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1.
J Am Chem Soc ; 146(12): 8737-8745, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38483446

RESUMO

The nature of the active sites and their structure sensitivity are the keys to rational design of efficient catalysts but have been debated for almost one century in heterogeneous catalysis. Though the Brønsted-Evans-Polanyi (BEP) relationship along with linear scaling relation has long been used to study the reactivity, explicit geometry, and composition properties are absent in this relationship, a fact that prevents its exploration in structure sensitivity of supported catalysts. In this work, based on interpretable multitask symbolic regression and a comprehensive first-principles data set, we discovered a structure descriptor, the topological under-coordinated number mediated by number of valence electrons and the lattice constant, to successfully address the structure sensitivity of metal catalysts. The database used for training, testing, and transferability investigation includes bond-breaking barriers of 20 distinct chemical bonds over 10 transition metals, two metal crystallographic phases, and 17 different facets. The resulting 2D descriptor composing the structure term and the reaction energy term shows great accuracy to predict the reaction barriers and generalizability over the data set with diverse chemical bonds in symmetry, bond order, and steric hindrance. The theory is physical and concise, providing a constructive strategy not only to understand the structure sensitivity but also to decipher the entangled geometric and electronic effects of metal catalysts. The insights revealed are valuable for the rational design of the site-specific metal catalysts.

2.
J Med Chem ; 67(2): 922-951, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-38214982

RESUMO

Lysine specific demethylase 1 (LSD1), a transcriptional modulator that represses or activates target gene expression, is overexpressed in many cancer and causes imbalance in the expression of normal gene networks. Over two decades, numerous LSD1 inhibitors have been reported, especially some of which have entered clinical trials, including eight irreversible inhibitors (TCP, ORY-1001, GSK-2879552, INCB059872, IMG-7289, ORY-2001, TAK-418, and LH-1802) and two reversible inhibitors (CC-90011 and SP-2577). Most clinical LSD1 inhibitors demonstrated enhanced efficacy in combination with other agents. LSD1 multitarget inhibitors have also been reported, exampled by clinical dual LSD1/histone deacetylases (HDACs) inhibitors 4SC-202 and JBI-802. Herein, we present a comprehensive overview of the combination of LSD1 inhibitors with various antitumor agents, as well as LSD1 multitarget inhibitors. Additionally, the challenges and future research directionsare also discussed, and we hope this review will provide new insight into the development of LSD1-targeted anticancer agents.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Histona Desmetilases/metabolismo
3.
J Sci Food Agric ; 103(14): 7273-7283, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37450639

RESUMO

BACKGROUND: Bazi Bushen is a Chinese patented medicine with multiple health benefits and geroprotective effects, yet, no research has explored its effects on intestinal homeostasis. In this study, we aimed to investigate the effect of Bazi Bushen on intestinal inflammation and the potential mechanism of gut microbiota dysbiosis and intestinal homeostasis in senescence-accelerated mouse prone 6 (SAMP6). The hematoxylin and eosin (H&E) staining and immunohistochemistry were performed to assess the function of the intestinal mucosal barrier. The enzyme-linked immunosorbent assay (ELISA) and Western blotting were used to determine the level of intestinal inflammation. The aging-related ß-galactosidase (SA-ß-gal) staining and Western blotting were used to measure the extent of intestinal aging. The 16S ribosomal RNA (16S rRNA) was performed to analyze the change in gut microbiota composition and distribution. RESULTS: Bazi Bushen exerted remarkable protective effects in SAMP6, showing a regulated mucosal barrier and increased barrier integrity. It also suppressed intestinal inflammation through down-regulating pro-inflammatory cytokines (IL-6, IL-1ß, and TNF-α) and inhibiting TLR4/NFκB signaling pathway (MYD88, p-p65, and TLR4). Bazi Bushen improved intestinal aging by reducing the area of SA-ß-gal-positive cells and the expression of senescence markers p16, p21, and p53. In addition, Bazi Bushen effectively rebuilt the gut microbiota ecosystem by decreasing the abundance of Bacteroides and Klebsiella, whiles increasing the ratio of Lactobacillus/Bacteroides and the abundance of Akkermansia. CONCLUSION: Our study shows that Bazi Bushen could serve as a potential therapy for maintaining intestinal homeostasis. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Microbioma Gastrointestinal , Receptor 4 Toll-Like , Animais , Camundongos , Receptor 4 Toll-Like/genética , Ecossistema , RNA Ribossômico 16S , NF-kappa B/genética , Homeostase , Transdução de Sinais , Inflamação
4.
Pharmacol Ther ; 245: 108417, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37075933

