A nanozyme multifunctional platform based on iron doped carbon dots derived from Tibetan Ganoderma lucidum waste for glucose sensing, anti-counterfeiting applications, and anticancer cell effect.

Implementing the concept of turning waste into treasure, the conversion of biomass waste into high-value carbon materials, especially carbon dots (CDs), has pointed out a new direction for disease diagnosis, tumor treatment, and other aspects. In this work, we have reported the GL-CDs(Fe) via a simple synthesis route exploiting Ganoderma lucidum waste as the precursor. Thanks to their excellent optical property and peroxidase mimetic activity, a novel GL-CDs(Fe)-based ratio fluorescence/colorimetric/smartphone triple mode sensing platform is cleverly fabricated for glucose determination with the LOD of 0.28, 0.37, and 0.52 µΜ separately. Especially, this triple mode biosensor is successfully utilized for glucose detection in serum samples with the relative error of less than ±8 % compared with clinical reports. Surprisingly, the GL-CDs(Fe) also presents immense application prospects in high-level anti-counterfeiting aspects due to their excellent luminescent properties, high water-solubility, and easy availability. Furthermore, GL-CDs(Fe) can catalyze excessive H2O2 inside tumor cells to produce massive hydroxyl radicals (·OH) which break down the redox levels of cancer cells and thereby eliminate tumor cells. Thus, this integrated "Three-in-One" multifunctional platform based on GL-CDs(Fe) unveils enormous research and application prospects for bio-sensing, anti-counterfeiting, cancer treatment.

Integrating Enrichment, Reduction, and Oxidation Sites in One System for Artificial Photosynthetic Diluted CO2 Reduction.

Artificial photosynthetic diluted CO2 reduction directly driven by natural sunlight is a challenging, but promising way to realize carbon-resources recycling utilization. Herein, a three-in-one photocatalytic system of CO2 enrichment, CO2 reduction and H2 O oxidation sites is designed for diluted CO2 reduction. A Zn-Salen-based covalent organic framework (Zn-S-COF) with oxidation and reductive sites is synthesized; then, ionic liquids (ILs) are loaded into the pores. As a result, [Emim]BF4 @Zn-S-COF shows a visible-light-driven CO2 -to-CO conversion rate of 105.88 µmol g-1 h-1 under diluted CO2 (15%) atmosphere, even superior than most photocatalysts in high concentrations CO2 . Moreover, natural sunlight driven diluted CO2 reduction rate also reaches 126.51 µmol g-1 in 5 h. Further experiments and theoretical calculations reveal that the triazine ring in the Zn-S-COF promotes the activity of H2 O oxidation and CO2 reduction sites, and the loaded ILs provide an enriched CO2 atmosphere, realizing the efficient photocatalytic activity in diluted CO2 reduction.

The Application of a Self-Made Integrated Three-in-One Microsensor and Commercially Available Wind Speed Sensor to the Cold Air Pipe of the Heating, Ventilation, and Air Conditioning in a Factory for Real-Time Wireless Measurement.

In this study, the integrated three-in-one (temperature, humidity, and wind speed) microsensor was made through the technology of the Micro-electro-mechanical Systems (MEMS) to measure three important physical quantities of the internal environment of the cold air pipe of the Heating, Ventilation and Air Conditioning (HVAC) in the factory, plan the installation positions of the integrated three-in-one microsensor and commercially available wind speed sensor required by the internal environment of the cold air pipe, and conduct the actual 310-h long term test and comparison. In the experiment, it was also observed that the self-made micro wind speed sensor had higher stability compared to the commercially available wind speed sensor (FS7.0.1L.195). The self-made micro wind speed sensor has a variation range of ±200 mm/s, while the commercially available wind speed sensor a variation range of ±1000 mm/s. The commercially available wind speed sensor (FS7.0.1L.195) can only measure the wind speed; however, the self-made integrated three-in-one microsensor can conduct real-time measurements of temperature and humidity according to the environment at that time, and use different calibration curves to know the wind speed. As a result, it is more accurate and less costly than commercially available wind speed sensors. The material cost of self-made integrated three-in-one microsensor includes chemicals, equipment usage fees, and wires. In the future, factories may install a large number of self-made integrated three-in-one microsensors in place of commercially available wind speed sensors. Through real-time wireless measurements, the self-made integrated three-in-one microsensors can achieve the control optimization of the HVAC cold air pipe's internal environment to improve the quality of manufactured materials.

