Impact of lockdown policies during the COVID-19 outbreak on a trauma center of a tertiary hospital in China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a major and costly public health emergency. AIM: To investigate the impact of China's lockdown policies during the COVID-19 outbreak on the level I trauma center of a tertiary comprehensive hospital of Traditional Chinese Medicine. METHODS: All patients admitted to our trauma center during a lockdown in 2020 and the same period in 2019 were enrolled. We collected data on demographics, daily visits, injury type, injury mechanism, injury severity score, and patient management for comparative analysis. RESULTS: The total number of patients in the trauma center of our hospital decreased by 50.38% during the COVID-19 Lockdown in 2020 compared to the same period in 2019. The average number of trauma visits per day in 2019 was 47.94, compared to 23.79 in 2020. Comparing the patients' demographic data, loss of employment was the most predominate characteristic in 2020 compared to 2019, while there was no significant difference in gender, age, and marital status between both periods. During the lockdown period, the proportion of traffic accident-related injuries, injuries due to falls greater than 1.5 m, and mechanical injuries decreased significantly, whereas the proportion of injuries caused by falls less than 1.5 m, cuts, assault, bites, and suicidal tendencies and other injuries increased relatively. In addition, the proportion of patients with minor injuries increased and serious injuries decreased during the lockdown. The hospitalization rate increased significantly, and there was no significant difference in emergency surgery and death rates. CONCLUSION: The lockdown policies during the COVID-19 outbreak significantly altered the number and mechanism of traumatic events in our hospital, which can be monitored regularly. Our results suggest that mandatory public health prevention and control measures by the government can reduce the incidence of traumatic events and the severity of traumatic injuries. Emergency surgery and mortality rates remain high, increased because of factors such as family injury and penetrating injury, and hospitalization rates have increased significantly. Therefore, our trauma center still needs to be fully staffed. Finally, from the perspective of the injury mechanism, indoor trauma is a major risk during a lockdown, and it is particularly important to develop prevention strategies for such trauma to reduce the medical burden of the next catastrophic epidemic.

Nanoparticle/Nanocarrier Formulation as an Antigen: The Immunogenicity and Antigenicity of Itself.

In antibody preparation, the immunogenicity of small molecules is limited due to the instability of adjuvant/hapten emulsions. Nanoparticle-based adjuvants overcome instability and effectively improve immune responses. Immunogenicity and antigenicity are fundamentally important, yet understudied, facets of nanoparticle formulations themselves. Herein, we studied the immunogenicity and antigenicity of nanoparticle formulations. In experiments in a rabbit model, simple inorganic nanoparticle (e.g., gold nanoparticle (AuNP) and silver nanoparticle (AgNP)) immunogens induced higher titers of antiserum. Moreover, several promising nanoparticle drug carrier immunogens (e.g., SiO2, oleylamine graft polysuccinimide (PSIOAm), oleylamine and N-(3-aminopropyl)imidazole cograft polysuccinimide (PSIOAm-NAPI), Fe3O4@O-dextran, etc.) showed excellent immunogenicity. Cross-reactivity calculations revealed that the antigenicity properties of AgNP and AuNP antigens are highly size-dependent. Meanwhile, four nanoparticle drug carriers generate antibody-specific immune responses to their antigens. The reactivity of the anti-NP antibodies with nanoparticle antigens was confirmed using immunoassays. This study systematically identified the immunogenicity and antigenicity of the nanoparticle formulation itself. These findings provide insights into the immunological properties of the nanoparticle formulation itself in an organism.

Tumor cellular membrane camouflaged liposomes as a non-invasive vehicle for genes: specific targeting toward homologous gliomas and traversing the blood-brain barrier.

Gene therapy aimed at malignant gliomas has shown limited success to date due in part to the inability of conventional gene vectors to achieve widespread and specific gene transfer throughout the highly disseminated tumor zone within the brain. Herein, cationic micelles assembled from vitamin E succinate-grafted ε-polylysine (VES-g-PL) polymers were first exploited to condense TRAIL plasmids (pDNA). Thereafter, the condensed pDNA was further encapsulated into liposomes camouflaged with tumor cellular membrane. The condensed pDNA was successfully encapsulated into the inner aqueous compartments of the liposomes instead of the surface, which was proved based on the TEM morphology and decreased cytotoxicity toward HUVEC and PC-12 cells. Moreover, glioma cell membrane (CM) was easily inlaid into the lipid layer of the pDNA-loaded liposomes to form T@VP-MCL, as shown via TEM, AFM, and SDS-PAGE analysis. T@VP-MCL exhibited good particle size stability at strong ion strength and effectively protected pDNA from DNase I induced degradation. Owing to the CM-associated proteins, T@VP-MCL specifically targeted not only ICAM-1 overexpressed in glioma RBMECs but also homogenous glioma cells. Moreover, in vivo imaging showed that T@VP-MCL was effectively located in orthotopic gliomas of rats after intravenous administration, resulting in effective tumor growth inhibition, prolonging the lives of the rats. The mechanism of T@VP-MCL traversing the BBB was highly associated with the down-regulation of the tight junction-associated proteins ZO-1 and claudin-5. Conclusively, T@VP-MCL designed herein may be a potential carrier for therapeutic genes.

