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This systematic review and meta-analysis were conducted to compare the accuracy of component positioning, alignment and balancing techniques employed, patient-reported outcomes, and complications of robotic-arm assisted total knee arthroplasty (RATKA) with manual TKA (mTKA) and the associated learning curve. Searches of PubMed, Medline and Google Scholar were performed in October 2020 using PRISMA guidelines. Search terms included "robotic", "knee" and "arthroplasty". The criteria for inclusion were published clinical research articles reporting the learning curve for RATKA and those comparing the component position accuracy, alignment and balancing techniques, functional outcomes, or complications with mTKA. There were 198 articles identified, following full text screening, 16 studies satisfied the inclusion criteria and reported the learning curve of rTKA (n=5), component positioning accuracy (n=6), alignment and balancing techniques (n=7), functional outcomes (n=7), or complications (n=5). Two studies reported the learning curve using CUSUM analysis to establish an inflexion point for proficiency which ranged from 7 to 11 cases and there was no learning curve for component positioning accuracy. The meta-analysis showed a significantly lower difference between planned component position and implanted component position, and the spread was narrower for RATKA compared with the mTKA group (Femur coronal: mean 1.31, 95% confidence interval (CI) 1.08-1.55, p<0.00001; Tibia coronal: mean 1.56, 95% CI 1.32-1.81, p<0.00001). Three studies reported using different alignment and balancing techniques between mTKA and RATKA, two studies used the same for both group and two studies did not state the methods used in their RATKA groups. RATKA resulted in better Knee Society Score compared to mTKA in the short-to-mid-term follow up (95%CI [- 1.23, - 0.51], p=0.004). There was no difference in arthrofibrosis, superficial and deep infection, wound dehiscence, or overall complication rates. RATKA demonstrated improved accuracy of component positioning and patient-reported outcomes. The learning curve of RATKA for operating time was between 7 and 11 cases. Future well-powered studies on RATKAs should report on the knee alignment and balancing techniques utilised to enable better comparisons on which techniques maximise patient outcomes.Level of evidence III.
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Artroplastia do Joelho , Procedimentos Cirúrgicos Robóticos , Artroplastia do Joelho/métodos , Humanos , Articulação do Joelho/cirurgia , Medidas de Resultados Relatados pelo Paciente , Procedimentos Cirúrgicos Robóticos/métodos , Tíbia/cirurgiaRESUMO
Introduction: This article describes the experience of the Singapore Armed Forces (SAF) implementing telemedicine consultations for COVID-19-positive patients recovering within community recovery facilities (CRFs) in a semi-inpatient setting. Materials and Methods: The SAF adopted a systematic approach to telemedicine implementation and scaling up, with Phase 1 being the deployment of medical teams operating on-site clinics daily at six CRFs and telemedicine only provided for after-hours medical consultations on an ad hoc basis. Subsequently in Phase 2, most clinical consultations in the CRFs were conducted virtually. Results: Phases 1 and 2 recorded 1,902 and 449 clinical consultations, respectively. The mean number of clinical encounters was 33 per 1,000 occupants per day in Phase 1, and 12 per 1,000 occupants per day in Phase 2 (p < 0.001). Acute respiratory illness (52.3% in Phase 1 and 46.7% in Phase 2) was the most common reason for consultations. With full telemedicine in Phase 2, there was reduction in the mean number of clinical encounters per 1,000 occupants per day (p = 0.001), lower man-hours in personal protective equipment (PPE) (p < 0.001), and rise in escalation of care (p < 0.001) but without adverse events reported. Conclusions: Telemedicine for patients was safe, improved medical manpower efficiency, and reduced man-hours in PPE. The increased escalation of care in Phase 2 due to the lack of physical examination capabilities was to be expected to ensure patients' safety. Overall, it is recommended that for stable and mild medical conditions, telemedicine is a viable, safe, and efficient health care delivery tool in crisis situations similar to COVID-19.
