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Pulmonary arterial hypertension (PAH) is a pathophysiological syndrome that is extremely difficult to manage, and there is currently no effective treatment. We want to elucidate the therapeutic effect of ethyl pyruvate (EP) on PAH and its possible mechanism. Pulmonary artery endothelial cells (PAECs) were cultured in conventional low-oxygen environments, and cellular proliferation was monitored after treatment with EP. Expression of p-PI3K/Akt, LC3-II, and Beclin-1 was detected by Western blot. After hyperkinetic PAH rabbits' models were treated with EP, hemodynamic data were collected. Right ventricular hypertrophy and pulmonary vascular remodeling were evaluated. Expression of p-PI3K/Akt, LC3-II, and Beclin-1 protein was also detected after using autophagy inhibitor and agonists. We found that EP could inhibit PAECs proliferation. After EP treatment, expression of p-PI3K/Akt was upregulated in vitro and in vivo. LC3-II and Beclin-1 were inhibited and their expression was lower after autophagy inhibitor was given, while after administration of autophagy agonists, their expression was higher than that in the EP alone group. Besides, EP attenuated PAH, and right ventricular hypertrophy and pulmonary vascular remodeling were also reversed. EP can reduce PAH and reverse vascular remodeling which is associated with inhibition of autophagy in PAECs based on PI3K-Akt signaling pathway. The results of this study can provide surgical opportunities for patients with severe PAH caused by congenital heart disease in clinical cardiovascular surgery.
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BACKGROUND: Laparoscopic pancreatoduodenectomy (LPD) is one of the most challenging operations and has a long learning curve. Artificial intelligence (AI) automated surgical phase recognition in intraoperative videos has many potential applications in surgical education, helping shorten the learning curve, but no study has made this breakthrough in LPD. Herein, we aimed to build AI models to recognize the surgical phase in LPD and explore the performance characteristics of AI models. METHODS: Among 69 LPD videos from a single surgical team, we used 42 in the building group to establish the models and used the remaining 27 videos in the analysis group to assess the models' performance characteristics. We annotated 13 surgical phases of LPD, including 4 key phases and 9 necessary phases. Two minimal invasive pancreatic surgeons annotated all the videos. We built two AI models for the key phase and necessary phase recognition, based on convolutional neural networks. The overall performance of the AI models was determined mainly by mean average precision (mAP). RESULTS: Overall mAPs of the AI models in the test set of the building group were 89.7% and 84.7% for key phases and necessary phases, respectively. In the 27-video analysis group, overall mAPs were 86.8% and 71.2%, with maximum mAPs of 98.1% and 93.9%. We found commonalities between the error of model recognition and the differences of surgeon annotation, and the AI model exhibited bad performance in cases with anatomic variation or lesion involvement with adjacent organs. CONCLUSIONS: AI automated surgical phase recognition can be achieved in LPD, with outstanding performance in selective cases. This breakthrough may be the first step toward AI- and video-based surgical education in more complex surgeries.
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Inteligência Artificial , Laparoscopia , Pancreaticoduodenectomia , Gravação em Vídeo , Pancreaticoduodenectomia/métodos , Pancreaticoduodenectomia/educação , Humanos , Laparoscopia/métodos , Laparoscopia/educação , Curva de AprendizadoRESUMO
INTRODUCTION: While laparoscopic splenectomy (LS) has been widely used in benign splenic tumor, more concerns have been raised for postoperatively short-term and long-term complications. Laparoscopic partial splenectomy (LPS) is a surgical option, to preserve splenic function, and reduce postoperative complications. The aim of our study was to retrospectively identify the safety and feasibility of LPS compared with LS in patients with splenic benign tumor. MATERIALS AND METHODS: From 2014 to 2024, a total of 165 patients diagnosed with occupational splenic lesions underwent splenectomy, of whom 87 underwent LPS and 78 underwent LS. We compare the perioperative parameters and long term follow up between these two groups. RESULTS: The etiology of splenic space-occupying lesions was nonparasitic splenic cysts, followed by splenic lymphangioma and splenic hemangioma. Of the patients with LPS, 55 underwent conventional surgery with blockage of the splenic arterial branch and resection along the ischemic line (RAIL), and 32 underwent with our modified total splenic blood supply blockade followed by resection alone the tumor edge (RATE). The tumor size, the operative time and estimated blood loss were comparable between the LPS and LS groups. One patient developed abnormal signs during the LPS procedure and was promptly referred for LS. The LPS group had fewer pancreatic leakage, incision infection, and pulmonary infection. As for different vascular types, patients with LS under all branches of the splenic artery had a longer time to resume postoperative feeding. As for the comparison of RAIL and RATE, estimated blood and operative time were significantly reduced in patients receiving RATE. Postoperative complications were the same in patients underwent each surgical procedures. CONCLUSION: LPS is a viable approach for patients with splenic benign tumor. We introduce the tumor artery supply types to indicate the resection region. Our RATE technique has proven to be clinically effective and safety.
