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Objective: To evaluate the effectiveness and safety of pericapsular nerve group (PENG) block for hip fracture surgery under spinal anesthesia. Methods: This meta-analysis was registered on INPLASY (INPLASY202270005). PubMed, Embase, Cochrane, CNKI, and Wanfang databases were searched to collect the randomized controlled trials of the PENG block applied to hip fracture surgery in the setting of spinal anesthesia, with the search period from inception to 1 May 2023. Two independent researchers gradually screened the literature, evaluated the quality, extracted the data, and eventually pooled data using RevMan 5.4. Results: Fifteen articles with 890 patients were enrolled. The combined results showed that the PENG block reduced pain scores during position placement (SMD = -0.35; 95% CI [-0.67, 0.02]; P=0.04; I2 = 0%). Subgroup analyses showed that compared to the unblocked group, the PENG block reduced pain scores at 12 h, 24 h, and 48 h postoperatively. The incidence of postoperative hypokinesia was reduced (RR = 0.11; 95% CI [0.01, 0.86]; P=0.04; I2 = 0.00%). The time to first walking was advanced (SMD = -0.90; 95% CI [-1.17, 0.63]; P < 0.00001; I2 = 0%). Conclusion: The PENG block can reduce postoperative pain and pain during spinal anesthesia positioning, which is helpful to improve the operability and comfort of spinal anesthesia and facilitate postoperative muscle strength recovery and early activity.
Assuntos
Raquianestesia , Fraturas do Quadril , Humanos , Raquianestesia/efeitos adversos , Nervo Femoral , Fraturas do Quadril/cirurgia , Dor Pós-Operatória/prevenção & controle , Bases de Dados FactuaisRESUMO
Objective: To evaluate the effect of scalp nerve block (SNB) on postoperative analgesia and stress response in patients undergoing craniotomy by meta-analysis. Methods: PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases were searched for randomized controlled trials involving SNB for elective craniotomy under general anesthesia from inception to August 1, 2022. Meta-analysis was performed using RevMan 5.4 and Stata MP17.0. Based on scalp block operation time (preoperative block, postoperative block), different control groups (no block, normal saline), local anesthetic types (bupivacaine, levobupivacaine, ropivacaine), the postoperative pain score at different time points was analyzed by subgroup analysis. Results: 23 studies involving 1515 patients were included. The combined results showed that SNB could significantly reduce the pain scores at all time points compared with the control group (P < .05). Subgroup analysis showed that the analgesic effect of preoperative scalp nerve block was better than that of postoperative block, and the effect of ropivacaine and levobupivacaine was better than bupivacaine. SNB could reduce morphine consumption within 48 hours after surgery (SMD = -1.51, 95% CI -2.80 -0.21, P = .02, I2 = 89%). The first rescue analgesia time was significantly longer in the SNB group than the control group (SMD = 0.57, 95% CI 0.16-0.99, P = .01, I2 = 68.76%). Compared with the control group, the levels of postoperative angiotensin, intraoperative blood glucose, and both intraoperative and postoperative cortisol levels were significantly decreased (P < .05). SNB can inhibit hemodynamic changes caused by surgical stimulation and effectively reduce the incidence of postoperative nausea and vomiting (RR = 0.71, 95% CI 0.51~0.97, P = .03). Conclusion: Scalp nerve block is an effective analgesic that reduces pain within 48 hours after craniotomy. It effectively inhibit the stress response caused by surgical stimulation, stabilize hemodynamics, and reduce the incidence of postoperative nausea and vomiting.
Assuntos
Craniotomia , Bloqueio Nervoso , Dor Pós-Operatória , Couro Cabeludo , Humanos , Anestésicos Locais/administração & dosagem , Craniotomia/efeitos adversos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Couro Cabeludo/inervação , Couro Cabeludo/cirurgiaRESUMO
The development of stealth and effective antitumor nanodrugs has been drawing great attention. Herein, generation five poly(amide amine) dendrimer (G5 PAMAM) was modified by zwitterionic material carboxybetaine methacrylamide (CBMAA) on its surface to prepare zwitterionic dendrimer (G5-CBMAAn). The results showed that G5-CBMAA30 had the longest blood circulation time due to its thickest zwitterionic layer, and its residual rate after injection into mice at 2 and 12 h was as high as 47.22 % and 14.37 %, respectively. Nanodrug G5-CBMAA30-ICG was prepared by containing indocyanine green (ICG) in the cavity of G5-CBMAA30. G5-CBMAA30-ICG had better tumor targeting ability and antitumor effect than free ICG in mice after laser irradiation, and the tumor inhibition rate was 96.6 % after 14 days' treatment. The prepared G5-CBMAA30-ICG has great potential applications in the field of antitumor by phototherapy.
