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1.
BMC Musculoskelet Disord ; 23(1): 418, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35509075

RESUMO

BACKGROUND: The purpose of this study was to compare the serum inflammatory indicators and radiographic results of conventional manual total knee arthroplasty (CM-TKA) with those of MAKO-robotic assisted total knee arthroplasty (MA-TKA). METHODS: We retrospectively analysed 65 patients with knee osteoarthritis who underwent unilateral TKA from December 2020 to November 2021 in our department, which included 34 patients who underwent MA-TKA and 31 patients who underwent CM-TKA. The tourniquet time and estimated blood loss (EBL) were compared between the two groups. Knee function was evaluated using range of motion (ROM), functional score and pain score. Leukocytes, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), creatine kinase (CK), and neutrophil-to-lymphocyte ratio (NLR) were recorded at 3 time points (preoperative, and on the first and third postoperative days). The hip-knee-ankle angle (HKA) and the femoral and tibial component angles in the coronal and sagittal planes were used for postoperative radiographic evaluation. RESULTS: The postoperative MA-TKA group had less EBL (496.9 ± 257.8 vs. 773.0 ± 301.3 ml, p < 0.001). There was no significant difference in knee function scores at 6 weeks postoperatively (p > 0.05). IL-6 levels were significantly lower in the MA-TKA group on the 1st postoperative day (11.4 (5.2, 21.0) vs. 24.6 (86.3, 170.8), p = 0.031). This difference in inflammatory indices became more pronounced at 72 hours after the operation because CRP, ESR, IL-6, and CK values were significantly lower in the MA-TKA group on the 3rd postoperative day (72 h) (p < 0.05). Postoperative radiographic examinations performed 2 days after the MA-TKA group suggested that only 2 cases of HKA had outlier values, which was remarkably better than the 12 cases found in the CM-TKA group (5.9% vs. 38.7%, p < 0.001). The frontal femoral component was significantly closer to the expected value of 90° in the MA-TKA group (90.9 (90.5, 92.3) vs. 92.4 (91.3, 93.7), p = 0.031). The remaining imaging evaluation parameters were not significantly different between the two groups (p > 0.05). CONCLUSIONS: In Chinese patients with OA, there was a milder systemic inflammatory response in the early postoperative period after MA-TKA compared to that of CM-TKA, as well as better radiographic outcomes. However, the tourniquet time was prolonged, and no advantages were observed in terms of functional score or pain score in the short-term follow-up.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Procedimentos Cirúrgicos Robóticos , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , China , Humanos , Inflamação/diagnóstico por imagem , Interleucina-6 , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Dor , Estudos Retrospectivos
2.
Endocrinology ; 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35536227

RESUMO

Obesity has recently been defined as a chronic low-grade inflammatory disease. Obesity-induced inflammation of adipose tissue (AT) is an essential trigger for insulin resistance (IR) and related metabolic diseases. Although the underlying molecular basis of this inflammation has not been fully identified, there is consensus that the recruited and activated macrophages in AT are the most important culprits of AT chronic inflammation. Adipose tissue macrophages (ATMs) are highly plastic and could be polarized from an anti-inflammatory M2 to pro-inflammatory M1 phenotypes upon stimulation by micro-environmental signals from obese AT. Many efforts have been made to elucidate the molecular signaling pathways of macrophage polarization, however, the upstream drivers governing and activating macrophage polarization have rarely been summarized, particularly regulatory messages from the AT micro-environment. In addition to adipocytes, the AT bed also contains a variety of immune cells, stem cells, as well as vascular, neural and lymphatic tissues throughout, which together orchestrate the AT micro-environment. Here, we summarized how the aforesaid neighbors of ATMs in the AT micro-environment send messages to ATMs and thus regulate its phenotype during obesity. Deciphering the biology and polarization of ATMs in the obese environment is expected to provide a precise immunotherapy for adipose inflammation and obesity-related metabolic diseases.

