[The efficacy and safety profile of ixazomib/lenalidomide/dexamethasone in relapsed/refractory multiple myeloma: a multicenter real-world study in China].

Objective: To evaluate the efficacy and safety profile of ixazomib/lenalidomide/dexamethasone (IRd) in Chinese patients with relapsed/refractory multiple myeloma (MM) . Methods: This study comprising 14 medical centers in China included patients with relapsed/refractory MM who received at least. Ixazomib at an initial oral dose of 4 mg was administered. Seven patients had dose adjustment to 3 mg at the time of first dose. The lenalidomide doses were adjusted according to creatinine clearance rate. The efficacy and safety were evaluated every cycle. Results: In the study cohort of 74 patients, the median age was 65 years and 11 (14.9% ) patients received over three lines of therapy. Overall response rate (ORR) was 54.1% (40/74) , and 7 (9.5% ) , 14 (18.9% ) , and 19 (25.7% ) patients achieved stringent complete response or complete response, very good partial response, and partial response, respectively. The median progression-free survival and overall survival were 9.9 and 20 months, respectively. The median time to response was 1 month. The efficacy and survival outcome were similar to those reported in the Tourmaline-MM1 China Continuous Study. The ORR of patients refractory to bortezomib, lenalidomide, and bortezomib plus lenalidomide were 52.0% (13/25) , 57.1% (4/7) , and 33.3% (6/18) , respectively. The rate of grade 3-4 adverse events was 36.5% (27/74) . Common hematological toxicities were anemia, thrombocytopenia, lymphopenia, and neutropenia. Common non-hematological toxicities were fatigue, gastrointestinal symptoms, and infections. Two cases of grade 3 peripheral neuropathy were reported. The patients eligible for the Tourmaline-MM1 China Continuous Study had a higher ORR than the ineligible patients [77.8% (14/18) vs 46.4% (26/56) , P=0.020]. There was no difference in the rate of grade 3-4 adverse events [33.3% (6/18) vs 37.5% (21/56) , P=0.749]. Conclusion: The IRd regimen had good efficacy and acceptable toxicity in Chinese patients with relapsed/refractory MM.

[Surgery treatment and prognosis analysis of 129 small cell carcinoma of the esophagogastric junction].

Objective: To analysis the prognosis related factors of patients with small cell cancer of the esophagogastric junction treated by surgery. Methods: The clinicopathologic data of 129 patients with small cell cancer of the esophagogastric junction underwent surgery treatment in the Fourth Hospital of Hebei Medical University from January 2004 to December 2010 were retrospectively analyzed. Univariate survival survival was performed by Kaplan-Meier method and Log rank test. Multivariate survival was analyzed by using Cox proportional hazard model. Results: Radical surgery was performed in 123 patients, whereas other 6 cases were conducted palliative operation. The 5-year overall survival (OS) rate of this cohort was 21.0% and median survival time was 25.7 months. The 5-year progression free survival (PFS) rate of this cohort was 11.0% and median PFS time was 19.1 months. The univariate analysis result showed that operation manner, radical or not, tumor length, lymph node metastasis, TNM stage, intravascular cancer embolus surgical margin positive or not, the expression of Syn, comprehensive treatment and radiochemotherapy after progression were associated with the OS of these patients (P<0.05). Multivariate analysis result showed that lymph node metastasis, radiochemotherapy after progression were independent risk factors of OS (P<0.05). Univariate analysis result showed that operation manner, radical or not, tumor length, TNM stage, lymph node metastasis, intravascular cancer embolus, surgical margin positive or not, the expression of Syn, comprehensive treatment and radiochemotherapy after progression were associated with PFS (P<0.05). Multivariate analysis showed that lymph node metastasis and radiochemotherapy after progression were independent risk factors of PFS (P<0.05). Conclusions: The prognosis of small cell cancer of the esophagogastric junction patients remains poor. Lymph node metastasis and radiochemotherapy after progression are regarded as independent prognostic factors of these patients.