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BACKGROUND: Delayed gastric emptying (DGE) commonly occurs after pancreaticoduodenectomy (PD). Risk factors for DGE have been reported in open PD but are rarely reported in laparoscopic PD (LPD). This study was designed to evaluate the perioperative risk factors for DGE and secondary DGE after LPD in a single center. METHODS: This retrospective cohort study included patients who underwent LPD between October 2014 and April 2023. Demographic data, preoperative, intraoperative, and postoperative data were collected. The risk factors for DGE and secondary DGE were analyzed. RESULTS: A total of 827 consecutive patients underwent LPD. One hundred and forty-two patients (17.2%) developed DGE of any type. Sixty-five patients (7.9%) had type A, 62 (7.5%) had type B, and the remaining 15 (1.8%) had type C DGE. Preoperative biliary drainage (p = 0.032), blood loss (p = 0.014), and 90-day any major complication with Dindo-Clavien score ≥ III (p < 0.001) were independent significant risk factors for DGE. Seventy-six (53.5%) patients were diagnosed with primary DGE, whereas 66 (46.5%) patients had DGE secondary to concomitant complications. Higher body mass index, soft pancreatic texture, and perioperative transfusion were independent risk factors for secondary DGE. Hospital stay and drainage tube removal time were significantly longer in the DGE and secondary DGE groups. CONCLUSION: Identifying patients at an increased risk of DGE and secondary DGE can be used to intervene earlier, avoid potential risk factors, and make more informed clinical decisions to shorten the duration of perioperative management.
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Esvaziamento Gástrico , Laparoscopia , Pancreaticoduodenectomia , Complicações Pós-Operatórias , Humanos , Pancreaticoduodenectomia/efeitos adversos , Masculino , Feminino , Estudos Retrospectivos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Idoso , Fatores de Risco , Esvaziamento Gástrico/fisiologia , Gastroparesia/etiologia , Gastroparesia/epidemiologia , AdultoRESUMO
OBJECTIVE: Achieving textbook outcome (TO) implies a smooth recovery post-operation without specified composite complications. This study aimed to evaluate TO in laparoscopic pancreaticoduodenectomy (LPD) and identify independent risk factors associated with achieving TO. METHODS: We conducted a retrospective analysis of data from a randomized controlled trial on LPD at West China Hospital (ChiCTR1900026653). Patients were categorized into the TO and non-TO groups. Perioperative variables were compared between these groups. Multivariate logistic regression was utilized to identify the risk factors. RESULTS: A total of 200 consecutive patients undergoing LPD were included in this study. TO was achieved in 82.5% (n = 165) of the patients. Female patients (OR: 2.877, 95% CI: 1.219-6.790; P = 0.016) and those with a hard pancreatic texture (OR: 2.435, 95% CI: 1.018-5.827; P = 0.046) were associated with an increased likelihood of achieving TO. CONCLUSIONS: TO can be achieved in more than 80% of patients in a high-volume LPD center. Independent risk factors associated with achieving TO included gender (male) and pancreatic texture (soft).
