[Analysis of conventional echocardiographic features in apical hypertrophic cardiomyopathy patients complicated with left ventricular apical aneurysm].

Objective: To explore the basic characteristics of conventional echocardiography of apical hypertrophic cardiomyopathy (ApHCM) patients complicating with left ventricular apical aneurysm (LVAA). Methods: This is a retrospective study. Patients who underwent echocardiography and cardiac magnetic resonance (CMR) and were diagnosed with ApHCM complicated with LVAA by CMR at Fuwai Hospital, Chinese Academy of Medical Sciences from August 2012 to July 2017 were enrolled. According to whether LVAA was detected by echocardiography, the enrolled patients were divided into two groups: LVAA detected by echocardiography group and LVAA not detected by echocardiography group. Clinical data of the two groups were compared to analyze the causes of missed diagnosis by echocardiography. Results: A total of 21 patients were included, of whom 67.0% (14/21) were males, aged (56.1±16.5) years. Patients with chest discomfort accounted for 81.0% (17/21), palpitation 38.1% (8/21), syncope 14.3% (3/21). ECG showed that 21 (100%) patients had ST-T changes and 18 (85.7%) had deep T-wave invertion. Echocardiography revealed ApHCM in 17 cases (81.0%) and LVAA in 7 cases (33.3%). The mean left ventricular apical aneurysm diameter was 33.0 (18.0, 37.0) mm, and left ventricular ejection fraction was (66.5±6.6) %, and left ventricular apex thickness was (21.0±6.3) mm. Left ventricular outflow tract obstruction was presented in 4 cases and middle left ventricular obstruction in 10 cases. The mean left ventricular apical aneurysm diameter of LVAA detected by echocardiography was greater than that of LVAA not detected by echocardiography (25.0 (18.0, 28.0) mm vs. 16.0 (12.3, 21.0) mm, P=0.006). Conclusions: Conventional echocardiography examination has certain limitations in the diagnosis of ApHCM. Smaller LVAA complicated with ApHCM is likely to be unrecognized by echocardiography. Clinicians should improve their understanding of this disease.

Applications of microbial co-cultures in polyketides production.

Polyketides are a large group of natural biomolecules that are normally produced by bacteria, fungi and plants. These molecules have clinical importance due to their anti-cancer, anti-microbial, anti-oxidant and anti-inflammatory properties. Polyketides are biosynthesized from units of acyl-CoA by different polyketide synthases (PKSs), which display wide diversity of functional domains and mechanisms of action between fungi and bacteria. Co-culture of different micro-organisms can produce novel products distinctive from those produced during single cultures. This study compared the new polyketides produced in such co-culture systems and discusses aspects of the cultivation systems, product structures and identification techniques. Current results indicate that the formation of new polyketides may be the result of activation of previously silent PKSs genes induced during co-culture. This review indicated a potential way to produce pure therapeutic polyketides by microbial fermentation and a potential way to develop functional foods and agricultural products using co-co-culture of different micro-organisms. It also pointed out a new perspective for studies on the process of functional foods, especially those involving multiple micro-organisms.

[Efficacy and peripheral immunity analysis of allogeneic natural killer cells therapy in patients with hepatocellular carcinoma].

OBJECTIVE: To evaluate the safety and efficacy of allogeneic natural killer (NK) cells in the treatment of primary hepatocellular carcinoma (HCC), and to elucidate the mechanism of NK cells therapy. METHODS: Twenty-one patients with primary HCC treated with allogeneic NK cells at the Fifth Medical Center of the PLA General Hospital were followed up for 1 year. Peripheral blood mononuclear cells (PBMCs) were isolated from patient-related donors and cultured in vitro for 15 days and infused to the patients in two consecutive days. Clinical data and laboratory data were collected and analyzed, including survival, clinical features, imaging changes, hematology, immunology, and biochemical indicators to evaluate the safety and efficacy of allogeneic NK cell therapy. The changes of peripheral blood lymphocyte subsets after treatment were also analyzed to explore the possible anti-tumor mechanisms. RESULTS: (1) Of the 21 patients with primary HCC, 11 patients were treated once, 5 patients were treated twice, and 5 patients were treated 3 times. After allogeneic NK cells infusion, 10 patients had fever, 1 patient had slight hepatalgia and 1 patient had slight headache, no other adverse events occurred including acute and chronic graft-versus-host disease (GVHD). They resolved spontaneously within 8 hours without other treatment. (2) The total disease control rate was 76.2% during one-year follow-up. Among them, the patients with Barcelona clinic liver cancer (BCLC) stage A had a disease control rate of 100%, stable disease (SD) in 10 cases; BCLC stage B patients had a disease control rate of 60%, partial response (PR) in 1 case, and SD 2 in cases; BCLC stage C patients had a disease control rate of 50%, complete response (CR) in 1 case, and 2 cases of PR. (3) The frequencies of NK cells and CD8+ T cells in peripheral blood were significantly lower than that before at 24 hours after treatment, and the frequencies of CD4+ T cells and CD4/CD8 were significantly higher than the baseline. CONCLUSION: Allogeneic NK cells have good safety and efficacy in the treatment of primary HCC. The anti-tumor effect of the allogeneic NK cells may play an important role in the activation of the patient's natural immune system and delay disease progression, suggesting that allogeneic NK cells combined with sorafenib may be a very effective treatment for advanced HCC, and further large-sample multicenter randomized controlled clinical trials are needed to validate this result.