RESUMO

With the booming development of precision medicine, molecular targeted therapy has been widely used in clinical oncology treatment due to a smaller number of side effects and its superior accuracy compared to that of traditional strategies. Among them, human epidermal growth factor receptor 2 (HER2)-targeted therapy has attracted considerable attention and has been used in the clinical treatment of breast and gastric cancer. Despite excellent clinical effects, HER2-targeted therapy remains in its infancy due to its resulting inherent and acquired resistance. Here, a comprehensive overview of HER2 in numerous cancers is presented, including its biological role, involved signaling pathways, and the status of HER2-targeted therapy.


Assuntos
Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Transdução de Sinais
5.
Materials (Basel) ; 16(4)2023 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-36837157

RESUMO

Biomass-derived raw bamboo charcoal (BC), NaOH-impregnated bamboo charcoal (BC-I), and magnetic bamboo charcoal (BC-IM) were fabricated and used as bio-adsorbents and Fenton-like catalysts for methylene blue removal. Compared to the raw biochar, a simple NaOH impregnation process significantly optimized the crystal structure, pore size distribution, and surface functional groups and increase the specific surface area from 1.4 to 63.0 m2/g. Further magnetization of the BC-I sample not only enhanced the surface area to 84.7 m2/g, but also improved the recycling convenience due to the superparamagnetism. The maximum adsorption capacity of BC, BC-I, and BC-IM for methylene blue at 328 K was 135.13, 220.26 and 497.51 mg/g, respectively. The pseudo-first-order rate constants k at 308 K for BC, BC-I, and BC-IM catalytic degradation in the presence of H2O2 were 0.198, 0.351, and 1.542 h-1, respectively. A synergistic mechanism between adsorption and radical processes was proposed.

6.
Mikrochim Acta ; 190(3): 98, 2023 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-36806988

RESUMO

Graphdiyne (GDY) has attracted a lot of interest in electrochemical sensing application with the advantages of a large conjugation system, porous structure, and high structure defects. Herein, to further improve the sensing effect of GDY, conductive MWCNTs were chosen as the signal accelerator. To get a stable composite material, polydopamine (PDA) was employed as connecting bridge between GDY and MWCNTs-NH2, where DA was firstly polymerized onto GDY, followed by covalently linking MWCNTs-NH2 with PDA through Michael-type reaction. The formed GDY@PDA/MWCNTs-NH2 composite was then explored as an electrochemical sensor for benomyl (Ben) determination. GDY assists the adsorption and accumulation of Ben molecules to the sensing surface, while MWCNTs-NH2 can enhance the electrical conductivity and electrocatalytic activity, all of which contributing to the significantly improved performance. The proposed sensor displays an obvious oxidation peak at 0.72 V (vs. Hg|Hg2Cl2) and reveals a wide linear range from 0.007 to 10.0 µM and a low limit of detection (LOD) of 1.8 nM (S/N = 3) toward Ben detection. In addition, the sensor shows high stability, repeatability, reproducibility, and selectivity. The feasibility of this sensor was demonstrated by detecting Ben in apple and cucumber samples with a recovery of 94-106% and relative standard deviations (RSDs) less than 2.3% (n = 5). A sensitive electrochemical sensing platform was reported for benomyl (Ben) determination based on a highly stable GDY@PDA/MWCNTs-NH2 composite.


