Multiarmed DNA jumper and metal-organic frameworks-functionalized paper-based bioplatform for small extracellular vesicle-derived miRNAs assay.

Small extracellular vesicle-derived microRNAs (sEV-miRNAs) have emerged as promising noninvasive biomarkers for early cancer diagnosis. Herein, we developed a molecular probe based on three-dimensional (3D) multiarmed DNA tetrahedral jumpers (mDNA-Js)-assisted DNAzyme activated by Na+, combined with a disposable paper-based electrode modified with a Zr-MOF-rGO-Au NP nanocomplex (ZrGA) to fabricate a novel biosensor for sEV-miRNAs Assay. Zr-MOF tightly wrapped by rGO was prepared via a one-step method, and it effectively aids electron transfer and maximizes the effective reaction area. In addition, the mechanically rigid, and nanoscale-addressable mDNA-Js assembled from the bottom up ensure the distance and orientation between fixed biological probes as well as avoid probe entanglement, considerably improving the efficiency of molecular hybridization. The fabricated bioplatform achieved the sensitive detection of sEV-miR-21 with a detection limit of 34.6 aM and a dynamic range from100 aM to 0.2 µM. In clinical blood sample tests, the proposed bioplatform showed results highly consistent with those of qRT-PCRs and the signal increased proportionally with the NSCLC staging. The proposed biosensor with a portable wireless USB-type analyzer is promising for the fast, easy, low-cost, and highly sensitive detection of various nucleic acids and their mutation derivatives, making it ideal for POC biosensing.

Modularized Enzymatic Tandem Reaction for tsRNA Detection.

tRNA-derived small RNA (tsRNA) has emerged as a new biomarker for early diagnosis and prognosis prediction of breast cancer. Like the detection of other small non-coding RNAs, the traditional DNA circuit could be used for the tsRNA detection. However, the highly coupling DNA strands in the circuit increase the difficulty of design and could raise a false-positive signal. Here, we demonstrated a versatile modularized enzymatic tandem reaction, namely, reverse-transcribed nicking exponential truncation (RT-NExT). This enzymatic reaction was constructed by cohesive modules, which can work independently or in assembly. Each module could amplify and initiate the downstream module. The RT-NExT reaction could detect 10-18 M ts-66 or ts-86 within 10 min and exhibited excellent consistency to the qRT-PCR when measuring the tsRNA expression level of breast cancer or healthy patients. RT-NExT provides an appealing detection strategy for further research on the clinical diagnosis with tsRNAs.

Cellular Lnc_209997 suppresses Bombyx mori nucleopolyhedrovirus replication by targeting miR-275-5p in B. mori.

Long non-coding RNA (lncRNA) is a type of non-coding RNA molecule, which exceeds 200 nucleotides in length and participates in the regulation of a variety of life activities. Recent studies showed that lncRNAs play important roles in viral infection and host immunity. At present, the researches on insect lncRNAs are relatively few. In this study, we found the expression of Lnc_209997 was significantly down-regulated in silkworm fat body infected with Bombyx mori nucleopolyhedrosis virus (BmNPV). Inhibition of Lnc_209997 promoted BmNPV replication. Enhancing the expression of Lnc_209997 inhibited the proliferation of BmNPV. miR-275-5p was up-regulated in silkworm fat body infected with BmNPV. Dual luciferase reporter gene system confirmed the interaction between Lnc_209997 and miR-275-5p. Over-expression of Lnc_209997 inhibited the expression of miR-275-5p, while inhibition of Lnc_209997 enhanced the expression of miR-275-5p. Further, over-expression of miR-275-5p can facilitate the replication of BmNPV. These results suggested that BmNPV could increase the expression of miR-275-5p by inhibiting cellular Lnc_209997 expression to promote their own proliferation. Our results are helpful for better understanding the role of lncRNAs in BmNPV infection, and provide insights into elucidating the molecular mechanism of interaction between Bombyx mori and virus.

Transcriptome of miRNA during inhibition of Bombyx mori nuclear polyhedrosis virus by geldanamycin in BmN cells.