[The application of failure mode and effect analysis to improve the hand hygiene compliance of medical staff in eye hospital].

Objective: To discuss the application of failure mode and effect analysis to improve the hand hygiene compliance of medical staff in eye hospital. Methods: To form failure mode and effect analysis (FMEA) quality control team. By using FMEA method of risk management, to analyze the risk factors of hand hygiene compliance of medical staff in eye hospital. By performing analysis, to determine the high risk factors, develop and implement the improvement measures to reduce the risk of these factors. Results: the awareness rate of hand hygiene knowledge was increased significantly after the implementation of failure mode and effect analysis (P<0.01) , the correct rate of hand-washing method, and the implementing rate of 5 hand hygiene were increased significantly (P<0.05) . After the implementation of FMEA, the usage amount of hand washing liquid and quick hand disinfectant was increased from 13 292 ml to 28 390 ml, and difference of the hand hygiene qualification rate was statistically significant (P<0.05) . Conclusion: The application of FMEA contributes to analyze the causes of hand hygiene failure, and guide the development of improvement measures, which can effectively improve the hand hygiene compliance of medical staff, thereby reducing nosocomial infection.

Monoclonal antibody against macrophage colony-stimulating factor suppresses circulating monocytes and tissue macrophage function but does not alter cell infiltration/activation in cutaneous lesions or clinical outcomes in patients with cutaneous lupus erythematosus.

This study's objective was to assess the effects of PD-0360324, a fully human immunoglobulin G2 monoclonal antibody against macrophage colony-stimulating factor in cutaneous lupus erythematosus (CLE). Patients with active subacute CLE or discoid lupus erythematosus were randomized to receive 100 or 150 mg PD-0360324 or placebo via intravenous infusion every 2 weeks for 3 months. Blood and urine samples were obtained pre- and post-treatment to analyse pharmacokinetics and pharmacodynamic changes in CD14(+) CD16(+) monocytes, urinary N-terminal telopeptide (uNTX), alanine/aspartate aminotransferases (ALT/AST) and creatine kinase (CK); tissue biopsy samples were taken to evaluate macrophage populations and T cells using immunohistochemistry. Clinical efficacy assessments included the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Among 28 randomized/analysed patients, peak/trough plasma concentrations increased in a greater-than-dose-proportional manner with dose increases from 100 to 150 mg. Statistically significant differences were observed between active treatment and placebo groups in changes from baseline in CD14(+) CD16(+) cells, uNTX, ALT, AST and CK levels at most time-points. The numbers, density and activation states of tissue macrophages and T cells did not change from baseline to treatment end. No between-group differences were seen in CLASI. Patients receiving PD-0360324 reported significantly more adverse events than those receiving placebo, but no serious adverse events. In patients with CLE, 100 and 150 mg PD-0360324 every 2 weeks for 3 months suppressed a subset of circulating monocytes and altered activity of some tissue macrophages without affecting cell populations in CLE skin lesions or improving clinical end-points.

The toxicity of cadmium to three aquatic organisms (Photobacterium phosphoreum, Daphnia magna and Carassius auratus) under different pH levels.

