Synthesis of pH-responsive ß-CD-based star polymer and impact of its self-assembly behavior on pectinase activity.

A novel type of pH-responsive star polymer based on ß-cyclodextrin (ß-CD) was synthesized and further covalently conjugated with enzyme. The impact of its self-assembly behavior on enzyme activity was investigated. In our design, azide containing the polymer (N3 )7 -ß-CD-(PtBA)14 was synthesized via atom transfer radical polymerization of tert-butyl acrylate using (N3 )7 -ß-CD-(Br)14 as the multifunctional initiator. The final product (N3 )7 -ß-CD-(PAA)14 was obtained via hydrolysis and covalently conjugating pectinase onto pH-responsive polyacrylic acid (PAA) arms. PAA can change its conformation with the self-assembly by altered pH, leading its nanostructure into micellar nanoparticles in aqueous solution and further affecting the activity of immobilized pectinase. The results were proved by fluorescence spectroscopy and dynamic light scattering. This system proves that the activity of immobilized enzyme can be tailored predictably, and this pH-responsive polymer holds great potential for controllable delivery of enzymes.

Hexapeptide decorated ß-cyclodextrin delivery system for targeted therapy of bone infection.

Successfully treating bone infections is a major orthopedic challenge. Clinically, oral, intravenous, or intramuscular injections of drugs are usually used for direct or complementary treatment. However, once the drug enters the system, it circulates throughout the body, leading to an insufficient local dose and limiting the therapeutic effect because of the lack of targeting in the drug system. In this study, ß-cyclodextrin, modified with poly (ethylene glycol) [PEG] and aspartic acid hexapeptide (Asp6-ß-CD), was used to specifically target the hydroxyapatite (HA) component of the bone. It was then loaded with norfloxacin (NFX) to treat bone infections. The antibacterial ability of NFX was enhanced by loading it into Asp6-ß-CD, because the solubility of Asp6-ß-CD@NFX increased significantly. Moreover, Asp6-ß-CD could target bone tissue in nude mice and showed significantly enhanced accumulation (10 times) than the unmodified ß-CD. In addition, in a rat model of osteomyelitis, Asp6-ß-CD@NFX targeted HA well and exerted its antibacterial activity, which reduced inflammation and promoted bone tissue repair. This study indicates that the Asp6-ß-CD based drug delivery system can efficiently target bone tissue to enable potential applications for treating bone-related diseases.

Analysis of medical malpractice litigation following vertebral augmentation therapy in China from 2008 to 2018.

The first case of vertebral augmentation therapy in mainland China was reported in 2000. Since then, it has been widely used in China as a minimally invasive procedure to treat vertebral compression fractures. However, the characteristics of malpractice litigation involving vertebral augmentation therapy remains unclear. This study aims to analyze the characteristics of medical malpractice litigation involving vertebral augmentation therapy in mainland China for the past 10 years. Two online legal databases were queried for court verdicts involving vertebral augmentation therapy from Jan 2009 to Dec 2018 in mainland China. Each case file was then thoroughly reviewed and data pertaining to defendants, plaintiffs, case outcomes, allegations, and verdicts were abstracted, and descriptive analyses were performed. Level of evidence: LEVEL III. A total of 96 cases were enrolled for final analysis. The number of claims increased by five times during the past 10 years. More than two thirds (67.7%, n = 65) of the cases underwent percutaneous vertebroplasty, and 22.9% (n = 22) underwent percutaneous kyphoplasty, the rest (9.4%, n = 9) remained undefined. Paralysis was alleged in 35.4% of cases (n = 34), followed by significant physical injury (34.4%, n = 33). Cement leakage to spinal canal (44.8%, n = 43) is the most commonly cited reason for litigation, followed by incomplete informed consent (42.7%, n = 41), accidental dural puncture (20.8%, n = 20), unsatisfactory clinical outcome (18.8%, n = 18), and misdiagnosis (12.5%, n = 12). Acute pulmonary cement embolism (4.2%, n = 4), wrong-level vertebrae procedure (3.1%, n = 3) and postoperative infection (2.1%, n = 2) were less common causes for concern. Doctors successfully defended themselves only in 8 (8.3%) cases, which resulted in no indemnity payment. The rest 88 (91.7%) cases were closed with a mean verdict payout of 361,580 Yuan (51,654 US dollars). There is a quickly rising trend in the number of medical malpractice litigation involving vertebral augmentation therapy in China. Identifying the most common reasons for litigation and summarizing their characteristics may help decrease litigation rate and improve the patient experience.

Poly[2-(methacryloyloxy)ethyl choline phosphate] functionalized polylactic acid film with improved degradation resistance both in vitro and in vivo.

In this study, the surface-initiated atom transfer radical polymerization (SI-ATRP) of 2-(methacryloyloxy) ethyl choline phosphate (MCP) was successfully carried out via the ATRP initiator immobilized on the surfaces of polylactic acid (PLA) films. Different amounts of PMCP polymer brushes were constructed on the PLA surface to investigate the effects of the biological and degradation properties before and after modification. The results showed that the hydrophilicity of the surface of PLA were improved by MCP modification. In addition, there are no significant influence on the structure and crystallinity of the film before and after modification, except for the increased slightly thermal stability. Since the PMCP polymer brush forms a "protection" effect on the surface, the films showed an excellent property of resistant to hydrolysis even with obviously improved hydrophilicity. Furthermore, with the increase of the amount of introduced MCP monomer, the hydrophilicity and degradation resistance have been further improved. The in vivo animal experiment also verified this degradation resistance. Thereby, this strategy can be used to modulate the degradation rate of degradable polymers via surface modification.