3.
BMC Nephrol ; 23(1): 185, 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35568810

RESUMO

OBJECTIVE: To explore the technical specifications and clinical outcomes of thrombosed aneurysmal haemodialysis arteriovenous fistula (AVF) treated with ultrasound-guided percutaneous transluminal angioplasty combined with minimal aneurysmotomy. METHODS: This case series study included 11 patients who had thrombosed aneurysmal AVF and underwent salvage procedures over a 13-month period. All procedures were performed under duplex guidance. Minimal aneurysmotomy was performed, along with manual thrombectomy and thrombolytic agent infusion, followed by angioplasty to macerate the thrombus and sufficiently dilate potential stenoses. A successful procedure was defined as immediate restoration of flow through the AVF. RESULTS: The 11 patients (four males and seven females) had a mean age of 49.6 years ± 11.9 years. Six patients (54.5%) had two or more aneurysms. The mean aneurysm maximal diameter was 21.5 mm (standard deviation: ± 5.0 mm), and the mean thrombus length was 12.9 cm (8-22 cm). Ten (83.3%) of the 12 procedures were technically successful. The mean duration of operation was 150.9 minutes (standard deviation: ± 34.2 minutes), and mean postoperative AVF blood flow was 728.6 ml/min (standard deviation: ± 53.7 mi/min). The resumption of hemodialysis was successful in all 11 cases, with a clinical success rate of 100%. The primary patency rates were 90.0% and 75.0% at three and four months over a mean follow-up time of 6.3 months (3-12 months). The secondary patency rates were 90.4% at three and four months. CONCLUSION: A hybrid approach combining ultrasound-guided percutaneous transluminal angioplasty and minimal aneurysmotomy might be a safe and effective method for thrombosed aneurysmal AVF salvage.

4.
World J Surg Oncol ; 20(1): 156, 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35568949

RESUMO

BACKGROUND: Chemotherapy is a common approach for cancer treatment, but intrinsic genetic mutations in different individuals may cause different responses to chemotherapy, resulting in unique histopathological changes. The genetic mutation along with the distinct histopathological features may indicate new tumor entities. BCOR-CCNB3 sarcomas is a kind of Ewing-like sarcomas (ELS) occurring mostly in bone and soft tissues. No gene fusion other than BCOR-CCNB3 has been found in this type of tumor. CASE PRESENTATION: We herein report a case of 17-year-old male patient, presented with a mass on his left shoulder that was diagnosed as undifferentiated small round cell sarcoma according to core biopsy. The patient received 5 courses of preoperational chemotherapy, and the tumor was resected and analyzed. Primitive small round cells and larger myoid cells in the resected tumor tissue but not in biopsy were observed, and arterioles stenosis and occlusion were also detected, indicating a dramatic change of histopathological features of this tumor. In addition, the immunohistochemical results showed the altered staining patterns of BCOR, bcl2, CyclinD1, TLE1, AR, SMA, CD117, STAB2, CD56, and CD99 in tumor tissues after chemotherapy. Notably, RNA sequencing revealed a RNF213-SLC26A11 fusion in the tumor sample. CONCLUSIONS: The BCOR-CCNB3 sarcoma with RNF213-SLC26A11 fusion may indicate a subset of tumors that undergo histopathological changes in response to chemotherapy. More similar cases in the future may help to clarify the clinical meanings of RNF213-SLC26A11 fusion in BCOR-CCNB3 sarcomas and the underlying mechanisms.

5.
Nutr Cancer ; : 1-11, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35533004

RESUMO

To investigate the impact of preoperative objective nutritional indices on the prognosis of patients with hepatocellular carcinoma (HCC) who underwent radical hepatectomy and to compare their predictive value for prognosis.The clinical data of 661 patients were retrospectively reviewed to analyze the risk factors associated with prognosis; explore the role of the prognostic nutritional index (PNI), nutritional risk index (NRI), and control nutritional status (CONUT) in HCC prognosis; and compare their predictive value.Several independent risk factors for overall survival (OS) were identified, including neutrophil count, prealbumin level, microvascular invasion (MVI), Barcelona Clinic Liver Cancer (BCLC) stage, and PNI. The following factors were confirmed to be associated with recurrence-free survival (RFS): alpha-fetoprotein (AFP) level, prothrombin time (PT), tumor size, tumor capsule, MVI, BCLC stage, and PNI. Compared with the corresponding subgroups, patients in the high PNI (>45) group and the high NRI (>100) group had better RFS and OS (P < 0.05). However, patients in the low CONUT score (≤3) group had a similar prognosis to patients in the high CONUT (>3) group (P = 0.050). Receiver operating characteristic (ROC) curve results showed that the area under the curve (AUC) of the PNI was significantly higher than that of the CONUT for RFS or OS but similar to that of the NRI.The predictive ability of the PNI for HCC prognosis was significantly better than that of the CONUT but similar to that of the NRI.