This study investigated the effect of pH on cadmium toxicity to three aquatic organisms: Photobacterium phosphoreum, Daphnia magna and Carassius auratus. The acute toxicity of Cd(2+) to P. phosphoreum and D. magna at five pH values (5.0, 6.0, 7.0, 8.0, and 9.0) was assessed by calculating EC50 values. We determined that Cd(2+) was least toxic under acidic conditions, and D. magna was more sensitive to the toxicity of Cd than P. phosphoreum. To evaluate Cd(2+)-induced hepatic oxidative stress in C. auratus at three pH levels (5.0, 7.25, 9.0), the activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase), the level of glutathione and the malondialdehyde content in the liver were measured. Oxidative damage was observed after 7d Cd exposure at pH 9.0. An important finding of the current research was that Cd(2+) was generally more toxic to the three test organisms in alkaline environments than in acidic environments.

[Investigation and exploration of online medical education carried out by Oral and Maxillofacial Deformity Group of Shanghai Ninth People's Hospital during the COVID-19 pandemic].

As the national key discipline and the initiator of oral and maxillofacial deformity group, the Department of Oral and Maxillofacial Surgery persisted in teaching, designed a novel teaching form combining theoretical knowledge and online software practice according to the characteristics of our discipline and carried out "cloud training" via the National Oral Telemedicine Education Platform. Ten lecturers, 325 theoretical students and 50 practical students were investigated by questionnaire in the present study with questions focusing on the geographical distribution and composition of personnel, etc. The results showed that the online course covered a wide range of students and achieved high acceptance and satisfaction rate. The first online software operation course was conducted in an orderly manner, with timely interaction between teachers and students. The students were able to master the design process skillfully. This "cloud training" has achieved good results, but there are still a series of problems that have yet to be resolved, such as network stalls and protection of intellectual property rights. Under the new form, the exploration and analysis of the new mode of online telemedicine specialist education will provide some practical reference for the National Clinical Research Center for Oral Diseases to carry out online telemedicine teaching in the future.

Metformin inhibits LPS-induced inflammatory response in VSMCs by regulating TLR4 and PPAR-γ.

OBJECTIVE: This study aims to explore whether the inhibitory role of metformin could inhibit LPS-induced inflammatory response in vascular smooth muscle cells (VSMCs) and its underlying mechanism. MATERIALS AND METHODS: VSMCs were extracted from aorta of Sprague Dawley rats. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay was performed to detect VSMCs viability after treatment with different concentrations of metformin. Levels of monocyte chemoattractant protein-1 (MCP-1), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in VSMCs were detected by ELISA (enzyme-linked immunosorbent assay) and qRT-PCR (quantitative Real time-polymerase chain reaction). Protein and mRNA levels of toll like receptor 4 (TLR4) and peroxisome proliferators activated receptor γ (PPAR-γ) in VSMCs were detected by Western blot and qRT-PCR, respectively. Finally, VSMCs were treated with the PPAR-γ antagonist GW9662 and inflammatory indicators in cells were detected. RESULTS: No significant difference in VSMCs viability was found after 0-2 mM metformin treatment or 500 µg/L LPS induction for 24 h. After 500 µg/L LPS induction in VSMCs for 24 h, levels of MCP-1, TNF-α and IL-6 were remarkably elevated. Both mRNA and protein levels of TLR4 in VSMCs were upregulated after 500 µg/L LPS induction for 24 h, which were remarkably reversed by the treatment of different concentrations of metformin. Knockdown of TLR4 remarkably inhibited LPS-induced inflammatory response in VSMCs, manifesting as decreased levels of MCP1, TNF-α and IL-6, which were further downregulated after combination treatment of TLR4 knockdown and 20 mM metformin. Furthermore, both mRNA and protein levels of PPAR-γ in VSMCs were downregulated after 500 µg/L LPS induction for 24 h, which were remarkably reversed by the treatment of different concentrations of metformin. GW9662 treatment resulted in elevated expressions of MCP-1, TNF-α and IL-6, which were reversed by metformin treatment. CONCLUSIONS: Metformin can effectively inhibit the mRNA and protein expressions of IL-6, MCP-1, and TNF-α in LPS-induced VSMCs. The anti-inflammatory effects of metformin inhibit the inflammatory response through downregulating rely on the downregulation of TLR4 expression and upregulation ofng PPAR-γ activity.

[Endoscopic selective lateral neck dissection via a chest-breast approach for papillary thyroid carcinoma: preliminary experience in 20 cases].