Identification of peroxiredoxin 6 as a potential lung-adenocarcinoma biomarker for predicting chemotherapy response by proteomic analysis.

The prognosis of lung cancer remains poor due to the limited biomarker selection for treating patients with optimal chemotherapy. The aim of this study is to discover and identify new biomarkers with the value of predicting chemotherapy responses in a lung adenocarcinoma (AD) specimen. In this study, six pairs of pre-treatment fresh primary lung AD-cancer tumors with varied chemotherapy responses were used to discover new biomarkers by two-dimensional difference gel electrophoresis (2D DIGE). Among the matched protein spots, 19 were up-regulated and 18 were down-regulated in chemo-sensitive tumors versus chemo-resistant tissues. These differentially expressed proteins could be divided into five classes: redox regulation protein, the cytoskeletal protein, cell metabolism enzymes or proteins, apoptosis, signal transduction mediated molecules, and other functional proteins. Proteins of interest, including PRDX2, PRDX6, and Gelsolin, were differentially expressed in chemo-sensitive tumors versus chemo-resistant tissues and these observations were validated by immunohistochemistry in 92 formalin-fixed and paraffin-embedded (FFPE) specimens. Our results demonstrated that PRDX6 protein expression was closely related to tumor response (cc2 = 5.57, P < 0.05), whereas no relationship of PRDX2 and Gelsolin were obtained with tumor response (cc2 = 0.51 P > 0.05, cc2 = 0.41 P > 0.05). This tissue proteomics study provides evidence that PRDX6 may be regarded as a predictive biomarker for poor chemotherapy response, which can be helpful in guiding pretreatment protocols.

Key aroma compounds identified in Cheddar cheese with different ripening times by aroma extract dilution analysis, odor activity value, aroma recombination, and omission.

To determine the odor-active compounds in Cheddar cheeses with different ripening times (6, 10, and 14 mo), 39 potent odorants of Cheddar cheeses were identified with a flavor dilution factor range between 1 and 512 by aroma extract dilution analysis. To further determine their contribution to the overall aroma profile of Cheddar cheeses, odor activity values of 38 odorants with flavor dilution factors ≥1 were calculated. A Cheddar cheese matrix was developed to determine the concentrations and the odor thresholds of these key aroma compounds. The result of the aroma recombinant experiment prepared by mixing the key aroma compounds in the concentrations in which they occurred in Cheddar cheeses showed that the overall aroma profile of the recombinant sample was very similar to that of Cheddar cheese. The main different compounds in Cheddar cheese with different ripening time were acetic acid, butanoic acid, dimethyl trisulfide, methional, hexanal, (E)-2-nonenal, acetoin, 1-octen-3-one, δ-dodecalactone, furaneol, hexanoic acid, heptanal, and ethyl caproate. This study could provide important information for researching and developing Cheddar cheese-related products.

[Expanding the pandemic influenza preparedness framework to the epidemic of COVID-19].

On March 11, 2020, WHO officially declared that COVID-19 had become Pandemic. As of March 31, the epidemic had affected more than 178 countries and regions, with more than 780 000 confirmed cases. The Pandemic Influenza Preparedness Framework for the sharing of influenza viruses and access to vaccines and other benefits (the 'PIP Framework' or 'Framework') is an international arrangement adopted by the World Health Organization in May 2011 to improve global pandemic influenza preparedness and response. Since the transmission route and transmission capacity of COVID-19 are similar to that of influenza A (H1N1) in 2009, which conforms to the basic elements of "human pandemic", and the epidemic scale has exceeded that of influenza A (H1N1)， it is probable to incorporate COVID-19 epidemic response into PIPF, and at the same time to verify and improve PIPF in practice. It is recommended that WHO, other international organizations and relevant countries make full use of the PIPF system to respond to the epidemic and better coordinate national actions at the global level. At the same time, China should also make the planning and deploy of domestic epidemic prevention and control and international epidemic cooperation under the framework.

[Impact of KIT D816 mutation on salvage therapy in relapsed acute myeloid leukemia with t(8;21) translocation].