Reconstruction of large segmental bone defects in rabbit using the Masquelet technique with α-calcium sulfate hemihydrate.

BACKGROUND: Large segmental bone defects can be repaired using the Masquelet technique in conjunction with autologous cancellous bone (ACB). However, ACB harvesting is severely restricted. α-calcium sulfate hemihydrate (α-CSH) is an outstanding bone substitute due to its easy availability, excellent biocompatibility, biodegradability, and osteoconductivity. However, the resorption rate of α-CSH is too fast to match the rate of new bone formation. The objective of this study was to investigate the bone repair capacity of the Masquelet technique in conjunction with isolated α-CSH or an α-CSH/ACB mix in a rabbit critical-sized defect model. METHODS: The rabbits (n = 28) were randomized into four groups: sham, isolated α-CSH, α-CSH/ACB mix, and isolated ACB group. A 15-mm critical-sized defect was established in the left radius, followed by filling with polymethyl methacrylate spacer. Six weeks after the first operation, the spacers were removed and the membranous tubes were grafted with isolated α-CSH, isolated ACB, α-CSH/ACB mix, or none. Twelve weeks later, the outcomes were evaluated by manual assessment, radiography, and spiral-CT. The histopathological and morphological changes were examined by H&E staining. The levels of alkaline phosphatase and osteocalcin were analyzed by immunohistochemistry and immunofluorescence staining. RESULTS: Our results suggest that the bone repair capacity of the α-CSH/ACB mix group was similar to the isolated ACB group, while the isolated α-CSH group was significantly decreased compared to the isolated ACB group. CONCLUSION: These results highlighted a promising strategy in the healing of large segmental bone defect with the Masquelet technique in conjunction with an α-CSH/ACB mix (1:1, w/w) as they possessed the combined effects of sufficient supply and low resorption.

Homing of ICG-loaded liposome inlaid with tumor cellular membrane to the homologous xenografts glioma eradicates the primary focus and prevents lung metastases through phototherapy.

Currently, phototherapy initiated by local irradiation with a near-infrared (NIR) laser has emerged as a promising strategy for cancer treatment owing to its low toxicity. However, a key problem for effective phototherapy is how to specifically deliver a sufficient dose of photosensitizers to a tumor focus. Herein, indocyanine green (ICG), a United States Food and Drug Administration (US FDA)-approved photosensitizer, was first encapsulated in an inner aqueous compartment of liposome (ICG-LIP) to improve its stability. Thereafter, tumor cell membranes were isolated from native glioma cells and subsequently inlaid in the bilayer lipid membrane of ICG-LIP to construct cell-like liposomes (ICG-MCLs). ICG was easily encapsulated into the ICG-MCLs with a very high encapsulation efficiency, reaching 78.01 ± 0.72% and its concentration in the final formulation reached 200 µg mL-1. The ICG-MCLs displayed a spherical morphology with a hydrodynamic diameter (Dh) of 115.0 ± 0.5 nm, a PDI of 0.14, and a zeta potential of -11.2 ± 0.9 mV. Moreover, ICG-MCLs exhibited a good stability in terms of particle size and significantly improved the chemical stability of ICG in pH 7.4 PBS at 37 °C. In addition, the temperature of the ICG-MCLs rapidly increased to 63 °C after 10 min irradiation and this was maintained for a longer time. Owing to the cancer cell membrane associated protein, the ICG-MCLs were specifically internalized by homogenous glioma C6 cells in vitro, which resulted in the strong red fluorescence of ICG in cytoplasm. Moreover, in vivo imaging showed that the ICG-MCLs were effectively homed to the tumor site of C6 glioma-bearing Xenograft nude mice through vein injection, which resulted in the temperature of the tumor site rapidly rising, allowing the killing of tumor cells after local NIR irradiation. After treatment with the ICG-MCLs, the primary tumor focus was completely eradicated and lung metastases were effectively inhibited. In conclusion, liposomes inlaid with tumor cellular membranes may serve as an excellent nanoplatform for homologous-targeting phototherapy using ICG.

