical coastal urban site with good air quality to reveal HCHO mechanism and effects on O3 pollution mechanism during spring and autumn, when photochemical pollution events still frequently appeared. Positive Matrix Factorization model results showed that secondary photochemical formation made the largest contributions to HCHO (69 %) in this study. Based on the photochemical model, the HCHO loss rates in autumn were significantly higher than those in spring (P < 0.05), indicating that strong photochemical conditions constrain high HCHO levels in certain situations. HCHO mechanism increased the ROx concentrations by 36 %, and increased net O3 production rates by 31 %, manifesting that the reduction of HCHO and its precursors' emissions would effectively mitigate O3 pollution. Therefore, the pollution characteristics and photochemical effects of HCHO provided significant guidance for future photochemical pollution control in relatively clean areas.

15.
Front Endocrinol (Lausanne) ; 13: 994707, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339408

RESUMO

Purpose: An end-of-fast insulin level ≥ 3 µIU/ml, C-peptide level ≥ 0.6 ng/ml, and proinsulin level ≥ 5 pmol/l with end-of-fast glucose level ≤ 3.0 mmol/l have been established as the criteria for endogenous hyperinsulinemic hypoglycemia. However, all these criteria have been proposed based on patients in Western populations. This study aimed to determine the optimal criteria using a large series of Chinese patients. Methods: This retrospective study comprised 144 patients with surgically proven insulinoma and 40 controls who underwent a 72-h fasting test at the Peking Union Medical College Hospital(PUMCH) from 2000 to 2020. Receiver operating characteristic curves were used for analysis. Results: In this series of patients, the optimal diagnostic criteria for endogenous hyperinsulinemic hypoglycemia were insulin ≥ 5.5 µIU/ml, C-peptide ≥ 0.7 ng/ml, and proinsulin ≥ 12 pmol/l with end-of-fast glucose ≤ 2.8 mmol/l; the sensitivity and specificity were 99% and 100% for insulin, 100% and 100% for C-peptide, and 93% and 100% for proinsulin, respectively. The diagnostic efficacy of the criteria based on Western populations was then tested. The sensitivity and specificity of end-of-fast insulin ≥ 3 µIU/ml, C-peptide ≥ 0.6 ng/ml, and proinsulin ≥ 5 pmol/l with end-of-fast glucose ≤ 3.0 mmol/l were 100% and 83%, 100% and 80%, and 97% and 78%, respectively. Conclusions: New and optimized diagnostic criteria for endogenous hyperinsulinemic hypoglycemia in Chinese populations have been proposed, and these criteria yield satisfactory accuracy.


Assuntos
Hiperinsulinismo Congênito , Neoplasias Pancreáticas , Humanos , Proinsulina , Peptídeo C , Estudos Retrospectivos , Jejum , Neoplasias Pancreáticas/diagnóstico , Insulina , Glucose , China/epidemiologia
16.
Medicine (Baltimore) ; 101(42): e31280, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36281156

RESUMO

BACKGROUND: The study aims to provide a comprehensive account of the association between the epidermal growth factor (EGF) + 61A/G polymorphism (rs4444903) and susceptibility to virus-related hepatocellular carcinoma (HCC). METHODS: Electronic searching of the Chinese National Knowledge Infrastructure, Wanfang, Chinese Scientific Journal Database (VIP), PubMed, Web of Science, and Embase was conducted to select eligible studies. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to assess the strength of the association. RESULTS: In this study, a total of 18 articles were included with 2692 cases and 5835 controls for assessing the association between rs4444903 and HCC risk. The pooled results showed that the EGF + 61A/G polymorphism was significantly associated with the risk of virus-related HCC in all genetic models. Stratified analyses were conducted based on ethnicity, study quality, source of controls, type of controls, number of cases and genotyping method. The results showed that EGF + 61A/G polymorphisms significantly affect HCC susceptibility in different stratified populations. High heterogeneity was observed across included studies, and meta-regression analysis demonstrated that race, type of controls, and study quality contribute to the observed heterogeneity. CONCLUSION: This pooled analysis found that EGF + 61A/G polymorphism was significantly associated with the risk of HCC.


Assuntos
Carcinoma Hepatocelular , Hepatite , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Fator de Crescimento Epidérmico/genética , Fator de Crescimento Epidérmico/metabolismo , Neoplasias Hepáticas/patologia , Predisposição Genética para Doença , Fatores de Risco , Vírus de Hepatite/metabolismo , Polimorfismo de Nucleotídeo Único
17.
Front Endocrinol (Lausanne) ; 13: 1002118, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36277706

