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1.
World J Clin Cases ; 12(9): 1649-1659, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38576729

RESUMO

BACKGROUND: Postoperative pancreatic fistula (POPF) contributes significantly to morbidity and mortality after pancreaticoduodenectomy (PD). However, the underlying mechanisms remain unclear. This study explored this pathology in the pancreatic stumps and elucidated the mechanisms of POPF following PD. CASE SUMMARY: Pathological analysis and 16S rRNA gene sequencing were performed on specimens obtained from two patients who underwent complete pancreatectomy for grade C POPF after PD. Gradient inflammation is present in the pancreatic stump. The apoptosis was lower than that in the normal pancreas. Moreover, neutrophil-dominated inflammatory cells are concentrated in the ductal system. Notably, neutrophils migrated through the ductal wall in acinar duct metaplasia-formed ducts. Additionally, evidence indicates that gut microbes migrate from the digestive tract. Gradient inflammation occurs in pancreatic stumps after PD. CONCLUSION: The mechanisms underlying POPF include high biochemical activity in the pancreas, mechanical injury, and digestive reflux. To prevent POPF and address pancreatic inflammation and reflux, breaking the link with anastomotic dehiscence is practical.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 416-421, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38660845

RESUMO

OBJECTIVE: To explore the effect of shikonin on autophagy and apoptosis of human promyelocytic leukemia cells and its possible mechanism. METHODS: Human promyelocytic leukemia cells NB4 in the logarithmic growth phase were divided into control group (untreated NB4 cells), shikonin group (0.3 µmol/L shikonin treatment), 740Y-P group (15 µmol/L PI3K/Akt/mTOR pathway activator 740Y-P treatment), shikonin+740Y-P group (0.3 µmol/L shikonin and 15 µmol/L 740Y-P co-treatment), after 24 hours of treatment, the cells were used for subsequent experiments. CCK-8 method was used to detect cell viability, monodansylcadaverine (MDC) staining to detect the aggregation of autophagic vesicles, flow cytometry to detect cell apoptosis, and Western blot to detect the expression of Beclin1, LC3, p62, Bax, cleaved caspase-3, Bcl-2 and PI3K/Akt/mTOR pathway related proteins. RESULTS: Compared with the control group, the purple punctate fluorescence intensity, apoptosis rate, Beclin1, LC3-Ⅱ/LC3-Ⅰ, cleaved caspase-3, and Bax protein expression in NB4 cells were increased in the shikonin group, while OD450 value (24, 48 h) and the expressions of Bcl-2 and p62 proteins were decreased (all P < 0.05). Compared with the control group, the purple punctate fluorescence intensity, apoptosis rate, Beclin1, LC3-Ⅱ/LC3-Ⅰ, cleaved caspase-3, and Bax protein expression in NB4 cells were decreased, while OD450 value (24, 48 h) and the expressions of Bcl-2 and p62 proteins were increased in the 740Y-P group (all P < 0.05). Compared with the shikonin group, the purple punctate fluorescence intensity, apoptosis rate, Beclin1, LC3-Ⅱ/LC3-Ⅰ, cleaved caspase-3, and Bax protein expression in NB4 cells were decreased, while OD450 value (24, 48 h) and the expressions of Bcl-2 and p62 proteins were increased in the shikonin+740Y-P group (all P < 0.05). Compared with the control group, the expression of PI3K/Akt/mTOR pathway related proteins p-PI3K, p-Akt, and p-mTOR in NB4 cells were significantly decreased in the shikonin group, while those in the 740Y-P group were increased (all P < 0.05). Compared with the shikonin group, the expressions of p-PI3K, p-Akt, and p-mTOR proteins in NB4 cells were significantly increased in the shikonin+740Y-P group (all P < 0.05). CONCLUSION: Shikonin may promote autophagy and apoptosis of NB4 cells by inhibiting PI3K/Akt/mTOR pathway.