Ratiometric delivery of two therapeutic candidates with inherently dissimilar physicochemical property through pH-sensitive core-shell nanoparticles targeting the heterogeneous tumor cells of glioma.

Currently, combination drug therapy is one of the most effective approaches to glioma treatment. However, due to the inherent dissimilar pharmacokinetics of individual drugs and blood brain barriers, it was difficult for the concomitant drugs to simultaneously be delivered to glioma in an optimal dose ratio manner. Herein, a cationic micellar core (Cur-M) was first prepared from d-α-tocopherol-grafted-ε-polylysine polymer to encapsulate the hydrophobic curcumin, followed by dopamine-modified-poly-γ-glutamic acid polymer further deposited on its surface as a anion shell through pH-sensitive linkage to encapsulate the hydrophilic doxorubicin (DOX) hydrochloride. By controlling the combinational Cur/DOX molar ratio at 3:1, a pH-sensitive core-shell nanoparticle (PDCP-NP) was constructed to simultaneously target the cancer stem cells (CSCs) and the differentiated tumor cells. PDCP-NP exhibited a dynamic diameter of 160.8 nm and a zeta-potential of -30.5 mV, while its core-shell structure was further confirmed by XPS and TEM. The ratiometric delivery capability of PDCP-NP was confirmed by in vitro and in vivo studies, in comparison with the cocktail Cur/DOX solution. Meanwhile, the percentage of CSCs in tumors was significantly decreased from 4.16% to 0.95% after treatment with PDCP-NP. Overall, PDCP-NP may be a promising carrier for the combination therapy with drug candidates having dissimilar physicochemical properties.

CoQ10-loaded liposomes combined with UTMD prevented early nephropathy of diabetic rats.

Nephropathy is one of the most severe complications of diabetic patients. The therapeutic strategies for diabetic patients should not only focus on the control of blood glucose but also pay attention to the occurrence of diabetic nephropathy (DN). Coenzyme Q10 (CoQ10) has great therapeutic potential for DN. However, the clinical application of CoQ10 has been limited because of its low water-solubility and non-specific distribution. Liposomes were supposed to be an effective way for delivering CoQ10 to kidney. CoQ10 was effectively encapsulated into the liposome (CoQ10-LIP) with a high entrapment efficiency of 86.15 %. The CoQ10-LIP exhibited a small hydrodynamic diameter (180 ± 2.1 nm) and negative zeta potential (-18.20 mV). Moreover, CoQ10-LIP was combined with ultrasound-mediated microbubble destruction (UTMD) to enhance specific distribution of CoQ10 in kidney. In early stage of diabetic mellitus (DM), rats were administrated with CoQ10-LIP followed by UTMD (CoQ10-LIP+UTMD) to prevent occurrence of DN. Results revealed that CoQ10-LIP+UTMD effectively prevented the renal morphology and function of diabetics rats from damage. The protective mechanism of CoQ10-LIP was highly associated with protecting podocyte, promoting vascular repair and inhibiting cell apoptosis. Conclusively, CoQ10-LIP in combination with UTMD might be a potential strategy to prevent occurrence of DN.

Glioma-Targeted Delivery of a Theranostic Liposome Integrated with Quantum Dots, Superparamagnetic Iron Oxide, and Cilengitide for Dual-Imaging Guiding Cancer Surgery.

Herein, a theranostic liposome (QSC-Lip) integrated with superparamagnetic iron oxide nanoparticles (SPIONs) and quantum dots (QDs) and cilengitide (CGT) into one platform is constructed to target glioma under magnetic targeting (MT) for guiding surgical resection of glioma. Transmission electron microscopy and X-ray photoelectron spectroscopy confirm the complete coencapsulation of SPIONs and QDs in liposome. Besides, CGT is also effectively encapsulated into the liposome with an encapsulation efficiency of ∼88.9%. QSC-Lip exhibits a diameter of 100 ± 1.24 nm, zeta potential of -17.10 ± 0.11 mV, and good stability in several mediums. Moreover, each cargo shows a biphasic release pattern from QSC-Lip, a rapid initial release within initial 10 h followed by a sustained release. Cellular uptake of QSC-Lip is significantly enhanced by C6 cells under MT. In vivo dual-imaging studies show that QSC-Lip not only produces an obvious negative-contrast enhancement effect on glioma by magnetic resonance imaging but also makes tumor emitting fluorescence under MT. The dual-imaging of QSC-Lip guides the accurate resection of glioma by surgery. Besides, CGT is also specifically distributed to glioma after administration of QSC-Lip under MT, resulting in an effective inhibition of tumors. The integrated liposome may be a potential carrier for theranostics of tumor.