RESUMO

Aim: This study aimed to explore the relationship between lower-limb muscle mass/visceral fat area and diabetic kidney disease (DKD) progression in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 879 participants with T2DM were divided into 4 groups according to the prognosis of CKD classification from Kidney Disease: Improving Global Outcomes (KDIGO). Rectus femoris cross-sectional area (RFCSA) was measured through ultrasound, and visceral fat area (VFA) was evaluated with bioelectric impedance analysis (BIA). Results: T2DM patients with high to very high prognostic risk of DKD showed a reduced RFCSA (male P < 0.001; female P < 0.05), and an enlarged VFA (male P < 0.05; female P < 0.05). The prognostic risk of DKD was negatively correlated with RFCSA (P < 0.05), but positively correlated with VFA (P < 0.05). Receiver-operating characteristic analysis revealed that the cutoff points of T2DM duration combined with RFCSA and VFA were as follows: (male: 7 years, 6.60 cm2, and 111 cm2; AUC = 0.82; 95% CI: 0.78-0.88; sensitivity, 78.0%; specificity, 68.6%, P < 0.001) (female: 9 years, 5.05 cm2, and 91 cm2; AUC = 0.73; 95% CI: 0.66-0.81; sensitivity, 73.9%; specificity, 63.3%, P < 0.001). Conclusion: A significant association was demonstrated between reduced RFCSA/increased VFA and high- to very high-prognostic risk of DKD. T2DM duration, RFCSA, and VFA may be valuable markers of DKD progression in patients with T2DM. Clinical trial registration: http://www.chictr.org.cn, identifier ChiCTR2100042214.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Masculino , Feminino , Diabetes Mellitus Tipo 2/complicações , Gordura Intra-Abdominal/diagnóstico por imagem , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Biomarcadores , Músculos
18.
Cell Death Dis ; 13(10): 877, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36257938

RESUMO

Long non-coding RNAs (lncRNAs) is known to play vital roles in modulating tumorigenesis. We previously reported that LCAT1, a novel lncRNA, promotes the growth and metastasis of lung cancer cells both in vitro and in vivo. However, the underlying mechanism(s) of LCAT1 as an oncogenic regulator remains elusive. Here, we showed that LCAT1 physically interacts with and stabilizes IGF2BP2, an m6A reader protein, by preventing its degradation via autolysosomes. IGF2BP2 is overexpressed in lung cancer tissues, which is associated with poor survival of non-small cell lung cancer patients, suggesting its oncogenic role. Biologically, IGF2BP2 depletion inhibits growth and survival as well as the migration of lung cancer cells. Mechanistically, the LCAT1/IGF2BP2 complex increased the levels of CDC6, a key cell cycle regulator, by stabilizing its mRNA in an m6A-dependent manner. Like IGF2BP2, CDC6 is also overexpressed in lung cancer tissues with poor patient survival, and CDC6 knockdown has oncogenic inhibitory activity. Taken together, the LCAT1-IGF2BP2-CDC6 axis appears to play a vital role in promoting the growth and migration of lung cancer cells, and is a potential therapeutic target for lung cancer. Importantly, our finding also highlights a previously unknown critical role of LCAT1 in m6A-dependent gene regulation by preventing autolytic degradation of IGF2BP2.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proliferação de Células/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Linhagem Celular Tumoral , Carcinogênese/genética , RNA Mensageiro , Proteínas Nucleares/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ligação a RNA/metabolismo
19.
Med Educ Online ; 27(1): 2136559, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36250891

RESUMO

Medical education assessments are becoming more complex, resulting in the inappropriateness of traditional methods primarily consisting of direct observations, oral examinations, and multiple-choice tests. Advancements in research methods have led to the formation of new modalities, namely performance assessments, which are, on the other hand, always costly in development and implementation. Proposing using the Program Effectiveness and Cost Generalization flow within an assessment context (PRECOG-A), this brief report explores the real financial cost drivers associated with an assessment case in the context of medical education, presents the steps in bridging the effectiveness with its psychometric properties via cost-effectiveness analysis, and evaluates the two-side outcomes for further evaluation decision-making. Referentially providing a framework to investigators and researchers, the illustration of PRECOG-A in this study outlines instructional guidelines for conducting cost-effectiveness analysis in a performance assessment.


Assuntos
Educação Médica , Análise Custo-Benefício , Humanos , Psicometria
20.
ACS Nano ; 16(11): 19328-19334, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36282211

RESUMO

Cytotoxic T lymphocytes (CTLs) are important immune cells, and their activation is a key step for cancer immunotherapy. Precise evaluation of CTL activity in vivo provides a powerful tool for monitoring cancer-immunotherapeutic outcomes, yet it faces tremendous challenges. Herein, by rationally designing a near-infrared (NIR) fluorescence probe Cys(StBu)-Ile-Glu-Phe-Asp-Lys(Cy5.5)-CBT (Cy5.5-CBT) and employing a reduction-instructed CBT-Cys click condensation reaction, we developed the fluorescence "dual quenched" nanoparticles Cy5.5-CBT-NPs for imaging of granzyme B (GraB), a biomarker tightly associated with the tumoricidal activity of CTLs. Upon GraB cleavage, Cy5.5-CBT-NPs disassembled, subtly turning the fluorescence signal "on". With this fluorescence "turn-on" property, Cy5.5-CBT-NPs enabled sensitive and real-time monitoring of GraB-mediated CTL responses against cancer cells in vitro. Animal experiments demonstrated that, at 16 h post injection, the fluorescence imaging signal of Cy5.5-CBT-NPs showed a 3.1-fold increase on the tumor sites of mice treated by an immune-activating drug S-(2-boronoethyl)-L-cysteine hydrochloride. We envision that Cy5.5-CBT-NPs may provide a powerful tool for noninvasive and sensitive evaluation of immunotherapeutic efficacy of cancer in the near future.


Assuntos
Nanopartículas , Neoplasias , Animais , Camundongos , Granzimas , Linfócitos T Citotóxicos , Carbocianinas , Neoplasias/diagnóstico por imagem , Neoplasias/terapia
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