Three-in-One Strategy Constructing the First High-Performance Nonlinear Optical Sulfide Crystallizing with the P43 Space Group.

The balance between large nonlinear optical (NLO) effect and wide bandgap is the key scientific issue for the exploration of infrared NLO materials. Targeting this issue, two new pentanary chalcogenides KGaGe1.37 Sn0.63 S6 (1) and KGaGe1.37 Sn0.63 Se6 (2) are obtained by the three-in-one strategy, viz. three types of fourfold-coordinated metal elements co-occupying the same site. They crystallize in the tetragonal P43 (1) and monoclinic Cc (2) space group. Their structures can be evolved from benchmark AgGaS2 (AGS) by suitable substitution. Remarkably, 1 is the first NLO sulfide crystallizing with the P43 space group, representing a new structure-type NLO material. The structural relationship between 1 and 2 and the evolution from 1, 2 to AGS are also analyzed. Both 1 and 2 show balanced NLO properties. Specifically, 1 exhibits phase-matchable SHG response of 0.6 × AGS, a wide bandgap of 3.50 eV, and a high laser damage threshold of 6.24 × AGS. Theoretical calculation results suggest that the Ga/Ge/Sn element ratios of the co-occupied sites of 1 and 2 are the most appropriate for stabilizing the structures. The strategy adopted here will provide some inspiration for exploring new high-performance NLO materials.

Discovery of orally effective and safe GPR40 agonists by incorporating a chiral, rigid and polar sulfoxide into ß-position to the carboxylic acid.

GPR40 is primarily expressed in pancreatic islet ß-cells, and its activation by endogenous ligands of medium to long-chain free fatty acids or synthetic agonists is clinically proved to improve glycemic control by stimulating glucose-dependent insulin secretion. However, most of the reported agonists are highly lipophilic, which might cause lipotoxicity and the off-target effects in CNS. Particularly, the withdrawal of TAK-875 from clinical trials phase III due to liver toxicity concern threw doubt over the long-term safety of targeting GPR40. Improving the efficacy and the selectivity, thus enlarging the therapeutic window would provide an alternative to develop safe GPR40-targeted therapeutics. Herein, by employing an innovative "three-in-one" pharmacophore drug design strategy, the optimal structural features for GPR40 agonist was integrated into one functional group of sulfoxide, which was incorporated into the ß-position of the propanoic acid core pharmacophore. As a result, the conformational constraint, polarity as well as chirality endowed by the sulfoxide significantly enhanced the efficacy, selectivity and ADMET properties of the novel (S)- 2-(phenylsulfinyl)acetic acid-based GPR40 agonists. The lead compounds (S)-4a and (S)-4s exhibited robust plasma glucose-lowering effects and insulinotropic action during an oral glucose tolerance test in C57/BL6 mice, excellent pharmacokinetic profile and little hepatobiliary transporter inhibition, marginal cell toxicities against human primary hepatocyte at 100 µM.

A 20-Year Retrospective Study of Children and Adolescents Treated by the Three-in-One Procedure for Patellar Realignment.

