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1.
BMC Surg ; 24(1): 265, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39285467

RESUMO

BACKGROUND: Early postoperative mobilization is important for enhanced recovery but can be hindered by orthostatic intolerance. However, study on postoperative orthostatic intolerance in thoracoscopic lung resection is limited. Thus, this investigation aims to examine the prevalence and variables contributing to orthostatic intolerance on the first day following thoracoscopic lung cancer resection. METHODS: A prospective observational study was conducted from February 01 to May 05, 2023, at the First Affiliated Hospital of Chongqing Medical University. Typically, 215 subjects subjected to thoracoscopic lung resection were enrolled in this study. Their general information, disease, and treatment information were collected, and the occurrence of orthostatic intolerance was recorded. RESULTS: Typically, 64 patients (29.77%) demonstrated orthostatic intolerance during early mobilization, and 43.75% failed to walk. The prevalence of nausea, dizziness, and impaired vision was 60.94%, 92.19%, and 25.00%, respectively, and no patient experienced syncope. The factors shown to be independently linked with orthostatic intolerance were being female (OR = 2.98, 1.53 to 5.82) and high pain level during sitting (OR = 2.69, 1.79 to 4.04). Individuals with orthostatic intolerance had a longer postoperative hospital stay with a mean of 5.42 days against 4.25 days (p = 0.003). CONCLUSIONS: Orthostatic intolerance was prevalent following thoracoscopic lung cancer resection and affected patients' capability to mobilize and prolonged postoperative hospitalization. Being female and having high pain levels during sitting were identified as independent factors for orthostatic intolerance. This suggests that more emphasis should be given to risky patients, and for these groups, we may optimize pain management to adjust the risk of emerging orthostatic intolerance, facilitating early mobilization and early postoperative rehabilitation.


Assuntos
Deambulação Precoce , Neoplasias Pulmonares , Intolerância Ortostática , Pneumonectomia , Complicações Pós-Operatórias , Humanos , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Neoplasias Pulmonares/cirurgia , Intolerância Ortostática/etiologia , Intolerância Ortostática/epidemiologia , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Idoso , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Cirurgia Torácica Vídeoassistida/métodos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Prevalência , Adulto , Tempo de Internação/estatística & dados numéricos
2.
Small ; 20(35): e2310416, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38660815

RESUMO

Synergistic therapy has shown greater advantages compared with monotherapy. However, the complex multiple-administration plan and potential side effects limit its clinical application. A transformable specific-responsive peptide (TSRP) is utilized to one-step achieve synergistic therapy integrating anti-tumor, anti-angiogenesis and immune response. The TSRP is composed of: i) Recognition unit could specifically target and inhibit the biological function of FGFR-1; ii) Transformable unit could self-assembly and trigger nanofibers formation; iii) Reactive unit could specifically cleaved by MMP-2/9 in tumor micro-environment; iv) Immune unit, stimulate the release of immune cells when LTX-315 (Immune-associated oncolytic peptide) exposed. Once its binding to FGFR-1, the TSRP could cleaved by MMP-2/9 to form the nanofibers on the cell membrane, with a retention time of up to 12 h. Through suppressing the phosphorylation levels of ERK 1/2 and PI3K/AKT signaling pathways downstream of FGFR-1, the TSRP significant inhibit the growth of tumor cells and the formation of angioginesis. Furthermore, LTX-315 is exposed after TSRP cleavage, resulting in Calreticulin activation and CD8+ T cells infiltration. All above processes together contribute to the increasing survival rate of tumor-bearing mice by nearly 4-folds. This work presented a unique design for the biological application of one-step synergistic therapy of bladder cancer.