Assuntos
Apoptose , Autofagia , Leucemia Promielocítica Aguda , Naftoquinonas , Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TOR , Humanos , Autofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Naftoquinonas/farmacologia , Linhagem Celular Tumoral , Leucemia Promielocítica Aguda/patologia , Serina-Treonina Quinases TOR/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Sobrevivência Celular/efeitos dos fármacos , Caspase 3/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteína Beclina-1/metabolismo
4.
Front Psychol ; 14: 1025577, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37818421

RESUMO

Objective: This study aimed to investigate the clinical application effect of an augmented reality (AR) plasticity model on the postoperative visual function recovery of children with concomitant exotropia. Methods: Between September 2019 and October 2021, 28 patients with concomitant exotropia who visited Shenzhen Children's Hospital (9 male and 19 female) were enrolled in this study. The average age of the patients was 6.4 ± 1.8 years. Postoperative rehabilitation training was conducted using a personalized AR binocular visual perception plasticity model developed based on the patient's examination results. After 1 month, 3 months, and 6 months of training, the patients returned to the hospital for examinations of perceptual eye position, static zero-order stereopsis, dynamic first-order fine stereopsis, and dynamic second-order coarse stereopsis to compare the changes in eye position control and stereovision function. Results: After 6 months of eye position training, the horizontal perception eye position of the 28 patients was significantly lower than that before training. The difference in eye position at the first and third months compared with that before training was not statistically significant (1st month: z = -2.255, p = 0.024 > 0.017; 3rd month: z = -2.277, p = 0.023 > 0.017; 6th month: z = -3.051, p = 0.002 < 0.017). The difference in vertical perceptual eye position after training compared with that before training was not statistically significant (1st month: z = -0.252, p = 0.801 > 0.017; 3rd month: z = -1.189, p = 0.234 > 0.017; 6th month: z = -2.225, p = 0.026 > 0.017). The difference in 0.8-m static zero-order stereopsis before and after training was not statistically significant (1st month: z = -2.111, p = 0.035 > 0.017; 3rd month: z = -1.097, p = 0.273 > 0.017; 6th month: z = -1.653, p = 0.098 > 0.017). The 1.5-m static zero-order stereopsis was improved after 1 month, 3 months, and 6 months of training compared with that before training (1st month: z = -3.134, p = 0.002 < 0.017; 3rd month: z = -2.835, p = 0.005 < 0.017; 6th month: z = -3.096, p = 0.002 < 0.017). Dynamic first-order fine stereopsis and dynamic second-order coarse stereopsis were measured in the 28 patients before and after training. Patients 1 and 18 had no dynamic first-order fine stereopsis before training, but both regained dynamic stereopsis after 1 month, 3 months, and 6 months of training. Patient 16 had no dynamic first-order fine stereopsis or dynamic second-order coarse stereopsis before training, but first-order and second-order stereopsis had been reconstructed after 1 month, 3 months, and 6 months of training. Conclusion: Concomitant exotropia surgery improved the basic problem of eye position at the ocular muscle level, but the patient's perceptual eye position and visual function defects at the brain visual level remained. This might partly explain the poor postoperative clinical effect. The AR plasticity model can improve patients' horizontal perceptual eye position and multi-dimensional stereoscopic function, and its clinical effect warrants further study.

5.
Biomed Environ Sci ; 36(8): 715-724, 2023 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-37711083

RESUMO

Objective: This study aimed to reveal the insomnia burden and relevant influencing factors among informal caregivers (ICs) of hospitalized patients with lung cancer. Methods: A cross-sectional study on ICs of hospitalized patients with lung cancer was conducted from December 31, 2020 to December 31, 2021. ICs' burden was assessed using the Caregiver Reaction Assessment (CRA), Hospital Anxiety and Depression Scale (HADS), and Insomnia Severity Index (ISI). Linear and logistic regression models were used to identify the influencing factors. Results: Among 289 ICs of hospitalized patients with lung cancer, 83 (28.72%), 53 (18.34%), and 14 (4.84%) ICs experienced mild, moderate, and severe insomnia, respectively. The scores concerning self-esteem, lack of family support, financial problems, disturbed schedule, and health problems were 4.32 ± 0.53, 2.24 ± 0.79, 2.84 ± 1.14, 3.63 ± 0.77, and 2.44 ± 0.95, respectively. ICs with higher Activities of Daily Living Scale (ADLS) scores were associated with a lower risk of insomnia, with an odd ratio ( OR) and 95% confidence interval ( CI) of 0.940 (0.898-0.983). Among the ICs, female gender ( OR = 2.597), alcohol consumption ( OR = 3.745), underlying medical conditions ( OR = 11.765), long-term caregiving experience ( OR = 37.037), and higher monthly expenses ( OR = 5.714) were associated with a high risk of insomnia. Conclusion: Of the hospitalized patients with lung cancer, 51.9% experienced insomnia. Patients' ADL, ICs gender, alcohol consumption, underlying medical conditions, caregiving duration, and monthly expenses were influencing factors. Therefore, prompt screening and early intervention for ICs of patients with lung cancer is necessary.


