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1.
Front Med ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958922

RESUMO

Corona virus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has affected the whole world. Acquired thrombotic thrombocytopenic purpura (TTP) has been reported after administration of mRNA- or adenoviral vector-based COVID-19 vaccines, including Ad26.COV2-S, BNT162b2, mRNA-1273, and ChAdOx1 nCov-19. However, whether inactivated vaccines, such as CoronaVac, could cause TTP and whether the symptoms in TTPs caused by inactivated vaccines are different from previously reported cases are unknown. In this study, two cases were reported. Both cases developed TTP after the second CoronaVac vaccination shot, but not the first. They demonstrated symptoms of fever, neurological abnormalities, renal dysfunction, thrombocytopenia, and hemolysis. Both patients achieved complete remission through several sessions of plasma exchanges and immune suppression. The incidence of TTP in Nanjing area was analyzed. The number of patients with TTP was 12 in 2019, 6 in 2020, 16 in 2021, and 19 in 2022. To the authors' knowledge, this report is the first report of TTP associated with inactivated COVID-19 vaccine (CoronaVac). The rarity and delayed onset may be due to the relatively milder immune response caused by the inactivated vaccines than mRNA-based ones. Timely plasma exchange is a vital treatment for CoronaVac-related TTP, similar to activated vaccine-related TTP.

2.
Oncogenesis ; 13(1): 23, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38906857

RESUMO

Lacking effective therapeutic targets heavily restricts the improvement of clinical prognosis for patients diagnosed with esophageal squamous cell carcinoma (ESCC). Ubiquitin Specific Peptidase 21 (USP21) is dysregulated in plenty of human cancers, however, its potential function and relevant molecular mechanisms in ESCC malignant progression as well as its value in clinical translation remain largely unknown. Here, in vitro and in vivo experiments revealed that aberrant upregulation of USP21 accelerated the proliferation and metastasis of ESCC in a deubiquitinase-dependent manner. Mechanistically, we found that USP21 binds to, deubiquitinates, and stabilizes the G3BP Stress Granule Assembly Factor 1 (G3BP1) protein, which is required for USP21-mediated ESCC progression. Further molecular studies demonstrated that the USP21/G3BP1 axis played a tumor-promoting role in ESCC progression by activating the Wnt/ß-Catenin signaling pathway. Additionally, disulfiram (DSF), an inhibitor against USP21 deubiquitylation activity, markedly abolished the USP21-mediated stability of G3BP1 protein and significantly displayed an anti-tumor effect on USP21-driving ESCC progression. Finally, the regulatory axis of USP21/G3BP1 was demonstrated to be aberrantly activated in ESCC tumor tissues and closely associated with advanced clinical stages and unfavorable prognoses, which provides a promising therapeutic strategy targeting USP21/G3BP1 axis for ESCC patients.

3.
Sci Rep ; 14(1): 14247, 2024 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902417

RESUMO

Megalurothrips usitatus (Bagnall) (Thysanoptera: Thripidae) is an important pest in Vigna unguiculata (L.) Walp. Neoseiulus barkeri (Hughes) (Acari: Phytoseiidae) is widely used for control of pest mites and insects worldwide. We evaluated its effect on M. usitatus when predators (N. barkeri) or insecticides (Spinetoram) were applied in the fields. Neoseiulus barkeri Hughes consumed 80% of M. usitatus prey offered within 6 h, and predation showed Type III functional response with prey density. The maximum consumption of N. barkeri was 27.29 ± 1.02 individuals per d per arena (1.5 cm diameter), while the optimal prey density for the predatory mite was 10.35 ± 0.68 individuals per d per arena (1.5 cm diameter). The developmental duration of N. barkeri fed with M. usitatus was significantly shorter than those fed with the dried fruit mite, Carpoglyphus lactis (L.) (Acari: Astigmata). In field trials, the efficiency of N. barkeri against M. usitatus was not significantly different from that of applications of the insecticide spinetoram. Biodiversity of other insects in treated fields was assessed, and there were 21 insect species in garden plots treated with N. barkeri releases. The total abundance (N), Shannon's diversity index (H), Pielou's evenness index (J) and Simpson's diversity index (D) of the garden plots treated with predatory mites were all significantly higher than that in the garden plots treated with spinetoram, where we found no species of predators or parasitoids and 7 herbivores. Our results show that N. barkeri is a potential means to control M. usitatus while preserving arthropod diversity at the level of treated gardens.


