Phase 2 study of pegylated liposomal doxorubicin plus cyclophosphamide, vincristine/vindesine, and prednisone in newly diagnosed PTCL: 8-year results.

BACKGROUND: Pegylated liposomal doxorubicin (PLD) is a liposome-encapsulated form of doxorubicin with equivalent efficacy and less cardiotoxicity. This phase 2 study evaluated the efficacy and safety of the PLD-containing CHOP regimen in newly diagnosed patients with aggressive peripheral T-cell lymphomas (PTCL). METHODS: Patients received PLD, cyclophosphamide, vincristine/vindesine, plus prednisone every 3 weeks for up to 6 cycles. The primary endpoint was the objective response rate at the end of treatment (EOT). RESULTS: From September 2015 to January 2017, 40 patients were treated. At the EOT, objective response was achieved by 82.5% of patients, with 62.5% complete response. As of the cutoff date (September 26, 2023), median progression-free survival (mPFS) and overall survival (mOS) were not reached (NR). The 2-year, 5-year, and 8-year PFS rates were 55.1%, 52.0%, and 52.0%. OS rate was 80.0% at 2 years, 62.5% at 5 years, and 54.3% at 8 years. Patients with progression of disease within 24 months (POD24) had worse prognosis than those without POD24, regarding mOS (41.2 months vs NR), 5-year OS (33.3% vs 94.4%), and 8-year OS (13.3% vs 94.4%). Common grade 3-4 adverse events were neutropenia (87.5%), leukopenia (80.0%), anemia (17.5%), and pneumonitis (17.5%). CONCLUSION: This combination had long-term benefits and manageable tolerability, particularly with less cardiotoxicity, for aggressive PTCL, which might provide a favorable benefit-risk balance. CLINICALTRIALS.GOV IDENTIFIER: Chinese Clinical Trial Registry, ChiCTR2100054588; IRB Approved: Ethics committee of Fudan University Shanghai Cancer Center (Date 2015.8.31/No. 1508151-13.

Ultralight Multifunctional Carbon-Based Aerogels by Combining Graphene Oxide and Bacterial Cellulose.

Nanostructured carbon aerogels with outstanding physicochemical properties have exhibited great application potentials in widespread fields and therefore attracted extensive attentions recently. It is still a challenge so far to develop flexible and economical routes to fabricate high-performance nanocarbon aerogels, preferably based on renewable resources. Here, ultralight and multifunctional reduced graphene oxide/carbon nanofiber (RGO/CNF) aerogels are fabricated from graphene oxide and low-cost, industrially produced bacterial cellulose by a three-step process of freeze-casting, freeze-drying, and pyrolysis. The prepared RGO/CNF aerogel possesses a very low apparent density in the range of 0.7-10.2 mg cm-3 and a high porosity up to 99%, as well as a mechanically robust and electrically conductive 3D network structure, which makes it to be an excellent candidate as absorber for oil clean-up and an ideal platform for constructing flexible and stretchable conductors.

Bacterial Cellulose: A Robust Platform for Design of Three Dimensional Carbon-Based Functional Nanomaterials.

Three dimensional (3D) carbon nanomaterials exhibit great application potential in environmental protection, electrochemical energy storage and conversion, catalysis, polymer science, and advanced sensors fields. Current methods for preparing 3D carbon nanomaterials, for example, carbonization of organogels, chemical vapor deposition, and self-assembly of nanocarbon building blocks, inevitably involve some drawbacks, such as expensive and toxic precursors, complex equipment and technological requirements, and low production ability. From the viewpoint of practical application, it is highly desirable to develop a simple, cheap, and environmentally friendly way for fabricating 3D carbon nanomaterials in large scale. On the other hand, in order to extend the application scope and improve the performance of 3D carbon nanomaterials, we should explore efficient strategies to prepare diverse functional nanomaterials based on their 3D carbon structure. Recently, many researchers tend to fabricate high-performance 3D carbon-based nanomaterials from biomass, which is low cost, easy to obtain, and nontoxic to humans. Bacterial cellulose (BC), a typical biomass material, has long been used as the raw material of nata-de-coco (an indigenous dessert food of the Philippines). It consists of a polysaccharide with a ß-1,4-glycosidic linkage and has a interconnected 3D porous network structure. Interestingly, the network is made up of a random assembly of cellulose nanofibers, which have a high aspect ratio with a diameter of 20-100 nm. As a result, BC has a high specific surface area. Additionally, BC hydrogels can be produced on an industrial scale via a microbial fermentation process at a very low price. Thus, it can be an ideal platform for design of 3D carbon-based functional nanomaterials. Before our work, no systematic work and summary on this topic had been reported. This Account presents the concepts and strategies of our studies on BC in the past few years, that is, converting cheap biomass into high value-added 3D carbon nanomaterials and designing diverse functional materials on 3D carbon structure. We first briefly introduce the history, constituent, and microstructure features of BC and discuss its advantages as a raw material for preparing the CNF aerogels. Then, we summarize the methods and strategies for preparing various 3D carbon-based nanomaterials from BC. In addition, the potential applications of the developed CNF aerogel based functional materials are also highlighted in this Account, including stretchable conductors, oxygen reduction reaction catalysts, supercapacitors, lithium-ion battery, and oil cleanup. Finally, we give some prospects on the future challenges in this emerging research area of designing CNF aerogel based functional nanomaterials from BC.