An Injectable, Bifunctional Hydrogel with Photothermal Effects for Tumor Therapy and Bone Regeneration.

Significant attention has been focused on bone tumor therapy recently. At present, the treatment in clinic typically requires surgical intervention. However, a few tumor cells remain around bone defects after surgery and subsequently proliferate within several days. Thus, fabrication of biomaterials with dual functions of tumor therapy and bone regeneration is significant. Herein, the injectable hydrogel containing cisplatin (DDP) and polydopamine-decorated nano-hydroxyapatite is prepared via Schiff base reaction between the aldehyde groups on oxidized sodium alginate and amino groups on chitosan. The hydrogel exhibits sustained release properties for DDP due to the immobilization of DDP via abundant functional groups on polydopamine (PDA). Additionally, given the intense absorption of PDA in the near-infrared region, the hydrogel exhibits excellent photothermal effects when exposed to the NIR laser (808 nm). Based on the properties, the hydrogel effectively ablates tumor cells (4T1 cells) in vitro and suppresses tumor growth in vivo. Furthermore, the hydrogel promotes the adhesion and proliferation of bone mesenchymal stem cells in vitro due to the abundant functional groups on PDA and further induces bone regeneration in vivo. Therefore, the study extends research on novel biomaterials with dual functions of tumor therapy and bone regeneration.

Feasibility and simulation model of a pilot scale membrane bioreactor for wastewater treatment and reuse from Chinese traditional medicine.

The lack and pollution of water resource make wastewater reuse necessary. The pilot scale long-term tests for submerged membrane bioreactor were conducted to treat the effluents of anaerobic or aerobic treatment process for the high-strength Chinese traditional medicine wastewater. This article was focused on the feasibility of the wastewater treatment and reuse at shorter hydraulic retention time (HRT) of 5.0, 3.2 and 2.13 h. MLSS growth, membrane flux, vacuum values and chemical cleaning periods were also investigated. The experimental results of treating two-phase anaerobic treatment effluent demonstrated that the CODfilt was less than 100 mg/L when the influent COD was between 500-10000 mg/L at HRT of 5.0 h, which could satisfy the normal discharged standard in China. The experimental results to treat cross flow aerobic reactor effluent demonstrated that the average value of CODfilt was 17.28 mg/L when the average value of influent COD was 192.84 mg/L at HRT of 2.13 h during 106 d, which could completely meet the normal standard for water reuse. The maximum MLSS and MLVSS reached 24000 and 14500 mg/L at HRT of 3.2 h respectively. Membrane flux had maximal resume degrees of 94.7% at vacuum value of 0.02 MPa after cleaning. Chemical cleaning periods of membrane module were 150 d. A simulation model of operational parameters was also established based on the theory of back propagation neural network and linear regression of traditional mathematical model. The simulation model showed that the optimum operational parameters were suggested as follows: HRT was 5.0 h, SRT was 100 d, the range of COD loading rate was between 10.664-20.451 kg/(m3xd), the range of MLSS was between 7543-13694 mg/L.

High-dose methotrexate, etoposide, dexamethasone and pegaspargase (MEDA) combination chemotherapy is effective for advanced and relapsed/refractory extranodal natural killer/T cell lymphoma: a retrospective study.

Extranodal natural killer/T cell lymphoma, nasal type (ENK/TCL), is an aggressive and rare hematological malignancy. Patients with advanced and relapsed/refractory disease have very poor outcomes. In this study, we retrospectively assessed the efficacy and safety of MEDA regimen (methotrexate, etoposide, dexamethasone and pegaspargase) in the treatment of advanced and relapsed/refractory ENK/TCL patients. Thirteen patients received a total of 55 cycles of MEDA, with a median of four cycles. At the completion of treatment, the overall response rate was 76.9 %, with a complete response rate of 61.5 %. The 1-year overall survival rate was 69.2 %, and 1-year progression-free survival was 61.5 %. Treatment-related toxicity was monitored in all patients. Grade 3/4 neutropenia occurred in 46.2 % of patients. Serious infections happened in two cases (15.4 %). Grade 3/4 thrombocytopenia occurred in 30.8 % of patients, and 23.1 % received platelet transfusion. Grade 3/4 anemia was observed in 23.1 % of patients. Hepatotoxicity and low fibrinogen were common, but mild. These results show that MEDA regimen is very effective with tolerable adverse effects in the treatment of advanced and relapsed/refractory ENK/TCL. Further prospective trials are expected to validate the efficacy of MEDA in an expanded number of patients.

Performance and model of a novel multi-sparger multi-stage airlift loop membrane bioreactor to treat high-strength 7-ACA pharmaceutical wastewater: effect of hydraulic retention time, temperature and pH.

In this study, three novel multi-sparger multi-stage airlift loop membrane bioreactors (Ms(2)ALMBRs) were set up in parallel for treating synthetic high-strength 7-ACA pharmaceutical wastewater under different HRTs, temperatures and pHs, respectively. During the 200-day operating time, average COD removal efficiencies were 94.96%, 96.05% and 93.9%. While average 7-ACA removal efficiencies were 66.44%, 59.04% and 59.60%, respectively. The optimal conditions were 10h, 15-35°C and 7-9 for HRT, temperature and pH, respectively. Moreover, the sludge characteristics and microorganism drug-resistances were explored. Results showed that different temperatures and pHs influenced contaminant removals by affecting MLSS concentration and ß-lactamase activity significantly. In addition, mathematical statistical models, built on the polynomial and linear regression techniques, were developed for exploring the inner relationships between HRT, temperature and pH changes and MLSS concentrations, ß-lactamase activities and contaminant removals of the Ms(2)ALMBR system.