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Laparoscopia , Pancreaticoduodenectomia , Humanos , Pancreaticoduodenectomia/métodos , Pancreaticoduodenectomia/efeitos adversos , Feminino , Masculino , Laparoscopia/métodos , Pessoa de Meia-Idade , Fatores de Risco , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Estudos Prospectivos , China/epidemiologia , Adulto , Hospitais com Alto Volume de Atendimentos , Complicações Pós-Operatórias/epidemiologiaRESUMO
AIM: Hyperkinetic pulmonary arterial hypertension (PAH) is a complication of congenital heart disease. Gene therapy is a new experimental treatment for PAH, and ultrasound-mediated gene-carrying microbubble targeted delivery is a promising development for gene transfer. METHODS: This study successfully established a hyperkinetic PAH rabbit model by a common carotid artery and jugular vein shunt using the cuff style method. Liposome microbubbles carrying the hepatocyte growth factor (HGF) gene were successfully constructed. An in vitro experiment evaluated the appropriate intensity of ultrasonic radiation by Western blots and 3H-TdR incorporation assays. In an in vivo experiment, after transfection of ultrasound-mediated HGF gene microbubbles, catheterisation was applied to collect haemodynamic data. Hypertrophy of the right ventricle was evaluated by measuring the right ventricle hypertrophy index. Western blot and immunohistochemistry analyses were used to detect the expression of human (h)HGF and angiogenic effects, respectively. RESULTS: The most appropriate ultrasonic radiation intensity was 1.0 W/cm2 for 5 minutes. Two weeks after transfection, both systolic pulmonary arterial pressure and mean pulmonary arterial pressure were attenuated. Hypertrophy of the right ventricle was reversed. hHGF was transplanted into the rabbits, resulting in a high expression of hHGF protein and an increase in the number of small pulmonary arteries. Ultrasound-mediated HGF gene microbubble therapy was more effective at attenuating PAH and increasing the density of small pulmonary arteries than single HGF plasmid transfection. CONCLUSIONS: Ultrasound-mediated HGF gene microbubbles significantly improved the target of gene therapy in a rabbit PAH model and enhanced the tropism and transfection rates. Thus, the technique can effectively promote small pulmonary angiogenesis and play a role in the treatment of PAH without adverse reactions.
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Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Animais , Coelhos , Humanos , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/terapia , Hipertensão Pulmonar/diagnóstico , Microbolhas , Fator de Crescimento de Hepatócito/genética , Hipertensão Pulmonar Primária Familiar , HipertrofiaRESUMO
A 37-year-old male patient with corrected transposition of great arteries (ccTGA) with cor triatriatum sinister (CTS), left superior vena cava, and atrial septal defects is reported in our case. None of these impacted the patient's growth or development, nor daily work until age 33. Later, the patient developed symptoms of obvious impaired heart function, which improved after medical treatment. However, the symptoms reappeared and gradually worsened two years later, and we decided to treat it with surgery. In this case, we selected tricuspid mechanical valve replacement, cor triatriatum correction, and atrial septal defect repair. During the follow-up of five years, the patient had no obvious symptoms, ECG did not change significantly from five years ago, and the cardiac color Doppler ultrasound showed RVEF 0.51.
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Coração Triatriado , Cardiopatias Congênitas , Comunicação Interatrial , Transposição dos Grandes Vasos , Masculino , Humanos , Adulto , Coração Triatriado/complicações , Coração Triatriado/diagnóstico , Coração Triatriado/cirurgia , Veia Cava Superior/cirurgia , Comunicação Interatrial/complicações , Comunicação Interatrial/diagnóstico , Comunicação Interatrial/cirurgia , Transposição dos Grandes Vasos/complicações , Transposição dos Grandes Vasos/diagnóstico , Transposição dos Grandes Vasos/cirurgiaRESUMO
Mass spectrometry (MS) has emerged as an excellent tool for the characterization of metal-organic frameworks (MOFs) based on the characteristic metal ions and organic ligands. Mass measurement of intact MOF nanocrystals, however, remains a challenge for MS technology. Here, we reported the development of a probe particles based charge detection-quadrupole ion trap mass spectrometry (probe CD-QIT MS) method, where charge detection and mass measurement of a single MOF nanocrystal were achieved under the assistance of probe particles of micrometer size. As a validation of the method, the masses of a series of polystyrene (PS) size standards from 493 nm to 1.6 µm were measured with 3 µm PS particles as probes, and the measured masses were found to match well with their certified masses. Then, charge detections and mass analysis of single ZIF-8 and GOx@ZIF-8 with a size around 600 nm were achieved successfully. The method presented here demonstrates simplicity, high speed, and accuracy. Notably, it allows quantitative measurement of the amount of immobilized GOx enzyme by using the mass difference between ZIF-8 and GOx@ZIF-8. In addition, based on the determined mass, the size analysis of these MOF particles with irregular shape was carried out and demonstrated to be complementary to transmission electron microscopy (TEM).