Skin-penetrating polymeric nanoparticles incorporated in silk fibroin hydrogel for topical delivery of curcumin to improve its therapeutic effect on psoriasis mouse model.

A poor percutaneous penetration capability for most topical anti-inflammatory drugs is one of the main causes compromising their therapeutic effects on psoriatic skin. Even though curcumin has shown a remarkable efficacy in the treatment of psoriasis, its effective penetration through the stratum corneum is still a major challenge during transdermal delivery. The aim of our study was to design skin-permeating nanoparticles (NPs) to facilitate delivery of curcumin to the deeper layers of the skin. A novel amphiphilic polymer, RRR-α-tocopheryl succinate-grafted-ε-polylysine conjugate (VES-g-ε-PLL) was synthesized and self-assembled into polymeric nanoparticles. The nanoparticles of VES-g-ε-PLL exhibiting an ultra-small hydrodynamic diameter (24.4nm) and a positive Zeta potential (19.6mV) provided a strong skin-penetrating ability in vivo. Moreover, curcumin could effectively be encapsulated in the polymeric nanoparticles with a drug loading capacity of 3.49% and an encapsulating efficiency of 78.45%. In order to prolong the retention time of the ultra-small curcumin-loaded nanoparticles (CUR-NPs) in the skin, silk fibroin was used as a hydrogel-based matrix to further facilitate topical delivery of the model drug. In vitro studies showed that CUR-NPs incorporated in silk fibroin hydrogel (CUR-NPs-gel) exhibited a slower release profile of curcumin than the plain CUR-gel, without compromising the skin penetration ability of CUR-NPs. In vivo studies on miquimod-induced psoriatic mice showed that CUR-NPs-gel exhibited a higher therapeutic effect than CUR-NPs as the former demonstrated a more powerful skin-permeating capability and a more effective anti-keratinization process. CUR-NPs-gel was therefore able to inhibit the expression of inflammatory cytokines (TNF-α, NF-κB and IL-6) to a greater extent. In conclusion, the permeable nanoparticle-gel system may be a potential carrier for the topical delivery of lipophilic anti-psoriatic drugs.

Dual Regulations of Thermosensitive Heparin-Poloxamer Hydrogel Using ε-Polylysine: Bioadhesivity and Controlled KGF Release for Enhancing Wound Healing of Endometrial Injury.

Hydrogel was not only used as an effective support matrix to prevent intrauterine adhesion after endometrial injury but also served as scaffold to sustain release of some therapeutics, especially growth factor. However, because of the rapid turnover of the endometrial mucus, the poor retention and bad absorption of therapeutic agents in damaged endometrial cavity were two important factors hindering their pharmacologic effect. Herein, a mucoadhesive hydrogel was described by using heparin-modified poloxamer (HP) as the matrix material and ε-polylysine (EPL) as functional excipient. Various EPL-HP hydrogels formulations are screened by rheological evaluation and mucoadhesion studies. It was found that the rheological and mucoadhesive properties of EPL-HP hydrogels were easily controlled by changing the amount of EPL in formulation. The storage modulus of EPL-HP hydrogel with 90 µg/mL of EPL (EPL-HP-90) was elevated to be 1.9 × 105 Pa, in accordance with the adhesion force rising to 3.18 N (10-fold higher than HP hydrogels). Moreover, in vitro release of model drug keratinocyte growth factor (KGF) from EPL-HP hydrogel was significantly accelerated by adding EPL in comparison with HP hydrogel. Both strong mucoadhesive ability and the accelerated drug release behavior for EPL-HP-90 made more of the encapsulated KGF absorbed by the uterus basal layer and endometrial glands after 8 h of administration in uterus cavity. Meanwhile, the morphology of endometrium in the injured uterus was repaired well after 3 d of treatment with KGF-EPL-HP-90 hydrogels. Compared with KGF-HP group, not only proliferation of endometrial epithelial cell and glands but also angiogenesis in the regenerated endometrium was obviously enhanced after treatment with KGF-EPL-HP-90 hydrogels. Alternatively, the cellular apoptosis in the damaged endometrium was significantly inhibited after treatment with KGF-EPL-HP-90 hydrogels. Overall, the mucoadhesive EPL-HP hydrogel with a suitable KGF release profile may be a more promising approach than HP hydrogel alone to repair the injured endometrium.