Bombyx mori nuclear polyhedrosis virus (BmNPV) is one of several viruses that cause great harm to the sericulture industry, and its pathogenic mechanism is still being explored. Geldanamycin (GA), a kind of HSP90 inhibitor, has been verified to suppress BmNPV proliferation. However, the molecular mechanism by which GA inhibits BmNPV is unclear. MicroRNAs (miRNAs) have been shown to play a key role in regulating virus proliferation and host-pathogen interactions. In this study, BmN cells infected with BmNPV were treated by GA and DMSO for 72 h, respectively, then transcriptome analysis of miRNA was performed from the GA group and the control group. As a result, a total of 29 miRNAs were differentially expressed (DE), with 13 upregulated and 16 downregulated. Using bioinformatics analysis, it was found that the target genes of DEmiRNAs were involved in ubiquitin-mediated proteolysis, phagosome, proteasome, endocytosis pathways, and so on. Six DEmiRNAs were verified by quantitative reverse-transcription polymerase chain reaction. DElong noncoding RNA (DElncRNA)-DEmiRNA-messenger RNA (mRNA) regulatory networks involved in apoptosis and immune pathways were constructed in GA-treated BmN cells, which included 12 DEmiRNA, 132 DElncRNA, and 69 mRNAs. This regulatory network enriched the functional role of miRNA in the BmNPV-silkworm interactions and improved our understanding of the molecular mechanism of HSP90 inhibitors on BmNPV proliferation.

Strain-controlled electronic and magnetic properties of tVS2/hVS2 van der Waals heterostructures.

The structural, electronic and magnetic properties of the T-phase and H-phase of the VS2 monolayer and their heterobilayers are studied by means of first-principles calculations. We find that the two phases of the VS2 monolayer are both ferromagnetic (FM) semiconductors and that these two monolayers form a typical van der Waals (vdW) heterostructure with a weak interlayer interaction. By comparing the energy of different magnetic configurations, the FM state of the tVS2/hVS2 heterostructure is found to be in the ground state under normal conditions or biaxial strains. Under compressive strains, the anti-FM (AFM) and FM states degenerate. Based on the band structure obtained and the work function, it is found that the T-phase and H-phase are capable of forming an efficient p-n heterostructure. Due to spontaneous charge transfer at the interface, a gapless semiconductor is formed in our HSE06 calculations. We also find that the twist angle between the monolayers has a negligible impact on the band structure of the heterostructure in its spin-down channel. Moreover, the tVS2/hVS2 heterostructure is found to switch from a gapless semiconductor to a metal or a half-metal under some given biaxial or uniaxial strains. Therefore, the heterostructure could be a half-metallic property with strains, realizing 100% polarization at the Fermi level. Our study provides the possibility of realizing 100% spin-polarization at the Fermi level in these FM vdW heterostructures, which is significant for further spin transport exploration.

Genome-wide association study provides insights into the genetic architecture of bone size and mass in chickens.

Bone size is an important trait for chickens because of its association with osteoporosis in layers and meat production in broilers. Here, we employed high density genotyping platforms to detect candidate genes for bone traits. Estimates of the narrow heritabilities ranged from 0.37 ± 0.04 for shank length to 0.59 ± 0.04 for tibia length. The dominance heritability was 0.12 ± 0.04 for shank length. Using a linear mixed model approach, we identified a promising locus within NCAPG on chromosome 4, which was associated with tibia length and mass, femur length and area, and shank length. In addition, three other loci were associated with bone size or mass at a Bonferroni-corrected genome-wide significance threshold of 1%. One region on chicken chromosome 1 between 168.38 and 171.82 Mb harbored HTR2A, LPAR6, CAB39L, and TRPC4. A second region that accounted for 2.2% of the phenotypic variance was located around WNT9A on chromosome 2, where allele substitution was predicted to be associated with tibia length. Four candidate genes identified on chromosome 27 comprising SPOP, NGFR, GIP, and HOXB3 were associated with tibia length and mass, femur length and area, and shank length. Genome partitioning analysis indicated that the variance explained by each chromosome was proportional to its length.

[The Implementation of the Right to Equality in the Care of a Vulnerable Medical Population: Pregnant and Postpartum Lesbians].

Medical equality is a basic right for patients, and awareness of the need for friendly medical care is increasing alongside international trends of promoting gender equality. Whether clinical professionals are sufficiently enabled and motivated to maintain justice and protect their patients, especially those from vulnerable populations, is an issue that deserves greater attention. We examined the situation of pregnant and postpartum lesbian woman to assess the ethical abilities of clinical professionals. We reflect on whether these patients received appropriate medical care and treatment from the perspective of medical equality. To date, nursing education has placed significantly greater emphasis on protecting the autonomy of patients and on ethical decision-making abilities than on instituting medical equality. In clinical practice, the ethical responses of clinical professionals to equality directly impact vulnerable populations. How clinicians collect clinical data and judge individual cases may cause patients to feel neglected. To carry out friendly medical care effectively, steps must be taken to improve the quality of care. As clinical professionals provide medical treatment, they should be more empathetic toward lesbian postpartum women, maintain an attitude of equality, and refrain from judging the sexual tendencies of individual cases, and protect the privacy of their patients. Regarding the special needs of vulnerable populations, clinical professionals should continue learning and spending time reflecting on methods to improve quality of care.