Assuntos
Peptídeos , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Animais , Humanos , Linhagem Celular Tumoral , Peptídeos/química , Peptídeos/farmacologia , Camundongos , Nanofibras/química
3.
Exp Ther Med ; 27(3): 113, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38361514

RESUMO

There remains no consensus on the prognostic value of lactate in predicting adverse outcomes such as mortality, rebleeding and higher intensive care unit (ICU) admission rates in patients with upper gastrointestinal bleeding (UGIB). The present study aimed to determine the prognostic accuracy of lactate level in predicting adverse clinical outcomes in patients with acute UGIB. Systematic literature search was conducted in PubMed Central, SCOPUS, EMBASE, MEDLINE, Google Scholar and ScienceDirect databases for studies published up to February 2023. Random-effects model was used for the meta-analysis and the results were presented as pooled standardized mean differences or odds ratio (OR) with 95% confidence interval (CIs). A total of 11 studies were included in the present review. Most of the studies had a high risk of bias. Pooled OR were as follows: 1.39 (95% CI: 1.29-1.51; I2=85%) for the prediction of mortality; 1.29 (95% CI: 1.17-1.42; I2=85.9%) for prediction of ICU admission, 1.14 (95% CI: 1.06-1.23; I2=42.4%) for rebleeding and 2.84 (95% CI: 2.14-3.77; I2=8.1%) for the need of packed red blood cell (pRBC) transfusion. Sensitivity and specificity for the mortality prediction were 72% (95% CI: 57-83%) and 75% (95% CI: 61-85%), respectively, with the area under the curve of 0.79 (95% CI: 0.72-0.85). In conclusion, the results showed that lactate level is a moderately accurate early prediction marker of most adverse clinical outcomes such as mortality, rebleeding, ICU admission and the need for pRBC transfusion in acute UGIB patients.

4.
Nano Lett ; 24(5): 1510-1521, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38285667

RESUMO

α-PD-L1 therapy has shown encouraging results at harnessing the immune system to combat cancer. However, the treatment effect is relatively low due to the dense extracellular matrix (ECM) and tumor immunosuppressive microenvironment (TIME). Therefore, an ultrasound (US)-responsive nanosensitizer (URNS) is engineered to deliver losartan (LST) and polyethylenimine (PEI) to remolde the TME, driving "cold"-"hot" tumor transformation and enhancing the sensitivity of α-PD-L1 therapy. In the tumor site, noninvasive US can make MTNP generate ROS, which cleave ROS-sensitive bonds to dissociate MTNPtK@LST-PEI, shedding PEI and releasing LST from mesoporous spheres. The results demonstrated that URNS combined with α-PD-L1 therapy effectively inhibited tumor growth with an inhibition rate as high as 90%, which was 1.7-fold higher than that of the α-PD-L1 treatment in vivo. In summary, the URNS improves the sensitivity of α-PD-L1 therapy by remodeling the TME, which provides promising insights for optimizing cancer immunotherapy.


Assuntos
Antígeno B7-H1 , Neoplasias , Humanos , Espécies Reativas de Oxigênio , Matriz Extracelular , Imunossupressores , Imunoterapia , Losartan , Polietilenoimina , Microambiente Tumoral
5.
FASEB J ; 37(9): e23118, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37531296

RESUMO

Renal cancer stem cells (RCSCs) derived from clear cell renal cell carcinoma (ccRCC) tissues with higher microvessel density (MVD) have strong stemness and endothelial progenitor cells-like (EPCs-like) characteristics. A high level of lncRNA PVT1 expression is essential for simultaneously retaining strong RCSC stemness and EPCs-like characteristics. PVT1 binds with TAZ protein and prevents its phosphorylation, which promotes RCSC stemness. Moreover, RCSCs support endothelial differentiation and angiogenesis, which are mediated via the PVT1/miR-15b/KDR axis. This report provides insight into the determinants of RCSC impact on stemness and highlights the critical role of RCSC in angiogenesis. The presented findings suggest that targeting RCSC through PVT1 expression may be a new treatment strategy for ccRCC.