6.
Hemoglobin ; : 1-4, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35535583

RESUMO

We report a rare hemoglobin (Hb) variant on the ß-globin gene, which was detected in a female from Yulin City, Guangxi Autonomous Region, People's Republic of China (PRC), during routine thalassemia screening. The Hb variant remained unnoticed using capillary electrophoresis (CE) and high performance liquid chromatography (HPLC), while an additional peak was observed by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry (MS). DNA sequencing revealed the GCC>GTC substitution at codon 13 on the ß-globin gene, causing a substitution of alanine to valine. The mutation is only described in the ITHANET database but no Hb variant name and other information, so we named it Hb Yulin after the place of origin of the proband in this study. Hb Yulin is clinically silent and easily leads to misdiagnosis during hemoglobinopathies screening based on the common methods of HPLC and CE.

7.
J Am Chem Soc ; 144(15): 6871-6881, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35410472

RESUMO

Elansolid A is a structurally complex polyketide macrolactone natural product that exhibits promising antibacterial properties. Its challenging asymmetric total synthesis was achieved by a convergent strategy, in which the tetrahydroindane core of the molecule and an eastern vinyl iodide moiety were combined as the main fragments. The central tetrahydroindane motif was constructed with high stereoselectivity by a bioinspired intramolecular Diels-Alder cycloaddition, generating four stereogenic centers in a single step. The stereocontrol of this key step could be achieved by virtue of a 1,3-allylic strain generated by the temporary introduction of a steric-directing iodine substituent on the substrate. The formation of the macrolactone motif that completes the synthesis was achieved via two different retrosynthetic disconnections, namely, a Suzuki-Miyaura cross-coupling or an alternative Mukaiyama esterification reaction.


Assuntos
Antibacterianos , Produtos Biológicos , Antibacterianos/química , Reação de Cicloadição , Macrolídeos/química , Estereoisomerismo
8.
J Prosthet Dent ; 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35469646

RESUMO

STATEMENT OF PROBLEM: Limited data are available regarding the reliability of short implants (≤8.5 mm) in patients with resorbed completely edentulous jaws. PURPOSE: The purpose of this systematic review and meta-analysis was to compare the clinical outcomes of short implants (intervention) versus long implants (≥10 mm, comparison) in the rehabilitation of completely edentulous jaws. MATERIAL AND METHODS: The PubMed, Embase, and Cochrane CENTRAL databases were searched for randomized controlled trials (RCTs) comparing short and long implants supporting fixed or removable prostheses in completely edentulous jaws. Outcome measures included implant survival, marginal bone loss (MBL), and biological and technical complications. The risks of bias within and across the studies were assessed, and meta-analyses, sensitivity analyses, and subgroup analyses by types of prostheses, jaw locations, and follow-up length were performed. RESULTS: A total of 4 RCTs with 158 participants were included. No significant difference was found between short implants and long implants regarding implant survival (RR=1.01, 95% CI: 0.97 to 1.05, P=.710, I2=70%) or MBL (MD=-0.19 mm, 95% CI: -0.39 to 0.02, P=.070, I2=94%). In subgroup analyses, when supporting fixed prostheses, short implants showed significantly less MBL than long implants (P<.001). In the mandible, short implants showed higher implant survival (P=.008) and less MBL (P<.001). Participants receiving long implants combined with bone augmentation procedures reported more postsurgery pain. CONCLUSIONS: For completely edentulous jaws, short implants provide a reliable treatment alternative, as survival and MBL were not different when compared with those of long implants. However, additional high-level evidence is still needed to determine the long-term clinical outcomes of short implants in completely edentulous jaws.