BACKGROUND: Patellar instability is the most common disorder of the knee during childhood and adolescence. Surgical treatment significantly reduces the rate of redislocation, but the underlying pathologies and pattern of instability may affect the results. We aimed to report the clinical and functional outcomes of the three-in-one procedure for patellar realignment in a cohort of skeletally immature patients with or without syndromes and various patterns of chronic patellar instability. METHODS: We retrospectively investigated 126 skeletally immature patients (168 knees) affected by idiopathic or syndromic patellar instability, who underwent patella realignment through a three-in-one procedure. We classified the instability according to the score proposed by Parikh and Lykissas. RESULTS: Patellar dislocation was idiopathic in 71 patients (94 knees; 56.0%) and syndromic in 55 (74 knees; 44.0%). The mean age at surgery was 11.5 years (range 4-18) and was significantly lower in syndromic patients. Syndromic patients also exhibited more severe clinical pattern at presentation, based on the Parikh and Lykissas score. The mean follow-up was 5.3 years (range 1.0-15.4). Redislocation occurred in 19 cases, with 10 cases requiring further realignment. The Parikh and Lykissas score and the presence of congenital ligamentous laxity were independent predictors of failure. A total of 22 knees in 18 patients required additional surgical procedures. The post-operative Kujala score was significantly lower in patients with syndromic patellar instability. CONCLUSIONS: The type of instability and the presence of underlying syndromes negatively affect the rate of redislocation and the clinical and functional outcome following patellar realignment through the three-in-one procedure. We recommend the consideration of alternative surgical strategies, especially in children with severe syndromic patellar dislocation.

The comparison of postoperative analgesic efficacy of three-in-one-block versus fascia-iliaca blocks following femoral fracture orthopedics surgical procedures under spinal anesthesia, Gondar, Ethiopia, 2021: A prospective cohort study.

INTRODUCTION: Femoral bone fracture is the predominant, lower limb orthopedic surgery that is associated with severe acute and persistent chronic pain that needs better postoperative pain management. Untreated postoperative pain results inability to do physiotherapy resulting in stiffens of joints and immobility. This study aimed to compare the postoperative analgesic efficacy of three-in-one-block versus fascia iliaca block in patients who underwent surgically treated femoral fractured patients under spinal anesthesia. METHODS: A prospective cohort study was conducted on 110 elective surgically treated femoral fractured orthopedic patients from January to October 2021. Data were entered into epi-data 4.4.2 and imported into a statistical package of social science version 22 for analysis. Shapiro-Wilk normality test was used to check the normality of the data and normally distributed data were analyzed using Student's independent t-test, whereas non-normally distributed variables were analyzed with Mann-Whitney U-test. The comparisons of categorical parameters were analyzed using the chi-square test and Fisher's exact test. Finally p-value < 0.05 was declared to be statistically significant. RESULT: The median and interquartile range of the postoperative numerical rating scale at rest and on movement was significantly less in three-in-one-block (3IN1B) as compared with fascia-iliaca block (FICB). But at 30 min no significantly different between the two pain management modalities. Moreover, the meantime to seek the first request of analgesia was significantly prolonged in 3IN1B compared with FICB. Regarding the total analgesic consumption, the mean total tramadol consumption was 97. 27 ± 53. 07 and 180 ± 72.96 (p < 0.001) and Diclofenac 53.18 ± 29.28 and 72 ± 43.54 (p < 0. 001) in 3IN1 and FICB, respectively. CONCLUSION: The present study concludes that three-in-one-block provides more effective analgesia, reduced postoperative analgesic requirements, and prolonged first analgesics requests compared with fascia iliaca block, and Landmark technique fascia-iliaca block (FICB) is an alternative pain management modality in a resource-limited setting.

A Comparison on Efficiency and Aerosol Generation between "Modified and Conventional Technique of Bracket Bonding".

Introduction: The novel COVID-19 which spread's primarily through oral and nasal passage poses a major threat of spread during dental treatments. It is important for dental practitioners to use minimal aerosol techniques. The aim of this study is to compare the time taken, efficiency and aerosol generated between modified and conventional technique (CT) of bracket bonding. Methods: This study includes 40 patients who required complete orthodontic treatment. In all 40 patients, one of the arches was bonded with modified technique (MT) and the opposing with CT. The time taken to prepare tooth in both the techniques were accessed. The efficiency of bond was seen over a period of 6 months. The amount of aerosol particulate matter generated during CT and MT was observed using a laser air quality monitor. Conclusion: There is no significant difference in the bond failure and time taken between both the techniques. The aerosol generated in MT was minimal or almost negligible when compared to the use of CT.