Objective:To explore the feasibility of endoscopic selective lateral neck dissection(SLND) via a chest-breast approach.Method:We retrospectively reviewed 20 patients who underwent endoscopic total thyroidectomy along with SLND, between January 2017 and May 2018. Result: All the 20 patients underwent total thyroidectomy, central lymph nodes dissection and selective lateral lymph nodes dissection with endoscopic surgery via chest-breast approach. In this study, lymphatic leakage, transient voice hoarseness, internal jugular vein injury and external jugular vein injury were repectively found in one patient, and 4 patients suffered from transient parathyroid hypofunction, without other serious complications.Conclusion: Endoscopic lymph node dissection including levels Ⅱ,Ⅲ and Ⅳ is feasible. It has good cosmetic effect, and haven't serious adverse events.

On the fracture mechanisms of nacre: Effects of structural orientation.

The nacre of mollusk shells is distinguished by an exceptional mechanical efficiency which is derived essentially from its lamellar structure and frequently acts as a source of inspiration for the development of biomimetic materials. The structure and mechanical properties of nacre have been intensively investigated with a special focus on its toughening strategies; nevertheless, the fracture mechanisms, more specifically the critical stress/strain conditions for the failure of nacre, and the effects of structural orientation and hydration state remain largely unexplored. Here uniaxial compression tests were performed on nacre of both dry and hydrated states with different off-axis angles, i.e., the inclination of loading axis with respect to the lamellar structure, ranging from 0° to 90°. The mechanical properties and fracture characteristics of nacre and their dependences on the structural orientation and hydration state were elucidated in terms of mechanics behind failure. Quantitative relationships were established between the mechanical properties and off-axis angle based on different failure criteria. The competition between the fracture modes of fragmentation and shearing was quantified by comparing their respective driving force and resistance on the interfacial plane. This study may aid the understanding on the mechanical behavior of nacre and nacre-inspired synthetic materials and promote a better replication of the underlying design principles of nacre in man-made systems.

Should we pay attention to the aberrant nerve communication between the lingual and mylohyoid nerves?

An unusual communication between the lingual and mylohyoid nerves has been identified as one reason for incomplete mandibular anaesthesia, and for neuropathy. However, its anatomical features and function are poorly understood and its relations with neighbouring structures, which are valuable in reducing the side effects of surgical operations, have not been sufficiently described. The aim of this study, therefore, was to describe the communication between the nerves and to assess the implications for oral and maxillofacial surgery. We explored the communication between the mylohyoid nerves of 62 embalmed, and 16 fresh, hemifaces. The diameter, length of the communication, and other variables were measured, and the junctions with the two nerves microdissected. The nervous communications of fresh specimens and relative nerves were stained histochemically for acetylcholinesterase. Of the 62 embalmed specimens, 19 had a communication that pierced the mylohyoid muscle, and staining showed that this was a sensory nerve. Our results suggest that the sensory communication between the lingual and mylohyoid nerves pierces the mylohyoid muscle and connects these otherwise unrelated nerves, thereby contributing to the likelihood of operative side effects.

A randomised controlled trial of stepwise sputum collection to increase yields of confirmed tuberculosis.

The proportion of bacteriologically confirmed tuberculosis (TB) in China has decreased far below the worldwide average. To investigate whether stepwise measures to ensure sputum quality can improve the rate of bacteriologically confirmed TB. We enrolled 980 adults with suspected TB from three counties in China during 2017 for this multicentre randomised controlled trial. Half the participants (n = 490) were randomly assigned to intervention groups that received instructions by a study nurse, and sputum induction, if necessary. In the remaining 490 patients, sputum samples were collected without observation. The primary outcome was the proportion of patients detected as bacteriologically positive on smear, culture or molecular assays (EasyNAT or Xpert). Bacteriological confirmation rates were significantly higher in the intervention than in the control group: overall (159/490 [32%] vs. 122/490 [25%]; P = 0.009); confirmation using smear (17% vs. 11%; P = 0.010); confirmation using culture (28% vs. 21%; P = 0.021); and confirmation using molecular assays (27% vs. 18%; P = 0.001). Most of the improvement was in patients who received instruction alone, while improvement was greatest in younger patients (adjusted odds ratio 1.27, 95%CI 1.05-1.53 per 10 years). If implemented effectively in resource-limited primary care clinics, our simple stepwise procedure combining instruction and sputum induction could increase the proportion of bacteriologically confirmed TB significantly. .

Bone marrow stromal cells reduce ischemia-induced astrocytic activation in vitro.