Assuntos
Biodiversidade , Ácaros , Comportamento Predatório , Animais , Comportamento Predatório/fisiologia , Ácaros/fisiologia , Controle Biológico de Vetores/métodos , Inseticidas/farmacologia , Artrópodes/fisiologia , Macrolídeos
4.
Food Chem ; 457: 139925, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38917567

RESUMO

Blueberry leaves (BBL) are a natural source with strong antioxidant activity, but bioactive compounds and their seasonal variation remain vague. Here, two major classes of compounds including four caffeoylquinic acids and eight flavonoids were identified in two southern highbush cultivars ("Lanmei" #1 and "Jewel") grown in China. Major bioactive compounds were discovered using an online HPLC post-column derivatization system and determined as neochlorogenic acid (NeoCA), chlorogenic acid (CA), rutin, hyperoside, and isoquercitrin. CA contributed the most to the BBL antioxidant activity. "Lanmei" showed significant advantages in terms of rutin content and antioxidant activity over "Jewel" (P < 0.05). The highest CA content (CAC) of juvenile "Jewel" leaves reached 17.9%. July was the optimum harvest time for both cultivars after fruiting stage. Total phenolic content (TPC) and Trolox equivalent antioxidant capacity (TEAC) of fresh BBL were accurately predicted by a portable near-infrared (NIR) device in a rapid, low-cost, and non-destructive way in situ.

5.
Updates Surg ; 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38555536

RESUMO

Achieving ideal abdominal wall reconstruction in giant ventral incisional hernia has been a challenging for surgeons. This study aimed to verify the safety and efficacy of bridging repair by comparing it with primary fascial closure (PFC) repair in the treatment of giant ventral incisional hernia. We retrospectively analyzed the clinical data of 92 patients with giant ventral incisional hernia who underwent mesh repair at our medical institution from January 1, 2014 to December 31, 2020. Patients were divided into 2 groups: the bridging repair group with 40 patients in whom repair was completed using the bridging technique and the PFC group with 52 patients in whom primary fascial closure was achieved and all patients underwent mesh reinforcement during the operation. The main outcome measures were recurrence rate and morbidity, especially intra-abdominal hypertension (IAH). Follow-up time of both groups lasted at least 24 months after surgery. After a median of 46 months and 65 months of follow-up, respectively, in the two groups, bridging repair did not increase the long-term recurrence rate (2.56%) in the larger defect area group compared to the PFC group (1.96%). There were no significant differences in perioperative morbidity, IAH, incidence of postoperative chronic pain, and sensory impairment of the abdominal wall between both groups. The application of bridging surgery in the treatment of complex giant ventral incisional hernias is safe and effective and does not significantly increase the postoperative recurrence rate.

6.
Oncogene ; 43(12): 899-917, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38317006

RESUMO

Dysregulation of MOF (also known as MYST1, KAT8), a highly conserved H4K16 acetyltransferase, plays important roles in human cancers. However, its expression and function in esophageal squamous cell carcinoma (ESCC) remain unknown. Here, we report that MOF is highly expressed in ESCC tumors and predicts a worse prognosis. Depletion of MOF in ESCC significantly impedes tumor growth and metastasis both in vitro and in vivo, whereas ectopic expression of MOF but not catalytically inactive mutant (MOF-E350Q) promotes ESCC progression, suggesting that MOF acetyltransferase activity is crucial for its oncogenic activity. Further analysis reveals that USP10, a deubiquitinase highly expressed in ESCC, binds to and deubiquitinates MOF at lysine 410, which protects it from proteosome-dependent protein degradation. MOF stabilization by USP10 promotes H4K16ac enrichment in the ANXA2 promoter to stimulate ANXA2 transcription in a JUN-dependent manner, which subsequently activates Wnt/ß-Catenin signaling to facilitate ESCC progression. Our findings highlight a novel USP10/MOF/ANXA2 axis as a promising therapeutic target for ESCC.