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PURPOSE: The purpose of this study was to compare the outcomes of arthroscopic rotator cuff repair (ARCR) in patients with preoperative stiffness to those without. METHODS: A total of 135 patients were prospectively evaluated for 2 years after ARCR for small to medium sized rotator cuff tears at our institution. Patients were divided into stiff (<100° of passive forward flexion) and non-stiff cohorts. The stiff group underwent manipulation under anesthesia (MUA) before ARCR was performed. Outcomes were measured using visual analog scale (VAS), Constant Shoulder Score (CSS), and Oxford Shoulder Score (OSS) recorded at the preoperative, 6- , 12-, and 24-month time points. The results of ARCR between the cohorts were then compared. RESULTS: A total of 123 out of 135 patients (91.1%) completed the follow-up (stiff n = 46, non-stiff n = 77). There were significant improvements in the mean CSS scores at 6 (mean, 59.87; P < .001) and 12 months (mean, 65.88; P = .021) in the stiff group. There were no significant differences detectable in the CSS and OSS scores between the stiff and non-stiff groups at 6, 12, and 24 months. However, the percentage of patients achieving minimal clinically important difference was significantly higher in the stiff group (97.8%) compared with the non-stiff group (75.3%; P = .001). The VAS scores, forward flexion, and strength in both groups were found to be comparable. CONCLUSIONS: The results of our study showed no significant differences in outcomes scores in patients with stiff shoulders who underwent MUA combined with ARCR compared with patients with non-stiff shoulders who underwent ARCR alone. Therefore, early surgical repair should be considered in patients with rotator cuff tears and concomitant shoulder stiffness. LEVEL OF EVIDENCE: Level II, prospective cohort study.
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Artroscopia/métodos , Bursite/etiologia , Bursite/cirurgia , Lesões do Manguito Rotador/complicações , Lesões do Manguito Rotador/cirurgia , Idoso , Anestesia , Artroplastia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Amplitude de Movimento Articular , Manguito Rotador/cirurgia , Articulação do Ombro/cirurgia , Resultado do TratamentoRESUMO
Background: Halofuginone hydrobromide (1) is recognized as an effective drug against several species of Eimeria (E.) in poultry. In this paper, we describe a convenient and low cost preparation method for the compound, as well as primary validation of its activity. Methods: First, 7-bromo-6-chloroquinazolin-4(3H)-one (2) was prepared from m-chlorotoluene by a conventional process, and then chloroacetone was creatively introduced in two steps. Finally, halofuginone hydrobromide (1) was obtained from 7-bromo-6-chloro-3-(3-cholroacetonyl) quinazolin-4(3H)-one (4) by a four-step reaction sequence including condensation, cyclization, deprotection and isomerization. The structures of the relative intermediates and target compound were characterized by melting point, IR, MS and ¹H-NMR. Besides, the protective effect of compound 1-supplemented chicken diet at doses of 6, 3 and 1.5 mg per 1 kg were evaluated on chickens infected with E. tenella, by reduction in mortality, weight loss, fecal oocyst excretion and gut pathology, respectively. Results: Halofuginone hydrobromide (1) was prepared successfully by and improved and innovative method based on traditional research. Moreover, the synthesized halofuginone hydrobromide significantly exhibited an anti-coccidial property. Conclusions: The fruitful work described in this Communication has resulted in halofuginone hydrobromide, which has a good pharmaceutical development prospects, becoming more available for large-scale production.
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Antiprotozoários/síntese química , Antiprotozoários/farmacologia , Coccídios/efeitos dos fármacos , Piperidinas/síntese química , Piperidinas/farmacologia , Quinazolinonas/síntese química , Quinazolinonas/farmacologia , Animais , Antiprotozoários/química , Galinhas , Estrutura Molecular , Piperidinas/química , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/parasitologia , Quinazolinonas/químicaRESUMO
BACKGROUND: Clinical outcomes of terrible triad injuries (TTIs) of the elbow are historically poor. To date, it is still debatable whether the coronoid needs to be fixed and if so, how and in which sequence. METHODOLOGY: Between 2010 and 2013, 13 patients were treated surgically for acute TTIs of the elbow at a Tertiary Level 1 Trauma Centre by a single surgeon, using a standardized protocol, which included coronoid-brachialis complex fixation via pull-through trans-osseous sutures, radial head fixation or prosthetic replacement and a repair of the lateral ulnar collateral ligament. Repair of the medial collateral ligament (MCL) was done if valgus-stress test demonstrated persistent instability. Patients were then followed-up with clinical and radiological evaluation by the senior author until fracture union and elbow range of motion reached a plateau. Outcomes measured were range of motion, DASH scores and MEPS, as well as surgical complications. RESULTS: Intraoperative stability was achieved in all 13 cases, MCL repair was required in 3 cases and application of external fixation was not required in any case. Patients were followed-up for an average length of 27.7 months and the minimum follow-up period was 12 months. The average age of patients was 46.4 years (range 35-79 years old) at the time of trauma. This included eight Regan-Morrey Type I and five Regan-Morrey Type II coronoid fractures, with ten Mason Type I/II and three Mason Type III radial head fractures. The average arc of ulno-humeral motion was 105.0° (range 80°-135°). The average flexion contracture was 15.0° (range 0°-40°). The average supination-pronation arc was 114.9° (range 0°-180°). The average MEPS was 85 of 100 (range 45-100) and the average DASH score was 21.2 of 100 (range 1.7-61.2). A single case of radio-ulnar synostosis, heterotropic ossification and two cases of recurrent elbow instability were noted. CONCLUSIONS: The coronoid-first surgical approach, using a suture-lasso fixation method, has technical benefits for us and showed good clinical success in our series. This is important with postero-medial rotatory instability being common in our series of TTIs. We emphasize not to miss a TTI in an apparently isolated low Mason class radial head fracture.