Real-Time Monitoring of the Temperature, Flow, and Pressure Inside High-Temperature Proton Exchange Membrane Fuel Cells.

The proton exchange membrane fuel cell (PEMFC) system is a highly efficient and environmentally friendly energy conversion technology. However, the local temperature, flow, and pressure inhomogeneity within the fuel cell during the electrochemical reaction process may lead to depletion of PEMFC material and uneven fuel distribution, thus affecting the performance and service life of high-temperature PEMFCs. In this study, micromachining technology is used to develop a three-in-one flexible micro-sensor that is resistant to a high-temperature electrochemical environment (120~200 °C). Appropriate materials and process parameters are used to protect the micro-sensor from failure or damage under long-term testing, and to conduct a real-time micro-monitor of the local temperature, flow, and pressure distribution inside high-temperature PEMFCs.

The "Three in One" Bone Repair Strategy for Osteoporotic Fractures.

In aging society, osteoporotic fractures have become one major social problem threatening the health of the elderly population in China. Compared with conventional fractures, low bone mass, bone defect and retarded healing issues of osteoporotic fractures lead to great difficulties in treatment and rehabilitation. Addressing major concerns in clinical settings, we proposed the "three in one" bone repair strategy focusing on anti-osteoporosis therapies, appropriate bone grafting and fracture healing accelerating. We summarize misconceptions and repair strategies for osteoporotic fracture management, expecting improvement of prognosis and clinical outcomes for osteoporotic fractures, to further improve therapeutic effect and living quality of patients.

Real-Time Monitoring of HT-PEMFC.

During the electrochemical reaction of a high temperature proton exchange membrane fuel cell (HT-PEMFC), (in this paper HT-PEMFC means operating in the range of 120 to 200 °C) the inhomogeneity of temperature, flow rate, and pressure in the interior is likely to cause the reduction of ion conductivity or thermal stability weight loss of proton exchange membrane materials, and it is additionally likely to cause uneven fuel distribution, thereby affecting the working performance and service life of the HT-PEMFC. This study used micro-electro-mechanical systems (MEMS) technology to develop a flexible three-in-one microsensor which is resistant to high temperature electrochemical environments; we selected appropriate materials and process parameters to protect the microsensor from failure or damage under long-term tests. The proposed method can monitor the local temperature, flow rate, and pressure distribution in HT-PEMFC in real time.

Analgesic efficacy of posterior and anterior psoas compartment block: Lumbar plexus versus three -in-one nerve block after lower limb orthopedic surgery under spinal anesthesia: A prospective cohort study.

INTRODUCTION: Postoperative pain is the most common complaint in patients who underwent orthopedic surgery. Regarding with the severity of pain, orthopedic patients suffered more than non-orthopedic patients in the immediate post-operative period. Therefore, pain management is crucial for better patient outcome. Lumbar plexus (LB) and three -in-one (3IN1) nerve blocks have been routinely practiced as pain management techniques in the study area but the analgesic efficacy was not studied yet. Thus, this study was aimed to compare the analgesic efficacy of the LBP versus 3IN1B as postoperative pain management after thigh orthopedic surgery under spinal anesthesia. METHOD: An institutional-based prospective cohort study was conducted from October 10, 2020 to March 30, 2021 at the University comprehensive specialized hospital. Non-probability convenient sampling was used to select participants in both groups. The time to first analgesic request, severity of pain and total analgesia consumption within the first postoperative 24 h were measured. RESULT: The mean and standard deviation to seek the first analgesia request time was 11. 55 ± 2. 82hr and 13. 35 ± 2. 58hr (p- 0.07) in patients who received LPB and 3IN1B respectively. Pain severity at rest and on movement was also comparable. The total tramadol consumption was 67. 65 ± 27. 20 mg and 70. 59 ± 37. 19 mg (p- 0.71), while total Diclofenac consumption was 63. 23 ± 45. 74 mg and 44. 88 ± 34. 72 mg (p-0.07) in LPB and 3IN1B groups respectively. CONCLUSION: The study showed that there was no significant difference in the time to first analgesia request, postoperative pain, both at rest and movement and total analgesic consumption, between the LPB and 3IN1B.