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Estruturas Metalorgânicas , Nanopartículas , Enzimas Imobilizadas/química , Íons , Estruturas Metalorgânicas/química , PoliestirenosRESUMO
Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) has emerged as a powerful tool for studying the spatial distribution of various types of molecules. Matrix deposition is a critical step for obtaining high-quality imaging data. An automatic device named SoniCoat was fabricated based on an ultrasonic nozzle driven by a pizeoelectric ceramic for matrix coating in the present study. Compared with the minihumidifier developed previously by our group for matrix deposition, SoniCoat realized automation, and the ultrasonic nozzle of this device is easy to clean and less likely to get clogged, indicating a longer life. Compared with commercial and homemade instruments such as the TM-Sprayer and electrospray matrix coating device, our newly developed device achieved a good nebulization effect without the need for high-pressure gas flow and high voltage. Matrix deposition by SoniCoat generated more homogeneous matrix crystals with diameters of about 10 µm and reduced the occurrence of molecular diffusion to a greater extent, compared with the results by TM-Sprayer. Repeatable high-spatial-resolution MS imaging data were obtained with the help of SoniCoat. Furthermore, the newly developed device can also be successfully applied for in situ derivatization.
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Lasers , Ultrassom , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodosRESUMO
The diagnosis of bladder cancer (BC) is currently based on cystoscopy, which is invasive and expensive. Here, we describe a noninvasive profiling method for carbonyl metabolic fingerprints in BC, which is based on a desorption, separation, and ionization mass spectrometry (DSI-MS) platform with N,N-dimethylethylenediamine (DMED) as a differential labeling reagent. The DSI-MS platform avoids the interferences from intra- and/or intersamples. Additionally, the DMED derivatization increases detection sensitivity and distinguishes carboxyl, aldehyde, and ketone groups in untreated urine samples. Carbonyl metabolic fingerprints of urine from 41 BC patients and 41 controls were portrayed and 9 potential biomarkers were identified. The mechanisms of the regulations of these biomarkers have been tentatively discussed. A logistic regression (LR) machine learning algorithm was applied to discriminate BC from controls, and an accuracy of 85% was achieved. We believe that the method proposed here may pave the way toward the point-of-care diagnosis of BC in a patient-friendly manner.
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Neoplasias da Bexiga Urinária , Aldeídos , Biomarcadores , Biomarcadores Tumorais/urina , Humanos , Espectrometria de Massas , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urinaRESUMO
BACKGROUND: It is 1 of the standard treatment options for metastasis pancreatic cancer to receive nab-paclitaxel (125 mg/m2) plus gemcitabine (1000 mg/m2) on days 1, 8 and 15 every 28 days. Some patients showed intolerance and inconvenience to this therapeutic regimen. Thus, we conducted this retrospective real-world study to determine the efficacy and tolerability of a modified 21-day nab-paclitaxel plus gemcitabine (nab-P/Gem) regimen for the first-line treatment of locally advanced or metastatic pancreatic cancer. METHODS: Patients with locally advanced and metastatic pancreatic cancer treated with nab-paclitaxel (125 mg/m2) plus gemcitabine (1000 mg/m2) on days 1 and 8 every 21-day at West China Hospital and Shang Jin Hospital of Sichuan University from Mar 2018 to Dec 2021 were reviewed retrospectively. Clinical characteristics of patients were collected. The progression-free survival, overall survival, objective response rate, disease control rate, and toxicity were evaluated. RESULTS: A total of 113 patients who received the modified regimen of 21-day nab-P/Gem chemotherapy were included. The median overall survival was 9.3 months and the median progression-free survival was 4.4 months. The objective response rate and disease control rate were 18.6% and 56.7%, respectively. The median relative dose intensity for this modified regimen was 65%. The adverse events were mild to moderate, and the most common grade 3 or 4 treatment-related adverse events were neutropenia (21%) and leukopenia (16%). CONCLUSIONS: Our study showed that this modified regimen of 21-day nab-P/Gem for locally advanced and metastatic pancreatic cancer had comparable efficacy and tolerable toxicity. This treatment may provide a considerable option for pancreatic cancer patients who desire a modified schedule. The modified regimen of 21-day nab-P/Gem is also an option worth considering during the coronavirus disease 2019 pandemic for minimizing the number of visits and limiting the risk of exposure.