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Ossos do Braço , Lesões no Cotovelo , Articulação do Cotovelo , Cotovelo , Adulto , Idoso , Ossos do Braço/diagnóstico por imagem , Ossos do Braço/lesões , Ossos do Braço/fisiopatologia , Ossos do Braço/cirurgia , Cotovelo/diagnóstico por imagem , Cotovelo/fisiopatologia , Cotovelo/cirurgia , Articulação do Cotovelo/diagnóstico por imagem , Articulação do Cotovelo/fisiopatologia , Articulação do Cotovelo/cirurgia , Humanos , Pessoa de Meia-Idade , Procedimentos Ortopédicos , Amplitude de Movimento Articular , Resultado do TratamentoRESUMO
Tilorone dihydrochloride (1) has great potential for inducing interferon against pathogenic infection. In this paper, we describe a convenient preparation method for 2,7-dihydroxyfluoren-9-one (2), which is a usual pharmaceutical intermediate for preparing tilorone dihydrochloride (1). In the novel method, methyl esterification of 4,4'-dihydroxy-[1,1'-biphenyl]-2-carboxylic acid (4) was carried out under milder conditions with higher yield and played an important role in the preparation of compound 2. The structures of the relative intermediates and target compound were characterized by melting point, IR, MS, and ¹H-NMR. Furthermore, the synthesized tilorone dihydrochloride exhibited an obvious effect on induction of interferon-α (IFN-α) in mice within 12 h, and the peak level was observed until 24 h. This fruitful work has resulted in tilorone dihydrochloride becoming available in large-scale and wide application in clinics, which has a good pharmaceutical development prospects.
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Indutores de Interferon/síntese química , Indutores de Interferon/farmacologia , Interferon-alfa/metabolismo , Tilorona/síntese química , Tilorona/farmacologia , Animais , Camundongos , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
This research aims to explore the degradation properties of polyethylene terephthalate (PET) by PET hydrolase (WCCG) in high-temperature composting and its impact on microbial communities. PET degradation, composting parameters and microbial communities were assessed in 220 L sludge composters with PET and WCCG using high-throughput sequencing. Results showed that WCCG addition led to a deceleration of the humification process and a reduction in the relative abundance of thermophilic genera. Potential PET degrading microbiota, e.g. Acinetobacter, Bacillus, were enriched in the plastisphere in the composters where PET reduced by 26 % without WCCG addition. The external introduction of the WCCG enzyme to compost predominantly instigates a chemical reaction with PET, concurently curtailing the proliferation of plastic-degrading bacteria, leading to a 35 % degradation of PET. Both the WCCG enzyme and the microbiota associated with plastic-degradation showed the potential for reducing PET, offering a novel method for mitigating pollution caused by environmental microplastics.