Assuntos
Anexina A2 , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Via de Sinalização Wnt/genética , Neoplasias Esofágicas/patologia , Proliferação de Células/genética , Acetiltransferases/metabolismo , Epigênese Genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Movimento Celular , Histona Acetiltransferases/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Anexina A2/metabolismo
7.
Acta Pharmacol Sin ; 45(5): 1060-1076, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38228910

RESUMO

Paclitaxel resistance is associated with a poor prognosis in non-small cell lung cancer (NSCLC) patients, and currently, there is no promising drug for paclitaxel resistance. In this study, we investigated the molecular mechanisms underlying the chemoresistance in human NSCLC-derived cell lines. We constructed paclitaxel-resistant NSCLC cell lines (A549/PR and H460/PR) by long-term exposure to paclitaxel. We found that triptolide, a diterpenoid epoxide isolated from the Chinese medicinal herb Tripterygium wilfordii Hook F, effectively enhanced the sensitivity of paclitaxel-resistant cells to paclitaxel by reducing ABCB1 expression in vivo and in vitro. Through high-throughput sequencing, we identified the SHH-initiated Hedgehog signaling pathway playing an important role in this process. We demonstrated that triptolide directly bound to HNF1A, one of the transcription factors of SHH, and inhibited HNF1A/SHH expression, ensuing in attenuation of Hedgehog signaling. In NSCLC tumor tissue microarrays and cancer network databases, we found a positive correlation between HNF1A and SHH expression. Our results illuminate a novel molecular mechanism through which triptolide targets and inhibits HNF1A, thereby impeding the activation of the Hedgehog signaling pathway and reducing the expression of ABCB1. This study suggests the potential clinical application of triptolide and provides promising prospects in targeting the HNF1A/SHH pathway as a therapeutic strategy for NSCLC patients with paclitaxel resistance. Schematic diagram showing that triptolide overcomes paclitaxel resistance by mediating inhibition of the HNF1A/SHH/ABCB1 axis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Diterpenos , Resistencia a Medicamentos Antineoplásicos , Compostos de Epóxi , Proteínas Hedgehog , Fator 1-alfa Nuclear de Hepatócito , Neoplasias Pulmonares , Paclitaxel , Fenantrenos , Compostos de Epóxi/farmacologia , Compostos de Epóxi/uso terapêutico , Humanos , Fenantrenos/farmacologia , Fenantrenos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Hedgehog/metabolismo , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Fator 1-alfa Nuclear de Hepatócito/genética , Animais , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Camundongos Nus , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Camundongos , Camundongos Endogâmicos BALB C , Células A549
8.
J Org Chem ; 88(21): 14978-14988, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37830913

RESUMO

An efficient and atom-economical silver-mediated [2 + 2 + 1] cyclization protocol for the selective synthesis of 2,4- or 3,4-dicarbonylselenophenes has been developed. Readily accessible substrates, commercially available elemental selenium, and good functional group tolerance make this procedure attractive for the selective synthesis of dicarbonylselenophenes. Preliminary mechanistic investigations indicated that silver acetylene species are possible intermediates for the formation of 3,4-dicarbonylselenophenes.

9.
Asia Pac J Public Health ; 35(6-7): 429-432, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37688405

RESUMO

This study aimed to explore the associations of screen time (ST) and its' changes with follow-up body mass index (BMI) in preschool children. Parents of 805 preschoolers participated in our study at baseline and were followed up after 1 year in China. Linear regression models were used to analyze the dynamic relationship between ST and BMI in preschool children. A total of 662 preschoolers, including 342 boys (51.7%) and 320 girls (48.3%) were followed up. The changes in ST (from the initial ≤1 h/day to >1 h/day at follow-up vs keep ≤1 h/d, ß(SE) = 0.21(0.09), P = .016) and follow-up ST of preschool children (>1 h/d vs ≤1 h/d, ß(SE) = 0.17(0.07), P = .013) were significantly associated with an increase in the preschoolers' z-scored BMI at follow-up after adjusting for potential confounding factors. We concluded that the unfavorable change in ST was associated with increased BMI in preschool children.