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Antimetabólitos Antineoplásicos , Paclitaxel , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , GencitabinaRESUMO
BACKGROUND: Outcomes of pancreaticojejunostomy without pancreatic duct during open pancreaticoduodenectomy (OPD) are unknown and controversial, and corresponding reports in laparoscopic surgery are lacking. METHODS: Patients were evaluated at West China Hospital, and standard laparoscopic pancreaticoduodenectomy (LPD) was planned. A prospective randomized trial was conducted, in which the patients were randomly assigned to the no-stent and internal-stent groups in a single-center trial. The primary outcomes were the incidence of clinically relevant postoperative pancreatic fistula (CR-POPF) and 90-day mortality. Preliminary results were reported. RESULTS: From November 2019 to March 2021, we enrolled 90 patients (41 in the no-stent group and 49 in the internal-stent group) in the study. All baseline parameters of both groups, including age, sex ratio, pancreatic duct diameter, and intraoperative blood loss, were comparable between the two groups except for pathological diagnosis and the texture of remnants. Twenty-seven (65.9%) and 19 (38.8%) patients in the no-stent and internal-stent groups, respectively, had soft pancreatic remnants (P = 0.010). The total incidence of CR-POPF was 5.6% and included two patients (4.9%) in the no-stent group and three patients (6.1%) in the internal-stent group (P = 1.000). Only one patient in the internal-stent group died of heart failure within 90 days after the operation. No significant difference in other postoperative complications was observed between the groups except for biochemical fistula [no-stent group vs. internal-stent group = 31.7% vs. 12.2%, (P = 0.024)]. CONCLUSIONS: In a high-volume LPD center, duct-to-mucosa pancreaticojejunostomy without pancreatic duct stent is safe and reliable. In addition, duct-to-mucosa pancreaticojejunostomy without pancreatic duct stent was more challenge. We recommend using the stent during anastomosis and pulling it out after the procedure.
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Laparoscopia , Pancreaticojejunostomia , Humanos , Laparoscopia/efeitos adversos , Ductos Pancreáticos/cirurgia , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Fístula Pancreática/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticojejunostomia/efeitos adversos , Pancreaticojejunostomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Estudos Prospectivos , Stents/efeitos adversosRESUMO
Volatile organic compounds (VOCs) from exhaled breath (EB) are considered to be promising biomarkers for lung diseases. A convenient and sensitive point-of-care (POC) testing method for EB VOCs is essential. Here, we developed a POC test paper for the analysis of EB aldehydes, which are potential biomarkers for lung cancer. A probe molecule, 4-aminothiophenol (4-ATP), was anchored on a paper substrate to specifically capture gas-phase aldehydes through the Schiff base reaction. Meanwhile, thin-film reaction acceleration was utilized to increase capture efficiency. By directly coupling the test paper to a mass spectrometer through paper spray, high sensitivity (0.1 ppt) and a wide quantification linear range (from 10 ppt to 1 ppm) were obtained. Analysis of EB from lung cancer patients with the test paper showed a significant increase in several reported aldehyde markers compared to EB from healthy volunteers, indicating the potential of this method for sensitive, low-cost, and convenient lung cancer screening and diagnosis.