9.
Crit Rev Eukaryot Gene Expr ; 32(1): 67-78, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35377982

RESUMO

The migration and angiogenesis of endothelial progenitor cells require the involvement of WTAPP1. Cell migration and angiogenesis are critical for cancer development, we therefore speculated that WTAPP1 may participate in cancer biology. This study aimed to explore the role of WTAPP1 in triple-negative breast cancer (TNBC). A total of 68 patients (females, 38 to 67 years old, mean age 52.1 ± 5.9 years old) were enrolled in this study. The effects of over-expression of WTAPP1 and miR-34a on EEF2K were evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot. Transient cell transfections were performed to explore the interactions between genes. Cell proliferation assay was used to analyze cell proliferation. Transwell assays were performed to detect cell invasive and migration. Flow cytometry was used to evaluate apoptosis. WTAPP1 was upregulated in tumor tissues of TNBC patients and high expression levels of WTAPP1 in tumor tissues predicted poor survival. In contrast, miR-34a was downregulated in TNBC. Correlation analysis showed that WTAPP1 and miR-34a were negatively correlated with each other. In cancer cells, overexpression of WTAPP1 resulted in downregulation of miR-34a. Remarkably, overexpression of WTAPP1 increased the expression levels of EEF2K, a target of miR-34a. Overexpression of WTAPP1 and EEF2K increased proliferation, invasion and migration of TNBC cells, while overexpression of miR-34a showed different results. In addition, overexpression of miR-34a enhanced the effects of overexpression of WTAPP1 and EEF2K on apoptosis. WTAPP1 may promote TNBC cell proliferation by downregulating miR-34a.


Assuntos
MicroRNAs , Neoplasias de Mama Triplo Negativas , Adulto , Idoso , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
11.
Proc Natl Acad Sci U S A ; 119(17): e2119016119, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35452312

RESUMO

SignificanceResistivity comparison methodology was developed to measure and analyze the contact-induced Fermi-level shift (CIFS) as well as the interfacial charge transfer in low-dimensional semimetal-semiconductor (Sm-S) systems. The Fermi-level catch-up model was further built to depict the gate-tunable CIFS in such Sm-S systems. The Schottky barrier height for the Sm-S junction can be modified by introducing the CIFS term. The progress in this work will have an important role in promoting the research of Sm-S junctions, which are essential building blocks for future low-dimensional nanodevices.

12.
RSC Adv ; 12(3): 1471-1478, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35425193

RESUMO

Supercapacitors are known as promising excellent electrochemical energy storage devices because of their attractive features, including quick charge and discharge, high power density, low cost and high security. In this work, a series of litchi-like Ni-Co selenide particles were synthesized via a simple solvothermal method, and the Ni-Co compositions were carefully optimized to tune the charge storage performance, charge storage kinetics, and conductivity for battery-like supercapacitors. Interestingly, the optimal sample Ni0.95Co2.05Se4 exhibits a high capacity of 1038.75 F g-1 at 1 A g-1 and superior rate performance (retains 97.8% of the original capacity at 4 A g-1). Moreover, an asymmetric supercapacitor device was assembled based on the Ni0.95Co2.05Se4 cathode and activated carbon anode. The device of Ni0.95Co2.05Se4//active carbon (AC) reveals a peak energy density of 37.22 W h kg-1, and the corresponding peak power density reaches 800.90 W kg-1. This work provides a facile and effective way to synthesize transition metal selenides as high-performance supercapacitor electrode materials.