Assuntos
Carcinoma de Células Renais , Células Progenitoras Endoteliais , Neoplasias Renais , MicroRNAs , RNA Longo não Codificante , Humanos , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Células Progenitoras Endoteliais/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , MicroRNAs/genética , Células-Tronco Neoplásicas/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
6.
Small ; 19(25): e2300060, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36929045

RESUMO

Nanoscale drug carriers play a crucial role in reducing side effects of chemotherapy drugs. However, the mononuclear phagocyte system (MPS) and the drug protonation after nanoparticles (NPs) burst release still limit the drug delivery efficiency. In this work, a self-disguised Nanospy is designed to overcome this problem. The Nanospy is composed of: i) poly (lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) loading doxorubicin is the core structure of the Nanospy. ii) CD47 mimic peptides (CD47p) is linked to NPs which conveyed the "don't eat me" signal. iii) 4-(2-aminoethyl) benzenesulfonamide (AEBS) as the inhibitor of Carbonic anhydrase IX (CAIX) linked to NPs. Briefly, when the Nanospy circulates in the bloodstream, CD47p binds to the regulatory protein α (SIRPα) on the surface of macrophages, which causes the Nanospy escapes from phagocytosis. Subsequently, the Nanospy enriches in tumor and the AEBS reverses the acidic microenvironment of tumor. Due to above characteristics, the Nanospy reduces liver macrophage phagocytosis by 25% and increases tumor in situ DOX concentration by 56% compared to PLGA@DOX treatment. In addition, the Nanospy effectively inhibits tumor growth with a 63% volume reduction. This work presents a unique design to evade the capture of MPS and overcomes the influence of acidic tumor microenvironment (TME) on weakly alkaline drugs.


Assuntos
Nanopartículas , Neoplasias , Humanos , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/química , Doxorrubicina/química , Neoplasias/tratamento farmacológico , Nanopartículas/química , Peptídeos/uso terapêutico , Liberação Controlada de Fármacos , Polietilenoglicóis/química , Microambiente Tumoral
7.
Front Biosci (Landmark Ed) ; 28(12): 334, 2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38179741

RESUMO

BACKGROUND: Pyroptosis plays a crucial role in anti-tumor immunity and in formation of the immune microenvironment. However, whether pyroptosis is involved in the progression of clear cell renal cell carcinoma (ccRCC) is still unclear. Personalized treatment of ccRCC requires detailed molecular classification to inform a specific therapy. METHODS: Molecular subtyping of ccRCC was performed based on consensus clustering of pyroptosis-related genes. The characteristics of these molecular subtypes were explored at the genome, transcriptome and protein levels. Single-cell RNA sequencing and CIBERSORT analysis were used to analyse the immune microenvironment of ccRCC, while Lasso regression was used to develop a prediction model based on hub genes. Expression of the pyroptosis-related gene GSDMB was also investigated at the tissue and cellular levels. RESULTS: Two molecular subtypes were identified based on the clustering of pyroptosis-related genes. Cluster 1 was associated with activation of classical oncogenic pathways, especially the angiogenesis pathway. Cluster 2 was associated with activation of immune-related pathways and high levels of immunosuppressive cells, exhausted CD8+ T cells, and tumor-associated fibroblast infiltration. Clusters 1 and 2 were thus defined as the angiogenic and inflamed subtypes, respectively. The two subtypes were predictive of the response of ccRCC to anti-angiogenic therapy and immunotherapy, with Cluster 1 patients benefiting from anti-angiogenic therapy and Cluster 2 patients showing better response to anti-PD1 inhibitor therapy. Furthermore, a 9-gene expression signature (HJURP, NUF2, KIF15, MELK, TPX2, PLK1, CDCA3, CTLA4, FOXP3) was identified that could predict outcome and response to immune checkpoint blockade therapy in test cohorts. Finally, GSDMB was found to be involved in the development of renal clear cell carcinoma. CONCLUSIONS: These results on pyroptosis-related genes in ccRCC provide a theoretical basis for understanding molecular heterogeneity and for the development of individualized treatment strategies.