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Compostagem , Microbiota , Polietilenotereftalatos , Microplásticos , Plásticos , Hidrolases , Temperatura , PolietilenoRESUMO
Postoperative distant metastasis and high recurrence rate causes a dilemma in treating triple-negative breast cancer (TNBC) owing to its unforeseeable invasion into various organs or tissues. The wealth of nutrition provided by vascular may facilitate the proliferation and angiogenesis of cancer cells, which further enhance the rates of postoperative metastasis and recurrence. Chemotherapy, as a systemic postoperative adjuvant therapy, is generally applied to diminish recurrence and metastasis of TNBC. Herein, an halofuginone-silver nano thermosensitive hydrogel (HTPM&AgNPs-gel) was prepared via a physical swelling method. The in vitro anticancer efficacy of HTPM&AgNPs-gel was analyzed by investigating cell proliferation, migration, invasion, and angiogenesis capacity. Furthermore, the in vivo anti-cancer activity of HTPM&AgNPs-gel was further appraised through the tumor suppression, anti-metastatic, anti-angiogenic, and anti-inflammatory ability. The optimized HTPM&AgNPs-gel, a thermosensitive hydrogel, showed excellent properties, including syringeability, swelling behavior, and a sustained release effect without hemolysis. In addition, HTPM&AgNPs-gel was confirmed to effectively inhibit the proliferation, migration, invasion, and angiogenesis of MDA-MB-231 cells. An evaluation of the in vivo anti-tumor efficacy demonstrated that HTPM&AgNPs-gel showed a stronger tumor inhibition rate (68.17%) than did HTPM-gel or AgNPs-gel used alone and exhibited outstanding biocompatibility. Notably, HTPM&AgNPs-gel also inhibited lung metastasis induced by residual tumor tissue after surgery and further blocked angiogenesis-related inflammatory responses. Taken together, the suppression of inflammation by interdicting the blood vessels adjoining the tumor and inhibiting angiogenesis is a potential strategy to attenuate the recurrence and metastasis of TNBC. HTPM&AgNPs-gel is a promising anticancer agent for TNBC as a local postoperative treatment.
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Antineoplásicos , Proliferação de Células , Hidrogéis , Piperidinas , Quinazolinonas , Prata , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Hidrogéis/administração & dosagem , Hidrogéis/química , Animais , Feminino , Prata/química , Prata/administração & dosagem , Humanos , Linhagem Celular Tumoral , Piperidinas/farmacologia , Piperidinas/administração & dosagem , Piperidinas/química , Proliferação de Células/efeitos dos fármacos , Quinazolinonas/química , Quinazolinonas/administração & dosagem , Quinazolinonas/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/química , Camundongos Endogâmicos BALB C , Camundongos , Movimento Celular/efeitos dos fármacos , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/química , Neovascularização Patológica/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos NusRESUMO
Canine mammary tumors (CMT) can severely compromise the life quality of the affected dogs through local recurrence, distant metastases and ultimately succumb to death. Recently, more attention has been given to the potential antimetastatic effect of maduramicin (MAD) on breast cancer. However, its poor aqueous solubility and toxicity to normal tissues limit its clinical application. Therefore, to address the drawbacks of MAD and enhance its anticancer and antimetastatic effects, MAD-loaded TPGS polymeric micelles (MAD-TPGS) were prepared by a thin-film hydration technique. The optimized MAD-TPGS exhibited excellent size distribution, stability and improved water solubility. Cellular uptake assays showed that TPGS polymer micelles could enhance drug internalization. Moreover, TPGS synergistically improved the cytotoxicity of MAD by targeting mitochondrial organelles, improving reactive oxygen species levels and reducing the mitochondrial transmembrane potential. More importantly, MAD-TPGS significantly impeded the metastasis of tumor cells. In vivo results further confirmed that, in addition to exhibiting excellent biocompatibility, MAD-TPGS exhibited greater antitumor efficacy than free MAD. Interestingly, MAD-TPGS displayed superior suppression of CMT metastasis via tail vein injection compared to oral administration, indicating its suitability for intravenous delivery. Overall, MAD-TPGS could be applied as a potential antimetastatic cancer agent for CMT.
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Antineoplásicos , Neoplasias Mamárias Animais , Cães , Animais , Micelas , Polietilenoglicóis , Antineoplásicos/farmacologia , Polímeros , Neoplasias Mamárias Animais/tratamento farmacológico , Vitamina E , Portadores de Fármacos , Linhagem Celular TumoralRESUMO
Contamination by pathogens, such as bacteria, can irritate a wound and prevent its healing, which may affect the physical fitness of the infected person. As such, the development of more novel nano-biomaterials able to cope with the inflammatory reaction to bacterial infection during the wound healing process to accelerate wound healing is required. Herein, a halofuginonesilver nano thermosensitive hydrogel (HTPM&AgNPs-gel) was prepared via a physical swelling method. HTPM&AgNPs-gel was characterized based on thermogravimetric analysis, differential scanning calorimetry, morphology, injectability, and rheological mechanics that reflected its exemplary nature. Moreover, HTPM&AgNPs-gel was further tested for its ability to facilitate healing of skin fibroblasts and exert antibacterial activity. Finally, HTPM&AgNPs-gel was tested for its capacity to accelerate general wound healing and treat bacterially induced wound damage. HTPM&AgNPs-gel appeared spherical under a transmission electron microscope and showed a grid structure under a scanning electron microscope. Additionally, HTPM&AgNPs-gel demonstrated excellent properties, including injectability, temperature-dependent swelling behavior, low loss at high temperatures, and appropriate rheological properties. Further, HTPM&AgNPs-gel was found to effectively promote healing of skin fibroblasts and inhibit the proliferation of Escherichia coli and Staphylococcus aureus. An evaluation of the wound healing efficacy demonstrated that HTPM&AgNPs-gel had a more pronounced ability to facilitate wound repair and antibacterial effects than HTPM-gel or AgNPs-gel alone, and exhibited ideal biocompatibility. Notably, HTPM&AgNPs-gel also inhibited inflammatory responses in the healing process. HTPM&AgNPs-gel exhibited antibacterial, anti-inflammatory, and scar repair features, which remarkably promoted wound healing. These findings indicated that HTPM&AgNPs-gel holds great clinical potential as a promising and valuable wound healing treatment.