13.
BMC Pediatr ; 22(1): 200, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35413820

RESUMO

BACKGROUND: Bronchopulmonary dysplasia (BPD) is one of the most common adverse consequence of premature delivery and the most common chronic lung disease in infants. BPD is associated with long-term lung diseases and neurodevelopmental disorders that can persist into the adulthood. The adverse consequences caused by severe BPD are more serious. However, there were few studies on the risk factors for severe BPD. METHODS: This is a retrospective study of preterm infants born less than 32-week gestational age (GA) and diagnosed with BPD. RESULTS: A total of 250 preterm infants with a diagnosis of BPD and GA < 32 weeks were included (137 boys [54.8%] and 113 girls [45.2%]). The birth weight ranged from 700 g to 2010 g and the mean birth weight was 1318.52 g (255.45 g). The GA ranged from 25 weeks to 31 weeks and 6 days (mean, 30 weeks). The number of cases of mild, moderate and severe BPD were 39 (15.6%), 185 (74.0%) and 26 (10.4%), respectively. There were significant differences in the rate of small for gestational age (SGA), intrauterine asphyxia, pulmonary hemorrhage, neonatal respiratory distress syndrome (NRDS), circulatory failure, pulmonary hypertension, patent ductus arteriosus (PDA), pulmonary surfactant (PS), aminophylline, caffeine, glucocorticoids, tracheal intubation, diuretics, and parenteral nutrition length among the three groups (P < 0.05). The time of parenteral nutrition (aOR = 3.343, 95%CI: 2.198 ~ 5.085) and PDA (aOR =9.441, 95%CI: 1.186 ~ 75.128) were independent risk factors for severe BPD compared with mild BPD. PDA (aOR = 5.202, 95%CI: 1.803 ~ 15.010) and aminophylline (aOR = 6.179, 95%CI: 2.200 ~ 17.353) were independent risk factors for severe BPD, while caffeine (aOR = 0.260, 95%CI: 0.092 ~ 0.736) was the protective factor for severe BPD compared with moderate BPD. The time of parenteral nutrition (aOR = 2.972, 95%CI: 1.989 ~ 4.440) and caffeine (aOR = 4.525, 95%CI: 1.042 ~ 19.649) were independent risk factors for moderate BPD compared with mild BPD. Caffeine (aOR = 3.850, 95%CI: 1.358 ~ 10.916) was the independent risk factor for moderate BPD, while PDA (aOR = 0.192, 95%CI: 0.067 ~ 0.555) and aminophylline (aOR = 0.162, 95%CI: 0.058 ~ 0.455) were protective factors for moderate BPD compared with severe BPD. The time of parenteral nutrition (aOR = 0.337, 95%CI: 0.225 ~ 0.503) and caffeine (aOR = 0.221, 95%CI: 0.051 ~ 0.960) were protective factors for mild BPD compared with moderate BPD. The time of parenteral nutrition (aOR = 0.299, 95%CI: 0.197 ~ 0.455) and PDA (aOR = 0.106, 95%CI: 0.013 ~ 0.843) were protective factors for mild BPD compared with severe BPD. CONCLUSION: The time of parenteral nutrition is the risk factor of moderate and severe BPD. PDA and aminophylline are risk factors for severe BPD. The role of caffeine in the severity of BPD is uncertain, and SGA is not related to the severity of BPD. Severe or moderate BPD can be avoided by shortening duration of parenteral nutrition, early treatment of PDA, reducing use of aminophylline and rational use of caffeine. TRIAL REGISTRATION: Retrospectively registered.


Assuntos
Displasia Broncopulmonar , Permeabilidade do Canal Arterial , Doenças do Prematuro , Adulto , Aminofilina , Peso ao Nascer , Displasia Broncopulmonar/complicações , Displasia Broncopulmonar/etiologia , Cafeína , Permeabilidade do Canal Arterial/complicações , Feminino , Retardo do Crescimento Fetal , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Estudos Retrospectivos , Fatores de Risco
14.
J Cardiothorac Surg ; 17(1): 77, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35421997

RESUMO

BACKGROUND: Sexual dysfunction after cardiac surgery can seriously affect patients' quality of life, but the impact of cardiac surgery on sexual function has long been neglected. Compared with conventional cardiac surgery, minimally invasive cardiac surgery has the advantages of aesthetic appearance and no disruption of the sternal structure, which can greatly improve the patient's quality of life. However, studies focusing on the effects of minimally invasive mitral valve surgery (MIMVS) on sexual function have not been reported. The objective of this research was to investigate the effects of totally endoscopic mitral valve surgery on health-related quality of life and sexual function in male patients and to provide possible recommendations. METHODS: Patients who underwent median sternotomy or totally endoscopic mitral valve surgery at our institution from January 2019 to December 2020 were selected using an electronic medical record system. Data were collected by questionnaires, including the MOS 36-item short-form health survey and the International Erectile Function Questionnaire. RESULTS: There were 156 male patients who participated in our study. Of these, 112 patients completed all questionnaires. Forty-five patients (40.18%) developed postoperative sexual dysfunction, including 15 patients (29.41%) in the MIMVS group and 30 patients (49.18%) in the conventional MVS group, indicating that the incidence of sexual dysfunction could be reduced by MIMVS and that the MIMVS group scored better on the International Erectile Function Questionnaire (P < 0.05). On the evaluation of health-related quality of life, the MIMVS group scored better than the MVS group on the mental health and bodily pain subscales of the MOS 36-item short-form health survey. In addition, our study showed that postoperative sexual dysfunction was associated with physical functioning and mental health. CONCLUSIONS: In our study, totally endoscopic mitral valve surgery had less adverse effects on sexual function in male patients than conventional mitral valve surgery. In terms of health-related quality of life, totally endoscopic mitral valve surgery was superior to conventional surgery. Patients who opt for totally endoscopic mitral valve surgery may have a more satisfying and healthier sexual life than those who undergo conventional mitral valve surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Disfunção Erétil , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Disfunção Erétil/etiologia , Feminino , Humanos , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Valva Mitral/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
15.
Acta Pharmacol Sin ; 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35396533