Assuntos
Nanotubos de Carbono , Nanotubos de Carbono/química , Técnicas Eletroquímicas , Benomilo , Reprodutibilidade dos Testes
7.
World J Gastroenterol ; 29(2): 241-256, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36687127

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has been a serious threat to global health for nearly 3 years. In addition to pulmonary complications, liver injury is not uncommon in patients with novel COVID-19. Although the prevalence of liver injury varies widely among COVID-19 patients, its incidence is significantly increased in severe cases. Hence, there is an urgent need to understand liver injury caused by COVID-19. Clinical features of liver injury include detectable liver function abnormalities and liver imaging changes. Liver function tests, computed tomography scans, and ultrasound can help evaluate liver injury. Risk factors for liver injury in patients with COVID-19 include male sex, preexisting liver disease including liver transplantation and chronic liver disease, diabetes, obesity, and hypertension. To date, the mechanism of COVID-19-related liver injury is not fully understood. Its pathophysiological basis can generally be explained by systemic inflammatory response, hypoxic damage, ischemia-reperfusion injury, and drug side effects. In this review, we systematically summarize the existing literature on liver injury caused by COVID-19, including clinical features, underlying mechanisms, and potential risk factors. Finally, we discuss clinical management and provide recommendations for the care of patients with liver injury.


Assuntos
COVID-19 , Hepatopatias , Humanos , Masculino , COVID-19/complicações , SARS-CoV-2 , Hepatopatias/etiologia , Hepatopatias/terapia , Hepatopatias/epidemiologia , Fatores de Risco
8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-970744

RESUMO

The underground environment is dark and humid, and it is easy to breed pathogenic microorganisms. A lump in the right lung of a coal mine underground transport worker was found druing occupational health examination. CT examination showed that the lump was located in the posterior segment of the upper lobe of the right lung, with point strip calcification, liquefaction necrosis, and proximal bronchial stenosis and occlusion. MRI examination FS-T(2)WI and DWI showed "target sign", annular low signal around the central high signal, and low mixed signal around the periphery, and annular high signal in the isosignal lesions on T(1)WI. Then the pulmonary aspergillus infection was confirmed by pathology.


Assuntos
Humanos , Carvão Mineral , Mineradores , Pneumonia , Pulmão , Aspergilose , Minas de Carvão
9.
Food Sci Nutr ; 10(11): 3865-3875, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36348791

RESUMO

Our general purpose was to examine the effect of condensed Fuzheng extract (CFE) on the alleviation of immunosuppression. A mouse model of immunosuppression was established by intraperitoneal injection of CTX. A healthy control group received no CTX and no CFE; different intragastric doses of CFE were administered to three groups of mice for 28 days (4500, 2250, or 1125 mg/kg/day); a negative control received CTX alone, and a positive control received CTX and levamisole hydrochloride. We evaluated the effects of CFE on the immune system organs, cells, and molecules by comparing the different groups. CFE significantly improved immune system organs (spleen and thymus indices and histology), stimulated immune cell activities (number of white blood cells and lymphocytes, phagocytosis of mononuclear phagocytes, proliferation of splenic lymphocytes, antibody formation, and NK cell activity), and increased the levels of immunoglobulins (IgA, IgG, and IgM) and cytokines (IL-2 and IFN-γ). Thus CFE effectively alleviated CTX-mediated immunosuppression and oxidative stress and enhanced the immunological functions of mice.

10.
Contrast Media Mol Imaging ; 2022: 1591507, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35854763

RESUMO

Objectives: Epidemiological evidence suggests that anion gap (AG) has been reported to serve as an independent predictor for mortality in different diseases. We studied the effect of AG on both short and long-term mortalities in critically ill patients with hip fracture. Methods: A large clinical database was utilized to perform retrospective cohort analysis. AG was subdivided into three groups. The Cox proportional hazards regression model was employed to approximate the hazard ratio (HR) with a confidence interval (CI) of 95% for the link between AG and mortality. 30-day mortality is the primary outcome, while 90-day and 1-year mortalities represented our secondary outcomes for this study. Results: The participants in this study were that who provided essential data on AG and the number of patients with hip fractures was 395, and they were all aged ≥16 years. The participants comprised 199 (50.4%) females as well as 196 (49.6%) males with an average age of 71.9 ± 19.4 years, and a mean AG of 12.4 ± 3.3 gmEq/L. According to an unadjusted model for 30-day all-cause mortality, the HR (95% CI) of AG ≥ 12.5 gmEq/L was 1.82 (1.11, 2.99), correspondingly, compared to the reference group (AG < 12.5 gmEq/L). This correlation was still remarkable after adjustment for r age, sex, race, SBP, DBP, WBC, heart failure, and serum chloride (HR = 1.70, 95% CI: 1.02-2.02; 2.82). For 90-day all-cause mortality, a similar correlation was observed. Conclusions: We noted that AG was an independent indicator of both short and long-term mortalities among hip fractures individuals in this retrospective single-center cohort study. AG is a simple, readily available, and inexpensive laboratory variable that can serve as a possible risk stratification tool for hip fracture.