Assuntos
População do Leste Asiático , Tempo de Tela , Masculino , Feminino , Humanos , Pré-Escolar , Índice de Massa Corporal , Seguimentos , Povo Asiático
10.
Surg Endosc ; 37(10): 8156-8164, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37653158

RESUMO

BACKGROUND: Right hemi-hepatectomy plus total caudate lobectomy is the appropriate procedure for type IIIa or partial type II pCCA. However, the laparoscopic implementation of this procedure remains technically challenging, especially hilar vascular dissection and en bloc resection of the total caudate lobe. Augmented reality navigation can provide intraoperative navigation to enhance visualization of invisible hilar blood vessels and guide the parenchymal transection plane. METHODS: Eleven patients who underwent laparoscopic right hemi-hepatectomy plus total caudate lobectomy from January 2021 to January 2023 were enrolled in this study. Augmented reality navigation technology and the anterior approach were utilized in this operation. Routine operative and short-term postoperative outcomes were assessed to evaluate the feasibility of the novel navigation method in this operation. RESULTS: Right hemi-hepatectomy plus total caudate lobectomy was successfully performed in all 11 enrolled patients. Among the 11 patients, the mean operation time was 454.5 ± 25.0 min and the mean estimated blood loss was 209.1 ± 56.1 ml. Negative surgical margins were achieved in all patients. The postoperative course of all the patients was uneventful, and the mean length of postoperative hospital stay was 10.5 ± 1.2 days. CONCLUSION: Laparoscopic right hemi-hepatectomy plus total caudate lobectomy via the anterior approach may be feasible and safe for pCCA with the assistance of augmented reality navigation.


Assuntos
Realidade Aumentada , Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Laparoscopia , Neoplasias Hepáticas , Humanos , Tumor de Klatskin/cirurgia , Hepatectomia/métodos , Estudos de Viabilidade , Neoplasias Hepáticas/cirurgia , Laparoscopia/métodos , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/cirurgia
11.
J Org Chem ; 88(18): 13042-13048, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37647572

RESUMO

An efficient silver-mediated [2 + 2 + 1] cyclization protocol of ortho-propioloylbenzonitriles with elemental selenium for the synthesis of 4H-indeno[1,2-c][1,2]selenazol-4-ones has been developed. One C-Se bond, one N-Se bond, and one C-C bond were rapidly constructed in one step. The reaction might proceed via the formation of a highly reactive selenoketene intermediate, followed by intramolecular cyclization.

13.
Tohoku J Exp Med ; 261(4): 257-265, 2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-37344419

RESUMO

Improving hepatic glucose and lipid metabolisms is an important strategy to treat type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease (T2DM-NAFLD). Silybin (SLB) has the potential hepatoprotection, while its oral bioavailability is poor. This study aims to investigate the functional role and mechanism of liposomal SLB in modulating glucose/lipid metabolism in T2DM-NAFLD. SLB was prepared by thin film dispersion method and characterized using dynamic light scattering, scanning electron microscope, high performance liquid chromatography and zeta potential analyzer. A rat model of T2DM-NAFLD was used to determine the role of liposomal SLB in regulating glycolipid metabolism and hepatic damage. Rat primary hepatocytes were used to demonstrate the hepatoprotection mechanism of liposomal SLB. The encapsulation efficiency was more than 80%, which showed the average particle size of 119.76 nm. Also, the average Zeta potential was -4.76 mV. These liposomes were spherical. In rats with T2DM-NAFLD, liposomal SLB alleviated insulin resistance and lipid metabolism, thereby improving hepatic lipid accumulation, inflammation and fibrosis. Besides, liposomal SLB elevated AMPK phosphorylation, and decreased collagen I/III, α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1) and the phosphorylation of Smad2/3. In hepatocyte model, compound C partially reversed the effects of liposomal SLB on cell viability, glycolipid metabolism and AMPK/TGF-ß1/Smad pathway activation. Liposomal SLB ameliorates hepatic glucose and lipid metabolisms in T2DM-NAFLD via activating AMPK/TGF-ß1/Smad pathway, providing an efficient strategy for treating T2DM-NAFLD.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Ratos , Animais , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Fator de Crescimento Transformador beta1/metabolismo , Metabolismo dos Lipídeos , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/farmacologia , Silibina/farmacologia , Silibina/uso terapêutico , Silibina/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose/metabolismo , Lipossomos/metabolismo , Lipossomos/farmacologia , Modelos Animais de Doenças , Fígado/metabolismo , Lipídeos/farmacologia , Glicolipídeos/metabolismo , Glicolipídeos/farmacologia
14.
Biomark Res ; 11(1): 65, 2023 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-37330575