Therapeutic supermolecular micelles of vitamin E succinate-grafted ε-polylysine as potential carriers for curcumin: Enhancing tumour penetration and improving therapeutic effect on glioma.

Severe toxicity and poor tumour penetration are two intrinsic limited factors to hinder the broad clinical application for most of first-line chemotherapeutics. In this study, a novel vitamin E succinate-grafted ε-polylysine (VES-g-PLL) polymer was synthesized by using ε-polylysine as backbone. By adjusting VES graft ratio, VES-g-PLL (50) with a theoretic VES graft ratio of 50% could self-assemble into a supermolecular micelle with a hydrodynamic diameter (Dh) of ca.20nm, and Zeta potential of 19.6mV. VES-g-PLL micelles themselves displayed a strong anti-tumour effect on glioma. The poorly water-soluble curcumin was effectively encapsulated in VES-g-PLL micelles with the drug loading amount and entrapment efficiency reaching 4.32% and 82.27%, respectively. In a physiologic medium, curcumin-loaded VES-g-PLL micelles (Cur-Micelles) not only remained stable without obvious drug leakage but also sustained the release of its encapsulated curcumin for a long time. Because of the ultra-small size and positively-charged surface, Cur-Micelles penetrated the deeper tumour zone than free curcumin, resulting in a significant inhibition of tumour spheroids growth. Moreover, in vivo strong antitumor effect of Cur-Micelles was also exhibited at assistance of ultrasound-targeted microbubble destruction and the real-time MRI imaging demonstrated a nearly complete suppression of glioma after 28days of treatment. TUNEL staining showed that the therapeutic mechanism of Cur-Micelles was relevant to the apoptosis of tumour cells. Finally, in vivo nontoxicity of Cur-Micelles against normal organs including heart, liver, spleen, lung and kidney tissues was also demonstrated by the HE staining. In conclusion, VES-g-PLL micelles may serve as a potential carrier for curcumin to enhance tumour penetration and improve therapeutic effect on glioma.

Liposomes with Silk Fibroin Hydrogel Core to Stabilize bFGF and Promote the Wound Healing of Mice with Deep Second-Degree Scald.

How to maintain the stability of basic fibroblast growth factor (bFGF) in wounds with massive wound fluids is important to accelerate wound healing. Here, a novel liposome with hydrogel core of silk fibroin (SF-LIP) is successfully developed by the common liposomal template, followed by gelation of liquid SF inside vesicle under sonication. SF-LIP is capable of encapsulating bFGF (SF-bFGF-LIP) with high efficiency, having a diameter of 99.8 ± 0.5 nm and zeta potential of -9.41 ± 0.10 mV. SF-LIP effectively improves the stability of bFGF in wound fluids. After 8 h of incubation with wound fluids at 37 °C, more than 50% of free bFGF are degraded, while only 18.6% of the encapsulated bFGF in SF-LIP are destroyed. Even after 3 d of preincubation with wound fluids, the cell proliferation activity and wound healing ability of SF-bFGF-LIP are still preserved but these are severely compromised for the conventional bFGF-liposome (bFGF-LIP). In vivo experiments reveal that SF-bFGF-LIP accelerates the wound closure of mice with deep second-degree scald. Moreover, due to the protective effect and enhanced penetration ability, SF-bFGF-LIP is very helpful to induce regeneration of vascular vessel in comparison with free bFGF or bFGF-LIP. The liposome with SF hydrogel core may be a potential carrier as growth factors for wound healing.

Temperature-sensitive heparin-modified poloxamer hydrogel with affinity to KGF facilitate the morphologic and functional recovery of the injured rat uterus.