Transplantation of bone marrow stromal cells (BMSCs) improves animal neurological functional recovery after stroke. To obtain insight into the mechanisms underlying the therapeutic benefit, we directed our attention to the interaction of BMSCs with astrocytes. Astrocytes become reactive (astrogliosis) after a brain injury, such as stroke. Astrogliosis plays both beneficial and detrimental roles in brain recovery. Previously, we have shown that administration of BMSCs to animals with stroke significantly reduces the thickness of the scar wall formed by reactive astrocytes. We tested the influence of mouse bone marrow stromal cell (mBMSC) on astrogliosis under oxygen-glucose deprivation (OGD)/reoxygenation conditions in vitro, employing an anaerobic chamber. Our data indicate that mBMSCs down-regulate glial fibrillary acidic protein (GFAP) expression in astrocytes after 2 h of OGD and an additional 16 h reoxygenation. mBMSCs protected astrocytes from ischemia, maintaining morphological integrity and proliferation. The IL-6/IL-6R/gp130 pathway is associated with astrogliosis in response to CNS (disorders. Therefore, we examined the effects of mBMSC on the IL-6/IL-6R/gp130 pathway as an underlying mechanism of mBMSC-altered astrogliosis. Furthermore, IL-6 siRNA was used to block IL-6 expression in astrocytes to further investigate IL-6 involvement in mBMSC-altered astrogliosis. Our results indicate that the mBMSC-conferred decline of astrogliosis post-ischemia may derive from the down-regulation of the IL-6/IL-6R/gp130 pathway.

[A comparison of fine needle nonaspiration cytology versus fine needle aspiration for thyroid nodules: a Meta-analysis].

Objective:To evaluate the differences of smear quality and diagnostic accuracy between thyroid nodules and fine needle nonaspiration cytology (FNNAC) and fine needle aspiration cytology (FNAC).Method:Databases were used to search the literature on FNNAC and FNAC. All statistical analyses were performed using Review Manager 5.3 Software.Result:A total of 10 studies were included in the study. Meta-analysis showed no significant difference in FNNAC and FNAC between low, middle and high quality smears. There was no significant difference in diagnostic accuracy.Conclusion:There were no difference in obtaining the smear quality and diagnostic accuracy, the person doing the piercing can freely choose which way according to the habit.

[Diagnostic accuracy and safety of US-guided core needle biopsy versus fine needle aspiration biopsy of thyroid nodules: a Meta analysis].

Objective:To evaluate the efficacy and safety of core needle biopsy (CNB) and fine neon needle aspiration biopsy (FNAB) in the diagnosis of thyroid nodules.Method:The CNKI, Wanfang database, China Biomedical Literature Database (CBM), PubMed, Cochrane Library, EMBASE, Web of Science database (the deadline of February 2017) were used to search the literature on CNB and FNABCNB. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data and evaluated the quality of the literature, and used RevMan 5.3 software for Meta analysis.Result:The accuracy of the CNB group was higher than that of the FNAB group(RR= 1.14, 95%CI: 1.06-1.22, P< 0.01). Meta analysis showed that the accuracy of CNB group compared with FNAB group was statistically significant the difference was statistically significant. There was no significant difference between the two groups (RR= 0.92, 95%CI:0.67-1.25, P> 0.05).Conclusion:CNB is safe and feasible in the diagnosis of thyroid nodules under the condition of mastery of puncture technique.

Anisotropic mechanical behaviors and their structural dependences of crossed-lamellar structure in a bivalve shell.

Crossed-lamellar structure is one of the most common organizations found in mollusk shells and may serve as a natural mimetic model for designing bio-inspired synthetic materials. Nonetheless, the mechanical behaviors and corresponding mechanisms have rarely been investigated for individual macro-layer of such structure. The integrated effects of orientation and hydration also remain unclear. In this study, the mechanical behaviors and their structural dependences of pure crossed-lamellar structure in Saxidomus purpuratus shell were systematically examined by three-point bending and compression tests. Mechanical properties and fracture mechanisms were revealed to depend strongly on the orientation, hydration state and loading condition. Three basic cracking modes of inter-platelet, trans-platelet, and along the interfaces between first-order lamellae were identified, and the interfacial separation was enhanced by hydration. Macroscopic compressive fracture was accomplished through axial splitting during which multiple toughening mechanisms were activated. The competition among different cracking modes was quantitatively evaluated by analyzing their driving stresses and resistances from fundamental mechanics. This study helps to clarify the mechanical behaviors of naturally occurring crossed-lamellar structure, and accordingly, aids in designing new bio-inspired synthetic materials by mimicking it.

