Relapsed/refractory multiple myeloma-transformed plasma-cell leukemia successfully treated with daratumumab followed by autologous stem cell transplantation.

Daratumumab is a humanized anti-CD38 IgG1 monoclonal antibody which could be used for multiple myeloma (MM). MM with plasma-cell leukemia (PCL) transformation is highly aggressive and is resistant to conventional therapy. Novel therapeutics are needed for PCL, and daratumumab may play role. We report a case of relapsed/refractory multiple myeloma (RRMM)-transformed PCL successfully treated with daratumumab. The case was a 42-year-old man who was diagnosed with MM 2 years ago and relapsed after six cycles of bortezomib-based chemotherapy. The patient rapidly developed hyperleukocytosis and disseminated intravascular coagulation, and was diagnosed with PCL. Daratumumab-based therapy was tried and the case miraculously obtained complete remission (CR) after four doses of a weekly infusion of daratumumab. Finally the patient received autologous hematopoietic stem-cell transplantation (auto-HSCT) and maintained CR. Moreover, we monitored the immune cell dynamics by flow cytometry (FCM) during daratumumab-based treatment. The immune cell subset analysis revealed significant down-regulation of CD38+ natural killer (NK) cells, regulatory T cells (Tregs) and regulatory B cells (Bregs). Meanwhile cytotoxic T-lymphocyte expansion was observed. In conclusion, daratumumab could rapidly decrease tumor burden, improve the condition of the PCL patient, and serve as a bridging salvage chemotherapy for further chimeric antigen recptor T cell therapy (Car-T) or HSCT, which could potentially improve patient survival. The immune cell dynamic findings in this case suggest that the immunomodulatory mechanism may contribute to the antimyeloma effect of daratumumab.

Silver recovery as Ag0 nanoparticles from ion-exchange regenerant solution using electrolysis.

Many silver (Ag) containing consumer-products (e.g. textiles) release Ag into the environment, posing ecotoxicological risks. Ag recovery mitigates environmental hazards, recycles Ag, and leads to sustainability. In the present work, Ag has been recovered as Ag0 nanoparticles from the spent solution (thiourea (TU) ~0.5 mol/L pH ~1.1-1.2, and Ag ~550 mg/L) obtained from the regeneration of an Ag-loaded resin using a simple undivided electrolytic cell. The reclaimed regenerant solution has been recycled and reused in a closed-loop scheme over multiple cycles. The process parameters, i.e., current (0.05 A) and stirring speed (600 r/min), have been optimized for Ag recovery of ~94% and TU loss of ~2%. The reclaimed regenerant solution has been shown to regenerate Ag-loaded resin samples with >90% regeneration efficiency over 4 cycles of consecutive extraction and regeneration. The recovered Ag0 nanoparticles are monodisperse, consistently spherical in shape, and have a mean diameter of ~6 nm with standard deviation of the Gaussian fit as ~2.66 nm.

Fabrication of porous chitin membrane using ionic liquid and subsequent characterization and modelling studies.

The application of green chemistry principles for the processing of biopolymers is a steadily increasing field of research. Chitin membranes were successfully prepared by using the ionic liquid 1-ethyl-3-methylimidazolium acetate ([C2mim][OAc]) as solvent media. The resulting materials were thoroughly characterized, revealing that freeze drying produced membranes that were highly porous. The drying methods and the concentration of chitin used defined many of the membrane properties, such as mechanical strength, porosity, and water absorbency. From these data, an empirical model was generated which could be used to correlate the different membrane properties. The model could be used to predict the properties of the chitin membrane made with different wt% of chitin-IL solutions, and the predicted values aligned with the experimental results. This allowed for prediction of the properties of the chitin membrane (e.g., tensile strength) and gives the ability to tune the properties of the biomaterial. The methods and structures described here provide a starting point for the design and fabrication of a family of polysaccharide-based sustainable materials with potentially broad applicability.

XIAP Limits Autophagic Degradation of Sox2 and Is A Therapeutic Target in Nasopharyngeal Carcinoma Stem Cells.