RESUMO

The most common kind of acute leukemia in adults is acute myeloid leukemia (AML), which is often treated with induction chemotherapy regimens followed by consolidation or allogeneic hematopoietic stem cell transplantation (HSCT). However, some patients continue to develop relapsed or refractory AML (R/R-AML). Small molecular targeted drugs require long-time administration. Not all the patients hold molecular targets. Novel medicines are therefore needed to enhance treatment outcomes. T cells and natural killer (NK) cells engineered with chimeric antigen receptors (CARs) that target antigens associated with AML have recently been produced and are currently being tested in both pre-clinical and clinical settings. This review provides an overview of CAR-T/NK treatments for AML.

15.
Front Oncol ; 13: 1169616, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37256170

RESUMO

Background: Rectal cancer has a high risk of recurrence and metastasis, with median survival ranging from 24 months to 36 months. K-RAS mutation is a predictor of poor prognosis in rectal cancer. Advanced rectal cancer can be stopped in its tracks by pelvic exenteration. Case summary: A 51-year-old woman was diagnosed with advanced rectal cancer (pT4bN2aM1b, stage IV) with the KRAS G12D mutation due to a change in bowel habits. The patient had experienced repeated recurrences of rectal cancer after initial radical resection, and the tumor had invaded the ovaries, sacrum, bladder, vagina and anus. Since the onset of the disease, the patient had undergone a total of seven surgeries and long-term FOLFIRI- or XELOX-based chemotherapy regimens, with the targeted agents bevacizumab and regorafenib. Fortunately, the patient was able to achieve intraoperative R0 resection in almost all surgical procedures and achieve tumor-free survival after pelvic exenteration. The patient has been alive for 86 months since her diagnosis. Conclusions: Patients with advanced rectal cancer can achieve long-term survival through active multidisciplinary management and R0 surgery.

16.
Org Lett ; 25(17): 3094-3098, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37087758

RESUMO

We report a four-component ring-opening reaction of pyrroles via C-N bond cleavage. In this process, elemental sulfur is used as the sulfur source of thiazole and thioamide and the reductant of olefin. A series of benzothiazoles functionalized with thiopropionamides at the C2 position were synthesized using this method. A plausible reaction mechanism is proposed based on the concise control experiments.

