The causal effects of genetically determined immune cells on gynecologic malignancies: a Mendelian randomization study.

Background: Evidence from observational studies suggested a connection between immune cells and gynecologic malignancies. To investigate potential causative associations between immunophenotype traits and gynecologic malignancies, we used a two-sample Mendelian randomization analysis. Methods: The genetic instrumental variables of 731 immunophenotypes of peripheral blood were obtained by the GWAS database; the GWAS data of common gynecologic cancers were obtained from FinnGen study. The main statistic method was the inverse-variance weighted method. We also used the weighted mode, weighted median, and MR Egger for evaluations. The MR Steiger directionality test was further used to ascertain the reverse causal relationship between immune cells and gynecologic cancers. Results: We identified 50 highly probable immunophenotypes and 65 possible ones associated with gynecologic malignancies. The majority of the B cell panel was protective factors in cervical cancer. However, there was a correlation found in the B cells panel with a probable factor associated with an elevated risk of endometrial cancer. Immunophenotypes in the monocyte panel were linked to a lower probability of ovarian cancer and vulvar cancer. All of the gynecologic cancers in our study had no statistically significant impact on immune cells, according to reverse MR analysis. Conclusion: Our study firstly emphasized the genetically predicted causality between immune cells and gynecologic malignancies. This knowledge will be critical to formulating the measures to prevent malignancies in female at risk in future clinical practice.

Origin and dispersal history of Hepatitis B virus in Eastern Eurasia.

Hepatitis B virus is a globally distributed pathogen and the history of HBV infection in humans predates 10000 years. However, long-term evolutionary history of HBV in Eastern Eurasia remains elusive. We present 34 ancient HBV genomes dating between approximately 5000 to 400 years ago sourced from 17 sites across Eastern Eurasia. Ten sequences have full coverage, and only two sequences have less than 50% coverage. Our results suggest a potential origin of genotypes B and D in Eastern Asia. We observed a higher level of HBV diversity within Eastern Eurasia compared to Western Eurasia between 5000 and 3000 years ago, characterized by the presence of five different genotypes (A, B, C, D, WENBA), underscoring the significance of human migrations and interactions in the spread of HBV. Our results suggest the possibility of a transition from non-recombinant subgenotypes (B1, B5) to recombinant subgenotypes (B2 - B4). This suggests a shift in epidemiological dynamics within Eastern Eurasia over time. Here, our study elucidates the regional origins of prevalent genotypes and shifts in viral subgenotypes over centuries.

Ancient Mitochondrial Genomes Provide New Clues to the Origin of Domestic Cattle in China.

Cattle are one of the six livestock species that have occupied an important place in Chinese history. Previous ancient DNA studies have indicated that Chinese taurine cattle (Bos taurus taurus) are exotic, but the exact route and diffusion by which they were introduced to China is unknown. In this study, we extracted the mitochondrial genomes of 34 cases of ancient taurine cattle (from the late Neolithic to Qin and Han dynasties) excavated from sites in northern China and the eastern Eurasian steppe, and successfully obtained 14 mitochondrial genome sequences. The results of ancient DNA analysis reveal that with cultural exchange and trade, there was close genetic exchange between domestic taurine cattle in different regions. The haplotypes shared by domestic cattle have genetic continuity, reflecting the strong cultural influence of the large capital city sites such as Taosi, Shimao and Erlitou on the surrounding areas. This study suggests that ancient northern Chinese taurine cattle may have accompanied the westward transmission of agricultural or painted pottery culture and thus had a maternal genetic contribution to modern Tibetan cattle.

Analysis of influencing factors on the duration of pediatric peripheral intravenous catheter.

BACKGROUND: The application of peripheral intravenous catheter has been an effective guarantee for the success of pediatric therapy. We aimed to investigate the correlative factors that impacting the duration of pediatric peripheral intravenous catheter. METHODS: From January 2017 to October 2017, 370 cases of pediatric patients in the First Hospital of Hunan University of Chinese Medicine were collected as the research object. Based on the indwelling time, the collected cases were divided into two groups, namely long time group (>72 h) and short time group (<72 h). The general data and laboratory test results of two groups were collected, and the correlation factors of indwelling time were analyzed by single factor and Logistic multiple factors. RESULTS: As the results revealed that compared with short time group, patients in long time group had statistically significant differences in puncture site, phlebitis, extravasation of blood vessels, hemoglobin, white blood cells, platelets, and 75% ethanol sterilization (p < 0.05). Logistic multivariate analysis indicated that scalp puncture was the independent protective factors that affecting the duration of pediatric peripheral intravenous catheter. Moreover, phlebitis represented the independent risk factor that influencing the indwelling time of pediatric peripheral intravenous catheter. And the differences were statistically significant (p < 0.05). CONCLUSIONS: Analyze factors influencing indwelling time of pediatric peripheral intravenous catheter and enhance the management of relevant factors are of great significance to prolong the indwelling time, reduce the pain of pediatric patients, and facilitate the clinical medication.