[The protective mechanism study of fengshiqing recipe against bone destruction in CIA rats].

OBJECTIVE: To explore the protective mechanism of Fengshiqing Recipe (FR) against bone destruction in collagen-induced arthritis (CIA) rats. METHODS: Rats were divided into four groups in the experiment,i.e., the blank control group, the model group, the MTX group (MTX, 1 mg/1 000 g), and the FR group (24 g crude FR/kg). The CIA model was prepared except the blank control group. Medication was started in the MTX group and the FR group from the 14th day after modeling to the 56th day. The toe volume was measured on every Tuesday and Friday. Expression levels of serum IL-17, RANKL, MIP-1alpha were detected after 3-and 6-week intervention. The bone scintigraphy with nuclide (SPECT), bone mineral density (BMD), and the pathological section were observed to assess the intervention of drugs of heat clearing blood activating actions in the bone destruction of CIA rats. RESULTS: From the 10th day of modeling, the volume of both toes started to swell and reached the peak at about 21 days. It was obviously shrunk at about 30 days. Of them, the swelling degree was milder in the MTX group and the FR group than in the model group. Compared with the model group at the same phase, the levels of IL-17 and RANKL decreased in the MTX group after 3 weeks of intervention (P < 0.01, P < 0.05). The IL-17 level decreased in the FR group after three weeks of intervention (P < 0.05). The RANKL level decreased in the MTX group and the FR group after 6 weeks of intervention (P < 0.01, P < 0.05). Compared with the model group and the MTX group, the overall BMD and ankle BMD increased in the FR group after 6 weeks of intervention (P < 0.01, P < 0.05). The ankle ROI/mandible and the toe ROI/mandible were elevated in the FR group after 3 weeks of intervention (P < 0.05). Pathological results suggested that the joint lacunae was significantly widened, the hyperplasia of the synovial tissue was so severe, and the bone tissue was destroyed in the model group. Compared with the model group, the aforesaid conditions were significantly improved in the MTX group and the FR group. The cartilage structure was complete. CONCLUSION: QR could inhibit decreased BMD, prevent bone destruction, which might be achieved by down-regulating expression levels of IL-17, RANKL, and MIP-1alpha through the osteo immunological Th/RANKL system,inhibiting maturation and differentiation of osteoclasts, thereby, inhibiting bone destruction.

Enhancing Macrophage Drug Delivery Efficiency via Co-Localization of Cells and Drug-Loaded Microcarriers in 3D Resonant Ultrasound Field.

In this study, a novel synthetic 3D molecular transfer system which involved the use of model drug calcein-AM-encapsulated poly(lactic-co-glycolic acid) microspheres (CAPMs) and resonant ultrasound field (RUF) with frequency of 1 MHz and output intensity of 0.5 W/cm2 for macrophage drug delivery was explored. We hypothesized that the efficiency of CAPMs-mediated drug delivery aided by RUF can be promoted by increasing the contact opportunities between cells and the micrometer-sized drug carriers due to effects of acoustic radiation forces generated by RUF. Through the fluoromicroscopic and flow cytometric analyses, our results showed that both DH82 macrophages and CAPMs can be quickly brought to acoustic pressure nodes within 20 sec under RUF exposure, and were consequently aggregated throughout the time course. The efficacy of cellular uptake of CAPMs was enhanced with increased RUF exposure time where a 3-fold augmentation (P < 0.05) was obtained after 15 min of RUF exposure. We further demonstrated that the enhanced CAPM delivery efficiency was mainly contributed by the co-localization of cells and CAPMs resulting from the application of the RUF, rather than from sonoporation. In summary, the developed molecular delivery approach provides a feasible means for macrophage drug delivery.

Connections between EM2-containing terminals and GABA/µ-opioid receptor co-expressing neurons in the rat spinal trigeminal caudal nucleus.

Endomorphin-2 (EM2) demonstrates a potent antinociceptive effect via the µ-opioid receptor (MOR). To provide morphological evidence for the pain control effect of EM2, the synaptic connections between EM2-immunoreactive (IR) axonal terminals and γ-amino butyric acid (GABA)/MOR co-expressing neurons in lamina II of the spinal trigeminal caudal nucleus (Vc) were investigated in the rat. Dense EM2-, MOR- and GABA-IR fibers and terminals were mainly observed in lamina II of the Vc. Within lamina II, GABA- and MOR-neuronal cell bodies were also encountered. The results of immunofluorescent histochemical triple-staining showed that approximately 14.2 or 18.9% of GABA-IR or MOR-IR neurons also showed MOR- or GABA-immunopositive staining in lamina II; approximately 45.2 and 36.1% of the GABA-IR and MOR-IR neurons, respectively, expressed FOS protein in their nuclei induced by injecting formalin into the left lower lip of the mouth. Most of the GABA/MOR, GABA/FOS, and MOR/FOS double-labeled neurons made close contacts with EM2-IR fibers and terminals. Immuno-electron microscopy confirmed that the EM2-IR terminals formed synapses with GABA-IR or MOR-IR dendritic processes and neuronal cell bodies in lamina II of the Vc. These results suggest that EM2 might participate in pain transmission and modulation by binding to MOR-IR and GABAergic inhibitory interneuron in lamina II of the Vc to exert inhibitory effect on the excitatory interneuron in lamina II and projection neurons in laminae I and III.