Assuntos
Neoplasias Pulmonares , Distúrbios do Início e da Manutenção do Sono , Humanos , Feminino , Cuidadores , Atividades Cotidianas , Estudos Transversais , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Neoplasias Pulmonares/epidemiologia
6.
Bioeng Transl Med ; 8(5): e10558, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37693059

RESUMO

High positive charge-induced toxicity, easy lysosomal degradation of nucleic acid drugs, and poor lesion sites targeting are major problems faced in the development of gene carriers. Herein, we proposed the concept of self-escape non-cationic gene carriers for targeted delivery and treatment of photocontrolled hepatocellular carcinoma (HCC) with sufficient lysosome escape and multiple response capacities. Functional DNA was bound to the surface of biotin-PEG2000-modified graphitic carbon nitride (Bio-PEG-CN) nanosheets to form non-cationic nanocomplexes Bio-PEG-CN/DNA. These nanocomposites could actively target HCC tissue. Once these nanocomplexes were taken up by tumor cells, the accumulated reactive oxygen species (ROS) generated by Bio-PEG-CN under LED irradiation would disrupt the lysosome structure, thereby facilitating nanocomposites escape. Due to the acidic microenvironment and lipase in the HCC tissue, the reversible release of DNA could be promoted to complete the transfection process. Meanwhile, the fluorescence signal of Bio-PEG-CN could be monitored in real time by fluorescence imaging technology to investigate the transfection process and mechanism. In vitro and in vivo results further demonstrated that these nanocomplexes could remarkably upregulate the expression of tumor suppressor protein P53, increased tumor sensitivity to ROS generated by nanocarriers, and realized effective gene therapy for HCC via loading P53 gene.

7.
Adv Healthc Mater ; 12(29): e2301485, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37463681

RESUMO

Hypoxia is an important feature, which can upregulate the hypoxia-inducible factor-1α (HIF-1α) expression and promote the activation of hepatic stellate cells (HSCs), leading to liver fibrosis. Currently, effective treatment for liver fibrosis is extremely lacking. Herein, a safe and effective method is established to downregulate the expression of HIF-1α in HSCs via targeted delivery of VA-PEG-modified CNs-based nanosheets-encapsulated (VA-PEG-CN@GQDs) HIF-1α small interfering RNA (HIF-1α-siRNA). Due to the presence of lipase in the liver, the reversible release of siRNA can be promoted to complete the transfection process. Simultaneously, VA-PEG-CN@GQD nanosheets enable trigger the water splitting process to produce O2 under near-infrared (NIR) irradiation, thereby improving the hypoxic environment of the liver fibrosis site and maximizing the downregulation of HIF-1α expression to improve the therapeutic effect, as demonstrated in liver fibrosis mice. Such combination therapy can inhibit the activation of HSCs via HIF-1α-mediated TGF-ß1/Smad pathway, achieving outstanding therapeutic effects in liver fibrosis mice. In conclusion, this study proposes a novel strategy for the treatment of liver fibrosis by regulating the hypoxic environment and the expression of HIF-1α at lesion site.


Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia , Fator de Crescimento Transformador beta1 , Camundongos , Animais , Fator de Crescimento Transformador beta1/metabolismo , RNA Interferente Pequeno/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Cirrose Hepática/terapia , Hipóxia
8.
J Shoulder Elbow Surg ; 32(11): e548-e555, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37263479

RESUMO

BACKGROUND: The injury mechanism of acromioclavicular (AC) dislocation combined with coracoid process (CP) fracture is not clear, and there is no consensus on its treatment. This study was performed to evaluate the diagnosis of CP fractures combined with AC dislocation and the effectiveness of operative treatment using a clavicular hook plate. METHODS: Eighteen patients with CP fractures combined with AC dislocation were treated with a clavicular hook plate from May 2012 to June 2021. The patients comprised 10 male and 8 female patients with an average age of 38 years (range, 16-54 years). The injury was caused by falling in 15 patients, traffic accidents in 2 patients, and falling from a height in 1 patient. The Eyres type of CP fracture was type II in 1 patient, type III in 11 patients, type IV in 3 patients, and type V in 3 patients. The Ogawa type of CP fracture was type I in 17 patients and type II in 1 patient. The Rockwood type of AC dislocation was type V in 1 patient, variation type III in 15 patients, and variation type V in 2 patients. The interval from injury to the operation was 3 days (range, 1-7 days). Postoperative complications and CP fracture healing were recorded. Functional assessment at the last follow-up was performed by an independent reviewer using the Constant score and visual analog scale score. RESULTS: All 18 patients were followed up for a mean period of 49 months (range, 12-123 months). Nine patients had acromion osteolysis and 3 patients had CP fracture nonunion (Eyres type II, III, and V in 1 patient each); however, no patients developed shoulder pain, incision infection, limitation of shoulder movement, clinical symptoms of subcoracoid impingement, or AC dislocation relapse. At the last follow-up, the mean Constant score was 99 (range, 94-100). CONCLUSIONS: The possibility of CP fracture should be considered in patients with AC dislocation to avoid a missed diagnosis. Fixation with a clavicular hook plate is a feasible treatment for CP fracture combined with AC dislocation and provides a satisfactory outcome. CP fracture healing may be related to the fracture morphology.


Assuntos
Articulação Acromioclavicular , Fraturas Ósseas , Luxações Articulares , Luxação do Ombro , Humanos , Masculino , Feminino , Adulto , Articulação Acromioclavicular/diagnóstico por imagem , Articulação Acromioclavicular/cirurgia , Articulação Acromioclavicular/lesões , Processo Coracoide , Fixação Interna de Fraturas , Luxação do Ombro/cirurgia , Fraturas Ósseas/complicações , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Luxações Articulares/complicações , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/cirurgia , Placas Ósseas , Resultado do Tratamento
9.
J Mater Chem B ; 11(14): 3186-3194, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-36946887

RESUMO

Lipid droplets (LDs) and their autophagy by lysosomes are closely related to a variety of physiological and pathological conditions. Therefore, identifying and tracking LDs and the dynamic process of autophagy can provide useful information for the diagnostics and treatment of related diseases. However, few organic small molecule-based fluorescent probes can specifically recognize LDs and dynamically track their autophagy process. Herein, we synthesized a "discoloration" fluorescent bioprobe DPABP-BI with distinguishable features including red fluorescence emission (630 nm), large Stokes shift (145 nm), two-photon excitation and outstanding photostability and biocompatibility. In particular, LDs could be specifically identified via the red fluorescence emission of DPABP-BI (colocalization constant of 0.98), while autophagolysosomes could be visualized via the green fluorescence emission of its acid-hydrolyzed product (colocalization constant of 0.90) to track the autophagy dynamic process. In addition, DPABP-BI enabled the specific recognition of fatty substances in zebrafish larvae. In this study, a two-photon excited red light small molecule probe was constructed to identify LDs and track their autophagy dynamic process by changing the fluorescence emission wavelength.


Assuntos
Técnicas Biossensoriais , Gotículas Lipídicas , Animais , Peixe-Zebra , Lisossomos , Autofagia
10.
J Pharm Pharmacol ; 75(5): 686-692, 2023 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-36892979

RESUMO

OBJECTIVES: Fluoxetine has been used as the first line for the therapy of depression. However, lack of therapeutic efficacy and time lag still limit the application of fluoxetine. Gap junction dysfunction is a potentially novel pathogenic mechanism for depression. To clarify the mechanism underlying these limitations, we investigated whether gap junction was related to the antidepressant effects of fluoxetine. METHODS AND KEY FINDINGS: After chronic unpredictable stress (CUS), animals showed decreases in gap junction intracellular communication (GJIC). Treatment with fluoxetine 10 mg/kg significantly improved GJIC and anhedonia of rats until six days. These results indicated that fluoxetine improved gap junction indirectly. Furthermore, to test the role of gap junction on antidepressant effects of fluoxetine, we blocked gap junction using carbenoxolone (CBX) infusion in the prefrontal cortex. CBX dampened fluoxetine-induced decrease in immobility time of mice in tail suspension test (TST). CONCLUSIONS: Our study suggested that gap junction dysfunction blocks antidepressant effects of fluoxetine, contributing to understanding the mechanism underlying the time lag of fluoxetine.