Immunoglobulin D Multiple Myeloma: Disease Profile, Therapeutic Response, and Survival.

OBJECTIVES: The long-term clinical characteristics, response to therapy, and survival in patients with immunoglobulin D (IgD) multiple myeloma (MM) were investigated. METHODS: A retrospective study was conducted that included 68 patients treated in the last 10 years, 37 of whom received bortezomib only (bortezomib group), 13 of whom received bortezomib and underwent autologous hematopoietic stem cell transplantation (bortezomib + ASCT group), and 18 of whom received conditional chemotherapy (non-bortezomib group). RESULTS: The ratio of males to females was 44:24, and the median age was 56.5 years. The overall response rate of each group was 91.9, 77.8, and 100%, respectively. The median overall survival (OS) and progression-free survival (PFS) were 24 and 15.5 months, respectively, among the 68 patients. The median OS of each group was 23, 21.5, and 27 months, respectively. The median PFS of each group was 18, 12, and 24 months, respectively. The 3- and 5-year OS were 64 and 45%, respectively, and the 3- and 5-year PFS were 39 and 13%, respectively, among the 68 patients. Cox regression showed that the percentage of bone marrow plasmacytosis was significantly associated with OS (p = 0.038). CONCLUSIONS: The survival of IgD patients is shorter than that of other MM patients. Treatment strategies with bortezomib followed by stem cell transplantation may boost the response rate and improve survival.

Analysis of clinical features, treatment response, and prognosis among 61 elderly newly diagnosed multiple myeloma patients: a single-center report.

BACKGROUND: We identified the clinical features of 61 cases of multiple myeloma (MM) patients over 65 years and analyzed the treatment and prognosis of the era of new drugs in elderly patients. METHODS: We identified 61 newly diagnosed symptomatic multiple myeloma (NDMM) among elderly Chinese patients more than 65 years old diagnosed from 2006 to 2012. RESULTS: Of the 205 consecutive MM patients whom we reviewed, 61 (29.76%) cases were NDMM patients aged more than 65 years and the others were younger than 65 years old. Among them, 40 (65.6%) cases were in end-stage (ISS stage III); meanwhile, 19 (31.2%) cases of them had MM with extramedullary plasmacytoma (EMP), observed in 42.1% patients at diagnosis, and the top three incidence of position were spinal canal, pleural, and soft tissue. In the whole column, the median follow-up was 38 months and median age was 72.5 years. Patients received bortezomib- or thalidomide-containing regimens as initial therapy. Comparing the two treatment groups, the complete remission (CR)/near-complete remission (nCR) rate was significantly higher in the bortezomib-containing regimens (61.5 vs.18.18%, P=0.001), no difference in progression-free survival (PFS) and overall survival (OS). Patients of age over 75 years had shorter OS than those of age over 65 years (49 vs. 24 months, P=0.001). The patients with EMP had shorter OS than those without EMP in two age groups (32 vs. 42 and 15 vs. 24 months, P=0.017 and 0.024, respectively). CONCLUSIONS: The results highlight that patients over 75 years and MM with EMP have a poorer outcome. While the CR rate is higher in bortezomib-containing regimens, no significant improvement is noted in respect to the survival outcomes; also, it cannot overcome the negative influence on survival of age and MM with EMP in elderly patients.

[Clinical observations of lenalidomide combination chemotherapy for relapsing or refractory multiple myeloma].