Natural djurleite with refined composition Cu61.39S32 revealing disorder of some Cu sites.

A djurleite crystal was discovered from a natural sample originally labelled as chalcocite. The djurleite crystal under investigation has a refined composition of Cu61.39S32, thus revealing a Cu deficiency compared to the originally reported Cu62S32 phase [Evans (1979). Z. Kristallogr. 150, 299-320], where all atomic sites are reported to be fully occupied. In addition, the current refinement revealed a splitting of eight of the Cu sites into pairs.

Effect of Solvent Residue in the Thin-Film Fabrication on Perovskite Solar Cell Performance.

Organic-inorganic Pb-based halide perovskite photoelectrical materials, especially perovskite solar cells (PSCs), have attracted attention due to the significant efforts in improving the power conversion efficiency (PCE) to above 25%. However, the stability issue of the PSCs restricts their further development for commercialization. Strategies are designed to keep moisture and oxygen out of the perovskite films, such as additive, surface passivation, and solvent engineering; however, usually, the corrosion of active films by the residual solvent is mostly ignored. Solvent residue is the paramount factor influencing the stability of the perovskite film prepared by the solution method, and most solvents can be easily absorbed and accelerate the perovskite film decomposition. Here, we studied the residual solvent effect on two kinds of perovskite films obtained by different annealing processes: hot air annealing and hot bench annealing. Several detection techniques were used to study the performance of two different annealing methods, including time-of-flight secondary ion mass spectrometry (ToF-SIMS), thermogravimetric analysis (TGA), and field-emission scanning electron microscopy (FESEM). The perovskite film obtained by hot air annealing shows less residual solvent and better device performance than the hot bench annealing method. This method is expected to provide insight into reducing solvent residue to improve the stability of the PSCs, especially for future commercialization.

Gas permeation and microstructure of reduced graphene oxide/polyethyleneimine multilayer films created via recast and layer-by-layer deposition processes.

Nowadays, graphene/polymer composite films with multilayer structure have attracted significant attention for gas barrier application. In this study, a series of reduced graphene oxide/polyethyleneimine (RGO/PEI) composite films were created via recast and layer-by-layer deposition processes. By using the recast process, the myriad PEI molecules in the precursor solution (the PEI : GO feeding ratio is 0.02 : 0.1, 0.05 : 0.1, 0.1 : 0.1, 0.3 : 0.1 and 0.5 : 0.1) ensure more effective reduction and surface modification of the graphene oxide (GO) sheets, while the undesirable free PEI molecules are eventually removed via a filtration process. Then, the RGO/PEI composite films were synthesized on PET substrate using a layer-by-layer assembly. The resulting films show a homogeneous and compact brick-wall structure with excellent gas barrier properties. Barriers against water vapor, nitrogen/oxygen, and carbon dioxide require different content of PEI in the composite film for optimal performance; the ideal values are 19.7, 23.8, and 24.1 wt%, respectively. These values are much lower compared with previously reported studies. Further, the permeability, free volumes, component ratio, morphology, and density of the RGO/PEI composite films have been carefully investigated and discussed. The results revealed that the mechanism behind the excellent gas barrier property of the RGO/PEI composite films is a synergistic effect created by the combination of the brick-wall structure, the small free volume holes, the suitable PEI content (ranging from 19.7 wt% to 24.1 wt%), the high density, and the hydrophobicity.

Record-Efficiency Flexible Perovskite Solar Cells Enabled by Multifunctional Organic Ions Interface Passivation.

Flexible perovskite solar cells (f-PSCs) have attracted great attention because of their unique advantages in lightweight and portable electronics applications. However, their efficiencies are far inferior to those of their rigid counterparts. Herein, a novel histamine diiodate (HADI) is designed based on theoretical study to modify the SnO2 /perovskite interface. Systematic experimental results reveal that the HADI serves effectively as a multifunctional agent mainly in three aspects: 1) surface modification to realign the SnO2 conduction band upward to improve interfacial charge extraction; 2) passivating the buried perovskite surface, and 3) bridging between the SnO2 and perovskite layers for effective charge transfer. Consequently, the rigid MA-free PSCs based on the HADI-SnO2 electron transport layer (ETL) display not only a high champion power conversion efficiency (PCE) of 24.79% and open-circuit voltage (VOC ) of 1.20 V but also outstanding stability as demonstrated by the PSCs preserving 91% of their initial efficiencies after being exposed to ambient atmosphere for 1200 h without any encapsulation. Furthermore, the solution-processed HADI-SnO2 ETL formed at low temperature (100 °C) is utilized in f-PSCs that achieve a PCE as high as 22.44%, the highest reported PCE for f-PSCs to date.

Association of the levels of heavy metals and trace elements during pregnancy with congenital heart defects in offspring: a prospective cohort study. / å­•æœŸé‡é‡‘å±žå ƒç´ å’Œå¾®é‡å ƒç´ æ°´å¹³ä¸Žå­ä»£å ˆå¤©æ€§å¿ƒè„ç— ç›¸å ³æ€§çš„å‰çž»æ€§é˜Ÿåˆ—ç ”ç©¶.