Assuntos
Antidepressivos , Fluoxetina , Ratos , Camundongos , Animais , Fluoxetina/farmacologia , Antidepressivos/farmacologia , Junções Comunicantes , Elevação dos Membros Posteriores , Depressão/tratamento farmacológico , Modelos Animais de Doenças
11.
J Asian Nat Prod Res ; 25(7): 641-649, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36264599

RESUMO

Two new dimers of ambuic acid, pestaloversicoloric acids A (1) and B (2), and a known derivative, 13(S)-hydroxyambuic acid (3), were isolated from the static fermentation product of Pestalotiopsis versicolor. The structural identification was accomplished via analyses on the data of HR-MS, 1 D and 2 D NMR, and ECD. Different from the well-known exo-type dimer, torreyanic acid, compounds 1 and 2 represent the first example of endo-type product derived from the intermolecular Diels-Alder reaction of two molecules of ambuic acid derivative with the identical absolute stereochemistry.


Assuntos
Cicloexanonas , Estrutura Molecular , Reação de Cicloadição , Cicloexanonas/química
12.
Curr Med Sci ; 43(1): 130-138, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36459302

RESUMO

OBJECTIVE: Thyroid-associated ophthalmopathy (TAO) is an autoimmune disorder involving the orbital tissue. This study aimed to understand the role of regulatory T cells (Tregs) in TAO during 12-week systemic glucocorticoid (GC) treatment. METHODS: Thirty-two moderate-severe TAO patients with a clinical activity score (CAS) ≥3/7 or with prolonged T2 relaxation time (T2RT) on at least one side of extraocular muscle (EOM) were enrolled. The percentage of the peripheral CD4+CD25(high)CD127(-/low) Tregs was analyzed using flow cytometry before and after the GC treatment. The activity and severity of TAO, T2RT, and the clinical outcomes after the GC treatment were assessed. Their correlation with the peripheral Tregs was investigated. RESULTS: There was no significant association between the baseline Treg fraction and the activity and severity of TAO or the treatment response. A significant reduction of Tregs was observed after the GC therapy merely in patients without any clinical improvement. CONCLUSION: Treg reduction after systemic GC therapy is indicative of a poor therapeutic response. Accordingly, dynamic alterations of Tregs could help to evaluate the effectiveness of the GC treatment.


Assuntos
Doenças Autoimunes , Oftalmopatia de Graves , Humanos , Oftalmopatia de Graves/tratamento farmacológico , Glucocorticoides , Linfócitos T Reguladores , Músculos Oculomotores
13.
Curr Oncol ; 29(11): 8235-8243, 2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36354710

RESUMO

Common treatment methods for malignant tumors include surgery, chemotherapy, radiotherapy, immunotherapy, targeted therapy, etc., among which chemotherapy plays an important role. However, chemotherapy brings corresponding side effects while killing tumor cells, and nausea and vomiting are the most common adverse reactions induced by chemotherapy. It not only affects the patient's appetite, resulting in malnutrition and electrolyte disturbances, but also reduces the patient's compliance with treatment, which further aggravates the disease. Thus, it is important to quickly prevent and cure nausea and vomiting induced by chemotherapy (CINV). In addition, with the continuous development of medicine, more and more antiemetic drugs have been developed. At present, the most common antiemetic agents for chemotherapy-induced nausea and vomiting are NK-1R antagonists, 5-HT3R antagonists, and dexamethasone. Surprisingly, olanzapine, often used as a psychotropic drug, has been found to be an effective antiemetic and is similar to other regimens on the safety of medicine. However, although there are numerous studies on the antiemetic effects of olanzapine, its comprehensive application remains unclear. Therefore, this review will elaborate the antiemetic effect of olanzapine in terms of the antiemetic mechanism and the safety, economic cost, dose, administration time, and drug delivery aspects.