RESUMO

Aberrant activation of cardiac fibroblasts is the main cause and character of cardiac fibrosis, and inhibition of cardiac fibrosis becomes a promising treatment for cardiac diseases. Platelet-activating factor (PAF) and Hippo pathway is recently recognized as key signaling mechanisms in cardiovascular diseases. In this study we explored the potential roles of PAF and Hippo signaling pathway in cardiac fibrosis. Myocardial infarction (MI) was induced in mice by left anterior descending artery ligation. After 28 days, the mice were sacrificed, and the hearts were collected for analyses. We showed that PAF receptor (PAFR) and yes-associated protein 1 (YAP1, a key effector in the Hippo pathway) were significantly increased in the heart of MI mice. Increased expression of PAFR and YAP1 was also observed in angiotensin II (Ang II)-treated mouse cardiac fibroblasts. In mouse cardiac fibroblasts, forced expression of YAP1 increased cell viability, resulted in collagen deposition and promoted fibroblast-myofibroblast transition. We showed that PAF induced fibrogenesis through activation of YAP1 and promoted its nuclear translocation via interacting with PAFR, while YAP1 promoted the expression of PAFR by binding to and activating transcription factor TEAD1. More importantly, silencing PAFR or YAP1 by shRNA, or using transgenic mice to induce the conditional deletion of YAP1 in cardiac fibroblasts, impeded cardiac fibrosis and improved cardiac function in MI mice. Taken together, this study elucidates the role and mechanisms of PAFR/YAP1 positive feedback loop in cardiac fibrosis, suggesting a potential role of this pathway as novel therapeutic targets in cardiac fibrosis.

16.
Anesth Analg ; 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35426836

RESUMO

BACKGROUND: Because it is traditionally difficult and time-consuming to identify the foramen ovale (FO) with fluoroscopy, we recently developed the H-figure method to acquire fluoroscopic view of FO with shorter procedure time and less radiation. However, the impact of such an H-figure approach on the clinical outcomes of trigeminal ganglion radiofrequency thermocoagulation (RFT) in treating idiopathic trigeminal neuralgia (ITN) remains unclear. METHODS: In a 12-month follow-up retrospective cohort study, patients with ITN had fluoroscopy-guided RFT of trigeminal ganglion via either classic approach (n = 100) or H-figure approach (n = 136) to identify FO. Data of continuous variables were analyzed with a Shapiro-Wilk test for normality and subsequently with a Mann-Whitney test, and the binary data were analyzed with a χ2 test. The primary outcome was the facial pain measured by a Visual Analog Scale (VAS) 1 year after the treatment. The secondary outcomes included the quality of the fluoroscopic FO views, the threshold voltage to provoke paresthesia, the procedure time, the number of fluoroscopic images, and the facial numbness VAS. RESULTS: Compared with the classic approach group, the H-figure approach group was associated with better long-term pain relief after the procedure, with significantly fewer patients had pain 3 months (6.6% vs 17.0%, P = .012) and 12 months (21.3% vs 38.0%, P = .005) after the procedure, and among patients who had pain after the procedure, patients in the H-figure group had significantly less pain 6 months after the procedure (VAS median [interquartile range (IQR)]: 3 [2-6] vs 6 [4-7], P < .001). Moreover, compared to the classic approach, the H-figure approach provided better fluoroscopic view of FO, lower threshold voltage to elicit paresthesia (median [IQR]: 0.2 [0.2-0.3] vs 0.4 [0.4-0.5] V, P < .0001), with shorter procedure time (median [IQR]: 7.5 [6.0-9.0] vs 14.0 [10.0-18.0] min, P < .0001), and required fewer fluoroscopic images (median [IQR]: 4.0 [3.0-5.0] vs 8.0 [6.0-10.0], P < .0001). CONCLUSIONS: RFT of the trigeminal ganglion using the H-figure approach is associated with superior longer term clinical pain relief than the classic approach in treating ITN.