17.
Front Cardiovasc Med ; 10: 1084851, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37077745

RESUMO

Background: Left subclavian artery (LSA) revascularization during thoracic endovascular aortic repair (TEVAR) is necessary to reduce postoperative complications in patients with Stanford type B aortic dissection and an insufficient proximal anchoring area. However, the efficacy and safety of different LSA revascularization strategies remain unclear. Here, we compared these strategies to provide a clinical basis for selecting an appropriate LSA revascularization method. Methods: In this study, we included 105 patients with type B aortic dissection who were treated using TEVAR combined with LSA reconstruction in the Second Hospital of Lanzhou University from March 2013 to 2020. They were divided into four groups according to the method used for LSA reconstruction, namely, carotid subclavian bypass (CSB; n = 41), chimney graft (CG; n = 29), single-branched stent graft (SBSG; n = 21), and physician-made fenestration (PMF; n = 14) groups. Finally, we collected and analyzed the baseline, perioperative, operative, postoperative, and follow-up data of the patients. Results: The treatment success rate was 100% in all the groups, and CSB + TEVAR was the most commonly used procedure in emergency settings compared with the other three procedures (P < 0.05). The estimated blood loss, contrast agent volume, fluoroscopic time, operation time, and limb ischemia symptoms during the follow-up were significantly different in the four groups (P < 0.05). Pairwise comparison among groups indicated that the estimated blood loss and operation time in the CSB group were the highest (adjusted P < 0.0083; P < 0.05). The contrast agent volume and fluoroscopy duration were the highest in the SBSG groups, followed by PMF, CG, and CSB groups. The incidence of limb ischemia symptoms was the highest in the PMF group (28.6%) during the follow-up. The incidence of complications (except limb ischemia symptoms) during the perioperative and follow-up periods was similar among the four groups (P > 0.05) The median follow-up time of CSB, CG, SBSG, and PMF groups was significantly different (P < 0.05), and the CSB group had the longest follow-up. Conclusion: Our single-center experience suggested that the PMF technique increased the risk of limb ischemia symptoms. The other three strategies effectively and safely restored LSA perfusion in patients with type B aortic dissection and had comparable complications. Overall, different LSA revascularization techniques have their advantages and disadvantages.

18.
Int Urol Nephrol ; 55(12): 3217-3224, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37093441

RESUMO

INTRODUCTION: Pretransplant osteoporosis and vascular calcification probably increase the risk of fractures and cardiovascular events after kidney transplantation. In the present study, we investigated the related risk factors of osteoporosis and vascular calcification among end-stage renal disease (ESRD) patients awaiting kidney transplantation. METHODS: A total of 221 ESRD patients (age, 43.4 ± 14.3 years; 125 males and 96 females; median dialysis duration, 61.0 m) awaiting kidney transplantation were enrolled in this cross-sectional study. Serum levels of bone turnover markers and intact parathyroid hormone (iPTH) were analyzed from fasting morning blood samples. Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD). Vascular calcification was evaluated by lateral abdominal radiography and plain radiographic films of the pelvis and hands. RESULTS: The osteoporosis prevalence was 27.6% in this cohort of kidney transplantation candidates, and the prevalence of vascular calcification was 51.1%. The related factors for osteoporosis and vascular calcification were similar and included older age, longer dialysis duration, parathyroid hyperplasia, and higher levels of iPTH and bone turnover markers. In the multivariable regression model, age and iPTH were independent risk predictors of both vascular calcification and osteoporosis. There were strong, positive correlations between iPTH and all bone turnover markers. The moderate and severe hyperparathyroidism (iPTH 600-1499 pg/ml and iPTH 1500 pg/ml) were related to reduced serum albumin and hemoglobin levels. CONCLUSION: The involvement of high iPTH levels in vascular calcification, osteoporosis, and malnutrition indicated the need of treating hyperparathyroidism early in patients awaiting kidney transplantation. Prospective studies are needed to further examine the utility of bone turnover markers.


Assuntos
Hiperparatireoidismo , Falência Renal Crônica , Transplante de Rim , Osteoporose , Calcificação Vascular , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Transplante de Rim/efeitos adversos , Estudos Transversais , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Densidade Óssea , Osteoporose/etiologia , Osteoporose/complicações , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Calcificação Vascular/etiologia , Hormônio Paratireóideo
19.
Zhongguo Zhong Yao Za Zhi ; 48(4): 1032-1042, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-36872274

