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OBJECTIVE: To systematically evaluate the difference in clinical efficacy between two surgical approaches, oblique lateral approach and intervertebral foraminal approach, in the treatment of degenerative lumbar spondylolisthesis. METHODS: English databases, including PubMed, Cochrane, Embase, and Web of Science, were systematically searched using keywords such as "oblique lumbar interbody fusion" and "transforaminal lumbar interbody fusion." Concurrently, Chinese databases, including CNKI, WanFang data, VIP, and CBM, were also queried using corresponding Chinese terms. The search spanned from January 2014 to February 2024, focusing on published studies in both Chinese and English that compared the clinical efficacy of OLIF and TLIF. The literature screening was conducted by reviewing titles, abstracts, and full texts. Literature meeting the inclusion criteria underwent quality assessment, and relevant data were extracted. Statistical analysis and a meta-analysis of the observational data for both surgical groups were performed using Excel and RevMan 5.4 software. Findings revealed a total of 14 studies meeting the inclusion criteria, encompassing 877 patients. Of these, 414 patients were in the OLIF group, while 463 were in the TLIF group. Meta-analysis of the statistical data revealed that compared to TLIF, OLIF had a shorter average surgical duration (P < 0.05), reduced intraoperative bleeding (P < 0.05), shorter average hospital stay (P < 0.05), better improvement in postoperative VAS scores (P < 0.05), superior enhancement in postoperative ODI scores (P < 0.05), more effective restoration of disc height (P < 0.05), and better correction of lumbar lordosis (P < 0.05). However, there were no significant differences between OLIF and TLIF in terms of the incidence of surgical complications (P > 0.05) and fusion rates (P > 0.05). CONCLUSION: When treating degenerative lumbar spondylolisthesis, OLIF demonstrates significant advantages over TLIF in terms of shorter surgical duration, reduced intraoperative bleeding, shorter hospital stay, superior improvement in postoperative VAS and ODI scores, better restoration of disc height, and more effective correction of lumbar lordosis.
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Vértebras Lumbares , Fusión Vertebral , Espondilolistesis , Humanos , Espondilolistesis/cirugía , Fusión Vertebral/métodos , Vértebras Lumbares/cirugía , Resultado del Tratamiento , Tempo Operativo , Tiempo de Internación , Masculino , Femenino , Complicaciones Posoperatorias/etiologíaRESUMEN
As one of the most frequent complications of critical illness, acute lung injury (ALI) carries a high risk of clinical morbidity and mortality. Cepharanthine (CPA) has significant anti-inflammatory activity, however, due to poor water solubility, low bioavailability, and short half-life, it fails to provide effective clinical management measures. Here, we explored the flexibility of an erythrocyte-anchoring strategy using CPA-encapsulated chitosan-coating nanoparticles (CPA-CNPs) anchored onto circulating erythrocytes for the treatment of ALI. CPA-CNPs adhered to erythrocytes successfully (E-CPA-CNPs) and exhibited high erythrocyte adhesion efficiency (>80%). Limited toxicity and favorable biocompatibility enabled further application of E-CPA-CNPs. Next, the reticuloendothelial system evasion features were analyzed in RAW264.7 macrophages and Sprague-Dawley rats. Compared with bare CPA-CNPs, erythrocyte-anchored CNPs significantly decreased cellular uptake in immune cells and prolonged circulation time in vivo. Notably, the erythrocyte-anchoring strategy enabled CNPs to be delivered and accumulated in the lungs (up to 6-fold). In the ALI mouse model, E-CPA-CNPs attenuated the progression of ALI by inhibiting inflammatory responses. Overall, our results demonstrate the outstanding advantages of erythrocyte-anchored CPA-CNPs in improving the pharmacokinetics and bioavailability of CPA, which offers great promise for a lung-targeted drug delivery system for the effective treatment of ALI.
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Recent studies have demonstrated that ivermectin (IVM) exhibits antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative virus of coronavirus disease 2019 (COVID-19). However, the repurposing of IVM for the treatment of COVID-19 has presented challenges primarily due to the low IVM plasma concentration after oral administration, which was well below IC50. Here, a red blood cell (RBC)-hitchhiking strategy was used for the targeted delivery of IVM-loaded nanoparticles (NPs) to the lung. IVM-loaded poly (lactic-co-glycolic acid) (PLGA) NPs (IVM-PNPs) and chitosan-coating IVM-PNPs (IVM-CSPNPs) were prepared and adsorbed onto RBCs. Both RBC-hitchhiked IVM-PNPs and IVM-CSPNPs could significantly enhance IVM delivery to lungs, improve IVM accumulation in lung tissue, inhibit the inflammatory responses and finally significantly alleviate the progression of acute lung injury. Specifically, the redistribution and circulation effects were related to the properties of NPs. RBC-hitchhiked cationic IVM-CSPNPs showed a longer circulation time, slower accumulation and elimination rates, and higher anti-inflammatory activities than RBC-hitchhiked anionic IVM-PNPs. Therefore, RBC-hitchhiking provides an alternative strategy to improve IVM pharmacokinetics and bioavailability for repurposing of IVM to treat COVID-19. Furthermore, according to different redistribution effects of different NPs, RBC-hitchhiked NPs may achieve various accumulation rates and circulation times for different requirements of drug delivery.