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Neoplasias Pulmonares , Compostos Orgânicos Voláteis , Aldeídos , Testes Respiratórios , Detecção Precoce de Câncer , Expiração , Humanos , Neoplasias Pulmonares/diagnóstico , Espectrometria de Massas , Testes ImediatosRESUMO
Current ambient ionization sources for mass spectrometry (MS) are typically connected to gas cylinders, high-voltage supply, injection pump, and other accessory equipment, which hinder the popularization of MS in the field of on-site detection. Here, we developed a wireless pocket-size "MasSpec Pointer" (weights 65 g) based on arc discharge powered by a 3.7 V polymer Li battery for ambient ionization MS. A high voltage of 5600 V and 20 kHz was generated from the boost coil to penetrate air and form a plasma. The relative standard deviation (RSD) of the high-voltage pulses is 3.8%, leading to a stable discharge and a good quantification performance. A mini diaphragm pump was used to cool the plasma from â¼600 to â¼40 °C and to blow the plasma into a jet, which facilitates sampling. MasSpec Pointer can work well at both positive- and negative-ion modes without any modification and can quickly test gaseous, liquid, or solid samples. The limit of detection of this device for atrazine (an agrochemical) is lower than 0.1 ng/mL. MasSpec Pointer has shown its ability to pinpoint the double-bond location of fatty acid isomers without derivatization reagents or light illumination. Agrochemicals from the surface of an apple and daily chemicals from the surface of a finger were detected successfully using MasSpec Pointer coupled with a miniature mass spectrometer. We believe the "point-and-shoot" device coupled with mini-MS brings the hope for an age of detecting chemicals on-site by nonprofessionals.
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Espectrometria de MassasRESUMO
Human esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers in human digestive system. It is necessary to discover novel antitumor agents for the treatment of esophageal cancers because of its poor prognosis. Indoline has been reported as an efficient anticancer fragment to design novel anticancer agents. In this work, indoline derivatives were designed, synthesized and explored their anticancer activity. Compound 9d, which exhibited potent antiproliferative activity with IC50 values of 1.84 µM (MGC-803 cells), 6.82 µM (A549 cells), 1.61 µM (Kyse30 cells), 1.49 µM (Kyse450 cells), 2.08 µM (Kyse510 cells) and 2.24 µM (EC-109 cells), respectively. The most active compound 9d was identified as a tubulin inhibitor targeting colchicine binding site with an IC50 value of 3.4 µM. Compound 9d could strongly suppress the tubulin polymerization in Kyse450 cells. The results of molecular docking also suggested compound 9d could tightly bind into the colchicine binding site of tubulin. Besides, compound 9d inhibited the growth of KYSE450 cells in a time and dose-dependent manner. All the results suggest that the indoline derivatives may be a class of novel tubulin inhibitors with potential anticancer activity, and which is worthy of further study.
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Antineoplásicos/farmacologia , Descoberta de Drogas , Indóis/farmacologia , Moduladores de Tubulina/farmacologia , Tubulina (Proteína)/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indóis/síntese química , Indóis/química , Estrutura Molecular , Polimerização/efeitos dos fármacos , Relação Estrutura-Atividade , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/químicaRESUMO
Human esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers in human digestive system. It is necessary to discover novel antitumor agents for the treatment of esophageal cancers because of its poor prognosis. Indoline has been reported as an efficient anticancer fragment to design novel anticancer agents. In this work, indoline derivatives were designed, synthesized and explored their anticancer activity. Compound 9d, which exhibited potent antiproliferative activity with IC50 values of 1.84 µM (MGC-803 cells), 6.82 µM (A549 cells), 1.61 µM (Kyse30 cells), 1.49 µM (Kyse450 cells), 2.08 µM (Kyse510 cells) and 2.24 µM (EC-109 cells), respectively. The most active compound 9d was identified as a tubulin inhibitor targeting colchicine binding site with an IC50 value of 3.4 µM. Compound 9d could strongly suppress the tubulin polymerization in Kyse450 cells. The results of molecular docking also suggested compound 9d could tightly bind into the colchicine binding site of ß-tubulin. Besides, compound 9d inhibited the growth of KYSE450 cells in time and dose-dependent manners. All the results suggest that the indoline derivatives might be a class of novel tubulin inhibitors with potential anticancer activity and is worthy of further study.