Endometrial injury usually results in intrauterine adhesion (IUA), which is an important cause of infertility and recurrent miscarriage in reproductive women. There is still lack of an effective therapeutic strategy to prevent occurrence of IUA. Keratinocyte growth factor (KGF) is a potent repair factor for epithelial tissues. Here, a temperature-sensitive heparin-modified poloxamer (HP) hydrogel with affinity to KGF (KGF-HP) was used as a support matrix to prevent IUA and deliver KGF. The rheology of KGF-HP hydrogel was carefully characterized. The cold KGF-HP solution was rapidly transited to hydrogel with suitable storage modulus (G') and loss modulus (G″) for the applications of uterus cavity at temperature of 33 °C. In vitro release demonstrated that KGF was released from HP hydrogels in sustained release manner for a long time. In vivo bioluminescence imaging showed that KGF-HP hydrogel was able to prolong the retention of the encapsulated KGF in injured uterus of rat model. Moreover, the morphology and function of the injured uterus were significantly recovered after administration of KGF-HP hydrogel, which were evaluated by two-dimensional ultrasound imaging and receptive fertility. Not only proliferation of endometrial glandular epithelial cells and luminal epithelial cells but also angiogenesis of injured uterus were observed by Ki67 and CD31 staining after 7 d of treatment with KGF-HP hydrogel. Finally, a close relatively relationship between autophagy and proliferation of endometrial epithelial cells (EEC) and angiogenesis was firstly confirmed by detecting expression of LC3-II and P62 after KGF treatment. Overall, KGF-HP may be used as a promising candidate for IUA treatment.

Implantable porous gelatin microspheres sustained release of bFGF and improved its neuroprotective effect on rats after spinal cord injury.

In this study, porous gelatin microspheres (GMSs) were constructed to improve the neuroprotective effect of basic fibroblast growth factor (bFGF) on spinal cord injury. GMSs were prepared by a W/O emulsion template, followed by cross-linking, washing and drying. The particle sizes and surface porosity of the blank GMSs were carefully characterized by scan electronic microscopy. The blank GMSs have a mean particle size of 35µm and theirs surface was coarse and porous. bFGF was easily encapsulated inside the bulk GMSs through diffusion along the porous channel. 200µg of bFGF was completely encapsulated in 100mg of GMSs. The bFGF-loaded GMSs displayed a continuous drug release pattern without an obvious burst release over two weeks in vitro. Moreover, the therapeutic effects of bFGF-loaded GMSs were also evaluated in spinal cord injury rat model. After implantation of bFGF-loaded GMSs, the recovery of the motor function of SCI rats were evaluated by behavioral score and foot print experiment. The motor function of SCI rats treated with bFGF-loaded GMSs was more obvious than that treated with free bFGF solution (P<0.05). At the 28th days after treatment, rats were sacrificed and the injured spinal were removed for histopathological and apoptosis examination. Compared with treatment with free bFGF solution, treatment with bFGF-loaded GMSs resulted in a less necrosis, less infiltration of leukocytes, and a reduced the cavity ratio and less apoptotic cells in injured spinal(P<0.01), indicating its better therapeutic effect. Implantable porous GMSs may be a potential carrier to deliver bFGF for therapy of spinal cord injury.

An injectable acellular matrix scaffold with absorbable permeable nanoparticles improves the therapeutic effects of docetaxel on glioblastoma.

Intratumoral drug delivery (IT) is an inherently appealing approach for concentrating toxic chemotherapies at the site of action. However, for most chemotherapies, poor tumor penetration and short retention at the administration site limit their anti-tumor effects. In this work, we describe permeable nanoparticles (NPs) prepared with a novel amphiphilic polymer, RRR-α-tocopheryl succinate-grafted-ε-polylysine conjugate (VES-g-ε-PLL). The nanoparticles (NPs) of VES-g-ε-PLL exhibited an ultra-small hydrodynamic diameter (20.8 nm) and positive zeta potential (20.6 mV), which facilitate strong glioma spheroid penetration ability in vitro. Additionally, the hydrophobic model drug docetaxel (DTX) could be effectively encapsulated in the nanoparticles with 3.99% drug loading and 73.37% encapsulation efficiency. To prolong the retention time of DTX-loaded nanoparticles (DTX-NPs) in the tumor, intact decellularized brain extracellular matrix (dBECM) derived from healthy rats was used as a drug depot to adsorb the ultra-small DTX-NPs. The intact DTX-NPs-adsorbing dBECM scaffold was further homogenized into an injectable DTX-NPs-dBECM suspension for intratumoral administration. The DTX-NPs-dBECM suspension exhibited slower DTX release than naked DTX-NPs without compromising the tumor penetration ability of DTX-NPs. An antitumor study showed that the DTX-NPs-dBECM suspension exhibited more powerful in vitro inhibition of tumor spheroid growth than free DTX solution or DTX-NPs. Due to strong tumor penetration ability and prolonged retention, DTX-NPs-dBECM led to complete suppression of glioma growth in vivo at 28 days after treatment. The therapeutic mechanism was due to enhanced proliferation inhibition and apoptosis of tumor cells and angiogenesis inhibition of glioma after treatment with DTX-NPs-dBECM. Finally, the safety of DTX-NPs-dBECM at the therapeutic dose was demonstrated via pathological HE assay from heart, liver, spleen, lung and kidney tissues. In conclusion, permeable nanoparticle-absorbing dBECM is a potential carrier for intratumoral delivery of common chemotherapeutics.

