Synthesis of indano[60]fullerene thioketone and its application in organic solar cells.

Evaporable indano[60]fullerene ketone (FIDO) was converted to indano[60]fullerene thioketone (FIDS) in high yield by using Lawesson's reagent. Three compounds with different substituents in para position were successfully converted to the corresponding thioketones, showing that the reaction tolerates compounds with electron-donating and electron-withdrawing substituents. Computational studies with density functional theory revealed the unique vibrations of the thioketone group in FIDS. The molecular structure of FIDS was confirmed by single-crystal X-ray analysis. Bulk heterojunction organic solar cells using three evaporable fullerene derivatives (FIDO, FIDS, C60) as electron-acceptors were compared, and the open-circuit voltage with FIDS was 0.16 V higher than that with C60.

An injectable collagen peptide-based hydrogel with desirable antibacterial, self-healing and wound-healing properties based on multiple-dynamic crosslinking.

Conventional collagen-based hydrogels as wound dressing materials are usually lack of antibacterial activity and easily broken when encountering external forces. In this work, we developed a collagen peptide-based hydrogel as a wound dressing, which was composed of adipic acid dihydrazide functionalized collagen peptide (Col-ADH), oxidized dextran (ODex), polyvinyl alcohol (PVA) and borax via multiple-dynamic reversible bonds (acylhydrazone, amine, borate ester and hydrogen bonds). The injectable hydrogel exhibited satisfactory self-healing ability, antibacterial activity, mechanical strength, as well as good biocompatibility and biodegradability. In vivo experiments demonstrated the rapid hemostasis, accelerated cell migration, and promoted wound healing capacities of the hydrogel. These results indicate that the multifunctional collagen peptide-based hydrogel has great potentials in the field of wound dressings.

Exploration of potential biomarkers and therapeutic targets for trauma-related acute kidney injury.

PURPOSE: Acute kidney injury (AKI) is one of the most common functional injuries observed in trauma patients. However, certain trauma medications may exacerbate renal injury. Therefore, the early detection of trauma-related AKI holds paramount importance in improving trauma prognosis. METHODS: Qualified datasets were selected from public databases, and common differentially expressed genes related to trauma-induced AKI and hub genes were identified through enrichment analysis and the establishment of protein-protein interaction (PPI) networks. Additionally, the specificity of these hub genes was investigated using the sepsis dataset and conducted a comprehensive literature review to assess their plausibility. The raw data from both datasets were downloaded using R software (version 4.2.1) and processed with the "affy" package19 for correction and normalization. RESULTS: Our analysis revealed 585 upregulated and 629 downregulated differentially expressed genes in the AKI dataset, along with 586 upregulated and 948 downregulated differentially expressed genes in the trauma dataset. Concurrently, the establishment of the PPI network and subsequent topological analysis highlighted key hub genes, including CD44, CD163, TIMP metallopeptidase inhibitor 1, cytochrome b-245 beta chain, versican, membrane spanning 4-domains A4A, mitogen-activated protein kinase 14, and early growth response 1. Notably, their receiver operating characteristic curves displayed areas exceeding 75%, indicating good diagnostic performance. Moreover, our findings postulated a unique molecular mechanism underlying trauma-related AKI. CONCLUSION: This study presents an alternative strategy for the early diagnosis and treatment of trauma-related AKI, based on the identification of potential biomarkers and therapeutic targets. Additionally, this study provides theoretical references for elucidating the mechanisms of trauma-related AKI.

Evaporable Fullerene Indanones with Controlled Amorphous Morphology as Electron Transport Layers for Inverted Perovskite Solar Cells.

Fullerenes are among the most commonly used electron-transporting materials (ETMs) in inverted perovskite solar cells (IPSCs). Although versatile functionalized fullerene derivatives have shown excellent performance in IPSCs, pristine [60]fullerene (C60) is still the most widely used in devices mainly because of its uniform morphology by thermal deposition. However, thermally evaporable fullerene derivatives have not yet been achieved. Herein, we developed a series of evaporable fullerene derivatives, referred to as fullerene indanones (FIDOs), affording IPSCs with high power conversion efficiency (PCE) and long-term storage stability. The FIDOs were designed with a unique architecture in which the fullerene moiety and a benzene ring moiety are linked via a five-membered carbon ring in benzene ring plane. This molecular arrangement affords exceptional thermal stability, allowing the FIDOs to withstand harsh thermal deposition conditions. Moreover, by manipulating the steric bulk of the functional groups, we could control the state of the organic film from crystalline to amorphous. Subsequently, we used FIDOs as an electron transport layer (ETL) in IPSCs. Thanks to the suitable energy level and dual-passivation effect of FIDOs compared with a reference ETL using C60, the device using FIDOs achieved an open-circuit voltage of 1.16 V and a fill factor of 0.77. As a result, the PCE reached 22.11%, which is superior to 20.45% of the best-performing reference device. Most importantly, the FIDO-based IPSC devices exhibited exceptional stability in comparison to the reference device due to the stability of the amorphous ETL films.