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Nanopartículas Metálicas , Piperidinas , Quinazolinonas , Prata , Humanos , Prata/farmacologia , Prata/química , Staphylococcus aureus , Cicatrização , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Hidrogéis/química , Anti-Inflamatórios/farmacologiaRESUMO
Coccidiosis is a worldwide epidemic intestinal disease with high incidence, which causes huge economic losses. Halofuginone hydrobromide (HF) is widely applied as an effective anticoccidial drug in the poultry industry. However, its therapeutic efficacy is severely restrained due to toxic effects, poor aqueous solubility and low permeability. Nanotechnology can improve the biological effect of drugs, and thus, reduce administered doses and toxic effects. The objective of this study was to investigate the therapeutic and preventive potential of novel HF-loaded D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) polymer micelles (HTPM) for preventing coccidiosis in chickens. The HTPM were approximately spherical with a hydrodynamic diameter of 12.65 ± 0.089 nm, a zeta potential of 8.03 ± 0.242 mV, a drug loading of 14.04 ± 0.12%, and an encapsulation efficiency of 71.1 ± 4.15%. HF was encapsulated in the polymer micelles through interactions with TPGS, as characterized by X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy. Cellular take up assays showed that TPGS polymer micelles could enhance drug internalization to alleviate intestinal apoptosis induced by coccidiosis and promote the necrosis of second-generation merozoites of E. tenella. Notably, clinical trials proved that 1.5 mg L-1 HTPM had a stronger anticoccidial effect on E. tenella than that of 3 mg kg-1 HF premix. Amplicon sequencing identified that HTPM could alleviate coccidiosis by restoring the structure of the gut microbiome. These findings indicated that the anticoccidial efficacy of HF was significantly enhanced after being encapsulated in polymer micelles, and further demonstrated the potential protective application of nano-encapsulating anticoccidial drugs as a promising approach to control coccidiosis in poultry. In summary, HTPM hold huge potential as an effective therapeutic agent for coccidiosis.
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Coccidiose , Coccidiostáticos , Eimeria tenella , Doenças das Aves Domésticas , Animais , Coccidiostáticos/farmacologia , Coccidiostáticos/uso terapêutico , Galinhas , Micelas , Espectroscopia de Infravermelho com Transformada de Fourier , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/prevenção & controle , Coccidiose/tratamento farmacológico , Coccidiose/veterinária , Coccidiose/epidemiologia , Polímeros/farmacologiaRESUMO
Upon extensive hepatocyte loss or impaired hepatocyte proliferation, liver regeneration occurs via biliary epithelial cell (BEC) transdifferentiation, which includes dedifferentiation of BECs into bipotential progenitor cells (BP-PCs) and then redifferentiation of BP-PCs to nascent hepatocytes and BECs. This BEC-driven liver regeneration involves reactivation of hepatoblast markers, but the underpinning mechanisms and their effects on liver regeneration remain largely unknown. Using a zebrafish extensive hepatocyte ablation model, we perform an N-ethyl-N-nitrosourea (ENU) forward genetic screen and identify a liver regeneration mutant, liver logan (lvl), in which the telomere maintenance 2 (tel2) gene is mutated. During liver regeneration, the tel2 mutation specifically inhibits transcriptional activation of a hepatoblast marker, hematopoietically expressed homeobox (hhex), in BEC-derived cells, which blocks BP-PC redifferentiation. Mechanistic studies show that Tel2 associates with the hhex promoter region and promotes hhex transcription. Our results reveal roles of Tel2 in the BP-PC redifferentiation process of liver regeneration by activating hhex.