Assuntos
Antieméticos , Antineoplásicos , Humanos , Olanzapina/uso terapêutico , Antieméticos/farmacologia , Antieméticos/uso terapêutico , Preparações Farmacêuticas , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Náusea/prevenção & controle , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Vômito/prevenção & controle , Antineoplásicos/efeitos adversos
14.
Clin Lab ; 68(11)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36377989

RESUMO

BACKGROUND: Metastatic or recurrent endometrial cancers with low survival rate had no standard or limited therapy choice. The aim of our study was to determine the efficiency and safety of tislelizumab combined with carboplatin-paclitaxel as a front-line therapy for patients with metastatic or recurrent endometrial cancer. METHODS: This clinical retrospective cohort study examined 24 Chinese patients with metastasis or recurrence but had not yet received treatment. The therapeutic regimen consisted of 6 cycles of intravenous paclitaxel (175 mg/m2) and carboplatin (target AUC: 5 mg/mL/min) with tislelizumab (200 mg) once every 3 weeks, and then intravenous tislelizumab (200 mg) once every 3 weeks until disease progression or unacceptable toxicity. RESULTS: At the 18-month follow-up, 8 patients were still receiving treatment, 13 were dead, and 3 withdrew. The objective response rate (ORR) was 62.5%, the disease control rate was 75.00%. The ORR was 77.78% for patients positive for PD-L1 and 69.23% for patients positive for MSI-H. The median overall survival time was 11.50 months, and the median progression-free survival time was 6.00 months. Half of the patients experienced 3 - 4 grade adverse events. There were no allergic reactions or treatment-related deaths. CONCLUSIONS: Tislelizumab combined with carboplatin-paclitaxel was used as a front-line therapy, had a beneficial effect and was safe for patients with metastatic or recurrent endometrial cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Endométrio , Feminino , Humanos , Carboplatina/uso terapêutico , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/induzido quimicamente , Paclitaxel/uso terapêutico , Paclitaxel/efeitos adversos , Neoplasias do Endométrio/tratamento farmacológico
15.
Hum Vaccin Immunother ; 18(6): 2121109, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36166751

RESUMO

A 74-yr-old man underwent thoracic laparoscopy combined with radical gastrectomy, and the postoperative pathological diagnosis was esophageal and gastric cardia cancer pT3N1M0, pStage IIB. Immunohistochemical staining for HER2 (3+) and PD-L1 (<5%) was positive. Adjuvant chemotherapy was not performed because the patient developed severe thrombocytopenia (platelet counts <30 × 109/L), which was never cured throughout the reporting period. At 10.7 months post-surgery, he suffered metastases in multiple organs, including the peritoneum, liver, lung, and bone. Following two cycles of first-line trastuzumab and pembrolizumab (200 mg), he developed immune-related myositis (G2), myocarditis (G2), and hepatitis (G1). Therefore, pembrolizumab was discontinued. Trastuzumab was administered as a monotherapy; meanwhile, adoptive cytokine-induced killer (CIK) cell infusions were initiated. Eight months after the initial immunotherapy, a solitary brain metastasis was detected, and the patient underwent CyberKnife radiosurgery. For second-line therapy, adoptive CIK cell immunotherapy plus trastuzumab was still used. At the time of reporting, the patient had achieved a complete response (CR) in the brain and liver and a partial response (PR) in the ilium, and he had been followed-up for 36.6 months, much longer than the median survival time for patients with advanced GEJ cancer. We suggest that HER2-targeted therapy and immunotherapy with pembrolizumab or CIK adoptive cell infusions prolonged the overall survival of an elderly patient with HER2-positive GEJ cancer with multiple metastases.