Ratio fluorescence test strip visualized by amino-functionalized metal-organic framework for rapid sensing of glyphosate.

As glyphosate is a broad-spectrum herbicide extensively used in agriculture worldwide, rapid glyphosate detection is essential for food safety and human health. Herein, a ratio fluorescence test strip was prepared and coupled with an amino-functionalized bismuth-based metal-organic framework (NH2-Bi-MOF) that bonded with copper ion for rapid visualization and determination of glyphosate. NH2-Bi-MOF had excellent fluorescence performance, and the copper ion, a Lewis acid, was selected as the quencher. The strong chelation of glyphosate with copper ion and its quick interaction with NH2-Bi-MOF would turn on the fluorescence signal, thus enabling the quantitative sensing of glyphosate, with a linear range of 0.10-200 µmol L-1, and recoveries between 94.8% and 113.5%. The system was then expanded to a ratio fluorescence test strip, in which the fluorescent ring sticker was set as a binding-in self-calibration to reduce errors from the angle and light dependency. The method realized the visual semi-quantitation referring to a standard card, as well as the ratio quantitation using the gray value output with LOD of 0.82 µmol L-1. And the as-developed test strip was accessible, portable, and reliable, thus offering a platform for the rapid on-site detection of glyphosate and other residual pesticides.

The collaborative monitored natural attenuation (CMNA) of soil and groundwater pollution in large petrochemical enterprises: A case study.

A large in-service petrochemical enterprises in Northeast China was taken as the research object, and the Collaborative Monitored Natural Attenuation (CMNA) for soil and groundwater pollution was carried out to remedy combined pollution and reduce environmental risks. The pollutants distributions were obtained based on detailed regional investigation (Mar. 2019), and feature pollutants in soil and groundwater were then screened. The spatiotemporal variations of feature pollutants and relative microbial responses were explored during the CMNA process. Furthermore, the CMNA efficiency of the contaminated site at initial stage was evaluated by calculation of natural attenuation rate constant. The results showed that the feature pollutants in soil were 2,2',5,5'-tetrachlorobiphenyl (2,2',5,5'-TCB) and petroleum hydrocarbons (C10∼C40), and the feature pollutant in groundwater was 1,2-dichloroethane (1,2-DCA). The concentrations of all feature pollutants decreased continuously during four years of monitoring. Feature pollutants played a dominant role in the variability of microbial species both in soil and groundwater, increasing the relative abundance of petroleum tolerant/biodegradation bacteria, such as Actinobacteria, Proteobacteria and Acidobacteriota. The average natural attenuation rate constant of 2,2',5,5'-TCB and C10∼C40 in soil was 0.0012 d-1 and 0.0010 d-1, respectively, meeting the screening value after four years' attenuation. The average natural attenuation rate constant of 1,2-DCA was 0.0004 d-1, which need strengthening measures to improve the attenuation efficiency.

SNAL: sensitive non-associative learning network configuration for the automatic driving strategy.