Rationale: Nasopharyngeal carcinoma (NPC) is the most frequent head and neck tumor in South China. The presence of cancer stem cells (CSCs) in NPC contributes to tumor maintenance and therapeutic resistance, while the ability of CSCs to escape from the apoptosis pathway may render them the resistant property to the therapies. Inhibitor of apoptosis proteins family proteins (IAPs), which are overexpressed in nasopharyngeal carcinoma stem cells, may play an important role in maintaining nasopharyngeal cancer stem cell properties. Here, we develop a novel CSC-targeting strategy to treat NPC through inhibiting IAPs. Methods: Human NPC S-18 and S-26 cell lines were used as the model system in vitro and in vivo. Fluorescence activated cell sorting (FACS) assay was used to detect nasopharyngeal SP cells and CD44+ cells. The characteristics of CSCs were defined by sphere suspension culture, colony formation assay and cell migration. The role of XIAP on the regulation of Sox2 protein stability and ERK1-mediated phosphorylation of Sox2 signaling pathway were analyzed using immunoblotting, immunoprecipitation, immunofluorescence, phosphorylation mass spectrometry, siRNA silencing and plasmid overexpression. The correlation between XIAP and Sox2 in NPC biopsies and their role in prognosis was performed by immunohistochemistry. APG-1387 or chemotherapies-induced cell death and apoptosis in S-18 and S-26 were determined by WST, immunoblotting and flow cytometry assay. Results: IAPs, especially X chromosome-linked IAP (XIAP), were elevated in CSCs of NPC, and these proteins were critically involved in the maintenance of CSCs properties by enhancing the stability of Sox2. Mechanistically, ERK1 kinase promoted autophagic degradation of Sox2 via phosphorylation of Sox2 at Ser251 and further SUMOylation of Sox2 at Lys245 in non-CSCs. However, XIAP blocked autophagic degradation of Sox2 by inhibiting ERK1 activation in CSCs. Additionally, XIAP was positively correlated with Sox2 expression in NPC tissues, which were associated with NPC progression. Finally, we discovered that a novel antagonist of IAPs, APG-1387, exerted antitumor effect on CSCs. Also, the combination of APG-1387 with CDDP /5-FU has a synergistic effect on NPC. Conclusion: Our study highlights the importance of IAPs in the maintenance of CSCs in NPC. Thus, XIAP is a promising therapeutic target in CSCs and suggests that NPC patients may benefit from a combination treatment of APG-1387 with conventional chemotherapy.

Conductive Textiles via Vapor-Phase Polymerization of 3,4-Ethylenedioxythiophene.

We fabricated electrically conductive textiles via vapor-phase polymerization of poly(3,4-ethylenedioxythiophene) (PEDOT) layers on cotton, cotton/poly(ethylene terephthalate) (PET), cotton/Lycra, and PET fabrics. We then measured the electrical resistivity values of such PEDOT-coated textiles and analyzed the effect of water treatment on the electrical resistivity. Additionally, we tested the change in the electrical resistance of the conductive textiles under cyclic stretching and relaxation. Last, we characterized the uniformity and morphology of the conductive layer formed on the fabrics using scanning electron microscopy and electron-dispersive X-ray spectroscopy.

A novel nomogram based on LODDS to predict the prognosis of epithelial ovarian cancer.

BACKGROUND: To develop and validate a nomogram based on log of odds between the number of positive lymph node and the number of negative lymph node (LODDS) in predicting the overall survival (OS) and cancer specific survival (CSS) for epithelial ovarian cancer (EOC) patients. MATERIALS AND METHODS: A total of 10,692 post-operative EOC patients diagnosed between 2004 and 2013 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training (n = 7,021) and validation (n = 3,671) cohorts. Multiple clinical pathological parameters were assessed and compared with outcomes. Parameters significantly correlating with outcomes were used to build a nomogram. Bootstrap validation was subsequently used to assess the predictive value of the model. RESULTS: In the training set, age at diagnosis, race, marital status, tumor location, stage, grade and LODDS were correlated significantly with outcome in both the univariate and multivariate analyses and were used to develop a nomogram. The nomogram demonstrated good accuracy in predicting OS and CSS, with a bootstrap-corrected concordance index of 0.757 (95% CI, 0.746-0.768) for OS and 0.770 (95% CI, 0.759-0.782) for CSS. Notably, in this population our model performed favorably compared to the currently utilized Federation of Gynecology and Obstetrics (FIGO) model, with concordance indices of 0.699 (95% CI, 0.688-0.710, P < 0.05) and 0.719 (95% CI, 0.709- 0.730, P < 0.05) for OS and CSS, respectively. Using our nomogram in the validation cohort, the C-indices were 0.757 (95% CI, 0.741-0.773, P < 0.05, compared to FIGO) for OS and 0.762 (95% CI, 0.746-0.779, P < 0.05, compared to FIGO) for CSS. CONCLUSIONS: LODDS works as an independent prognostic factor for predicting survival in patients with EOC regardless of the tumor stage. By incorporating LODDS, our nomogram may be superior to the currently utilized FIGO staging system in predicting OS and CSS among post-operative EOC patients.

Reactive oxygen species mediate oxaliplatin-induced epithelial-mesenchymal transition and invasive potential in colon cancer.