OBJECTIVE: To explore the clinical efficacies and toxicities of lenalidomide combination chemotherapy in the treatment of relapsing or refractory multiple myeloma (MM) patients. METHODS: A total of 14 MM patients were recruited to receive lenalidomide combination chemotherapy in Beijing Chaoyang hospital from June 2013 to October 2014. Lenalidomide 25 mg was taken orally daily or every alternate day for 21 days and resting for 7 days. The regimens were RD (lenalidomide and dexamethasone, n = 6), RCD (lenalidomide, ifosfamide and dexamethasone, n = 4), RDD (lenalidomide, liposomal doxorubicinand dexamethasone, n = 1), PRD (lenalidomide, velcade and dexamethasone, n = 1) and R+DECP (lenalidomide, cisplatin, etoposide, ifosfamide and dexamethasone, n = 2). RESULTS: Among them, two patients died during the first cycle of lenalidomide. Ten patients finished 2 cycles of treatment and 2 patients attained near complete remission or complete remission (nCR/CR), 6 partial remission (PR) and 2 stable disease (SD) with an overall response rate (ORR) of 8/10. Ten patients finished 3 cycles of treatment and 3 attained CR, 5 PR and 2 SD. Nine patients finished 4 cycles of treatment and 3 attained CR, 5 PR and 1 progressive disease (PD). Six patients finished 5 cycles of treatment and 1 attained CR, 3 PR and 2 PD. Three patients finished 6 cycles of treatment and 1 attained CR, 1 PR and 1 PD. And the most common adverse reactions were fatigue, loss of appetite and hypocytosis. Six patients died. CONCLUSION: The lenalidomide combination chemotherapy is both efficacious and safe in the treatment of relapsing or refractory MM.

[Design and analysis of a novel light visible spectrum imaging spectrograph optical system].

A novel visible spectrum imaging spectrograph optical system was proposed based on the negative dispersion, the arbitrary phase modulation characteristics of diffractive optical element and the aberration correction characteristics of freeform optical element. The double agglutination lens was substituted by a hybrid refractive/diffractive lens based on the negative dispersion of diffractive optical element. Two freeform optical elements were used in order to correct some aberration based on the aberration correction characteristics of freeform optical element. An example and frondose design process were presented. When the design parameters were uniform, compared with the traditional system, the novel visible spectrum imaging spectrograph optical system's weight was reduced by 22.9%, the total length was reduced by 26.6%, the maximal diameter was reduced by 30.6%, and the modulation transfer function (MTF) in 1.0 field-of-view was improved by 0.35 with field-of-view improved maximally. The maximal distortion was reduced by 1.6%, the maximal longitudinal aberration was reduced by 56.4%, and the lateral color aberration was reduced by 59. 3%. From these data, we know that the performance of the novel system was advanced quickly and it could be used to put forward a new idea for modern visible spectrum imaging spectrograph optical system design.

[Clinical observation of DECP combination chemotherapy for relapsing and refractory multiple myeloma patients with extramedullary plasmacytomas].

OBJECTIVE: To explore the clinical effect and toxicity of (cisplatin, etoposide, ifosfamide & dexamethasone) DECP combination chemotherapy in the treatment of relapsing and refractory multiple myeloma (MM) with extramedullary plasmacytomas. METHODS: A total of 20 relapsed and refractory MM patients with extramedullary plasmacytomas treated with DECP regimen from May 2005 to May 2013 were analyzed retrospectively. DECP protocols included cisplatin 20 mg/m(2), Day 1-3; etoposide 100 mg/d,Day 1-3; ifosfamide 500 mg·m(-2)·d(-1), Day 1-4; dexamethasone 20 mg/d, Day 1-4. Efficacy was evaluated after 2 therapeutic cycles. RESULTS: After 2 therapeutic cycles, the objective response rate (ORR) was 55% (11/20). After 3 therapeutic cycles, the ORR was 7/12.Seven patients completed 4 cycles with an ORR of 4/7. Two patients had finished 6 cycles and continued to maintain partial remission. The most common adverse events included gastrointestinal reaction and myelosuppression. The median follow-up time was 30 (12-80) months. The median time of overall survival (OS) was 30 (9-121) months. The 1-year OS was 73%, 2-year OS 28% and 3-year OS 21%. CONCLUSION: The DECP chemotherapy is both effective and safe in the treatment of relapsed and refractory MM patients with extramedullary plasmacytomas.

[Study and analysis of light infrared detection system with dual spectrum and wide temperature range].