Objective: To evaluate the impact of KIT D816 mutation on the salvage therapy in relapsed acute myeloid leukemia (AML) with t(8;21) translocation. Method: The characteristics of the first relapsed AML with t(8;21) translocation from 10 hospitals were retrospectively collected, complete remission (CR(2)) rate after one course salvage chemotherapy and the relationship between KIT mutation and CR(2) rate was analyzed. Results: 68 cases were enrolled in this study, and 30 cases (44.1%) achieved CR(2). All patients received KIT mutation detection, and KIT D816 mutation was identified in 26 cases. The KIT D816 positive group had significantly lower CR(2) compared with non-KIT D816 group (23.1% vs 57.1%, χ(2)=7.559, P=0.006), and patients with longer CR(1) duration achieved significantly higher CR(2) than those with CR(1) duration less than 12 months (74.1% vs 31.9%, χ(2)=9.192, P=0.002). KIT D816 mutation was tightly related to shorter CR(1) duration. No significant difference of 2 years post relapse survival was observed between KIT D816 mutation and non-KIT D816 mutation group. Conclusion: KIT D816 mutation at diagnosis was an adverse factor on the salvage therapy in relapsed AML with t(8;21) translocation, significantly related to shorter CR1 duration, and can be used for prediction of salvage therapy response. KIT D816 mutation could guide the decision-making of salvage therapy in relapsed AML with t(8;21) translocation.

Rapid host strain improvement by in vivo rearrangement of a synthetic yeast chromosome.

Synthetic biology tools, such as modular parts and combinatorial DNA assembly, are routinely used to optimise the productivity of heterologous metabolic pathways for biosynthesis or substrate utilisation, yet it is well established that host strain background is just as important for determining productivity. Here we report that in vivo combinatorial genomic rearrangement of Saccharomyces cerevisiae yeast with a synthetic chromosome V can rapidly generate new, improved host strains with genetic backgrounds favourable to diverse heterologous pathways, including those for violacein and penicillin biosynthesis and for xylose utilisation. We show how the modular rearrangement of synthetic chromosomes by SCRaMbLE can be easily determined using long-read nanopore sequencing and we explore experimental conditions that optimise diversification and screening. This synthetic genome approach to metabolic engineering provides productivity improvements in a fast, simple and accessible way, making it a valuable addition to existing strain improvement techniques.

Association between IRAK1 rs3027898 and miRNA-499 rs3746444 polymorphisms and rheumatoid arthritis : A case control study and meta-analysis.

BACKGROUND: The IRAK1 and miR-499 polymorphisms play an important role in the etiology of rheumatoid arthritis (RA). Several studies have been carried out to estimate the association between IRAK1 rs3027898 and miR-499 rs3746444 and RA risk; however, the results were inconsistent. AIM: A case control study was carried out to explore the association between IRAK1 rs3027898 and miR-499 rs3746444 and the RA risk in a Chinese population. Meta-analyses combining present with previous studies were conducted to further explore the association. MATERIAL AND METHODS: A total of 386 RA patients were enrolled along with 576 matched healthy controls. Genotyping was performed by using TaqMan genotyping assays on Fluidigm 192.24 system. For the meta-analysis, a systematic literature search was conducted to identify all relevant studies. RESULTS: This case control study showed that the IRAK1 rs3027898 C allele was associated with increased risk of RA with an odds ratio (OR) = 1.4 and 95 % confidence intervals (CI) = 1.093-1.793, P = 0.008 but miR-499 rs3746444 polymorphisms were not significantly associated with the risk for RA. The meta-analyses included a total of 4 case control studies on IRAK1 rs3027898 and 4 studies on miR-499 rs3746444. The IRAK1 rs3027898 C allele had an overall OR of 1.268 (95 % CI = 1.130-1.424, P < 0.001). After stratification by ethnicity the C allele had an OR of 1.238 (95 % CI = 1.096-1.398, P = 0.001) in Asians. No association between miR-499 rs3746444 polymorphism and RA was found in the overall and Asian populations. CONCLUSION: The results from our case control study and the meta-analyses indicate that the IRAK1 rs3027898 C allele is significantly associated with an increased risk of RA, especially in Asians.