RESUMO

Based on transcriptome sequencing technology, the mouse model of prediabetes treated with Huangjing Qianshi Decoction was sequenced to explore the possible mechanism of treating prediabetes. First of all, transcriptome sequencing was performed on the normal BKS-DB mouse group, the prediabetic model group, and the Huangjing Qianshi Decoction treatment group(treatment group) to obtain differentially expressed genes in the skeletal muscle samples of mice. The serum biochemical indexes were detected in each group to screen out the core genes of Huangjing Qianshi Decoction in prediabetes. Gene Ontology(GO) database and Kyoto Encyclopedia of Genes and Genomes(KEGG) database were used to conduct signaling pathway enrichment analysis of differentially expressed genes, and real-time quantitative polymerase chain reaction(RT-qPCR) was used to verify them. The results showed that the levels of fasting blood glucose(FBG), fasting insulin(FINS), insulin resistance index(HOMA-IR), total cholesterol(TC), triglycerides(TG), and low-density lipoprotein cholesterol(LDL-C) in the mouse model were significantly decreased after treatment with Huangjing Qianshi Decoction. In the results of differential gene screening, there were 1 666 differentially expressed genes in the model group as compared with the normal group, and there were 971 differentially expressed genes in the treatment group as compared with the model group. Among them, interleukin-6(IL-6) and NR3C2 genes, which were closely related to the regulation of insulin resis-tance function, were significantly up-regulated between the model group and the normal group, and vascular endothelial growth factor A(VEGFA) genes were significantly down-regulated between the model group and the normal group. However, the expression results of IL-6, NR3C2, and VEGFA genes were adverse between the treatment group and the model group. GO functional enrichment analysis found that the biological process annotation mainly focused on cell synthesis, cycle, and metabolism; cell component annotation mainly focused on organelles and internal components; and molecular function annotation mainly focused on binding molecular functions. KEGG pathway enrichment analysis found that it involved the protein tyrosine kinase 6(PTK6) pathway, CD28-dependent phosphoinositide 3-kinase/protein kinase B(PI3K/AKT) pathway, p53 pathway, etc. Therefore, Huangjing Qianshi Decoction can improve the state of prediabetes, and the mechanism may be related to cell cycle and apoptosis, PI3K/AKT pathway, p53 pathway, and other biological pathways regulated by IL-6, NR3C2, and VEGFA.


Assuntos
Estado Pré-Diabético , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , Fosfatidilinositol 3-Quinases , Fator A de Crescimento do Endotélio Vascular , Interleucina-6 , Transcriptoma , Proteína Supressora de Tumor p53 , Insulina , Colesterol
20.
J Rheumatol ; 50(5): 662-670, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36642437

RESUMO

OBJECTIVE: We aimed to validate and modify the renal risk score for antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN) in a Chinese cohort with a majority of myeloperoxidase (MPO)-positive patients. METHODS: A total of 285 patients with biopsy-proven AAGN in our center were retrospectively included. Patients were randomly assigned to the development set (n = 201) and the validation set (n = 84). We calculated the renal risk score and analyzed the clinicopathological characteristics and follow-up data. The nomogram was constructed based on the independent prognostic factors identified by the multivariable Cox regression and then compared with the renal risk score. RESULTS: Over a median follow-up period of 41.3 (range 20.0-63.8) months, 84 (29.5%) patients reached end-stage kidney disease (ESKD). In the development set, hypertension (hazard ratio [HR] 2.16, 95% CI 1.08-4.32, P = 0.03), high serum creatinine (HR 1.002, 95% CI 1.001-1.003, P < 0.001), high daily urine protein (HR 1.34, 95% CI 1.15-1.57, P < 0.001), high glomerular sclerosis (HR 13.98, 95% CI 3.50-55.92, P < 0.001), and interstitial fibrosis > 50% (HR 4.18, 95% CI 1.90-9.19, P < 0.001) were independent risk factors for ESKD, and these indicators were included in the nomogram. The C-indices of the nomogram model in the development set, validation set, and all-data set were 0.838 (range 0.785-0.891), 0.794 (range 0.774-0.814), and 0.822 (range 0.775-0.869), respectively, which were higher than those of the renal risk score model, 0.801 (range 0.748-0.854), 0.746 (range 0.654-0.838) and 0.783 (range 0.736-0.830), respectively. The net reclassification improvement and the integrated discrimination improvement further illustrated the higher predictive ability of the nomogram. CONCLUSION: We present a nomogram as a practical tool to predict renal outcomes in Chinese patients with MPO-ANCA glomerulonephritis.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glomerulonefrite , Falência Renal Crônica , Humanos , Anticorpos Anticitoplasma de Neutrófilos , Estudos Retrospectivos , Peroxidase , População do Leste Asiático , Prognóstico , Glomerulonefrite/patologia , Fatores de Risco
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