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Tratamiento Farmacológico de COVID-19 , Nanopartículas , Eritrocitos , Humanos , Ivermectina , Pulmón , SARS-CoV-2RESUMEN
Hyper-inflammation associated with cytokine storm syndrome causes high mortality in patients with COVID-19. Glucocorticoids, such as methylprednisolone sodium succinate (MPSS), effectively inhibit this inflammatory response. However, frequent and chronic administration of glucocorticoids at high doses leads to hormone dependence and serious side effects. The aim of the present study was to combine nanoparticles with erythrocytes for the targeted delivery of MPSS to the lungs. Chitosan nanoparticles loading MPSS (MPSS-CSNPs) were prepared and adsorbed on the surface of red blood cells (RBC-MPSS-CSNPs) by non-covalent interaction. In vivo pharmacokinetic study indicated that RBC-hitchhiking could significantly reduce the plasma concentration of the drug and prolong the circulation time. The mean residence time (MRT) and area under the curve (AUC) of the RBC-MPSS-CSNPs group were significantly higher than those of the MPSS-CSNPs group and the MPSS injection group. Moreover, in vivo imaging and tissue distribution indicated that RBC-hitchhiking facilitated the accumulation of nanoparticles loading fluorescein in the lung, preventing uptake of these nanoparticles by the liver. Furthermore, compared with the MPSS-CSNPs and MPSS treatment groups, treatment with RBC-MPSS-CSNPs considerably inhibited the production of inflammatory cytokines such as TNF-α and IL-6, and consequently attenuated lung injury induced by lipopolysaccharide in rats. Therefore, RBC-hitchhiking is a potentially effective strategy for the delivery of nanoparticles to the lungs for the treatment of acute lung injury and acute respiratory distress syndrome.
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COVID-19 , Quitosano , Nanopartículas , Preparaciones Farmacéuticas , Animales , Eritrocitos , Humanos , Pulmón , Metilprednisolona , Ratas , SARS-CoV-2RESUMEN
Traumatic brain injury (TBI) is known to activate poly (ADP-ribose) polymerase (PARP-1), which leads to pronounced negative effects on mitochondrial DNA (mt-DNA) repair and function. Notably, PARP inhibitors are reported to be beneficial in experimental models of TBI. A targeting strategy for the delivery of neuronal mitochondria-specific PARP inhibitors could result in a greater neuroprotective effect and be a safer approach for TBI treatment. In the present study, we developed the PARP inhibitor olaparib (Ola) as a model drug and devised red blood cell (RBC)-coated nanostructured lipid carriers (RBCNLCs) co-modified with C3 and SS31 peptide (C3/SS31-RBCNLCs) for brain neuronal mitochondria-targeting. Our results indicated that biomimetic nanosystems have the physical and chemical properties of the NLCs, as well as the biological properties of RBC. A high concentration of Ola delivered into brain mitochondria by C3/SS31-RBCNLCs-Ola effectively improved mitochondrial function and prevented neuronal cell death caused by excessive activation of injury-induced mitochondrial PARP (mt-PARP) in vitro and in vivo. Taken together, the results of this study support the preclinical feasibility of developing highly effective nano-drugs as part of precision medicine for TBI. STATEMENT OF SIGNIFICANCE: TBI-induced neuronal mitochondria DNA damage activates Poly(ADP-ribose) Polymerase (PARP1) which leads to a pronounced negative effect on mitochondrial DNA repair and mitochondrial function. In recent years, PARP inhibitors showed strong benefits in experimental models of TBI, more importantly PARP inhibitors specially target neuronal mitochondria may play a greater neuroprotective role and may be a safer approach for TBI treatment. Herein, we designed red blood cell (RBC) membrane-coated nanostructure lipid carriers dual-modified with C3 and SS31 (C3/SS31-RBCNLCs) to accomplish these objectives. After encapsulating Olaparib (Ola) as the model PARP inhibitor, the data demonstrated that C3/SS31-RBCNLCs, with brain neuronal mitochondria targeting, can reduce neuronal cell death and improve mitochondrial dysfunction triggered by mitochondrial PARP activation in vitro and in vivo.