Nowadays, there is a huge gap between autonomous vehicles and mankind in terms of the decision response against some dangerous scenarios, which would has stressed the potential users out and even made them nervous. To efficiently identify the possible sensitivity scenarios, a new neural network configuration, named sensitive non-associative learning network (SNAL), is proposed. In such structure, the modulated interneurons, excited by abnormal scene stimulation for scene processing, are well processed and utilized to improve the training structure which refers to the sensitization mechanism in non-associative learning in neurobiology and the neural structure of Aplysia. When encountering the sensitivity scenes that the automatic driving agent is not good at or has not seen, the modulated interneuron facilitates the full connection layer neurons for the decision-making process, so as to change the final automatic driving strategy. In the process of constructing the model, a method to measure the similarity of the convolution feature map is proposed, which provides a new investigation tool for the properties of convolution networks after the feature extraction. Based on the Morris-Lecar equation in neurobiology, the dynamic model of modulating interneurons in the network is constructed. The automatic control optimization of the model is carried out by imitating the biological properties. The optimization method provides a reference for introducing neurobiological mechanism into deep learning and automatic control. To validate the effectiveness of the proposed method, the simulation test are executed and the existing methods are compared accordingly. The results show that the proposed SNAL algorithm can effectively recognize the sensitivity mechanism. Furthermore, compared with the existing algorithms, such as CNN, LSTM, ViT, the proposed algorithm can make better defensive strategies for potentially dangerous scenes rarely seen or not seen in the training stage. This sensitivity mechanism is more in line with the human driving intuition when dealing with abnormal driving scenes, and makes the decision more interpretable, significantly improving the traffic ability of autonomous vehicles under the sensitive scenes. In addition, this configuration can be easily combined with the existing mainstream neural network models and has good expansibility.

The Emerging Role of Ferroptosis in Liver Diseases.

Ferroptosis is a newly discovered type of cell death mediated by iron-dependent lipid peroxide. The disturbance of iron metabolism, imbalance of the amino acid antioxidant system, and lipid peroxide accumulation are considered distinct fingerprints of ferroptosis. The dysregulation of ferroptosis has been intensively studied in recent years due to its participation in various diseases, including cancer, kidney injury, and neurodegenerative diseases. Notably, increasing evidence indicates that ferroptosis plays different roles in a wide spectrum of liver diseases. On the one hand, inhibiting ferroptosis may counteract the pathophysiological progression of several liver diseases, such as alcoholic liver injury, nonalcoholic steatosis hepatitis and fibrosis. On the other hand, inducing ferroptosis may restrict the emergence of secondary resistance to current medicines, such as sorafenib, for hepatocellular carcinoma (HCC) therapy. Here, we summarize the biological characteristics and regulatory signalling pathways of ferroptosis involved in liver disease. The current available medical agents targeting ferroptosis, including inducers or inhibitors applied in liver diseases, are also reviewed. This work aims to provide new insight into the emerging role of pathogenesis and therapeutic approaches for liver diseases.

Prediction of fatal adverse prognosis in patients with fever-related diseases based on machine learning: A retrospective study.

BACKGROUND: Fever is the most common chief complaint of emergency patients. Early identification of patients at an increasing risk of death may avert adverse outcomes. The aim of this study was to establish an early prediction model of fatal adverse prognosis of fever patients by extracting key indicators using big data technology. METHODS: A retrospective study of patients' data was conducted using the Emergency Rescue Database of Chinese People's Liberation Army General Hospital. Patients were divided into the fatal adverse prognosis group and the good prognosis group. The commonly used clinical indicators were compared. Recursive feature elimination (RFE) method was used to determine the optimal number of the included variables. In the training model, logistic regression, random forest, adaboost and bagging were selected. We also collected the emergency room data from December 2018 to December 2019 with the same inclusion and exclusion criterion. The performance of the model was evaluated by accuracy, F1-score, precision, sensitivity and the areas under receiver operator characteristic curves (ROC-AUC). RESULTS: The accuracy of logistic regression, decision tree, adaboost and bagging was 0.951, 0.928, 0.924, and 0.924, F1-scores were 0.938, 0.933, 0.930, and 0.930, the precision was 0.943, 0.938, 0.937, and 0.937, ROC-AUC were 0.808, 0.738, 0.736, and 0.885, respectively. ROC-AUC of ten-fold cross-validation in logistic and bagging models were 0.80 and 0.87, respectively. The top six coefficients and odds ratio (OR) values of the variables in the Logistic regression were cardiac troponin T (CTnT) (coefficient=0.346, OR = 1.413), temperature (T) (coefficient=0.235, OR = 1.265), respiratory rate (RR) (coefficient= -0.206,OR = 0.814), serum kalium (K) (coefficient=0.137, OR = 1.146), pulse oxygen saturation (SPO2) (coefficient= -0.101, OR = 0.904), and albumin (ALB) (coefficient= -0.043, OR = 0.958). The weights of the top six variables in the bagging model were: CTnT, RR, lactate dehydrogenase, serum amylase, heartrate, and systolic blood pressure. CONCLUSIONS: The main clinical indicators of concern included CTnT, RR, SPO2, T, ALB and K. The bagging model and logistic regression model had better diagnostic performance comprehesively. Those may be conducive to the early identification of critical patients with fever by physicians.