Assuntos
Estado Terminal , Fraturas do Quadril , Equilíbrio Ácido-Base , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Toxicol Appl Pharmacol ; 442: 115975, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35307376

RESUMO

BACKGROUND: Hepatic ischemia-reperfusion (HIR) injury is a pathological condition initiated by interrupted hepatic blood supply and exaggerated after reperfusion, which is one of the most lethal risks in liver transplantation and other liver surgeries. We aimed to investigate the protective mechanism of octreotide (Oct) against HIR injury. METHODS: The function of Oct was evaluated in the in vivo mouse model of HIR injury. Histological examinations were performed to assess the pathological changes. Serum parameters including ALT and AST were measured to evaluate the liver damage. qRT-PCR and western blot analysis were employed to determine the levels of long non-coding RNA SNHG12 (SNHG12) and autophagy or apoptosis-related proteins. RNA pull-down and RIP assays were used to verify the interaction between SNHG12 and TAF15. The transcriptional regulation of TAF15 in YAP1 was validated by ChIP and luciferase reporter assays. RESULTS: In the in vivo HIR injury model, Oct efficiently alleviated HIR-caused hepatic damage by suppressing apoptosis and activating autophagy. However, silencing of SNHG12 abrogated the protective effects of Oct via inactivating autophagy. Further mechanism investigation revealed that SNHG12 promoted the stabilization of Sirt1 and increased YAP1 transcriptional activity via interacting with TAF15. Up-regulation of Sirt1 and YAP1 was essential for maintaining the protective effect of Oct against HIR injury through increasing autophagic flux and suppressing apoptosis. CONCLUSIONS: Oct-induced up-regulation of SNHG12 attenuated HIR injury via promoting Sirt1 stabilization and YAP1 transcription to activate autophagy and repress apoptosis.


Assuntos
Hepatopatias , Octreotida , RNA Longo não Codificante , Traumatismo por Reperfusão , Sirtuína 1 , Fatores Associados à Proteína de Ligação a TATA , Proteínas de Sinalização YAP , Animais , Apoptose , Hepatopatias/tratamento farmacológico , Hepatopatias/patologia , Hepatopatias/prevenção & controle , Camundongos , Octreotida/farmacologia , Octreotida/uso terapêutico , RNA Longo não Codificante/genética , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Sirtuína 1/genética , Fatores Associados à Proteína de Ligação a TATA/farmacologia , Transcrição Gênica , Proteínas de Sinalização YAP/genética
12.
J Fungi (Basel) ; 8(2)2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35205867

RESUMO

Apple Valsa canker is one of the most serious diseases, having caused significant apple yield and economic loss in China. However, there is still no effective biological methods for controlling this disease. Our present study focused on the inhibitory activity and mechanisms of Trichoderma longibrachiatum (T6) fermentation on Valsa mali that causes apple Valsa canker (AVC). Our results showed that the T6 fermentation exhibited effective antifungal activity on the mycelial growth and conidia germination of V. mali, causing mycelium malformation and the hyphal disintegrating in comparison to the control. The activity of pathogenically related enzymes that are secreted from V. mali and the expression level of gene of V. mali were significantly inhibited and downregulated by treatment with T6 fermentation. In addition, the lesion area and number of pycnidia of V. mali formed on the branches were significantly reduced after treatment with the T6 fermentation through the pathogenicity test on the detached branches. Our results indicate that the possible mechanism of T6 fermentation against V. mali occurs through inhibiting its growth and reproduction, the pathogenic enzyme activity, and its related gene expression.