A biocatalytic peptidobiosensing molecular bridge for detecting osteosarcoma marker protein.

A biosensing scheme requiring only one-step sample incubation before signal collection, and using a compact "three-in-one" probe of target-binding, signal conversion, and amplification, may greatly simplify the design of biosensors. Therefore, sparing the multi-step addition of enzymes, protein, and nanomaterial, as well as the associated complexity and non-specific interactions. In this work, a peptide probe aimed at such compact features has been designed, based on protein-triggered, conformation-driven, and Cu (II) facilitated side-chain di-tyrosine cyclization. This design can use target-probe recognition to induce discriminated cross-linking and self-cleavage of the probe, resulting in retention or dissociation of a signal amplification motif from the search and consequently quantitative detection performance. The method has also been tested preliminarily in fractioned osteosarcoma clinical samples, showing an acceptable coherence between signal readout and clinical diagnosis. On the basis of these early findings, it is reasonable to assume that the proposed probe will be beneficial for the next development of tumor screening and prognosis sensors.

Engineering a "three-in-one" hirudin prodrug to reduce bleeding risk: A proof-of-concept study.

An ideal anticoagulant should have at least three properties including targeted delivery to the thrombosis site, local activation or releasing to centralize the anti-thrombosis effects and thus reduce the bleeding risks, and long persistence in circulation to avoid repeated administration. In the present study, we sought to test a "three-in-one" strategy to design new protein anticoagulants. Based on these criteria, we constructed two hirudin prodrugs, R824-HV-ABD and ABD-HV-R824. The R824 peptide can bind phosphatidylserine on the surface of the procoagulant platelets and thus guide the prodrug to the thrombosis sites; albumin-binding domain (ABDs) can bind the prodrug to albumin, and thereby increase its persistence in circulation; the hirudin (HV) core in the prodrug is flanked by factor Xa recognition sites, thus factor Xa at the thrombosis site can cleave the fusion proteins and release the activated hirudin locally. Hirudin prodrugs were able to bind with procoagulant platelets and human serum albumin in vitro with high affinity, targeted concentrated and prevented the formation of occlusive thrombi in rat carotid artery injury model. Their effective time was significantly extended compared to native hirudin, and R824-HV-ABD showed a significantly improved half-life of about 24 h in rats. The bleeding time of prodrug-treated mice was much shorter than that of hirudin-treated mice. The results from the proof-of-concept studies, for the first time, demonstrate that "three-in-one" prodrug strategy may be a good solution for protein or peptide anticoagulants to reduce their bleeding risks.

The Use of a Three-in-One Practice-Management-Innovation Training Model in the Construction of an Infection Control Team.

OBJECTIVE: This study aims to explore the role of a three-in-one practice, management, and innovation training model (also called as three-in-one practice-management-innovation training model) in the construction of an infection control team. METHODS: This study retrospectively analyzed the position structure, mastery of professional knowledge, and working methods of the full-time and part-time personnel of the Changzhou Cancer Hospital, compared the training content of Jiangsu Hospital Infection Control Center with the actual situation of the hospital, and formulated and implemented a three-in-one practice-management-innovation training model. First, the team members were selected for the construction and management of the Hospital Infection Management Department according to the relevant responsibility and management requirements, and their learning and mastery of the basic knowledge and skills concerning infection control were completed based on their professional roles. In line with the regulations of the hospital and department, full-time personnel were ensured of having the opportunity to participate in provincial- and municipal-level academic exchanges and then learn from each other, through collaboration between doctors and nurses, how to exercise basic management skills. At the same time, a fair competitive incentive mechanism was established through the three-level network of the hospital infection committee, the hospital infection management department, and nosocomial infection management department to implement innovative project-based management and cultivate an awareness of hospital infection control in all employees. RESULTS: The professional structure of the full-time infection control personnel has been optimized, the awareness of the infection control team concerning active participation in practice has gradually increased, and infection control management and innovation has been significantly improved. CONCLUSION: After the selection of an infection control management team and the delivery of well-planned training, the quality of infection control management has improved.