High-speed and Large-scale Privacy Amplification Scheme for Quantum Key Distribution.

State-of-art quantum key distribution (QKD) systems are performed with several GHz pulse rates, meanwhile privacy amplification (PA) with large scale inputs has to be performed to generate the final secure keys with quantified security. In this paper, we propose a fast Fourier transform (FFT) enhanced high-speed and large-scale (HiLS) PA scheme on commercial CPU platform without increasing dedicated computational devices. The long input weak secure key is divided into many blocks and the random seed for constructing Toeplitz matrix is shuffled to multiple sub-sequences respectively, then PA procedures are parallel implemented for all sub-key blocks with correlated sub-sequences, afterwards, the outcomes are merged as the final secure key. When the input scale is 128 Mb, our proposed HiLS PA scheme reaches 71.16 Mbps, 54.08 Mbps and 39.15 Mbps with the compression ratio equals to 0.125, 0.25 and 0.375 respectively, resulting achievable secure key generation rates close to the asymptotic limit. HiLS PA scheme can be applied to 10 GHz QKD systems with even larger input scales and the evaluated throughput is around 32.49 Mbps with the compression ratio equals to 0.125 and the input scale of 1 Gb, which is ten times larger than the previous works for QKD systems. Furthermore, with the limited computational resources, the achieved throughput of HiLS PA scheme is 0.44 Mbps with the compression ratio equals to 0.125, when the input scale equals up to 128 Gb. In theory, the PA of the randomness extraction in quantum random number generation (QRNG) is same as the PA procedure in QKD, and our work can also be efficiently performed in high-speed QRNG.

[Correlation of IgG Levels at Initial Diagnosis with Clinical Efficacy and Prognosis in 66 Patients with IgG Multiple Myeloma].

OBJECTIVE: To explore the IgG levels of newly diagnosed IgG-type multiple myeloma (MM) patients and analyze the relationship between the IgG levels and clinical efficacy and prognosis. METHODS: The clinical data of 66 newly diagnosed IgG-type MM patients in our hospital from September 2012 to October 2018 were collected. These 66 patients were divided into group A (IgG≤64 g/L, n=41), and group B (IgG ＞64 g/L, n=25), then the MM patients in 2 groups were divided into 2 subgroups thalidomide (TM)-treated group (n=35) and bortezomib (BTZ)-treated group (n=25) according to therapeutic regimens. The climical efficacy, PFS and OS time as well as the factors affecting prognosis of patients were compared and analyzed. RESULTS: The overall response rate (ORR) and CR+VGPR rate in group A were better than those in group B (P=0.008, P=0.036), the ORR of BTZ-treated group in group B was significantly better than that of TM-treated group (P=0.028), while the ORR of TM-treated group in group A was better than that of TM-treated group in group B (P=0.048), the CR+VGPR rate was better than that of TM-treated group in group B (P＜0.05). The number of patients with high risk cytogenetics (HRC) in group B was much more than that in group A (P=0.022). Spearman correlation analysis showed that serum IgG levels negatively correlated with albumin (r=-0.449，P=0.000) and hemoglobin (r=-0.608，P=0.000), and positively correlated with bone marrow plasma cells (r=0.328，P=0.007). Survival analysis showed that the PFS in group A was significantly better than that in group B (P=0.015), and the OS in group A was better than that in group B (P=0.049), but there was no significant difference in PFS and OS between TM group and BTZ group (PFS: P=0.695, OS: P=0.3250). Cox multivariate regression analysis showed that the ≥VGPR and standard-risk cytogenetics were independent prognostic factors for PFS and OS. CONCLUSION: IgG＞64g/L in patients with newly diagnosed IgG-type MM is a poor prognostic factor affecting PFS and OS. The higher level of serum IgG at the initial diagnosis, the higher the risk of HRCs, and the worse clinical efficacy and prognosis of patients.

A randomized phase II, open-label and multicenter study of combination regimens of bortezomib at two doses by subcutaneous injection for newly diagnosed multiple myeloma patients.