Therapeutic benefits offered by common chemotherapy drugs, such as oxaliplatin, are limited due to the development of resistance, which contributes to treatment failure and metastasis. The epithelial-mesenchymal transition (EMT) is a key event contributing to the development of resistance to chemotherapeutics. Although the relationship between oxaliplatin and chemotherapy resistance has been described for decades, the molecular mechanisms have remained elusive. The aim of the present study was to investigate the underlying mechanisms of oxaliplatin-mediated metastasis. Here, we identify reactive oxygen species (ROS) as mediators that promote the oxaliplatin-induced EMT. Following oxaliplatin treatment, the messenger RNA (mRNA) levels of most peroxiredoxin family genes, except for peroxiredoxin 1 (prdx1) gene, were constant or even decreased, resulting in ROS abundance. And the antioxidant guardian Nrf2 was unconspicuously raised both transcriptionally and translationally with oxaliplatin treatment as compared to those induced by topotecan treatment, which has been proved with no induced metastasis. In addition, the study evaluated high levels of ROS leading to EMT via activation of the known oncogenes Akt and Snail. Using the Akt inhibitor LY294002 or knocking down Snail expression via RNA interference (RNAi) reversed the effects of oxaliplatin on the EMT and metastasis. Our studies establish a role for the ROS-Akt-Snail axis as a mechanism by which chemotherapeutics induce EMT and cancer metastasis.

Association between CLPTM1L polymorphisms (rs402710 and rs401681) and lung cancer susceptibility: evidence from 27 case-control studies.

Genome-wide association studies have identified two SNPs (rs402710 and rs401681) of CLPTM1L at chromosome 5p15.33 as a new lung cancer (LC) susceptibility locus in populations of European descent. Since then, the relationship between these SNPs and LC has been reported in various ethnic groups; however, these studies have yielded inconsistent results. To investigate this inconsistency, we performed a meta-analysis of 27 studies involving a total of 60,828 cases and 109,135 controls for the two polymorphisms to evaluate its effect on genetic susceptibility for LC. An overall random-effects per-allele odds ratio of 1.14 (95% CI 1.11-1.16, P < 10(-5)) and 1.15 (95% CI 1.12-1.19, P < 10(-5)) was found for the rs401681 and rs402710 polymorphism, respectively. Significant results were also observed for under dominant and recessive genetic models. After stratified by ethnicity, significant associations were found among Caucasians and East Asians. In the subgroup analysis by sample size, significantly increased risks were found for these polymorphisms in all genetic models. In addition, we find both rs402710 and rs401681 conferred significantly greater risks for adenocarcinoma and squamous cell carcinoma when stratified by histological type of tumors. Furthermore, associations of these polymorphisms with LC risk were observed among current smokers and former smokers, as well as never smokers. Our findings demonstrated that rs402710 and rs401681 are risk-conferring factors for the development of lung cancer.

[Clinical distribution and drug resistance of Staphylococcus aureus isolated from hospitalized children].

OBJECTIVE: To learn about the clinical distribution and drug resistance of Staphylococcus aureus (S. aureus) isolated from inpatients and provide evidence for clinically reasonable use of antibiotics. METHODS: Data including clinical features and drug sensitivity of S. aureus isolated from hospitalized patients in the last two years were analyzed. RESULTS: 248 S. aureus strains were isolated from inpatients of our hospital in the last 2 years. The most common disease caused by S. aureus was pneumonia with a total of 163 patients. The second was skin and soft tissue infection with 21 patients in total. Sepsis occurred in 11 patients. The most commonly used antibiotics included oxacillin, nafcillin, cefathiamidine and vancomycin. The average course of antibiotic was 12.48 days. Treatment course of pneumonia and sepsis was 13.71 and 15.11 respectively. 96.31% (235/244) of S. aureus were resistant to penicillin. Vancomycin-resistant S. aureus has not been isolated. CONCLUSION: S. aureus pneumonia is the leading cause of hospitalization of children with S. aureus infection. S. aureus is highly resistant to commonly used antibiotics and related infections need longer therapy. Clinicians should pay more attention to S. aureus infection.

Cardiocerebral resuscitation vs cardiopulmonary resuscitation for cardiac arrest: a systematic review.