Heterobifunctional PEG-grafted black phosphorus quantum dots: "Three-in-One" nano-platforms for mitochondria-targeted photothermal cancer therapy.

Black phosphorus (BP) nano-materials, especially BP quantum dots (BPQDs), performs outstanding photothermal antitumor effects, excellent biocompatibility and biodegradability. However, there are several challenges to overcome before offering real benefits, such as poor stability, poor dispersibility as well as difficulty in tailoring other functions. Here, a "three-in-one" mitochondria-targeted BP nano-platform, called as BPQD-PEG-TPP, was designed. In this nano-platform, BPQDs were covalently grafted with a heterobifunctional PEG, in which one end was an aryl diazo group capable of reacting with BPQDs to form a covalent bond and the other end was a mitochondria-targeted triphenylphosphine (TPP) group. In addition to its excellent near-infrared photothermal properties, BPQD-PEG-TPP had much enhanced stability and dispersibility under physiological conditions, efficient mitochondria targeting and promoted ROS production through a photothermal effect. Both in vitro and in vivo experiments demonstrated that BPQD-PEG-TPP performed much superior photothermal cytotoxicity than BPQDs and BPQD-PEG as the mitochondria targeted PTT. Thus this "three-in-one" nanoplatform fabricated through polymer grafting, with excellent stability, dispersibility and negligible side effects, might be a promising strategy for mitochondria-targeted photothermal cancer therapy.

Diagnosis and treatment misunderstandings and "three in one" bone repair strategies in osteoporotic fractures / 中华创伤杂志

Osteoporotic fractures have become major social problems threatening the health of the elderly population in China. Compared with conventional fractures, low bone mass, bone defect and retarded healing issues of osteoporotic fractures contribute to the difficulty in treatment and rehabilitation. Addressing major concerns in clinical settings, the "three in one" bone repair strategy focuses on anti-osteoporosis therapies, appropriate bone graft and fracture healing promotion. The authors summarize misunderstandings in diagnosis and treatment of osteoporotic fractures and repair strategies, expecting to improve prognosis and clinically standardize the treatments for osteoporotic fractures, to further improve therapeutic effect and living quality of the patients.

Single CuO/Cu2O/Cu Microwire Covered by a Nanowire Network as a Gas Sensor for the Detection of Battery Hazards.

In this study, a strategy to prepare CuO/Cu2O/Cu microwires that are fully covered by a nanowire (NW) network using a simple thermal-oxidation process is developed. The CuO/Cu2O/Cu microwires are fixed on Au/Cr pads with Cu microparticles. After thermal annealing at 425 °C, these CuO/Cu2O/Cu microwires are used as room-temperature 2-propanol sensors. These sensors show different dominating gas responses with operating temperatures, e.g., higher sensitivity to ethanol at 175 °C, higher sensitivity to 2-propanol at room temperature and 225 °C, and higher sensitivity to hydrogen gas at ∼300 °C. In this context, we propose the sensing mechanism of this three-in-one sensor based on CuO/Cu2O/Cu. X-ray diffraction (XRD) studies reveal that the annealing time during oxidation affects the chemical appearance of the sensor, while the intensity of reflections proves that for samples oxidized at 425 °C for 1 h the dominating phase is Cu2O, whereas upon further increasing the annealing duration up to 5 h, the CuO phase becomes dominant. The crystal structures of the Cu2O-shell/Cu-core and the CuO NW networks on the surface were confirmed with a transmission electron microscope (TEM), high-resolution TEM (HRTEM), and selected area electron diffraction (SAED), where (HR)TEM micrographs reveal the monoclinic CuO phase. Density functional theory (DFT) calculations bring valuable inputs to the interactions of the different gas molecules with the most stable top surface of CuO, revealing strong binding, electronic band-gap changes, and charge transfer due to the gas molecule interactions with the top surface. This research shows the importance of the nonplanar CuO/Cu2O layered heterostructure as a bright nanomaterial for the detection of various gases, controlled by the working temperature, and the insight presented here will be of significant value in the fabrication of new p-type sensing devices through simple nanotechnology.