PURPOSE: Combinations of bortezomib (Velcade), cyclophosphamide and dexamethasone have shown significant efficacy and safety for patients of newly diagnosed multiple myeloma (NDMM). In this study, we compared the efficacy and safety of modified VCD regimens with novel changes in bortezomib dose and schedule for NDMM. METHODS: Eighty-five NDMM patients from multiple centers were randomly assigned to a high-dose (1.6 mg/m2) (group A) or a low-dose (1.3 mg/m2) (group B) bortezomib, administrated on days 1, 6, 11, and 16 subcutaneously in a 4-week cycle for nine cycles, combined with 40 mg dexamethasone on bortezomib days and cyclophosphamide 300 mg/m2 on days 1-3 intravenously. RESULTS: After four cycles, complete response (CR) or better in group A (43.6%) was higher than that in group B (12.8%) (P = 0.002). During induction, for patients with R-ISS stage III, the CR or better rate in group A was superior to that in group B (P = 0.01). Of patients < 65, the CR or better rate of group A was superior to that of group B (P = 0.004). Rapid onset of CR occurred in group A (P < 0.01). Meanwhile, rate of 3-4 diarrhea was higher in group A (P = 0.03), which caused higher rate of dose reduction for patients ≥ 65 (P = 0.041). No significant difference between the two groups in PFS and OS. CONCLUSIONS: The studied high-dose VCD as induction regimen had an improved CR rate, especially in patients < 65 or with R-ISS stage III, and is feasible for young and high-risk patients. Trial registration ClinicalTrials.gov: NCT02086942.

A self-powered triboelectric nanosensor for detecting the corrosion state of magnesium treated by micro-arc oxidation.

Magnesium (Mg) is frequently used as a biocompatible implantable material in the human body, but real-time detection of its corrosion state is not well understood. Fortunately, previous studies of triboelectric nanogenerators (TENG) as self-driven sensors in many fields have proposed solutions for this problem. In this work, Mg-based TENG was prepared as a self-driven sensor to detect the corresponding corrosion state of Mg treated by micro-arc oxidation (MAO-Mg). Mg-based sheets and polydimethylsiloxane (PDMS) film were used as triboelectric materials. The output of TENG was optimal under 350 V-800 Hz micro-arc oxidation (MAO) treatment of Mg, and the V oc, I sc and Q sc were 48.5 V, 35.3 µA and 44.2 nC, which were respectively 2.42, 3.42 and 3.27 times that of the untreated devices. Moreover, a linear relationship was found in simulated body fluid (SBF) immersion tests, showing that the rates of decrease in I sc and V oc were respectively 3.48 and 2.74 times the weight reduction rates of MAO-Mg sheets, indicating that our sensors successfully detected the corrosion of MAO-Mg. This work will lay a preliminary foundation for real-time detection of Mg as an implant in the human body (as do other implantable materials), and demonstrates a potential new application for TENG in the biomedical field.

Identification of potential key genes associated with severe pneumonia using mRNA-seq.

This study aimed to identify the potential key genes associated with severe pneumonia using mRNA-seq. Nine peripheral blood samples from patients with severe pneumonia alone (SP group, n=3) and severe pneumonia accompanied with chronic obstructive pulmonary disease (COPD; CSP group, n=3), as well as volunteers without pneumonia (control group, n=3) underwent mRNA-seq. Based on the sequencing data, differentially expressed genes (DEGs) were identified by Limma package. Following the pathway enrichment analysis of DEGs, the genes that were differentially expressed in the SP and CSP groups were selected for pathway enrichment analysis and coexpression analysis. In addition, potential genes related to pneumonia were identified based on the information in the Comparative Toxicogenomics Database. In total, 645 and 528 DEGs were identified in the SP and CSP groups, respectively, compared with the normal controls. Among these DEGs, 88 upregulated genes and 80 downregulated genes were common between the two groups. The functions of the common DEGs were similar to those of the DEGs in the SP group. In the coexpression network, the commonly downregulated genes (including ND1, ND3, ND4L, and ND6) and the commonly upregulated genes (including TSPY6P and CDY10P) exhibited a higher degree. In addition, 131 DEGs (including ND1, ND3, ND6, MIR449A and TAS2R43) were predicted to be potential pneumonia-related genes. In conclusion, the present study demonstrated that the common DEGs may be associated with the progression of severe pneumonia.

[Cost-Effectiveness Analysis of Different Chemotherapy Regimens in the Treatment of Patients with Multiple Myeloma].