Generalized energy failure criterion.

Discovering a generalized criterion that can predict the mechanical failure of various different structural materials is one of ultimate goals for scientists in both material and mechanics communities. Since the first study on the failure criterion of materials by Galileo, about three centuries have passed. Now we eventually find the "generalized energy criterion", as presented here, which appears to be one universal law for various different kinds of materials. The validity of the energy criterion for quantitatively predicting the failure is experimentally confirmed using a metallic glass. The generalized energy criterion reveals the competition and interaction between shear and cleavage, the two fundamental inherent failure mechanisms, and thus provides new physical insights into the failure prediction of materials and structural components.

Notch fatigue behavior: Metallic glass versus ultra-high strength steel.

Studying the effect of notch on the fatigue behavior of structural materials is of significance for the reliability and safety designing of engineering structural components. In this work, we conducted notch fatigue experiments of two high-strength materials, i.e. a Ti32.8Zr30.2Ni5.3Cu9Be22.7 metallic glass (MG) and a 00Ni18Co15Mo8Ti ultra-high strength steel (CM400 UHSS), and compared their notch fatigue behavior. Experimental results showed that although both the strength and plasticity of the MG were much lower than those of the UHSS, the fatigue endurance limit of the notched MG approached to that of the notched UHSS, and the fatigue ratio of the notched MG was even higher. This interesting finding can be attributed to the unique shear banding mechanism of MG. It was found that during fatigue process abundant shear bands formed ahead of the notch root and in the vicinity of the crack in the notched MG, while limited plastic deformation was observed in the notched UHSS. The present results may improve the understanding on the fatigue mechanisms of high-strength materials and offer new strategies for structural design and engineering application of MG components with geometrical discontinuities.

Phase I clinical trial of melphalan and 41.8 degrees C whole-body hyperthermia in cancer patients.

PURPOSE: To evaluate the biologic interactions and toxicities of melphalan (L-PAM) combined with 41.8 degrees C whole-body hyperthermia (WBH) for 60 minutes. PATIENTS AND METHODS: Sixteen patients with refractory cancer were treated (May 1992 to May 1995) with WBH alone during week 1) thereafter patients were randomized to receive either L-PAM alone on week 2 and L-PAM plus WBH on week 5, or the reverse sequence. Patients who demonstrated clinical improvement received WBH plus L-PAM monthly. Dose levels of L-PAM were 10 mg/m2 (n = 3), 15 mg/m2 (n = 3), 17.5 mg/m2 (n = 6), and 20 mg/m2 (n = 4). L-PAM was administered at target temperature; WBH was administered with an Aquatherm radiant-heat device (patent pending; Cancer Research Institute, New York, NY). RESULTS: Comparisons of mean WBC count and platelet nadirs for L-PAM alone and L-PAM plus WBH demonstrated that the addition of WBH resulted in nadir counts that were, on average, 25% lower. There were no instances of febrile neutropenia or bleeding. Toxicities allowed for escalation of L-PAM to 20 mg/m2; all four patients at this level experienced grade 4 myelosuppression. No significant myelosuppression was observed at 10 and 15 mg/m2. Grade 3 myelosuppression was observed in two of six patients at 17.5 mg/m2. Responses included complete remission (CR) of pancreatic cancer (10 mg/m2), partial remission (PR) of malignant melanoma in two patients (20 mg/m2), and transient clinical and/or serologic improvement in five patients. The pharmacokinetics of L-PAM were not altered by WBH. Observed cytokine induction by WBH is also discussed in detail. CONCLUSION: We conclude that L-PAM with 41.8 degrees C WBH is well tolerated. Clinical results are consistent with preclinical predictions and provide a foundation for second-generation trials now in progress.

Stepwise work hardening induced by individual grain boundary in Cu bicrystal micropillars.

Vast experiments have demonstrated that the external specimen size makes a large difference in the deformation behavior of crystalline materials. However, as one important kind of internal planar defects, the role of grain boundary (GB) in small scales needs to be clarified in light of the scarce and inconsistent experimental results at present. Through compression of Cu bicrystal and its counterpart monocrystal micropillars, it is found that, in contrast to the monocrystals, the bicrystals are characterized by work hardening with discrete strain bursts. Interestingly, the stress rise between two adjacent strain bursts of the bicrystals increases with the decrease of specimen size. The results suggest that GBs play a critical role in the work hardening of materials in small scales, which may provide important implications to further understand the general work hardening behaviors of materials in the future.