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Lesiones Traumáticas del Encéfalo , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Animales , Biomimética , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/metabolismo , Ratones , Mitocondrias/metabolismo , Neuronas/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacologíaRESUMEN
Acute lung injury (ALI) is a disease associated with suffering and high lethality, but to date without any effective pharmacological management in the clinic. In the pathological mechanisms of ALI, a strong inflammatory response plays an important role. Herein, based on macrophage 'homing' into inflammation sites and cell membrane coating nanotechnology, we developed a biomimetic anti-inflammation nanosystem (MM-CEP/NLCs) for the treatment of ALI. MM-CEP/NLCs were made with nanostructured lipid carriers (NLCs) coated with natural macrophage membranes (MMs) to achieve effective accumulation of cepharanthine (CEP) in lung inflammation to achieve the effect of treating ALI. With the advantage of suitable physicochemical properties of NLCs and unique biological functions of the macrophage membrane, MM-CEP/NLCs were stabilized and enabled sustained drug release, providing improved biocompatibility and long-term circulation. In vivo, the macrophage membranes enabled NLCs to be targeted and accumulated in the inflammation sites. Further, MM-CEP/NLCs significantly attenuated the severity of ALI, including lung water content, histopathology, bronchioalveolar lavage cellularity, protein concentration, and inflammation cytokines. Our results provide a bionic strategy via the biological properties of macrophages, which may have greater value and application prospects in the treatment of inflammation.
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Bencilisoquinolinas/farmacología , Macrófagos/metabolismo , Nanopartículas/química , Neumonía/tratamiento farmacológico , Animales , Animales no Consanguíneos , Bencilisoquinolinas/administración & dosificación , Biomimética , Preparaciones de Acción Retardada , Modelos Animales de Enfermedad , Portadores de Fármacos/química , Liberación de Fármacos , Células Endoteliales de la Vena Umbilical Humana , Humanos , Lípidos/química , Masculino , Ratones , Tamaño de la Partícula , Células RAW 264.7 , Distribución AleatoriaRESUMEN
Chromium poisoning has become one of the most common heavy metal poisoning occupational diseases with high morbidity and mortality. However, most antidotes detoxify the whole body and are highly toxic. To achieve hepato-targeted chromium poisoning detoxification, a novel hepato-targeted strategy was developed using aging erythrocyte membranes (AEMs) as biomimetic material coated with a dimercaptosuccinic acid (DMSA) nanostructured lipid carrier to construct a biomimetic nano-drug delivery system. The particle size, potential, drug loading, encapsulation rate, in vitro release, and stability of the nanoparticles (NPs) were characterized. Confocal microscopy and flow cytometry showed that the prepared NPs could be phagocytized by RAW264.7 macrophage cells. The efficacy of AEM-DMSA-NPs for targeted liver detoxification was evaluated by in vitro MTT analysis and an in vivo model of chromium poisoning. The results showed that the NPs could safely and efficiently achieve targeted liver chromium poisoning detoxification. All the results indicated that the biomimetic nano-drug delivery system mediated by aging erythrocyte membranes and containing DMSA nanoparticles could be used as a novel therapeutic drug delivery system potentially targeting liver detoxification.
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Antídotos/farmacología , Materiales Biomiméticos/metabolismo , Cromo/envenenamiento , Membrana Eritrocítica/metabolismo , Nanopartículas/química , Succímero/farmacología , Animales , Antídotos/administración & dosificación , Antídotos/farmacocinética , Química Farmacéutica , Portadores de Fármacos , Liberación de Fármacos , Hígado/efectos de los fármacos , Masculino , Ratones , Tamaño de la Partícula , Células RAW 264.7 , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Succímero/administración & dosificación , Succímero/farmacocinéticaRESUMEN
BACKGROUND: Although many therapeutic strategies for Alzheimer's disease (AD) have been explored, these strategies are seldom used in the clinic. Therefore, AD therapeutic research is still urgently needed. One major challenge in the field of nanotherapeutics is to increase the selective delivery of drugs to a targeted location. Herein, we devised and tested a strategy for delivery of nanoparticles to neurons to inhibit tau aggregation by directly targeting p-tau. RESULTS: Curcumin (CUR) is loaded onto red blood cell (RBC) membrane-coated PLGA particles bearing T807 molecules attached to the RBC membrane surface (T807/RPCNP). With the advantage of the suitable physicochemical properties of the PLGA nanoparticles and the unique biological functions of the RBC membrane, the RPCNP are stabilized and promote sustained CUR release, which provided improved biocompatibility and resulted in long-term presence in the circulation. Under the synergistic effects of T807, T807/RPCNP can not only effectively penetrate the blood-brain barrier (BBB), but they also possess high binding affinity to hyperphosphorylated tau in nerve cells where they inhibit multiple key pathways in tau-associated AD pathogenesis. When CUR was encapsulated, our data also demonstrated that CUR-loaded T807/RPCNP NPs can relieve AD symptoms by reducing p-tau levels and suppressing neuronal-like cells death both in vitro and in vivo. The memory impairment observed in an AD mouse model is significantly improved following systemic administration of CUR-loaded T807/RPCNP NPs. CONCLUSION: Intravenous neuronal tau-targeted T807-modified novel biomimetic nanosystems are a promising clinical candidate for the treatment of AD.