Assuntos
Fibroblastos Associados a Câncer , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Piroptose/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/terapia , Imunoterapia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Microambiente Tumoral/genética , Cinesinas , Proteínas de Ciclo Celular , Proteínas Serina-Treonina Quinases
8.
ACS Nano ; 16(4): 5515-5528, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35352555

RESUMO

Nearly half of pregnancies worldwide are unintended mainly due to failure of contraception, resulting in negative effects on women's health. Male contraception techniques, primarily condoms and vasectomy, play a crucial role in birth control, but cannot be both highly effective and reversible at the same time. Herein, an ultrasound (US)-induced self-clearance hydrogel capable of real-time monitoring is utilized for in situ injection into the vas deferens, enabling effective contraception and noninvasive recanalization whenever needed. The hydrogel is composed of (i) sodium alginate (SA) conjugated with reactive oxygen species (ROS)-cleavable thioketal (SA-tK), (ii) titanium dioxide (TiO2), which can generate a specific level of ROS after US treatment, and (iii) calcium chloride (CaCl2), which triggers the formation of the hydrogel. For contraception, the above mixture agents are one-time injected into the vas deferens, which can transform from liquid to hydrogel within 160 s, thereby significantly physically blocking the vas deferens and inhibiting movability of sperm. When fertility is needed, a noninvasive remedial ultrasound can make TiO2 generate ROS, which cleaves SA-tK to destroy the network of the hydrogel. Owing to the recanalization, the refertility rate is restored to 100%. Meanwhile, diagnostic ultrasound (D-US, 22 MHz) can monitor the occlusion and recanalization process in real-time. In summary, the proposed hydrogel contraception can be a reliable, safe, and reversible male contraceptive strategy that addresses an unmet need for men to control their fertility.


Assuntos
Hidrogéis , Sêmen , Gravidez , Masculino , Feminino , Humanos , Espécies Reativas de Oxigênio , Anticoncepção/métodos , Ultrassonografia
9.
Front Pediatr ; 9: 674414, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307252

RESUMO

Background: The incidence of twin pregnancies has risen recently. Such pregnancies are associated with an increased risk for poor maternal and infant outcomes. Gestational weight gain, particularly in singleton pregnancies, has been well-linked with maternal and infant outcomes. The aim of the current meta-analysis was to evaluate the effects of gestational weight gain on maternal and fetal outcomes in women with twin pregnancies. Methods: A systematic search was conducted using the PubMed, Scopus, and Google Scholar databases. Studies, either retrospective or prospective in design, evaluating the effects of gestational weight gain (defined using Institute of Medicine (IOM) guidelines) maternal and/or fetal/neonatal outcomes in women with twin pregnancies were included. Statistical analysis was performed using STATA software. Results: Eleven studies were included in the meta-analysis. Mothers with inadequate weight gain had increased risk for gestational diabetes mellitus (OR 1.19; 95% CI: 1.01, 1.40) and decreased risk for gestational hypertension (OR 0.58; 95% CI: 0.49, 0.68) and cesarean section (OR 0.94; 95% CI: 0.93, 0.96). Neonates born to mothers with inadequate weight gain were susceptible to increased risk for preterm delivery (OR 1.17; 95% CI: 1.03, 1.34), very preterm delivery (gestational age <32 weeks) (OR 1.84; 95% CI: 1.36, 2.48), small for gestational age status (OR 1.41; 95% CI: 1.15, 1.72), low birth weight status (<2,500 g) (OR 1.27; 95% CI: 1.17, 1.38), and neonatal intensive care unit (NICU) admission (OR 1.16; 95% CI: 1.08, 1.24). The pooled findings indicate an increased risk for gestational hypertension (OR 1.82; 95% CI: 1.60, 2.06) and cesarean section (OR 1.07; 95% CI: 1.05, 1.08) among mothers with excessive weight gain. Neonates born to mothers with excessive weight gain were susceptible to increased risk for preterm delivery and very preterm delivery, but were associated with a decreased risk for low birth weight status and small for gestational age status. Conclusions: Gestational weight gain in twin pregnancy, either lower or higher than IOM recommended guidelines, is associated with poor maternal and neonatal outcomes. Our findings call for incorporating counseling on optimal weight gain during pregnancy as part of routine antenatal visits.

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