OBJECTIVE: To compare the pharmaco-economic effect of 3 chemotherapeutic regimens in the treatment of patients with multiple myeloma(MM). METHODS: One hundred and thirty-eight newly diagnosed cases of MM in our hospital were analyzed retrospectively, and then MM patients were divided into group A, B and C group according to therapeutic regimen. Group A was treated with VCD therapeutic regimen (bortezomib + cyclophosphamide + dexamethasone, 63 cases), The patients in group B was treated with BiCTD therapeutic regimen (clarithromycin+cyclophosphamide+thalidomide+dexamethasone, 44 cases), The patients in group C was treated with CTD therapeutic regimen (cyclophosphamide+ thalidomide+dexamethasone, 33 cases). The clinical efficacy, adverse reaction, cost-effectiveness were observed and analysed after 4 courses of treatment among 3 groups. RESULTS: The overall response rates of group A, B and C were 96.83%, 81.82% and 64.52% with statistical significant difference (P<0.01). The high efficiency response rates of 3 groups were 82.5%, 59.09%, 32.26% with very significant statistical difference (P<0.01). The infection rate of group A was statistically and significantly higher than other 2 groups (P=0.048), and the constipation rate in group A was statistically and significantly higer than that in group B and C (P<0.05). The cost-effectiveness ratios of 3 groups were 69567.44, 20765.12 and 21475.48, respectively. The incremental cost-effectiveness ratio of group A and B were 183933.21 and 22259.09, as compared with group C. The result was in accordance with sensitivity test. CONCLUSION: Clinicial efficacy of group A is the best,but group B has advantages on cost-effectiveness ratio as compared with other groups, otherwise, group B has low incidence of adverse reaction. In the view of safety, therapeutic efficacy and pharmacoeconomics for treatment of patients with MM, the BiCTD regimen has been confirmed to be superior to the other 2 groups.

Clinical analysis of 215 consecutive cases with fever of unknown origin: A cohort study.

Fever of unknown origin (FUO) is a frequently observed phenomenon in clinical practice. The present study was aimed to investigate potential causes of FUO, thereby improving clinical diagnosis of this disorder.In this retrospective study, clinical data were collected from 215 patients who were diagnosed with FUO between January 2009 and December 2010, and an 18 to 36 months follow-up visit was also performed for these patients.Among these FUO cases, the most common causes of the disease were infectious diseases (IDs) (42.3%), followed by connective tissue diseases (CTDs) (32.1%), miscellaneous (Mi) (10.7%) and neoplasm (N) (6.5%), while the causes for the other 18 cases (8.4%) were still unknown. The most common types of ID, CTD, and N were tuberculosis (16/91, 17.6%), adult onset Still disease (AOSD) (37/69, 53.6%) and non-Hodgkin lymphoma (6/14, 42.9%), respectively.IDs still represent the most common causes of FUO. Regularly intermittent fever with urinary infections and irregularly intermittent fever with infective endocarditis may be regarded as some signs in clinical diagnosis of FUO.

[Effect and Clinical Significance of Bortezomib and Thalidomide on the Memory T Cells Subsets and Regulatory T Cells in Peripheral Blood of Patients with Multiple Myeloma].

OBJECTIVE: To investigate the effects of bortezomib(BTZ) and thalidomide(TM) on peripheral blood memory T-cells (Tm) and regulatory T cells(Tregs) in patients with multiple myeloma(MM). METHODS: Eighty-six MM patients received 2 courses of chemotherapy were divided into effective (partial response at least) group (63 cases) and ineffective (no partial response) group (17 cases) according to therapeutic efficacy; these 80 patients were divided into BTZ group (38 cases) and TM group (42 cases) yet according to therapeutic regimens, 20 newly diagnosed MM patients were used as baseline group, 30 healthy volunteers were used as healthy control group. The Tm subsets and Treg in peripheral blood of each groups were detected by flow cytometry. RESULTS: The CD4+ central memory T cells (CD4+ TCM) percentage of CD4+ Tm, the CD18+ TCM percentage of CD18+Tm and ratio of CD8+ TCM and CD8+ effector memory T cells (TEM) (CD8+ TCM/TEM) in baseline group were all significantly lower than those in healthy control group (P<0.05). After treatment with BTZ regimen or TM regimen, the CD8+TCM percentage of CD8+ Tm in effective group significantly increased to level of healthy control group (P<0.05); the Treg cell level in effective and in effective groups was not significantly different from that in baseline group(P>0.05), but the Treg percentage of CD4+ cells ineffective group was significantly higher than that in baseline group and ineffective group (P<0.05). According to ROC curve, the critical value of CD8+TCM/TEM for predicting chemotherapeutic response was 0.27 with sensitivity of 57.1% and specificity of 94.1%. CONCLUSION: When MM patients are in an immuno-exhanstive status, the treatment with BTZ or TM both can reverse the immuno-inhibitory status of MM patients, moreover, does not affect the Treg cell count; the Treg percentage in BTZ and TM effective groups both are significantly higher than that in baseline group and ineffective group. The ratio of CD8+TCM/TEM contributes to evaluating the chemotherapeutic efficacy.