OBJECTIVE: The objective of this study is to evaluate the efficacy of cardiocerebral resuscitation (CCR) vs cardiopulmonary resuscitation (CPR) for patients with out-of-hospital cardiac arrest (OHCA). METHODS: We conducted a systematic review of controlled trials and observational studies. We searched Cochrane Central Register of Controlled Trials; MEDLINE; Embase; and Chinese databases such as VIP, CNKI, WANFANG, and CBM from their inception to September 2010. Data from original studies were extracted and assessed with predefined criteria. RESULTS: Thirteen studies comprising 3 randomized controlled trials and 10 observational studies were included. Pooled analysis of 4 observational studies suggested that neurologically intact survival of patients with OHCA was improved in CCR group (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.07-1.97). Survival to hospital discharge in the CCR group was superior or at least equal to that in CPR group (randomized controlled trial OR, 1.25; 95% CI, 1.01-1.55; cohort studies OR, 1.15; 95% CI, 0.72-1.82; case-control studies OR 0.85; 95% CI, 0.65-1.12). In the subgroup analysis of patients with a shockable rhythm as an initial rhythm, survival to hospital discharge was significantly improved in the CCR group (cohort studies OR, 2.03; 95% CI, 1.44-2.86). However, when only noncardiac origin cardiac arrest was taken into consideration, survival rate was better in the CPR group (cohort studies OR, 0.87; 95% CI, 0.77-0.98). CONCLUSION: Cardiocerebral resuscitation might be equivalent or superior to CPR in patients with OHCA in both survival rate and neurologic benefits. Further work is needed to assess the efficacy of CCR for victims who had OHCA of noncardiac causes.

Characteristics and treatability of oil-bearing wastes from aluminum alloy machining operations.

Enomoto Industry Co., exclusively uses water-based cutting fluids in its aluminum alloy machining operations. Since the cost of disposal can be much greater than the cost of purchase, the treatability of spent cutting fluids is becoming a major criterion for cutting fluid selection. Samples were collected from the machining lines at Enomoto's facility to determine their characteristics and evaluate their treatability with centrifugation, chemical coagulation and electrochemical coagulation. As expected, oil and grease (O&G) and total suspended solids (TSS) are the main reasons that spent cutting fluids are prohibited from being discharged into local swage systems. The average O&G found in the spent cutting fluids is 87,354 mg/L with TSS of more than 70,000 mg/L. Both O&G and TSS are the major contributors to the high turbidity of these waste effluents. A centrifuge with a relative centrifugal force of 1318 x g, was able to reduce 60% of the turbidity. By adding the coagulant aluminum chloride, the oil-water emulsion was destabilized, and the turbidity was reduced from 3249 Formazin Attenuation Units (FAU) to around 314 FAU. With freshly generated aluminum ions in the spent cutting fluid, the electrochemical process destabilized the oil-water emulsion system. The coalesced oil droplets were adsorbed onto the highly dispersed aluminum coagulant. The oil-rich sludge that was generated in the operation was then floated to the surface, forming a blanket that was removed by skimming. The electrochemical treatment was able to reduce the turbidity to less than 14 FAU, which is the detection limit of the Hach DR/4000 UV-vis spectrophotometer.

Electrochemical coagulation for textile effluent decolorization.

The three most commonly used dyestuffs in textile industry are reactive, acid, and dispersed dyes. One dye from each group, C.I. Reactive Blue-19, C.I. Acid Red-266, and C.I. Disperse Yellow-218 was chosen to study the feasibility of coagulation for color removal. The dyes used in these experiments were chosen to represent the two major structural features: anthraquinone and azo dyes. Reactive Blue is an anthraquinone-based dye, and Acid Red and Disperse Yellow represent azo-based dyes. As there is no standard method to measure the color intensity, a Hach spectrophotometer was used to measure the absorbance before and after the dye solution was treated. Removal efficiencies on these dyes were obtained by measuring absorbance of a sample at 592 nm for Reactive Blue, 498 nm for Acid Red, and 428 nm for Disperse Yellow. Aluminum and ferric coagulants were produced in a parallel-plate electrochemical reactor by anodic dissolution. Removal efficiencies of more than 98%, in terms of absorbance, were observed in laboratory conditions. Removal was found highly dependent upon NaCl concentration, applied voltage, current density, and pH. The NaCl in the solution effectively reduced the power consumption and promoted the coagulant generation by depasivating the Al-water and Fe-water electrochemical systems. The processes were determined to be highly NaCl dependent. A mechanism was proposed for the corresponding liquid phase chemistry.

Cleaning Flue Gas from Sewage Sludge Incinerators Using an Electrostatic Precipitator and Polystage Chemical Scrubber.

A study of a wet electrostatic precipitator (ESP) and chemical scrubber for flue gas cleaning was conducted on the multiple hearth sewage sludge incinerator at the New England Treatment Company (NETCO) facility in Woonsocket, RI. The ESP achieved the highest removal rate for heavy metals and particulate matter to a submicron range, while the two-stage chemical scrubber was able to oxidize and dissolve the incoming NOx in the scrubbing solutions. This paper describes the details of sewage sludge incineration systems, NOx emissions from a multiple-hearth sludge incinerator, and the current regulatory status; it also presents the results obtained from the commercial-scale ESP and the portable scrubber.