Effects of dietary amylose/amylopectin ratio on growth performance, feed utilization, digestive enzymes, and postprandial metabolic responses in juvenile obscure puffer Takifugu obscurus.

The effect of dietary amylose/amylopectin (AM/AP) ratio on growth, feed utilization, digestive enzyme activities, plasma parameters, and postprandial blood glucose responses was evaluated in juvenile obscure puffer, Takifugu obscurus. Five isonitrogenous (430 g kg(-1) crude protein) and isolipidic (90 g kg(-1) crude lipid) diets containing an equal starch level (250 g kg(-1) starch) with different AM/AP ratio diets of 0/25, 3/22, 6/19, 9/16 and 12/13 were formulated. Each experimental diet was fed to triplicate groups (25 fish per tank), twice daily during a period of 60 days. After the growth trial, a postprandial blood response test was carried out. Fish fed diet 6/19 showed best growth, feed efficiency and protein efficiency ratio. Hepatosomatic index, plasma total cholesterol concentration, liver glycogen and lipid content, and gluconokinase, pyruvate kinase and fructose-1,6-bisphosphatase activities were lower in fish fed highest AM/AP diet (12/13) than in fish fed the low-amylose diets. Activities of liver and intestinal trypsin in fish fed diet 3/22 and diet 6/19 were higher than in fish fed diet 9/16 and diet 12/13. Activities of liver and intestinal amylase and intestinal lipase, and starch digestibility were negatively correlated with dietary AM/AP ratio. Fish fed diet 3/22 and diet 6/19 showed higher plasma total amino acid concentration than fish fed the other diets, while plasma urea nitrogen concentration and activities of alanine aminotransferase and aspartate aminotransferase showed the opposite trend. Equal values were found for viscerosomatic index and condition factor, whole body and muscle composition, plasma high-density and low-density lipoprotein cholesterol concentrations, and activities of lipase and hexokinase and glucose-6-phosphatase in liver. Postprandial plasma glucose and triglyceride peak value of fish fed diet 12/13 were lower than in fish fed the low-amylose diets, and the peak time of plasma glucose was later than in fish fed the other diets. Plasma glucose and triglyceride concentrations showed a significant difference at 2 and 4 h after a meal and varied between dietary treatments. According to regression analysis of weight gain against dietary AM/AP ratio, the optimum dietary AM/AP ratio for maximum growth of obscure puffer was 0.25. The present result indicates that dietary AM/AP ratio could affect growth performance and feed utilization, some plasma parameters, digestive enzyme as well as hepatic glucose metabolic enzyme activities in juvenile obscure puffer.

[Diagnosis of spontaneous isolated superior mesenteric artery dissection using computed tomography angiography].

OBJECTIVE: To investigate the characteristics of the spontaneous isolated superior mesenteric artery dissection (SISMAD) on computed tomography angiography (CTA). METHODS: Twenty-five patients with unexplained acute abdominal pain received CTA. RESULTS: Four cases with the SISMAD were found and all were male with a mean age of (45.3±6.7) years. Two patients had hypertension history. CT showed enlarged diameter of the superior mesenteric artery with dissection in 4 cases, intimal flap and visible false lumen in 2 cases, ulcer-like laceration in 1 case, and intramural hematoma in 1 case. The proximal lacerations or entries were all at the proximal segment of the superior mesenteric artery. CTA classifications were type Ia (n=2), IIb (n=1), and III (n=1). Two patients underwent repeated CTA when discharged, and progressive changes were discovered. CONCLUSION: CTA can clearly show the characteristics of the superior mesenteric artery dissection, confirm the diagnosis, and provide an important basis for the classification and follow-up observation.

Microsurgical anatomy of the abducens nerve.