A bibliometric study of literature on SLE research in PubMed (2002-2011).

OBJECTIVE: The objective of this paper is to study the distribution regularity, development tendency and research hot spots of systemic lupus erythematosus (SLE) literature published in journals indexed in PubMed over a 10-year period using the bibliometric analysis method. METHODS: Citations from 2002 to 2011 were downloaded from the PubMed database. The core of the search was the Medical Subject Headings (MeSH) "Lupus Erythematosus, Systemic." The period of study was set from 2002 to 2011. RESULTS: A total of 14,053 articles were retrieved. These articles were published in 1627 different journals, nine journals contributing to one-third of all the literature. The first three journals containing the most articles were CONCLUSION: SLE has become a field of interest over the period 2002 to 2011. However, lupus research publications in developing countries have lagged behind.

Local characteristics of cross-unit contamination around high-rise building due to wind effect: mean concentration and infection risk assessment.

In this present work, the characteristics of hazardous gas dispersion and possible cross-unit contamination around a complex-shaped high-rise residential building due to wind effect are thoroughly studied using physical modeling method. Experiments were performed in a boundary layer wind tunnel for a 1:30 scale model that represented a 10-story residential building in prototype. Tracer gas, simulating exhausted room air, was continuously released from different floor levels, and its concentrations on the adjacent envelope surfaces were measured using fast flame ionization detectors. The mean concentration fields were reported and analyzed under different configurations during the experiment to consider the effects on pollutant dispersion behavior due to changes in source position and approaching wind condition, with the main emphasis on the differences between open-window and closed-window conditions. In particular, the measured concentration fields were further examined from a practical point of view, with respect to hazard assessment. Understanding these hazardous plume dispersion features is useful for employing effective intervention strategies in modern residential building environment in case of hazardous substance release. The study on this physical process is not only helpful to reduce the hazardous effect of routine release of harmful pollutant near the building, but also useful for the purpose of prevention and control of accidental infectious diseases outbreak.

Increased expression of paxillin is found in human oesophageal squamous cell carcinoma: a tissue microarray study.

Oesophageal cancer is one of the most common cancers worldwide. Currently, the tumour, node, metastasis (TNM) staging system is the primary method for determining its extent and prognosis, however, data suggest this system does not predict prognosis accurately. Research has, therefore, concentrated on searching for specific biomarkers. Paxillin has been shown to play an important role in controlling cell spread and migration. Its over-expression is considered to correlate with the prognosis of some types of cancers, however, the relationship between paxillin expression and clinical outcome in oesophageal cancer has not been investigated. This study determined the expression of paxillin by immunohistochemistry on the tissue microarray of 100 oesophageal squamous cell cancer patients followed up for a mean of 55 months. Paxillin was over-expressed in tumours in 27/100 cases, compared with 6/100 cases for adjacent non-tumoural cells. No correlation occurred between expression of paxillin and overall patient survival, hence paxillin is not an effective prognostic marker in these patients.

Establishment of stable HeLa cell lines expressing enzymatically active hepatitis C virus RNA polymerase.

The hepatitis C virus RNA polymerase (NS5B) is strictly required for viral replication and thus represents an attractive target for antiviral drug development. In this study, stable HeLa cell lines with an integrated NS5B gene were selected by G418 and then confirmed by genome PCR. Subsequently, transcription and expression of the integrated NS5B genes were demonstrated by RT-PCR and Western blot analysis. Further analysis demonstrated enzymatic activity of the expressed NS5B polymerase. The stable HeLa cell lines should be useful for the identification of NS5B inhibitors and for studying the mechanisms of HCV replication.

[The measurement of IAA oxidase in "ping guo li" leaves].