13.
Ann Hepatol ; 27(2): 100676, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35093600

RESUMO

INTRODUCTION AND AIM: Chronic hepatitis B (CHB) is a global epidemic disease that results from hepatitis B virus (HBV) infection and may progress to liver cirrhosis. The relationship between hepatitis B virus-related cirrhosis (HBV-RC) and gut microbiota dysbiosis is still unclear. The aim of this study is to elucidate the compositional and functional characteristics of the gut microbiota in the patients with liver cirrhosis and healthy individuals. MATERIALS AND METHODS: We analyzed the gut microbiome in patients with HBV-RC and healthy individuals by 16S rRNA sequencing and metagenomic sequencing of fecal samples. A total of 113 genera, 85 families, 57 orders, 44 classes and 21 phyla were performed. RESULTS: Our results suggests that the composition of the gut microbiota had changed in the early stages of cirrhosis. We further identified more than 17 genera with different richness in compensated and decompensated cirrhosis groups. PICRUSt analysis showed that changes in bacterial composition can lead to significant changes in gene function, which may be one of the causes of liver cirrhosis. CONCLUSION: Our study demonstrated that the composition of gut microbiota changed at different phases of HBV-RC. Gut microbiome transformation may be a biological factor in the progression of cirrhosis.


Assuntos
Microbioma Gastrointestinal , Vírus da Hepatite B , Disbiose/microbiologia , Fezes/microbiologia , Vírus da Hepatite B/genética , Humanos , Cirrose Hepática , RNA Ribossômico 16S/genética
14.
Protein & Cell ; (12): 47-64, 2022.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-922492

RESUMO

As a sensor of cytosolic DNA, the role of cyclic GMP-AMP synthase (cGAS) in innate immune response is well established, yet how its functions in different biological conditions remain to be elucidated. Here, we identify cGAS as an essential regulator in inhibiting mitotic DNA double-strand break (DSB) repair and protecting short telomeres from end-to-end fusion independent of the canonical cGAS-STING pathway. cGAS associates with telomeric/subtelomeric DNA during mitosis when TRF1/TRF2/POT1 are deficient on telomeres. Depletion of cGAS leads to mitotic chromosome end-to-end fusions predominantly occurring between short telomeres. Mechanistically, cGAS interacts with CDK1 and positions them to chromosome ends. Thus, CDK1 inhibits mitotic non-homologous end joining (NHEJ) by blocking the recruitment of RNF8. cGAS-deficient human primary cells are defective in entering replicative senescence and display chromosome end-to-end fusions, genome instability and prolonged growth arrest. Altogether, cGAS safeguards genome stability by controlling mitotic DSB repair to inhibit mitotic chromosome end-to-end fusions, thus facilitating replicative senescence.

15.
Int J Gen Med ; 14: 8621-8630, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34849007

RESUMO

BACKGROUND: The aim of the study was to develop a nomogram to predict the overall survival (OS) of patients with solitary plasmacytoma of bone (SBP). MATERIALS AND METHODS: Patients diagnosed with SBP between 1993 and 2012 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. All eligible patients were randomly allocated to the training sets and the validation sets. The nomogram was developed with the training set and validated with the validation set using the concordance index (C-index), calibration plots, and decision curve analyses (DCA). RESULTS: Age, marital status, tumor grade, treatment were independent prognostic indicators for OS (P<0.05) and were integrated to construct the nomogram. C-indexes for OS prediction in the training and validation sets were 0.78 and 0.73, respectively. The calibration plots demonstrated good consistency between the predicted and actual survival. DCA demonstrated that the new model has great benefits. In the total cohort, the median OS of patients in the low- and high-risk groups were 12.17 (95% CI 11.92-12.42) and 3.92 (95% CI 2.83-5.01) years, respectively. CONCLUSION: The nomogram showed excellent applicability and accuracy, which could be a reliable tool for predicting OS in SBP patients.