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Sistema Biliar , Regeneração Hepática , Animais , Hepatócitos , Fígado , Regeneração Hepática/fisiologia , Proteínas Repressoras , Células-Tronco , Peixe-Zebra/fisiologia , Proteínas de Peixe-Zebra/genéticaRESUMO
OBJECTIVES: To determine the physiological effects of multiple stressors including energy deficit during a 62-day Ranger course in a hot-humid environment. DESIGN: Prospective cohort design. METHODS: Food intake data were collected daily and energy expenditure at each of the three phases of the course was estimated by the doubly-labeled water method. Anthropometry, hydration status, stress and metabolic hormones, handgrip strength and lower explosive power were measured at the start and at the end of each phase. RESULTS: Seventeen male participants (age: 24.5⯱â¯3.2â¯years, height: 173.9⯱â¯5.1â¯cm, body mass: 69.3⯱â¯3.2â¯kg, BMI: 22.9⯱â¯0.9â¯kg/m2, percent body fat: 14⯱â¯5%) completed the study. Mean total daily energy expenditure was 4756â¯kcal/day and mean daily energy intake was 3882â¯kcal/day. An 18% energy deficit resulted in an average body mass loss of 4.6â¯kg, comprising mostly fat mass. Participants with higher baseline adiposity (>15% body fat) lost more fat mass and gained (rather than lost) muscle mass compared to those with lower baseline adiposity. Handgrip strength declined only at the end of Phase I, while lower body explosive power declined progressively throughout the course. Lean mass in arms and legs was correlated with initial grip strength and lower body explosive power, but only at the start of the course. CONCLUSIONS: Physiologically demanding Ranger training in an equatorial environment is at least as metabolically demanding and stressful as other similar high-risk training courses, as demonstrated by the stress and metabolic endocrine responses, changes in body composition, and reduction in explosive power. Moreover, the smaller body size of Asian soldiers may confer an energetic advantage over larger sized Western counterparts.
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Militares , Adulto , Composição Corporal , Ingestão de Energia , Metabolismo Energético , Força da Mão , Humanos , Masculino , Metaboloma , Desempenho Físico Funcional , Estudos Prospectivos , Adulto JovemRESUMO
Background: Halofuginone (HF)-loaded TPGS polymeric micelles (HTPM) were successfully fabricated using the thin-film hydration technique. HTPM via intravenous injection have been demonstrated to exert an excellent anticancer effect against triple-negative breast cancer (TNBC) cells and subcutaneous xenografts. In the present study, we further explored the potential treatment effect and mechanism of orally administered HTPM alone and in combination with surgical therapy on TNBC in subcutaneous and orthotopic mouse models. Methods: Herein, the stability and in vitro release behavior of HTPM were first evaluated in the simulated gastrointestinal fluids. Caco-2 cell monolayers were then used to investigate the absorption and transport patterns of HF with/without encapsulation in TPGS polymeric micelles. Subsequently, the therapeutic effect of orally administered HTPM was checked on subcutaneous xenografts of TNBC in nude mice. Ultimately, orally administered HTPM, combined with surgical therapy, were utilized to treat orthotopic TNBC in nude mice. Results: Our data confirmed that HTPM exhibited good stability and sustained release in the simulated gastrointestinal fluids. HF was authenticated to be a substrate of P-glycoprotein (P-gp), and its permeability across Caco-2 cell monolayers was markedly enhanced via heightening intracellular absorption and inhibiting P-gp efflux due to encapsulation in TPGS polymeric micelles. Compared with HF alone, HTPM showed stronger tumor-suppressing effects in subcutaneous xenografts of MDA-MB-231 cells when orally administered. Moreover, compared with HTPM or surgical therapy alone, peroral HTPM combined with partial surgical excision synergistically retarded the growth of orthotopic TNBC. Fundamentally, HTPM orally administered at the therapeutic dose did not cause any pathological injury, while HF alone led to weight loss and jejunal bleeding in the investigated mice. Conclusion: Taken together, HTPM could be applied as a potential anticancer agent for TNBC by oral administration.