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Enfermedad de Alzheimer , Materiales Biomiméticos , Curcumina , Portadores de Fármacos , Nanopartículas/química , Animales , Apoptosis/efectos de los fármacos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacocinética , Barrera Hematoencefálica/metabolismo , Línea Celular , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacología , Modelos Animales de Enfermedad , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Hipocampo/efectos de los fármacos , Hipocampo/patología , Humanos , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Neuronas/metabolismo , Sustancias Protectoras/química , Sustancias Protectoras/farmacocinética , Sustancias Protectoras/farmacología , Proteínas tau/metabolismoRESUMEN
OBJECTIVE: To compare the clinical results between the Wiltse approach and traditional approach in lumbar fusion. METHODS: The clinical data of 70 patients with lumbar disc herniation or lumbar spondylolisthesis within Meyerding II degree who underwent lumbar fusion surgery from May 2016 to May 2017 were retrospectively analyzed. According to the surgical approach, the patients were divided into Wiltse approach group and traditional approach group. A total of 35 patients in Wiltse approach group, included 18 males and 17 females, with an average age of (52±11) years old;other 35 patients in traditional approach group, included 19 males and 16 females, with an average age of (51±14) years old. Included 38 patients with lumbar disc herniation and 32 patients with spondylolisthesis of Meyerding II degree. The operation time, intraoperative blood loss and postoperative drainage, the VAS score of low back pain and leg pain, the level of creatine phosphokinase (CK) and the cross-sectional area of multifidus muscl on MRI were recorded. RESULTS: The operation time, intraoperative blood loss and postoperative drainage in Wiltse approach group were less than in traditional approach group(P<0.05). There were significant differences in VAS score of low back pain at 7 days and 3 months after operation between two groups(P<0.05). VAS of back pain at both 7 days and 3 months showed better results (P<0.05); VAS of leg pain showed better results in 3 months but had no significant difference in 7 days. There was no significant difference in VAS score of leg pain at 7 days after operation between two groups(P>0.05), but at 3 months had significant difference(P<0.05). The peripheral blood CK levels at 1 day and 3 days after operation respectively were(400±103)U/L and (176±58)U/L in Wiltse approach group, while in traditional approach group were (598±57) U/L and (222±50) U/L, with statistical significance between the two groups(P<0.05). Preoperative cross-sectional area of multifidus muscl on MRI was (424±66) mm² in Wiltse approach group and (428±82) mm² in traditional approach group, there was no significant difference between two groups(P=0.8); at 3 months after operation, in Wiltse approach group was (347±73) mm² and in traditional approach group was(239±78)mm², there was significant difference between two groups(P<0.05). CONCLUSIONS: For lumbar spinal fusion surgery, compared with the traditional approach, Wiltse approach has advantages of shorter operation time, smaller paravertebral muscles injury, and obviously releasing postoperative low back and leg pain. However, in determining the surgery program, the surgical operater also should fully recognize that the anatomical differences of Wiltse approach may influence on operation.
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Fusión Vertebral , Espondilolistesis , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Vértebras Lumbares , Región Lumbosacra , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: To explore the methodology on prevalence study of chronic obstructive pulmonary disease (COPD) in line with the world, to obtain accurate epidemic data of COPD in China. METHODS: A national multi-center cross-sectional survey on prevalence, risk factors and burden of COPD was conducted in China. In each area, a population-based cluster sample of approximately 1450 individuals aged 40 years or older was interviewed, using standardized questionnaires that were revised on the methodology of burden of lung diseases (BOLD) study and according under the context of China. All participants were submitted to pre-bronchodilator spirometry. Those with airflow limitation received post-bronchodilator spirometry, physical examination, X-rays of chest and EKG (electrocardiogram) tests. The post-bronchodialators FEV1/FVC < 70% was identified as having COPD. RESULTS: Investigation has been completed with the same standardized procedures by all sites, up to the requirement of quality control. Over 85.0% of the spirometry tests and 95.0% of questionnaires had met the criteria of quality control in each area. Overall, 95.2% of the data was valid with acceptable spirometry and questionaire, and the valid response rate was 79.0%. CONCLUSION: The protocol was in line with the international standards, by which the prevalence of COPD in China was of adequate quality and valid.