16.
Protein & Cell ; (12): 394-410, 2021.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-880913

RESUMO

Traditional Chinese Medicine (TCM) has been extensively used to ameliorate diseases in Asia for over thousands of years. However, owing to a lack of formal scientific validation, the absence of information regarding the mechanisms underlying TCMs restricts their application. After oral administration, TCM herbal ingredients frequently are not directly absorbed by the host, but rather enter the intestine to be transformed by gut microbiota. The gut microbiota is a microbial community living in animal intestines, and functions to maintain host homeostasis and health. Increasing evidences indicate that TCM herbs closely affect gut microbiota composition, which is associated with the conversion of herbal components into active metabolites. These may significantly affect the therapeutic activity of TCMs. Microbiota analyses, in conjunction with modern multiomics platforms, can together identify novel functional metabolites and form the basis of future TCM research.

17.
International Journal of Surgery ; (12): 715-720, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-907511

RESUMO

Acute abdomen is often a general term for abdominal diseases with acute abdominal pain as the main manifestation. Common clinical acute abdomen includes acute appendicitis, acute cholecystitis, acute cholangitis, acute pancreatitis, gastrointestinal perforation, intestinal obstruction and other diseases, its characteristics are great changes, rapid progress, high misdiagnosis rate, high postoperative complication rate and high mortality rate, accurate diagnosis and early treatment can obtain a good prognosis. With our in-depth understanding of the occurrence and development of acute abdomen diseases and the development of evidence-based medicine, minimally invasive technology plays a pivotal role in the diagnosis and treatment of common acute abdomen. Laparoscopy on diagnosis can clarify disease diagnosis to a large extent. For those who cannot undergo surgery, decompression and drainage under endoscopy provides a diversified plan for treatment decisions. In addition, minimally invasive techniques are also used in etiological treatment and complications. Disease, prevention of recurrence in all aspects, Minimally invasive technology is beneficial to the etiological treatment of biliary pancreatitis, appendicitis and cholangitis, and endoscopic technology is more consistent with the minimally invasive concept in the treatment of complications.

18.
Acta Pharmaceutica Sinica ; (12): 445-455, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-873769

RESUMO

With high selectivity and potency, target protein degradation technology has recently emerged as a strategy for drug discovery and design. Proteolysis-targeting chimeras (PROTAC) function as inducers for the degradation of target proteins and are a research focus in drug development. Current research on PROTAC mainly revolves around the rational design of PROTAC molecules, the discovery of new E3 ubiquitin ligase ligands and improvement in drug targeting. In this review, we focus on the PROTAC linker and its effects on the generation of the E3 enzyme-PROTAC-target protein ternary complex from three standpoints: length, binding site and chemical properties. We discuss the influences of the linker on the efficacy and the selectivity of PROTAC molecules.