Assuntos
Dendrímeros , Nanopartículas , Neoplasias , Animais , Verde de Indocianina , Camundongos , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fototerapia/métodosRESUMO
In recent years, the antitumor application of photodynamic therapy (PDT) has gained widespread interest in treating solid tumors. Due to the hypoxic environment in tumors, the major limit of PDT seems to be the source of oxygen. In this work, we attempted to relieve hypoxia and enhance photodynamic therapy, and therefore, designed and assembled a catalytic cascade-enhanced PDT multifunctional nanoplatform. The mentioned platform termed UIO@Ca-Pt is based on porphyrinic metal-organic framework (UIO) combination, which is simultaneously loaded by CaO2 NPs with polydopamine (PDA) and then the Pt raw material to further improve biocompatibility and efficiency. In a tumor microenvironment, CaO2 could react with water to generate calcium hydroxide and hydrogen peroxide, which was further decomposed by Pt nanoparticles to form oxygen, thereby facilitating the generation of cytotoxic singlet oxygen by photosensitizer TCPP under laser irradiation. Both in vitro and in vivo experiment results confirmed the excellent oxygen production capacity and enhanced PDT effect of UIO@Ca-Pt. With guaranteed safety in PDT, the oxygen-supplying strategy might stimulate considerable interest in the development of various metal-organic materials with multifunctionality for tumor diagnosis and therapy.
Assuntos
Estruturas Metalorgânicas/química , Fotoquimioterapia/métodos , Porfirinas/química , Animais , Catálise , Linhagem Celular , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Análise Multivariada , Microambiente Tumoral/efeitos dos fármacosRESUMO
Poly(amido amine) dendrimers and indocyanine green have inevitable interaction with proteins and cells, which induces biological toxicity and reduces therapeutic efficacy in vivo. To overcome these shortcomings, a new drug delivery system G5MEK7C(n)-ICG with a "stealth" layer was prepared. The surface of G5MEK7C(n)-ICG was modified with double-layer super hydrophilic zwitterionic materials. In the "stealth" double-layer structure, the outer layer was consisted of zwitterionic Glu-Lys-Glu-Lys-Glu-Lys-Cys (EK7) peptide, and the inner layer was composed of amino and carboxyl groups with a ratio of 1:1. DLS results showed that the average hydrodynamic size of G5MEK7C(n)-ICG was about 25-30 nm, and the zeta potential was proven to undergo a slight charge reversal with the increasing pH values of solutions. Furthermore, G5MEK7C(n)-ICG exhibited excellent biocompatibility to red blood cells and proteins resistance. Photothermal and photodynamic experiments demonstrated that G5MEK7C(n)-ICG had a good photothermal conversion effect and generated singlet oxygen (1O2) under laser irradiation. The MTT and hemolysis results showed that the toxicity of G5 PAMAM was significantly reduced after modification double-layer structure. Cytotoxicity studies and flow cytometry showed G5MEK7C(70)-ICG under laser irradiation had a good effect on killing A549 cells. More importantly, the tumor inhibition rate of mice treated with G5MEK7C(70)-ICG (under laser irradiation) was 78.2% in vivo, which was higher than that of mice treated with free ICG. Compared with free ICG, G5MEK7C(70)-ICG caused less damage to the liver according to the enzyme activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Therefore, dendrimers modified with a zwitterionic double layer will be a promising candidate as a drug delivery system.
Assuntos
Dendrímeros , Hipertermia Induzida , Neoplasias , Fotoquimioterapia , Animais , Verde de Indocianina/uso terapêutico , Camundongos , Neoplasias/tratamento farmacológicoRESUMO
BACKGROUND: In the United States, COPD is a leading cause of mortality, with a substantial societal health and economic burden. With anticipated population growth, it is important for various stakeholders to have an estimate for the projected burden of disease. RESEARCH QUESTION: The goal of this study was to model the 20-year health and economic burden of COPD, from 2019 to 2038, in the United States. STUDY DESIGN AND METHODS: Using country-specific data from published literature and publicly available datasets, a dynamic open cohort Markov model was developed in a probabilistic Monte Carlo simulation. Population growth was modeled across different subgroups of age, sex, and smoking. The COPD prevalence rates were calibrated for different subgroups, and distributions of severity grades were modeled based on smoking status. Direct costs, indirect absenteeism costs, losses of quality-adjusted life years (QALYs), and number of exacerbations and deaths associated with COPD were projected. RESULTS: The 20-year discounted direct medical costs attributable to COPD were estimated to be $800.90 billion (95% credible interval [CrI], 565.29 billion-1,081.29 billion), with an expected $337.13 billion in male subjects and $463.77 billion in female subjects. The 20-year discounted indirect absenteeism costs were projected to be $101.30 billion (70.82 billion-137.41 billion). The 20-year losses of QALYs, number of exacerbations, and number of deaths associated with COPD were 45.38 million (8.63 million-112.07 million), 315.08 million (228.59 million-425.33 million), and 9.42 million (8.93 million-9.93 million), respectively. The proportion of disease burden attributable to continued smoking was 34% in direct medical costs, 35% in indirect absenteeism costs, and 37% in losses of QALYs over 20 years. INTERPRETATION: This study projects the substantial burden of COPD that the American society is expected to incur with current patterns for treatments and smoking rates. Mitigating such burden requires targeted budget appropriations and cost-effective interventions.