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To explore the fate and spreading mechanism of antibiotics resistance genes (ARGs) in antibiotics wastewater system, a laboratory-scale (1.47 L) Expanded Granular Sludge Bed (EGSB) bioreactor was implemented. The operating parameters temperature (T) and hydraulic retention time (HRT) were mainly considered. This result showed the removal of ARGs and COD was asynchronous, and the recovery speed of ARGs removal was slower than that COD removal. The decreasing T was attributed to the high growth rate of ARGs host bacteria, while the shortened HRT could promote the horizontal and vertical gene transfer of ARGs in the sludge. The analysis result of potential bacterial host showed more than half of the potential host bacteria carried 2 or more ARGs and suggested an indirect mechanism of co-selection of multiple ARGs. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to investigate the functional characteristics of bacterial community. This result showed the bacterial functional genes contributed 40.41% to the abundance change of ARGs in the sludge, which was higher that of bacterial community. And the function genes of "aromatic hydrocarbon degradation", "Replication, recombination and repair proteins" and "Flagellar assembly" were mainly correlated with the transfer of ARGs in the sludge. This study further revealed the mechanism of ARGs spread in the EGSB system, which would provide new ideas for the development of ARGs reduction technology.
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Esgotos , Águas Residuárias , Antibacterianos/farmacologia , Bactérias/genética , Resistência Microbiana a Medicamentos/genética , FilogeniaRESUMO
In this study, one lab-scale EGSB reactor (1.47 L volume) was designed to treat the antibiotic wastewater under different environmental factors, including the addition of cephalexin (CFX), Temperature (T) and Hydraulic Retention Time (HRT). The microbial community structure in EGSB reactor was analyzed with high-throughput sequencing technology to investigate their response to environmental factors changes, and then the random-matrix-theory (RMT)-based network analysis was used to investigate the microbial community's molecular ecological network in EGSB systems treating antibiotics wastewater. Moreover, the explanatory value of each environmental factor on the change of microbial community structure was obtained through the result of redundancy analysis (RDA). The results showed that the addition of cephalexin (CFX), decline of T and decline of HRT (8 h) would decrease the removal efficiency of COD decreasing. And the removal efficiency of CFX would not be affected by decline of T and HRT, except the producing and degrading process of CFX by-products was changed obviously. The result of RDA analysis suggested the environmental factors mainly affected bacterial and fungal microbial community structure but not archaeal ones. The result of high-throughput sequencing showed the relative abundance (RA) of Firmicutes had been obviously affected by T and HRT, which might be main reason leading to the decrease of COD removal efficiency. In addition, molecular ecological network analysis showed the growth of Bacteroidetes occupied the niche of functional microorganism and led to the unstable operation of EGSB when T declined. What's more, the molecular ecological network analysis revealed that Exophiala which belonged to fungi Ascomycota phylum was the hub genus to degrade complex refractory organic pollutants, and Aceticlastic methanogens Methanosaeta was the core functional archaea genus.