Because harmonic diffractive optics elements has special achromatism, athermalization and arbitrary phase modulation characteristics, an infrared detection system method with dual spectrum and wide temperature range was presented based on the most advanced infrared dual color detector which had a format of 320 X 240 and the pixel pitch of 30 microm. A hybrid refractive/ harmonic diffractive infrared detection system with dual spectrum and wide temperature range was designed. The working wavelength range was 3. 8 - 4. 2 and 8. 8 -11. 2 microm. The system was only consisted of three lenses, including one aspheric surfaces and a harmonic diffraction surface, which made the system have compact structure and light weight. In the temperature range -120 -200 degreesC, the RMS radius of spot diagram in 3. 8 approximately 4. 2 and 8. 8-11. 2 pm was 19. 07 and 17. 75 microm respectively, which is less than the pixel size of infrared detector with 30 m, the enclosed energy in 30 microm, the enclosed energy in 3. 8-4. 2 and 8. 8-11. 2 microm is 88. 7% and 82. 4% in two pixel size. The method and structure was convenient and predominant. It was proved that the design was feasible.

Integrating Pt nanoparticles with 3D Cu2- x Se/GO nanostructure to achieve nir-enhanced peroxidizing Nano-enzymes for dynamic monitoring the level of H2O2 during the inflammation.

The treatment of wound inflammation is intricately linked to the concentration of reactive oxygen species (ROS) in the wound microenvironment. Among these ROS, H2O2 serves as a critical signaling molecule and second messenger, necessitating the urgent need for its rapid real-time quantitative detection, as well as effective clearance, in the pursuit of effective wound inflammation treatment. Here, we exploited a sophisticated 3D Cu2- x Se/GO nanostructure-based nanonzymatic H2O2 electrochemical sensor, which is further decorated with evenly distributed Pt nanoparticles (Pt NPs) through electrodeposition. The obtained Cu2- x Se/GO@Pt/SPCE sensing electrode possesses a remarkable increase in specific surface derived from the three-dimensional surface constructed by GO nanosheets. Moreover, the localized surface plasma effect of the Cu2- x Se nanospheres enhances the separation of photogenerated electron-hole pairs between the interface of the Cu2- x Se NPs and the Pt NPs. This innovation enables near-infrared light-enhanced catalysis, significantly reducing the detection limit of the Cu2- x Se/GO@Pt/SPCE sensing electrode for H2O2 (from 1.45 µM to 0.53µM) under NIR light. Furthermore, this biosensor electrode enables in-situ real-time monitoring of H2O2 released by cells. The NIR-enhanced Cu2- x Se/GO@Pt/SPCE sensing electrode provide a simple-yet-effective method to achieve a detection of ROS (H2O2、-OH) with high sensitivity and efficiency. This innovation promises to revolutionize the field of wound inflammation treatment by providing clinicians with a powerful tool for accurate and rapid assessment of ROS levels, ultimately leading to improved patient outcomes.

Detection of lenalidomide metabolites in urine to discover drug-resistant compounds.

Lenalidomide is the first-line drug for the clinical treatment of multiple myeloma. However, its efficacy differs significantly among patients. Clinically, after lenalidomide treatment, few patients' conditions worsened, whereas others remained stable or improved. To clarify the reasons for this difference in efficacy, 20 patients with multiple myeloma who received maintenance treatment with lenalidomide were retrospectively included in this study. Lenalidomide metabolic compounds were detected in patient urine using mass spectrometry. A rapid and accurate ultra-performance liquid chromatography-time-of-flight tandem mass spectrometry (UPLC-TOF-MS/MS) method was used to characterize metabolites in the urine of different patients. Eleven metabolites, including four new compounds, were identified and characterized in all the samples. Among these, two metabolites were found to have obvious discrepancies in different groups of patients. One metabolite named Denitrified-2 glutarimide, a new potential compound, was only detected in the urine of ineffective and stable patients, whereas the other metabolite named 5-Hydroxy-lenalidomide was found only in the urine of effective patients.

A Universal Strategy for Enhancing the Circulating miRNAs' Detection Performance of Rolling Circle Amplification by Using a Dual-Terminal Stem-Loop Padlock.

Rolling circle amplification (RCA) is one of the most promising nucleic acid detection technologies and has been widely used in the molecular diagnosis of disease. Padlock probes are often used to form circular templates, which are the core of RCA. However, RCA often suffers from insufficient specificity and sensitivity. Here we report a reconstruction strategy for conventional padlock probes to promote their overall performance in nucleic acid detection while maintaining probe functions uncompromised. When two rationally designed stem-loops were strategically placed at the two terminals of linear padlock probes, the specificity of target recognition was enhanced and the negative signal was significantly delayed. Our design achieved the best single-base discrimination compared with other structures and over a 1000-fold higher sensitivity than that of the conventional padlock probe, validating the effectiveness of this reconstruction. In addition, the underlying mechanisms of our design were elucidated through molecular dynamics simulations, and the versatility was validated with longer and shorter padlocks targeting the same target, as well as five additional targets (four miRNAs and dengue virus - 2 RNA mimic (DENV-2)). Finally, clinical applicability in multiplex detection was demonstrated by testing real plasma samples. Our exploration of the structures of nucleic acids provided another perspective for developing high-performance detection systems, improving the efficacy of practical detection strategies, and advancing clinical diagnostic research.