Trimorphic extreme clubfoot deformities and their management by triple surgical skin expanders- DOLAR, DOLARZ and DOLARZ-E (evidence based mega-corrections without arthrodesis).

AIM/PURPOSE: Extreme congenital club foot deformities are common in developing countries, presenting at birth, persisting in children, adolescents and adults; as untreated/under-corrected by conservative and/or surgical means. Scores of confusing names exist in literature for such deformities with no good treatment available; mostly advocating unacceptable arthrodesis. The author researched this grey area for more than 40 years and successfully innovated improved surgical corrections, more acceptable to patients. METHODS: All were given a generic name: "extreme deformities", with 3 hierarchic grades. each 3D (trimorphic) because of their common aim: a good correction. The author started with anatomical dissections in clubfeet (zero cost), consistently reinforced with solid clinical background. Heterogeneous skin contractures, congenital with/without scars, were discovered as the primary cause with cramped deeper tissues and evolved, evidence based, 3D enlargement of skin chamber by triple expanding incisions: DOrso-LAteral Rotation skin flap (DOLAR- acronym) for grade I, DOLAR + Z-plasty (DOLARZ) for grade II and DOLAR + Z + VY-plasty (DOLARZ-E) for grade III, E means Extended. Patient satisfaction level (excellent, good, fair/poor) had been considered for grading results, rather than scoring systems because each clubfoot is different with countless variables. RESULTS & CONCLUSIONS: The author operated 1080 feet during the last 40 years with long term follow up, six months to 30 years, with an average of 12½ years. The results obtained were: excellent/good (96%) and fair/poor (4% including superficial skin necrosis only in 3%, evidence based). Triple surgical skin expansion consistently resulted in longer, flexible, joints sparing, good shaped, better functioning foot; even in adults.

Synergistic and complete reversal of the multidrug resistance of mitoxantrone hydrochloride by three-in-one multifunctional lipid-sodium glycocholate nanocarriers based on simultaneous BCRP and Bcl-2 inhibition.

Multidrug resistance (MDR) is a severe obstacle to successful chemotherapy due to its complicated nature that involves multiple mechanisms, such as drug efflux by transporters (P-glycoprotein and breast cancer resistance protein, BCRP) and anti-apoptotic defense (B-cell lymphoma, Bcl-2). To synergistically and completely reverse MDR by simultaneous inhibition of pump and non-pump cellular resistance, three-in-one multifunctional lipid-sodium glycocholate (GcNa) nanocarriers (TMLGNs) have been designed for controlled co-delivery of water-soluble cationic mitoxantrone hydrochloride (MTO), cyclosporine A (CsA - BCRP inhibitor), and GcNa (Bcl-2 inhibitor). GcNa and dextran sulfate were incorporated as anionic compounds to enhance the encapsulation efficiency of MTO (up to 97.8%±1.9%) and sustain the release of cationic MTO by electrostatic interaction. The results of a series of in vitro and in vivo investigations indicated that the TMLGNs were taken up by the resistant cancer cells by an endocytosis pathway that escaped the efflux induced by BCRP, and the simultaneous release of CsA with MTO further efficiently inhibited the efflux of the released MTO by BCRP; meanwhile GcNa induced the apoptosis process, and an associated synergistic antitumor activity and reversion of MDR were achieved because the reversal index was almost 1.0.