Assuntos
Neoplasias Esofágicas , Neoplasias Gástricas , Masculino , Humanos , Idoso , Junção Esofagogástrica/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Esofágicas/tratamento farmacológico , Trastuzumab , Imunoterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
16.
Phytother Res ; 36(11): 4167-4182, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35778992

RESUMO

Hepatocytes has been confirmed to undergo EMT and can be converted into myofibroblasts during hepatic fibrogenesis. However, the mechanism of hepatocyte EMT regulation in hepatic fibrosis, particularly through HSP27 (human homologue of rodent HSP25), remains unclear. Mangiferin (MAN), a compound extracted from Mangifera indica L, has been reported to attenuate liver injury. This study aimed to investigate the mechanisms underlying HSP27 inhibition and the anti-fibrotic effect of MAN in liver fibrosis. Our results revealed that the expression of HSP27 was remarkably increased in the liver tissues of patients with liver cirrhosis and CCl4 -induced fibrotic rats. However, HSP27 shRNA treatment significantly alleviated fibrosis. Furthermore, MAN was found to inhibit CCl4 - and TGF-ß1-induced liver fibrosis and reduced hepatocyte EMT. More importantly, MAN decreased HSP27 expression to suppress the JAK2/STAT3 pathway, and subsequently blocked TGF-ß1/Smad signaling, which were consistent with its protection against CCl4 -induced EMT and liver fibrosis. Together, these results suggest that HSP27 may play a crucial role in hepatocyte EMT and liver fibrosis by activating JAK2/STAT3 signaling and TGF-ß1/Smad pathway. The suppression of HSP27 expression by MAN may be a novel strategy for attenuating the hepatocyte EMT in liver fibrosis.


Assuntos
Transição Epitelial-Mesenquimal , Fator de Crescimento Transformador beta1 , Animais , Humanos , Ratos , Fibrose , Hepatócitos , Proteínas de Choque Térmico HSP27/metabolismo , Janus Quinase 2 , Cirrose Hepática/tratamento farmacológico , Fator de Transcrição STAT3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Proteínas Smad/metabolismo
17.
J Mater Chem B ; 10(28): 5430-5438, 2022 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-35775960

RESUMO

The construction of non-viral gene delivery faces two major challenges: cytotoxicity caused by high cationic charge units and easy degradation by lysosomes. Herein, highly water-dispersible polymeric carbon nitride (PCN) nanosheets were utilized as the core to construct a light-controlled non-cationic gene delivery system with sufficient lysosomal escape ability. In this system, these nanosheets exhibited efficient DNA condensation, outstanding biocompatibility, transfection tracking, light responsiveness and high transfection efficiency. Once PCN-DNA was taken up by the tumor cells, the accumulated ROS generated by photosensitizers (PSs) under light irradiation would destroy the structure of lysosomes, promote the escape of PCN-DNA and increase the efficiency of gene transfection. Simultaneously, the gene transfection process could be tracked in real time through fluorescence imaging technology, which was conducive to investigate the transfection mechanism. In vitro and in vivo experiments further confirmed that PCN nanosheets loaded with the P53 gene were beneficial to the regeneration of the P53 apoptotic pathway, increased tumor sensitivity to PSs, and further induced tumor cell apoptosis. In summary, the highly water-dispersible PCN nanosheets were applied to light-controlled self-escaping gene delivery for the first time, and tumor gene therapy was successfully realized.


Assuntos
Neoplasias , Humanos , Cátions/química , DNA/química , Lisossomos/metabolismo , Neoplasias/metabolismo , Neoplasias/terapia , Nitrilas , Polímeros/química , Água
18.
Am J Med Sci ; 364(5): 669-672, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35718121

RESUMO

Pericardial fistula is a rare complication. Generally, the diagnosis can be confirmed by imaging examination, but our patient was an exception. We present a 71-year-old female patient that complained of remnant gastric cancer for five months and dyspnea for seven days; the dyspnea became aggravated during the last two days. After admission, emergency thoracic computed tomography and echocardiography showed pericardial effusion, and pericardiocentesis was performed. After conventional treatment, the pericardial effusion was unchanged and no cancer cells were found in the pericardial drainage. However, the color changed from turbid to golden yellow and, finally, to green. After 20 days of repeated laboratory, imaging, and gastrointestinal contrast examinations, no cause was found. Moreover, a clinical diagnosis could not be obtained following numerous comprehensive clinical analyses. Given the color change of the pericardial drainage, we strongly suspected pericardial fistula, but the imaging examinations were negative. Finally, a methylene blue test confirmed the existence of a pericardial fistula. When the color of the pericardial effusion changes, the existence of a pericardial fistula must be considered in advance, and other methods should be evaluated if imaging cannot assist in the diagnosis.