Interferon regulatory factor-1 together with reactive oxygen species promotes the acceleration of cell cycle progression by up-regulating the cyclin E and CDK2 genes during high glucose-induced proliferation of vascular smooth muscle cells.

BACKGROUND: The high glucose-induced proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the development of diabetic vascular diseases. In a previous study, we confirmed that Interferon regulatory factor-1 (Irf-1) is a positive regulator of the high glucose-induced proliferation of VSMCs. However, the mechanisms remain to be determined. METHODS: The levels of cyclin/CDK expression in two cell models involving Irf-1 knockdown and overexpression were quantified to explore the relationship between Irf-1 and its downstream effectors under normal or high glucose conditions. Subsequently, cells were treated with high glucose/NAC, normal glucose/H2O2, high glucose/U0126 or normal glucose/H2O2/U0126 during an incubation period. Then proliferation, cyclin/CDK expression and cell cycle distribution assays were performed to determine whether ROS/Erk1/2 signaling pathway was involved in the Irf-1-induced regulation of VSMC growth under high glucose conditions. RESULTS: We found that Irf-1 overexpression led to down-regulation of cyclin D1/CDK4 and inhibited cell cycle progression in VSMCs under normal glucose conditions. In high glucose conditions, Irf-1 overexpression led to an up-regulation of cyclin E/CDK2 and an acceleration of cell cycle progression, whereas silencing of Irf-1 suppressed the expression of both proteins and inhibited the cell cycle during the high glucose-induced proliferation of VSMCs. Treatment of VSMCs with antioxidants prevented the Irf-1 overexpression-induced proliferation of VSMCs, the up-regulation of cyclin E/CDK2 and the acceleration of cell cycle progression in high glucose conditions. In contrast, under normal glucose conditions, H2O2 stimulation and Irf-1 overexpression induced cell proliferation, up-regulated cyclin E/CDK2 expression and promoted cell cycle acceleration. In addition, overexpression of Irf-1 promoted the activation of Erk1/2 and when VSMCs overexpressing Irf-1 were treated with U0126, the specific Erk1/2 inhibitor abolished the proliferation of VSMCs, the up-regulation of cyclin E/CDK2 and the acceleration of cell cycle progression under high glucose or normal glucose/H2O2 conditions. CONCLUSIONS: These results demonstrate that the downstream effectors of Irf-1 are cyclin E/CDK2 during the high glucose-induced proliferation of VSMCs, whereas they are cyclin D1/CDK4 in normal glucose conditions. The Irf-1 overexpression-induced proliferation of VSMCs, the up-regulation of cyclin E/CDK2 and the acceleration of cell cycle progression are associated with ROS/Erk1/2 signaling pathway under high glucose conditions.

Extract of Platycodon grandiflorum Prevents Doxorubicin-induced Cardiotoxicity in Breast Cancer.

Doxorubicin (Dox) is a first-line chemotherapeutic agent applied in cancer treatment. Its long-term anticancer efficacy is restricted mainly due to its subsequent cardiotoxicity for patients. Platycodon grandiflorum (PG), an important traditional Chinese herb, has been reported to eliminate phlegm, relieve cough, and reduce inflammatory diseases. Previous clinical studies found that PG has cardioprotective effects for early breast cancer patients who received Dox-based chemotherapy. However, the cellular and molecular mechanisms underlying PG-mediated cardiotoxic rescue remain elusive. This study aimed to explore the protective role and potential molecular mechanisms of PG on Dox-induced cardiac dysfunction in a mouse model of breast cancer. PG significantly alleviated myocardial damage and prevented cardiomyocyte apoptosis induced by Dox. The expression levels of cytochrome C and cleaved caspase-3 significantly decreased, and the levels of Bcl-XL and B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein increased following PG treatment. Furthermore, PG remarkably enhanced the antimetastatic efficacy (versus the Dox group) by regulating the balance of matrix metalloproteinases/tissue inhibitors of metalloproteinases.