IAA oxidase activity during the fruit bud differentiation of "Ping Guo Li" in leaves measured by UV-Vis method was studied. The method is less sample, simple operation and high sensitivity. The test of recovery and repetition shows that both the precision and accuracy accord with the demands.

[Development and application of the facial soft tissue 3D measuring system].

OBJECTIVE: To combine measurement and image technology as an objective means to help prosthodontists provide better service. METHODS: The system was developed by consisting of two CCD cameras, real time hardware for the recognition of markers and software for the 3D reconstruction. RESULTS: It allowed efficient, direct and noninvasive calculation of the 3D liner and angular measurements of the human face. CONCLUSION: This system is a useful way to get 3D information of the human face. It will be a good supplement to the classic cephalometric analyses.

[Clinico-pathologic study of 285 cases of ectopic pregnancy in intrauterine devices-users and non-intrauterine devices-users].

Two hundred eighty five cases of ectopic pregnancy in Beijing area from Jan. 1 to Dec. 31 1990 including 150 cases of intrauterine devices (IUD) and 135 cases of non-IUD users were studied. Clinico-pathological observation included the history of pelvic inflammatory disease, the site of ectopic pregnancy, the classification of previous tubal inflammation of the ectopic side and other pathologic lesions, the side of the corpus luteum of pregnancy and histology of endometrium, etc. Besides, using stereologic technique the cilia length and cilia density of endosalpinx were studied in 50 cases through image analysis system. Results showed that except for a significant higher frequency of ovarian pregnancy in IUD-users, there was no significant differences between the 2 groups. It indicated that the degree of injury of fallopian tubes and the factors causing the damage were similar in both groups. The authors concluded that IUD does not increase the risk of fallopian tube lesions.

[Balloon dilatation for prostatic obstruction].

Balloon catheter dilatation of the prostate (BCDP) was performed in 25 patients with prostatic hypertrophy. All patients suffered from dysuria or urinary retention. Follow-up for 8-14 months showed that 20 patients had satisfactory results. The balloon catheter of 25 mm x 50 mm was inflated at 4-6 atm for 10-15 minutes. BCDP was modified for the use in the local hospitals.

[The stereological study on normal and intrauterine growth retardation (IUGR) placentas].

The stereological study was carried out in 8 normal and 22 IUGR placentas through Image Analysis System of Cambridge Instruments Quantimet 970 and 10 indices were analysed. The results showed that in the IUGR group the placental indices of total surface area of acroteric villus, total volume of intervillous space, volume density of fetal capillaries, total volume of fetal capillaries and surface area density of vasculo-syncytial membrane were significantly reduced than those in the normal group. The vasculo-syncytial membrane became significantly thick in the IUGR placental group. It was confirmed that a close relation exists between IUGR and placental quantitative changes. The major pathological findings of the placenta were prematuration and hypoplasia.

[Scanning electron microscopic observations on Clonorchis sinensis cercariae].

The surface structure of Clonorchis sinensis cercariae was observed under scanning electron microscope. The cercaria was of the parapleuro-lophocercous type. The measurements of the cercariae were as follows: body 137-240 x 62-90 microns, tail 320-470 x 21-34 microns, oral sucker 27-46 x 23-33 microns. The ventral sucker was incompletely developed and much smaller than the oral one. The whole body surface was covered with backward pointing spines. Four horizontal rows of oral spines were found around the mouth opening of the oral sucker. These spines diminished in size with the distance of the rows from the opening and their numbers were 12, 18, 19 and 18 respectively. Transverse and longitudinal plicae formed from tegument were found on the surface of the tail, being in connection with dorsal and ventral fins along posterior half of the tail. Many sensory structures or papillae were observed on the body. They were of three different types: 1) papillae with long or short cilia distributed widely on the body surface and around the mouth opening, the number of papillae with cilia on the body surface being greater than that described by Komiya et al (1940); 2) a few sensory fossa on the tail, measuring 1.0 x 0.6 microns; 3) a few ring-type papillae with knob on the body surface with pore of 0.5 micron in diameter.