17.
BMC Med ; 20(1): 107, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35382819

RESUMO

BACKGROUND: Adding anti-angiogenics to neoadjuvant chemotherapy for localized gastric cancer is recognized as a promising strategy, but its clinical value remains to be defined. METHODS: This single-center, single-arm, phase 2 trial included patients with locally advanced (cT3/4aN+M0) adenocarcinoma of the stomach or gastroesophageal junction (GEJ) who received three cycles of intravenous oxaliplatin (135 mg/m2 on day 1), oral capecitabine (1000 mg/m2 twice daily on days 1 to 14), and oral apatinib for 21 days (250 mg once daily in the first two cycles, and further increased to 500 mg daily in the third cycle based on whether any adverse event of grade 3 or worse occurred), and an additional cycle of oxaliplatin plus capecitabine, followed by gastrectomy with D2 lymphadenectomy. The primary endpoint was the proportion of patients who achieved an objective response according to RECIST version 1.1. RESULTS: Between April 28, 2017, and October 23, 2019, 37 patients were screened and 35 participants were included. Of the 32 patients assessable for efficacy and safety, objective responses were achieved in 25 (78.1%; 95% confidence interval [CI], 60.0% to 90.7%) patients. Thirty-one (96.9%) patients received R0 resection, two (6.3%) patients achieved pathological complete response, and 11 (34.4%) patients achieved pathological response. At the data cutoff date (September 30, 2021), the median event-free survival was 42.6 (95% CI, 16.2 to not reached) months, and the median overall survival was not reached. The most common grade 3 or 4 treatment-emergent adverse events were hypertension (9/32, 28.1%), thrombocytopenia (7/32, 21.9%), and neutropenia (5/32, 15.6%). Seven (21.9%) patients developed surgical complications, and the most common one was intra-abdominal abscess (4/32, 12.5%). CONCLUSIONS: The concomitant use of apatinib, oxaliplatin, and capecitabine as neoadjuvant therapy showed promising efficacy and manageable safety profile in patients with locally advanced adenocarcinoma of the stomach or GEJ, and further phase 3 study is warranted. TRIAL REGISTRATION: This study was registered with ClinicalTrial.gov ( NCT03229096 ).


Assuntos
Adenocarcinoma , Terapia Neoadjuvante , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina/efeitos adversos , Junção Esofagogástrica/patologia , Humanos , Oxaliplatina/efeitos adversos , Piridinas
18.
Front Endocrinol (Lausanne) ; 13: 829565, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35299962

RESUMO

Diabetes, a disease characterized by hyperglycemia, has a serious impact on the lives and families of patients as well as on society. Diabetes is a group of highly heterogeneous metabolic diseases that can be classified as type 1 diabetes (T1D), type 2 diabetes (T2D), gestational diabetes mellitus (GDM), or other according to the etiology. The clinical manifestations are more or less similar among the different types of diabetes, and each type is highly heterogeneous due to different pathogenic factors. Therefore, distinguishing between various types of diabetes and defining their subtypes are major challenges hindering the precise treatment of the disease. T2D is the main type of diabetes in humans as well as the most heterogeneous. Fortunately, some studies have shown that variants of certain genes involved in monogenic diabetes also increase the risk of T2D. We hope this finding will enable breakthroughs regarding the pathogenesis of T2D and facilitate personalized treatment of the disease by exploring the function of the signal genes involved. Hepatocyte nuclear factor 1 homeobox A (HNF1α) is widely expressed in pancreatic ß cells, the liver, the intestines, and other organs. HNF1α is highly polymorphic, but lacks a mutation hot spot. Mutations can be found at any site of the gene. Some single nucleotide polymorphisms (SNPs) cause maturity-onset diabetes of the young type 3 (MODY3) while some others do not cause MODY3 but increase the susceptibility to T2D or GDM. The phenotypes of MODY3 caused by different SNPs also differ. MODY3 is among the most common types of MODY, which is a form of monogenic diabetes mellitus caused by a single gene mutation. Both T2D and GDM are multifactorial diseases caused by both genetic and environmental factors. Different types of diabetes mellitus have different clinical phenotypes and treatments. This review focuses on HNF1α gene polymorphisms, HNF1A-MODY3, HNF1A-associated T2D and GDM, and the related pathogenesis and treatment methods. We hope this review will provide a valuable reference for the precise and individualized treatment of diabetes caused by abnormal HNF1α by summarizing the clinical heterogeneity of blood glucose abnormalities caused by HNF1α mutation.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Células Secretoras de Insulina , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Gestacional/genética , Diabetes Gestacional/metabolismo , Feminino , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Humanos , Células Secretoras de Insulina/metabolismo , Fenótipo , Gravidez
19.
PLoS One ; 17(3): e0265551, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35303014