OBJECTIVE: To clarify the oriented classification, relationships, and variations of the abducens nerve and provide a detailed description of its microsurgical anatomic features. METHODS: A microsurgical anatomic dissection of the abducens nerve was performed in 100 specimens obtained from 50 adult cadaveric heads fixed in formalin and two adult cadaveric heads stained with hematoxylin and eosin for histological examination. Important neurovascular and structural relationships of the abducens nerve were observed. RESULTS: The abducens nerve was divided into five segments (cisternal, petroclival, internal carotid artery, fissural, and intraconal). It coursed in the petroclival venous confluence and there was a complex anatomic relationship. Two new types of abducens nerve variations were found. In one type, the duplicated nerve is split into two branches for a limited length in the cavernous sinus (CS). The other is a complex type, which has a complex course and pattern. This type of duplicated abducens nerve has a communicating branch in the cistern and numerous fasciculi in the CS. In addition, the two branches do not accompany each other for the entire course in the CS. CONCLUSION: The vulnerability of the abducens nerve results from diverse factors. The inferolateral trunk, which arises from the intracavernous segment of carotid artery (also called the artery of the inferior CS), is an important landmark for finding the abducens nerve and sympathetic nerve. Variations of the abducens nerve are not rare. Keeping variations of the nerve in mind is important during skull base operations and transvenous endovascular interventions. Understanding the relationship of the abducens nerve with adjacent structures will help us in preparing for safe surgery.

Short-term study of infliximab treatment for Crohn's disease in China.

OBJECTIVE: To determine the effectiveness and safety of short-term treatment of infliximab (IFX) in a group of Chinese patients with active Crohn's disease (CD). METHODS: Patients with established diagnosis of active CD were treated with IFX intravenously with a dose of 5 mg/kg at week 0, 2, 6. Clinical assessments were performed at baseline (week 0) and every week after IFX infusion until 8 weeks after the induction dose. RESULTS: Fourteen patients (nine male, five female) with a mean age of 29.7 years (range from 15 to 65 years) were included in the analysis. The mean subjective scores were decreased from 2.85 ± 0.57 at baseline to 1.3 ± 0.4 at week 14 (P < 0.05). The mean Harvey-Bradshaw index was 7.9 ± 1.5 at baseline and 2.3 ± 1.0 at week 14. The levels of erythrocyte sedimentation rate, serum C-reactive protein, total protein (TP) and albumin (ALB) were significantly improved during the 14-week period. Colonoscopy showed a remarkable improvement. Mild and transient adverse events including skin itching, headache and elevation of serum alanine aminotransferase and aspartate transaminase were each observed in one patient. Severe anemia, leucopenia and thrombocytopenia at week 27 after three infusions of IFX were observed in one patient. CONCLUSIONS: Treatment with three infusions of IFX at a dose of 5 mg/kg was effective for induction of remission for active CD patients who failed to respond to conventional therapies. Study of long-term efficacy and safety of IFX therapy is warranted for further investigations.

[A study of efficiacy of infliximab treatment for Crohn's disease.].

OBJECTIVE: To investigated the potential and safety of the monoclonal antibody to TNFalpha infliximab (IFX) in the treatment of active Crohn's disease (CD). METHODS: Patients who were confirmed diagnosis of CD and were unresponsive to the conventional treatments, or recurred after surgeries, or discontinued treatment due to drug intolerance, were treated with IFX intravenously in a dose of 5 mg/kg at week 0, 2, 6 (IFX infusion continued at an interval of every 8 weeks if respond to initial dosing). Clinical assessments, including disease activity, blood biological markers and colonoscopic findings, were performed at baseline (week 0) and each week (4 weeks or later for colonoscopy) after IFX infusion were conducted until the week before 4(th) infusion from initiated. RESULTS: Ten patients (8 male, 2 female) with mean age of 31.4 years (ranged from 15 to 65 years old) were included in the analysis. The mean subjective score from baseline to week 14 was decreased from 2.2 +/- 0.6 to 1.2 +/- 0.4 (P < 0.05). The mean Harvey-Bradshaw index was 6.6 +/- 1.6 at baseline and 2.1 +/- 1.0 at week 14. The levels of ESR, CRP, serum total protein (TP) and albumin (Alb) were significantly improved during the 14-week period. Colonoscopy showed a remarkable improvement of Crohn's Disease Endoscopic Index of Severity (CDEIS). No infusion-related reaction was observed in all patients during the treatment. Mild or transient skin itching and headache were respectively reported in two patients. Transient elevation of serum ALT and AST after 3(rd) infusion in one patient, and severe anemia including leucopenia and thrombocytopenia at week 35 after 1(st) infusion in one male patient were observed. CONCLUSIONS: Treatment with three infusions of IFX in a dose of 5 mg/kg was effective for induction of remission for active and complex CD patients who failed to respond to conventional treatment. Long-term safety of the therapy effect was warranted in further investigations.