Assuntos
Doença Pulmonar Obstrutiva Crônica/economia , Adulto , Idoso , Efeitos Psicossociais da Doença , Feminino , Previsões , Custos de Cuidados de Saúde , Humanos , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Método de Monte Carlo , Prevalência , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , Índice de Gravidade de Doença , Fumar , Exacerbação dos Sintomas , Estados Unidos/epidemiologiaRESUMO
A practical strategy of introducing ortho-methoxyl group was explored to achieve the fluorescence-enhancing and bathochromic-shift bi-functional optimization. It was tested in the Cys sensing ISOPH-X series, thus the successful case, ISOPH-2, was obtained. It realized the optimization in a simple and compatible way. The corresponding strategy was basically established during the confirmation of checkpoints including applicable steadiness (over 24 h), wide pH range (7.0-9.0), rapid response (20 min), good biocompatibility, high sensitivity (LOD = 0.072 nm), high selectivity and biological monitoring of Cys in living cells as well as C. elegans. In this work, the o-methoxyl introduction strategy led to a 15 nm red shift and a near 4-fold fluorescence enhancement. This strategy could be combined with the double bond-introducing approach. Compared with reported strategies, by breaking the dilemma between red shift and strong fluorescent intensity, this strategy might offer beneficial information for exploiting better sensors with more fluorophores and mechanisms for their targets.
RESUMO
The abnormal angiogenesis and insufficient oxygen supply in solid tumors lead to intratumoral hypoxia, which severely limits the efficacy of traditional photodynamic therapy (PDT). Here, a multifunctional nanoplatform (ZDZP@PP) based on a zeolitic imidazolate framework-67 (ZIF-67) core as a hydrogen peroxide catalyst, a zeolitic imidazolate framework-8 (ZIF-8) shell with a pH-responsive property, and a polydopamine-poly(ethylene glycol) (PDA-PEG) layer for improving the biocompatibility is fabricated for not only relieving tumor hypoxia but also enhancing the efficacy of combination chemo-photodynamic therapy. The chemotherapy drug doxorubicin (DOX) and photosensitizer protoporphyrin IX (PpIX) are encapsulated in different layers independently; thus, a unique two-stage stepwise release becomes possible. Moreover, the nanoplatform can effectively decompose hydrogen peroxide to produce oxygen and thus relieve tumor hypoxia, which further facilitates the production of cytotoxic reactive oxygen species (ROS) by PpIX under laser irradiation. Both in vitro and in vivo experimental results confirm that the combination chemo-photodynamic therapy with the ZDZP@PP nanoplatform can provide more effective cancer treatment than chemotherapy or PDT alone. Consequently, the oxygen self-sufficient multifunctional nanoplatform holds promising potential to overcome hypoxia and treat solid tumors in the future.
Assuntos
Antineoplásicos/uso terapêutico , Hipóxia Celular/efeitos dos fármacos , Portadores de Fármacos/química , Estruturas Metalorgânicas/química , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Antineoplásicos/farmacologia , Catálise , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Peróxido de Hidrogênio/química , Indóis/química , Camundongos Endogâmicos BALB C , Oxigênio/metabolismo , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Polímeros/química , Protoporfirinas/farmacologia , Protoporfirinas/uso terapêutico , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A series of novel pyrazoline derivatives containing methyl-1H-indole moiety were discovered as potential inhibitors for blocking APC-Asef interactions. The top hit Q19 suggested potency of inhibiting APC-Asef interactions and attractive preference for human-sourced colorectal cells. It was already comparable with the previous representative and the positive control Regorafenib before further pharmacokinetic optimization. The introduction of methyl-1H-indole moiety realized the Mitochondrial affection thus might connect the impact on the protein-interaction level with the apoptosis events. The molecular docking simulation inferred that bringing trifluoromethyl groups seemed a promising approach for causing more key interactions such as H-bonds. This work raised referable information for further discovery of inhibitors for blocking APC-Asef interactions.