Assuntos
Tamponamento Cardíaco , Fístula , Derrame Pericárdico , Humanos , Feminino , Idoso , Derrame Pericárdico/diagnóstico por imagem , Derrame Pericárdico/etiologia , Azul de Metileno , Pericardiocentese/efeitos adversos , Fístula/diagnóstico por imagem , Dispneia/complicações
19.
Mar Drugs ; 20(5)2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35621971

RESUMO

Microalgae host varied microbial consortium harboring cross-kingdom interactions with fundamental ecological significance in aquatic ecosystems. Revealing the complex biofunctions of the cultivable bacteria of phycosphere microbiota is one vital basis for deeply understanding the mechanisms governing these dynamic associations. In this study, a new light-yellow pigmented bacterial strain LZ-28 was isolated from the highly-toxic and harmful algal bloom-forming dinoflagellate Alexandrium catenella LZT09. Collective phenotypic and genotypic profiles were obtained to confidently identify this strain as a new Mameliellaalba member. Comparative genomic analysis showed that strain LZ-28 shared highly similar functional features with other four marine algae-derived M. alba strains in spite of their distinctive isolation sources. Based on the bioactivity assaying, the mutual growth-promoting effects between bacterial strain LZ-28 and algal strain LZT09 were observed. After the culture conditions were optimized, strain LZ-28 demonstrated an extraordinary production ability for its bioflocculanting exopolysaccharides (EPS). Moreover, the portions of two monosaccharides glucose and fucose of the EPS were found to positively contribute to the bioflocculanting capacity. Therefore, the present study sheds light on the similar genomic features among the selected M. alba strains, and it also reveals the potential pharmaceutical, environmental and biotechnological implications of active EPS produced by this new Mameliella alba strain LZ-28 recovered from toxic bloom-forming marine dinoflagellate.


Assuntos
Dinoflagelados , Microbiota , Rhodobacteraceae , Dinoflagelados/genética , Proliferação Nociva de Algas
20.
Huan Jing Ke Xue ; 43(3): 1170-1179, 2022 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-35258181

RESUMO

To investigate the PM2.5 pollution in the southern Sichuan urban agglomeration after the implementation of China's Air Pollution Prevention and Control Action Plan (APPCAP), PM2.5 samples were simultaneously collected in four cities (Neijiang, Zigong, Yibin, and Luzhou) from November 7 to 19, 2018. The pollution characteristics of PM2.5 and main water-soluble ions were analyzed in combination with the synoptic situation, and the influence of regional transport on atmospheric pollution was also discussed in this study. The results showed that the mean ρ(PM2.5) in this region was (67.2±38.3) µg·m-3, being highest in Luzhou and lowest in Neijiang. The proportion of SNA (SO42-, NO3-, and NH4+) in PM2.5 was 33.3%, among which NO3- was dominant. From the intermediate stage (2015) to the end(2018) of the implementation of APPCAP, ρ(PM2.5) values were increased by 13.8%, 47.2%, and 69.1% in Neijiang, Yibin, and Luzhou, respectively, though unchanged in Zigong. Due to the significant reduction in ρ(SO2) but slight decrease or increase in ρ(NO2), as well as the lack of controlling NH3 emissions, from 2015 to 2018, ρ(NO3-) had increased by 36.7%-116.0%, whereas ρ(SO42-) decreased by 19.8%-40.2%, and ρ(NH4+) changed slightly in four cities. On haze days, the nitrogen oxidation rate (NOR) increased by 60.0%-118.2%, whereas the sulfur oxidation rate (SOR) increased slightly or decreased, leading to a significant increase in ρ(NO3-) (2.7-3.0 times that on clean days) and NO3-/SO42- mass ratios (1.7-1.9 on haze days). These values indicated that the secondary formation of nitrate was the dominant chemical mechanism in this haze process. On haze days, the PM2.5 pollution in this region was mainly affected by the regional transport within Sichuan Basin, particularly by the northeasterly air masses passing through Chongqing.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar/prevenção & controle , China , Monitoramento Ambiental , Nitratos/análise , Material Particulado/análise , Estações do Ano , Água
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