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Micelas , Neoplasias de Mama Triplo Negativas , Animais , Células CACO-2 , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Nus , Piperidinas , Polímeros , Quinazolinonas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Vitamina ERESUMO
AIMS: This systematic review aims to compare the precision of component positioning, patient-reported outcome measures (PROMs), complications, survivorship, cost-effectiveness, and learning curves of MAKO robotic arm-assisted unicompartmental knee arthroplasty (RAUKA) with manual medial unicompartmental knee arthroplasty (mUKA). METHODS: Searches of PubMed, MEDLINE, and Google Scholar were performed in November 2021 according to the Preferred Reporting Items for Systematic Review and Meta--Analysis statement. Search terms included "robotic", "unicompartmental", "knee", and "arthroplasty". Published clinical research articles reporting the learning curves and cost-effectiveness of MAKO RAUKA, and those comparing the component precision, functional outcomes, survivorship, or complications with mUKA, were included for analysis. RESULTS: A total of 179 articles were identified from initial screening, of which 14 articles satisfied the inclusion criteria and were included for analysis. The papers analyzed include one on learning curve, five on implant positioning, six on functional outcomes, five on complications, six on survivorship, and three on cost. The learning curve was six cases for operating time and zero for precision. There was consistent evidence of more precise implant positioning with MAKO RAUKA. Meta-analysis demonstrated lower overall complication rates associated with MAKO RAUKA (OR 2.18 (95% confidence interval (CI) 1.06 to 4.49); p = 0.040) but no difference in re-intervention, infection, Knee Society Score (KSS; mean difference 1.64 (95% CI -3.00 to 6.27); p = 0.490), or Western Ontario and McMaster Universities Arthritis Index (WOMAC) score (mean difference -0.58 (95% CI -3.55 to 2.38); p = 0.700). MAKO RAUKA was shown to be a cost-effective procedure, but this was directly related to volume. CONCLUSION: MAKO RAUKA was associated with improved precision of component positioning but was not associated with improved PROMs using the KSS and WOMAC scores. Future longer-term studies should report functional outcomes, potentially using scores with minimal ceiling effects and survival to assess whether the improved precision of MAKO RAUKA results in better outcomes. Cite this article: Bone Joint J 2022;104-B(5):541-548.
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Artroplastia do Joelho , Procedimentos Cirúrgicos Robóticos , Artroplastia do Joelho/métodos , Humanos , Articulação do Joelho/cirurgia , Curva de Aprendizado , Ontário , Procedimentos Cirúrgicos Robóticos/métodosRESUMO
BACKGROUND: Halofuginone hydrobromide (HF) is a synthetic analogue of the naturally occurring quinazolinone alkaloid febrifugine, which has potential therapeutic effects against breast cancer, however, its poor water solubility greatly limits its pharmaceutical application. D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) is a water-soluble derivative of vitamin E, which can self-assemble to form polymeric micelles (PMs) for encapsulating insoluble anti-tumor drugs, thereby effectively enhancing their anti-cancer effects. METHODS: HF-loaded TPGS PMs (HTPMs) were manufactured using a thin-film hydration technique, followed by a series of characterizations, including the hydrodynamic diameter (HD), zeta potential (ZP), stability, drug loading (DL), encapsulation efficiency (EE), and in vitro drug release. The anti-cancer effects and potential mechanism of HTPMs were investigated in the breast cell lines MDA-MB-231 and MCF-7, and normal breast epithelial cell line Eph-ev. The breast cancer-bearing BALB/c nude mouse model was successfully established by subcutaneous injection of MDA-MB-231 cells and used to evaluate the in vivo therapeutic effect and safety of the HTPMs. RESULTS: The optimized HTPMs had an HD of 17.8±0.5 nm and ZP of 14.40±0.1 mV. These PMs exhibited DL of 12.94 ± 0.46% and EE of 90.6 ± 0.85%, along with excellent storage stability, dilution tolerance and sustained drug release in pH-dependent manner within 24 h compared to free HF. Additionally, the HTPMs had stronger inhibitory effects than free HF and paclitaxel against MDA-MB-231 triple-negative breast cancer cells, and little toxicity in normal breast epithelial Eph-ev cells. The HTPMs induced cell cycle arrest and apoptosis of MDA-MB-231 by disrupting the mitochondrial membrane potential and enhancing reactive oxygen species formation. Evaluation of in vivo anti-tumor efficacy demonstrated that HTPMs exerted a stronger tumor inhibition rate (68.17%) than free HF, and exhibited excellent biocompatibility. CONCLUSION: The findings from this study indicate that HTPMs holds great clinical potential for treating triple-negative breast cancer.