19.
International Journal of Surgery ; (12): 82-86,f4, 2020.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-799705

RESUMO

Objective@#To explore the safety and feasibility of laparoscopic liver resection in the treatment of intrahepatic cholangiocarcinoma (ICC).@*Methods@#The retrospective study was adopted. The clinical data of 58 patients with ICC who underwent laparoscopic liver resection in the Department of Hepatobiliary Minimally Invasive Surgery of the First Affiliated Hospital of Hu′nan Normal University were collected From January 2016 to December 2018. Among them, 34 patients were males and 24 were females, aged from 34 to 71 years with a median age of 54 years. Observation indicators: (1) Surgical treatment: surgical methods, operation time, intraoperative blood loss, intraoperative blood transfusion rate, intraoperative hepatic portal blocking time, conversion rate, postoperative complications, postoperative hospital stay. (2) Postoperative pathological conditions. (3) Follow-up.Follow-up visits were conducted using an outpatient clinic and telephone to understand patient survival after surgery. The follow-up period was until June 2019. Measurement data with normal distribution were expressed as (Mean±SD), count data was expressed as frequency and percentage.@*Results@#A total of 58 patients were included in this study, of which 48 patients underwent laparoscopic radical surgical resection of intrahepatic cholangiocarcinoma and 10 patients underwent laparoscopic conversion to laparotomy. (1) Surgical treatment: laparoscopic resection of the left liver (segments Ⅱ, Ⅲ and Ⅳ), laparoscopic resection of the right liver (segments Ⅴ, Ⅵ, Ⅶ and Ⅷ), laparoscopic resection of the right posterior lobe (segments Ⅵ and Ⅶ), laparoscopic extended resection of the right posterior lobe, laparoscopic resection of the middle lobe (Ⅳ, Ⅴ and Ⅷ), laparoscopic resection of the V and Ⅵ, laparoscopic resection of the left liver (segments Ⅱ, Ⅲ and Ⅳ) combined with the caudate lobe (segments I and Ⅸ), laparoscopic extended left hemihepatectomy, laparoscopic resection of the VI, laparoscopic resection of the Ⅶ and Ⅷ, laparoscopic resection of the left lateral lobe (segments Ⅱ and Ⅲ) and laparoscopic resection of the right hepatic mass; operation time: (320.38±107.68) min; intraoperative blood loss: (262.34±76.06); intraoperative blood loss: 0 (0/58); Intraoperative hepatic portal occlusion time: (48±15) min, the conversion rate was 17.2% (10/58); the incidence of postoperative biliary fistula was 6.8% (4/58), and the patient was discharged after conservative treatment and unobstructed drainage (T-tube vacuum suction); the postoperative gastrointestinal recovery time was (1.84±0.57) d; no other serious complications occurred.Postoperative hospital stay: (9.34±3.39) d; there were no deaths and unplanned surgeries during the perioperative period. (2) Pathological conditions: 32 cases received lymph node dissection during the operation, and 26 cases showed cholangiocarcinoma without lymph node dissection; pathological examination showed that the pathological reports of all tumor margins were negative, and 4 cases showed lymph node dissection and positive lymph node metastasis. (3) Follow-up results: of the 58 patients with ICC, 49 were followed up for 6 to 36 months. The tumor survival time was (4 to 36) months. 28 patients survived without tumor. 17 patients had intrahepatic metastasis with multiple lymph node metastasis. 4 patients were treated with microwave ablation after intrahepatic metastasis was found. 9 patients were lost to follow-up.@*Conclusion@#Laparoscopic treatment of intrahepatic cholangiocarcinoma is safe and feasible in experienced centers.

20.
Chinese Journal of Surgery ; (12): 114-118, 2020.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-799375

RESUMO

Objective@#To investigate the safety and feasibility of longitudinal transpancreatic U-sutures invaginated pancreatojejunostomy (Chen′s pancreaticojejunostomy technique) in laparoscopic pancreaticoduodenectomy (LPD) .@*Methods@#Clinical data of 116 consecutive patients who underwent LPD using Chen′s pancreaticojejunostomy technique in Hunan Provincial People′s Hospital from May 2017 to December 2018 were retrospectively analyzed. Among these patients, 66 were males and 50 were females. The median age was 58 years old (32-84 yeas old). All 116 patients underwent pure laparoscopic whipple procedure with Child reconstruction method, using Chen′s pancreaticojejunostomy technique. The intraoperative and postoperative data of patients were analyzed.@*Results@#All 116 patients underwent LPD successfully. The mean operative time was (260.3±33.5) minutes (200-620 minutes). The mean time of pancreaticojejunostomy was (18.2±7.6) minutes (14-35 minutes) . The mean time of hepaticojejunostomy was (14.6±6.3) minutes (10-25 minutes). The mean time of gastrojejunostomy was (12.0±5.5) minutes (8-20 minutes). The mean estimated blood loss was (106.0±87.6) ml (20-800 ml). Postoperative complications were: 11.2% (13/116) of cases had postoperative pancreatic fistula (POPF) , including 10.3% (12/116) of biochemical fistula and 0.9% (1/116) of grade B POPF, no grade C POPF occurred; 10.3% (12/116) had gastrojejunal anastomotic bleeding; 3.4% (4/116) had hepaticojejunal anastomotic fistula; 3.4% (4/116) had delayed gastric emptying; 4.3% (5/116) had localized abdominal infection; 12.1% (14/116) had pulmonary infection; postoperative mortality were 0(0/116) and 1.7% (2/116) within 30 days and 90 days, respectively. One patient died of massive abdominal bleeding secondary to Gastroduodenal artery pseudoaneurysm rupture, the other patient died of extensive tumor recurrence and metastasis after surgery.@*Conclusions@#Chen′s pancreaticojejunostomy technique is safe and feasible for LPD.It is an option especially for surgeons who have not completed the learning curve of LPD.

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