RESUMO

BACKGROUND: The major aim of this Bayesian network analysis was to determine the optimal treatment strategy for locoregionally advanced nasopharyngeal carcinoma (LANPC). METHOD: We systematically searched databases and extracted data from randomized clinical trials involving LANPC patients randomly assigned to receive induction chemotherapy followed by concurrent chemoradiotherapy (IC+CCRT), CCRT followed by adjuvant chemotherapy (CCRT+AC), or CCRT. RESULTS: In the network analysis, IC+CCRT was significantly better than CCRT alone for 5-year FFS (odds ratio [OR]: 1.63, 95% credible interval [CrI] 1.16-2.29), DMFS (OR: 1.56, 95% CrI 1.08-2.22), and LFRS (OR: 1.62, 95% CrI 1.02-2.59), but not OS (OR: 1.35, 95% CrI 0.92-2.00). Rank probabilities showed that IC+CCRT was ranked the best followed by CCRT+AC and CCRT for all 5-year outcomes. Although compared to IC+CCRT and CCRT, CCRT+AC did not significantly improve survival but had the highest 5-year survival rates. CONCLUSIONS: IC+CCRT could be recommended as a front-preferred primary definitive therapy for patients with LANPC.


Assuntos
Neoplasias Nasofaríngeas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Teorema de Bayes , Quimiorradioterapia , Humanos , Quimioterapia de Indução , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/patologia , Metanálise em Rede
20.
Cell Death Dis ; 13(3): 217, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35260554

RESUMO

Gastric cancer (GC) is a heterogeneous disease with poor prognosis. Tumor-derived extracellular vesicles (EVs) assume a role in intercellular communication by carrying various molecules, including proteins, RNA, and DNAs, which has been identified to exhibit oncogenic effect in GC. Therefore, this research aimed to figure out whether tumor-derived EVs transmit c-Myc to orchestrate the growth and metastasis of GC. KCNQ1OT1, microRNA (miR)-556-3p and CLIC1 expression of GC tissues was detected through RT-qPCR. EVs were isolated from GC cells, followed by RT-qPCR and Western blot analysis of c-Myc expression in EVs and GC cells. Next, GC cells were incubated with EVs or transfected with a series of mimic, inhibitor, or siRNAs to assess their effects on cell viability, migrative, invasive, and apoptotic potential. Relationship among c-Myc, KCNQ1OT1, miR-556-3p, and CLIC1 was evaluated by dual-luciferase reporter assay. PI3K/AKT pathway-related proteins were assessed through Western blot analysis. KCNQ1OT1 and CLIC1 were highly expressed but miR-556-3p in GC tissues. c-Myc was high-expressed in tumor-derived EVs and GC cells. Mechanistically, c-Myc could induce KCNQ1OT1 expression, and KCNQ1OT1 bound to miR-556-3p that negatively targeted CLIC1 to inactivate PI3K/AKT pathway. Tumor-derived EVs, EVs-c-Myc, KCNQ1OT1 or CLIC1 overexpression, or miR-556-3p inhibition promoted GC cell proliferative, invasive, and migrative capacities but repressed their apoptosis through activating PI3K/AKT pathway. Collectively, tumor-derived EVs carrying c-Myc activated KCNQ1OT1 to downregulate miR-556-3p, thus elevating CLIC1 expression to activate the PI3K/AKT pathway, which facilitated the growth and metastasis of GC.


Assuntos
Vesículas Extracelulares , MicroRNAs , Neoplasias Gástricas , Proliferação de Células/genética , Canais de Cloreto/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/patologia
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