Assuntos
Composição de Medicamentos , Micelas , Piperidinas/uso terapêutico , Polímeros/química , Quinazolinonas/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Vitamina E/química , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Nus , Paclitaxel/uso terapêutico , Piperidinas/farmacologia , Quinazolinonas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/ultraestruturaRESUMO
INTRODUCTION: Perforated colorectal malignancy is associated with numerous peri-operative complications and dismal long-term survival. The study aimed to review the outcome and factors predicting peri-operative complications and long-term survival of patients who underwent surgery for perforated colorectal malignancy. METHODS: A retrospective review of all patients who underwent operative intervention for perforated colorectal malignancy from February 2003 to April 2008 was performed. The severity of peritonitis was graded using the Mannheim peritonitis index (MPI). RESULTS: Forty-five patients, median age 67 years (36-97 years), formed the study group. Sigmoid colon (37.8%) and cecum (28.9%) were the most common sites of perforation. Sixteen (35.6%) patients had stage IV disease, while 14 (31.1%) had severe peritoneal contamination (MPI >26). Hartmann's procedure and right hemicolectomy were performed most frequently in 17 (37.8%) and 15 (33.4%) patients, respectively. The mortality rate in our series was 17.8%, with another 26.7% requiring surgical intensive care unit care. The independent variables predicting worse perioperative complications were American Society of Anesthesiologists (ASA) score >or= 3 and MPI >26. Left-sided perforation was the only independent factor predicting stoma creation. The only factor predicting long-term survival was the stage of malignancy (p<0.001). The overall mean survival time for stage II, III, and IV disease were 63.7, 38.1, and 13.8 months, respectively. CONCLUSIONS: Surgery for perforated colorectal malignancy is associated with high morbidity and mortality rates. Short-term outcome is determined by ASA score and severity of peritonitis, while long-term outcome is determined by staging of the cancer.
Assuntos
Povo Asiático , Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgia , Perfuração Intestinal/etiologia , Perfuração Intestinal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Singapura , Estomas Cirúrgicos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Ribosome biogenesis is essential for the cell growth and division. Disruptions in ribosome biogenesis result in developmental defects and a group of diseases, known as ribosomopathies. Here, we report a mutation in zebrafish urb1, which encodes an essential ribosome biogenesis protein. The urb1cq31 mutant exhibits hypoplastic digestive organs, which is caused by impaired cell proliferation with the differentiation of digestive organ progenitors unaffected. Knockdown of mtor or raptor leads to similar hypoplastic phenotypes and reduced expression of urb1 in the digestive organs. Overexpression of Urb1 results in overgrowth of digestive organs, and can efficiently rescue the hypoplastic liver and pancreas in the mtor and raptor morphants. Reduced syntheses of free ribosomal subunits and impaired assembly of polysomes are observed in the urb1 mutant as well as in the mtor and raptor morphants, which can be rescued by the Urb1 overexpression. These data demonstrate that Urb1 plays an important role in governing ribosome biogenesis and protein synthesis downstream of mammalian/mechanistic target of rapamycin complex 1 (mTORC1), thus regulating the development of digestive organs. Our study indicates the requirement of hyperactive protein synthesis for the digestive organ development.
Assuntos
Trato Gastrointestinal/embriologia , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Proteínas Nucleares/metabolismo , Ribossomos/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Diferenciação Celular , Proliferação de Células , Endoderma/citologia , Trato Gastrointestinal/citologia , Trato Gastrointestinal/metabolismo , Humanos , Camundongos , Mutação , Proteínas Nucleares/química , Proteínas Nucleares/genética , Transdução de Sinais , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/química , Proteínas de Peixe-Zebra/genéticaRESUMO
With the development of life science, pharmaceutical and biomedical analysis becomes more and more important in medical science. Further studies will be hopefully established if it is possible to use inorganic elemental standards or small organic compounds in the quantitative determination of all kinds of drugs, nucleotides and sulfur or phosphorus containing peptides and proteins at appropriate concentration with an acceptable accuracy. Since 1980, inductively coupled plasma mass spectrometry (ICP-MS) has emerged as a new and powerful analytical technique which is suitable for element and isotope analysis. It offers extremely wide detection range of element and co-analysis of most elements in the periodic table. Also, it can be applied to perform qualitative, semiquantitative, and quantitative analysis and isotopic ratios through mass-to-electric charge ratio. With the help of ICP-MS, the struggle of searching for an excellent quantification technique in, e.g. drugs and proteomics has come appreciably close to an end. This review mainly focuses on the introduction of application of ICP-MS in pharmaceutical and biomedical analysis. Some problems in application and the handling strategies are simply presented at the end.