[Establishment and Management of Multiple Myeloma Specimen Bank Applied for Molecular Biological Researches].

OBJECTIVE: To establish a multiple myeloma specimen bank applied for molecular biological researches and to explore the methods of specimen collection, transportation, storage, quality control and the management of specimen bank. METHODS: Bone marrow and blood samples were collected from multiple myeloma patients, plasma cell sorting were operated after the separation of mononuclear cells from bone marrow specimens. The plasma cells were divided into 2 parts, one was added with proper amount of TRIzol and then kept in -80 °C refrigerator for subsequent RNA extraction, the other was added with proper amount of calf serum cell frozen liquid and then kept in -80 °C refrigerator for subsequent cryopreservation of DNA extraction after numbered respectively. Serum and plasma were separated from peripheral blood, specimens of serum and plasma were then stored at -80 °C refrigerator after registration. Meantime, the myeloma specimen information management system was established, managed and maintained by specially-assigned persons and continuous modification and improvement in the process of use as to facilitate the rapid collection, management, query of the effective samples and clinical data. RESULTS: A total of 244 portions plasma cells, 564 portions of serum, and 1005 portions of plasma were collected, clinical characters were documented. CONCLUSION: A multiple myeloma specimen bank have been established initially, which can provide quality samples and related clinical information for molecular biological research on multiple myeloma.

[Research Progress on Molecular Mechanisms of Resistance to Bortezomib in Multiple Myeloma- Review].

Over the last decade, bortezomib(BTZ) has been extensively applied in the treatment of hematological malignancies, particularly in multiple myeloma and mantle cell lymphoma, however, the appearence of secondary resistance to BTZ has brought a huge challenge in MM treatment. In the present review, the mechanisms of resistance to bortezomib in MM are summarized, focusing on the action of ubiquitin-proteasome system(UPS), endoplasmin reticulum stress, antophagy, inducible pro-survival signalling and bone marrow microenvironment as well as exploration of the potential therapeutic strategies in the clinical perspective. With the understanding of the molecular mechanisms for resistance to BTZ, the novel histone deacetylase inhibitors(HDACi) have been approved for the treatment of replased/refractory MM and AKT inhibitor in the clinical trials. These novel combined therapies can enhance BTZ efficiency and improve the outcome of the patients.

MB4-2/MB4-3 transcripts of IGH-MMSET fusion gene in t(4;14)pos multiple myeloma indicate poor prognosis.

Multiple myeloma (MM) patients with t(4;14) is a heterogeneous group. Prognostic tools capable of predicting the outcome of patients are currently lacking. The MM SET domain (MMSET) protein is universally overexpressed and has been suggested to have an important tumorigenic role. This study analyzed whether the overexpression of full-length (MB4-1) or truncated forms (MB4-2 and MB4-3) of MMSET influence the prognosis of t(4;14)pos MM patients. A total of 53 symptomatic t(4;14)pos MM patients were retrospectively analyzed. RT-PCR was performed using cDNA from purified CD138+ bone marrow plasma cells to analyze expression and clinical significance of the IGH-MMSET fusion transcripts corresponding to MB4-1, MB4-2 and MB4-3 breakpoints. Among the patients, 25 (47.2%), 12 (22.6%) and 16 (30.2%) had the MB4-1, MB4-2 and MB4-3 breakpoints, respectively. When adjusted to the established prognostic variables including del(17p), ISS stage, serum LDH and serum calcium levels, the pooled MB4-2/MB4-3 subgroup remained a powerful independent adverse factor for PFS (P=0.013) and OS (P=0.029). Bortezomib-based therapy significantly improved the survival of the MB4-1 subgroup but could not overcome the negative effect of the MB4-2/MB4-3 breakpoints. Our results indicate that MB4-2/MB4-3 breakpoints with truncated forms of MMSET define a subset of t(4;14)posMM with poor prognosis.