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Antibacterianos/isolamento & purificação , Reatores Biológicos/microbiologia , Microbiota , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Antibacterianos/metabolismo , Archaea/classificação , Archaea/genética , Archaea/crescimento & desenvolvimento , Archaea/metabolismo , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Fungos/classificação , Fungos/genética , Fungos/crescimento & desenvolvimento , Fungos/metabolismo , Temperatura , Águas Residuárias/química , Poluentes Químicos da Água/metabolismoRESUMO
BACKGROUND: The present study aims to assess the preliminary outcomes of the effectiveness of wrapping the ligamentum teres hepatis (LTH) around the gastroduodenal artery stump for the prevention of erosion hemorrhage after laparoscopic pancreaticoduodenectomy (LPD). METHODS: We reviewed 247 patients who had undergone LPD between January 2016 and April 2019. The patients were divided into two groups according to whether LTH wrapped the stump of the gastroduodenal artery: group A (119 patients) who underwent the LTH wrapping procedure, and group B (128 patients) who did not undergo the procedure. The perioperative data from the two groups were reviewed to assess the effectiveness of the LTH procedure for the prevention of postpancreatectomy hemorrhage (PPH) and other complications. RESULTS: No differences were observed in the clinical characteristics between the two groups. The data from 247 patients were acceptable for analysis: 119 patients underwent wrapping, and 128 patients did not. The incidence of clinically relevant pancreatic fistula (8.4% vs 3.9%), biliary fistula (2.5% vs 1.6%), intra-abdominal infection (10.1% vs 3.9%) and delayed gastric emptying (13.4% vs 16.4%) showed no significant difference between group A and group B. The 90-day mortality and 90-day reoperation rates (0.8% vs 0.8% and 5.0% vs 3.1%) were also similar between group A and group B. Furthermore, postpancreatectomy hemorrhage of Grade B and C occurred in 0 patients (0.0%) in the wrapping group, which was significantly less frequent than the occurrence in the nonwrapping group (7 patients; 5.5%, P = 0.02). CONCLUSIONS: Wrapping the LTH around the gastroduodenal artery stump after LPD does not reduce the incidence of clinically relevant pancreatic fistula, biliary fistula or delayed gastric emptying. However, this procedure has a trend of reducing the rate of PPH of Grade B and C after LPD and is simple to perform.
Assuntos
Laparoscopia , Neoplasias Pancreáticas , Pancreaticoduodenectomia , Hemorragia Pós-Operatória/prevenção & controle , Ligamento Redondo do Fígado , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Hemorragia Pós-Operatória/etiologia , Estudos Retrospectivos , Ligamento Redondo do Fígado/cirurgiaRESUMO
BACKGROUND: With the recent emerge of dynamic prediction model on the use of diabetes, cardiovascular diseases and renal failure, and its advantage of providing timely predicted results according to the fluctuation of the condition of the patients, we aim to develop a dynamic prediction model with its corresponding risk assessment chart for clinically relevant postoperative pancreatic fistula after laparoscopic pancreaticoduodenectomy by combining baseline factors and postoperative time-relevant drainage fluid amylase level and C-reactive protein-to-albumin ratio. METHODS: We collected data of 251 patients undergoing LPD at West China Hospital of Sichuan University from January 2016 to April 2019. We extracted preoperative and intraoperative baseline factors and time-window of postoperative drainage fluid amylase and C-reactive protein-to-albumin ratio relevant to clinically relevant pancreatic fistula by performing univariate and multivariate analyses, developing a time-relevant logistic model with the evaluation of its discrimination ability. We also established a risk assessment chart in each time-point. RESULTS: The proportion of the patients who developed clinically relevant postoperative pancreatic fistula after laparoscopic pancreaticoduodenectomy was 7.6% (19/251); preoperative albumin and creatine levels, as well as drainage fluid amylase and C-reactive protein-to-albumin ratio on postoperative days 2, 3, and 5, were the independent risk factors for clinically relevant postoperative pancreatic fistula. The cut-off points of the prediction value of each time-relevant logistic model were 14.0% (sensitivity: 81.9%, specificity: 86.5%), 8.3% (sensitivity: 85.7%, specificity: 79.1%), and 7.4% (sensitivity: 76.9%, specificity: 85.9%) on postoperative days 2, 3, and 5, respectively, the area under the receiver operating characteristic curve was 0.866 (95% CI 0.737-0.996), 0.896 (95% CI 0.814-0.978), and 0.888 (95% CI 0.806-0.971), respectively. CONCLUSIONS: The dynamic prediction model for clinically relevant postoperative pancreatic fistula has a good to very good discriminative ability and predictive accuracy. Patients whose predictive values were above 14.0%, 8.3%, and 7.5% on postoperative days 2, 3, and 5 would be very likely to develop clinically relevant postoperative pancreatic fistula after laparoscopic pancreaticoduodenectomy.