Serum Abnormal Metabolites for Evaluating Therapeutic Response and Prognosis of Patients With Multiple Myeloma.

Aims: To evaluate abnormal metabolites related to treatment response and prognosis of multiple myeloma (MM) patients through ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS). Methods: Forty-six symptomatic MM patients were included in this study who had a prior high level of positive monoclonal proteins before receiving targeted therapy with bortezomib-based regimens. UPLC-MS along with traditional immunofixation was performed on MM diagnostic samples and effective serum samples, and UPLC-MS was used to target valuable metabolic markers related to M protein.MM patients were segregated into pre-therapy (pre-T) and post-therapy (post-T) groups according to the response after chemotherapy. A monoclonal protein could be detected at baseline in 33 newly diagnosed MM (NDMM), 13 refractory and relapsed MM (RRMM) patients and 20 healthy controls (HC) by immunofixation. Results: Between pre-T and post-T patients, the data showed that 32, 28 and 3 different metabolites were significantly correlated with M protein in IgG, IgA and light chain-type MM, respectively. These identified metabolites were significantly enriched in arginine and proline metabolism as well as glycerophospholipid metabolism pathways. Among them, PC (19:0/22:2) was displayed to increase significantly and consistently with M protein in each subtype of MM after treatment, which obviously indicated that it was related to the treatment response of MM. Further survival analysis of metabolic markers found that aspartic acid, LysoPE (16:0), SM (d18:1/17:0), PC (18:0/24:1), PC (16:0/16:0), TG (18:1/18:1/22:5) and LysoPE (18:2) reaching a certain cutoff value may be associated with shorter progression free survival (PFS). Finally, Cox multivariate regression analysis identified three factors were independent prognostic factors of MM. Moreover, there were significantly different in PC (19:0/22:2) and in aspartic acid between MM patients and healthy people. Conclusion: This work identified significant metabolic disorders in 46 pairs off pre- and post-therapy MM patients, specifically in arginine, proline and glycerophospholipid pathways. The abnormal metabolites have the potential to serve as new biomarkers for evaluating treatment response and prognosis, as well as early monitoring of disease activity. Therefore, these systematic studies on abnormal metabolites as biomarkers for diagnosis and treatment will provide the evidence for future precise treatment of MM.

Ixazomib-based maintenance therapy after bortezomib-based induction in patients with multiple myeloma not undergoing transplantation: A real-world study.

BACKGROUND: Maintenance therapy with proteasome inhibitors (PIs) can improve outcomes of multiple myeloma (MM) patients, however, the neurotoxicity and parenteral route of bortezomib limit its long-term use. An efficacious, tolerable, and convenient PI option is needed. METHODS: In this single-center, real-world study, we retrospectively analyzed the outcome and safety profile of ixazomib-based maintenance therapy in patients who plateaued with the responses of steady disease or better after bortezomib-based induction therapy in MM patients not undergoing transplantation. RESULTS: Of all the 71 patients, 37 cases (52.1%) were newly diagnosed MM (NDMM) and 34 cases (47.9%) were relapsed and/or refractory MM (RRMM). The overall response rate (ORR) was 81.7%, including 34 patients (47.9%) with a very good response rate or better (≥VGPR) after a median of nine cycles (6-14) of bortezomib-based induction therapy. Then the ORR was transformed to 74.6% including 39 patients of ≥VGPR (54.9%) after a median of six courses (2-25) of ixazomib-based maintenance therapy. Of these, 18 patients (25.4%) exhibited responses deepened. With 26.5 months median follow-up, median progression-free survival (PFS) was 28.4 and 16.5 months from the start of bortezomib and 16.2 and 10.0 months from the initiation of ixazomib in NDMM and RRMM group, respectively. Moreover, responses deepened during the maintenance phase (hazard ratio: 0.270, p = 0.007), and responses of ≥VGPR during the induction phase (hazard ratio: 0.218, p < 0.001) were confirmed to independently predict longer PFS after multivariate analyses. Severe adverse events (grade 3/4) were relatively rare. Bortezomib-emergent peripheral neuritis (PN) was significantly relived after the transition to ixazomib (p < 0.001). CONCLUSION: This real-world analysis has demonstrated oral ixazomib is a favorable option of long-term administration for maintenance with efficacy and feasibility and confirmed the association between deepening responses with ixazomib and prolonged PFS.