OBJECTIVES: To study the association of the levels of heavy metals and trace elements during pregnancy with congenital heart defects (CHD) in offspring, and to establish a model for predicting the probability of CHD based on the levels of heavy metals and trace elements during pregnancy. METHODS: Based on the prospective birth cohort study in Gansu Provincial Maternal and Child Health Hospital in 2010-2012, a nested case-control study was conducted for the follow-up observation of 14 359 pregnant women. Among the pregnant women, 97 pregnant women whose offspring were diagnosed with CHD during follow-up were enrolled as the CHD group, and 194 pregnant women whose offspring had no CHD were selected as the control group. Inductively coupled plasma mass spectrometry was used to measure the levels of heavy metals and trace elements in maternal blood samples and fetal umbilical cord blood samples. A multivariate logistic regression analysis was used to evaluate the association between heavy metal and trace elements and CHD in offspring. A nomogram model for predicting the probability of CHD in offspring was established based on the levels of heavy metals and trace elements during pregnancy. RESULTS: Compared with the control group, the CHD group had significantly higher levels of aluminum (Al), natrium (Na), calcium (Ca), titanium (Ti), selenium (Se), strontium (Sr), stannum (Sn), stibium (Sb), barium (Ba), and thorium (Th) in maternal blood samples (P<0.05), as well as significantly higher levels of Al, zinc (Zn), magnesium (Mg), kalium (K), Ca, Ti, chromium (Cr), copper (Cu), arsenic (As), Se, Sr, argentum (Ag), cadmium (Cd), Sn, and plumbum (Pb) in umbilical cord blood (P<0.05). The multivariate logistic regression analysis showed that the increase in the Sb level in maternal blood was associated with the increase in the risk of CHD in offspring [adjusted odds ratio (aOR)=4.81, 95% confidence interval (CI): 1.65-14.07, P=0.004], while in umbilical cord blood, the high levels of Al (aOR=4.22, 95%CI: 1.35-13.16, P=0.013), Mg (aOR=8.00, 95%CI: 1.52-42.08, P=0.014), and Pb (aOR=3.82, 95%CI: 0.96-15.23, P=0.049) were significantly associated with the risk of CHD in offspring. The levels of Al, Th, and Sb in maternal blood and levels of Al, Mg, and Pb in umbilical cord blood were included in the predictive model for CHD in offspring based on the levels of heavy metals and trace elements during pregnancy, and the calibration curve of the nomogram predictive model was close to the ideal curve. CONCLUSIONS: Increases in the levels of Al, Th, Sb, Mg, and Pb during pregnancy may indicate the increase in the risk of CHD in offspring, and the nomogram predictive model based on these indices can be used to predict the probability of CHD in offspring.

Acute porcine epidemic diarrhea virus infection reshapes the intestinal microbiota.

The intestinal microbiota is crucial to intestinal homeostasis. Porcine epidemic diarrhea virus (PEDV) is high pathogenic to intestines, causing diarrhea, even death in piglets. To investigate the detailed relationship between PEDV infection and intestinal microbiota, the composition and distribution of intestinal microbiota from pigs were first analyzed using 16S rRNA sequencing technology. The results demonstrated that the composition and distribution of microbes in different intestinal segments were quite similar between 1-week-old and 2-week-old piglets but different from 4-week-old (weaned) piglets. Then piglets at different ages were inoculated with PEDV. The results showed that the 1-week-old piglets exhibited the most severe pathogenicity comparing to the other age groups. Further investigations indicated that Lactobacillus, Escherichia coli, and Lactococcus in the intestinal microbiota of piglets were significantly changed by PEDV infection. These results strengthen our understanding of viruses influencing intestinal microbes and remind us of the potential association between PEDV and intestinal microbes.

Ancient genomes from northern China suggest links between subsistence changes and human migration.

Northern China harbored the world's earliest complex societies based on millet farming, in two major centers in the Yellow (YR) and West Liao (WLR) River basins. Until now, their genetic histories have remained largely unknown. Here we present 55 ancient genomes dating to 7500-1700 BP from the YR, WLR, and Amur River (AR) regions. Contrary to the genetic stability in the AR, the YR and WLR genetic profiles substantially changed over time. The YR populations show a monotonic increase over time in their genetic affinity with present-day southern Chinese and Southeast Asians. In the WLR, intensification of farming in the Late Neolithic is correlated with increased YR affinity while the inclusion of a pastoral economy in the Bronze Age was correlated with increased AR affinity. Our results suggest a link between changes in subsistence strategy and human migration, and fuel the debate about archaeolinguistic signatures of past human migration.

Aptamer-antibody dual probes on single-walled carbon nanotube bridged dielectrode: Comparative analysis on human blood clotting factor.

Haemophilia is a blood clotting disorder known as 'Christmas disease' caused when the blood has defect with the clotting factor(s). Bleeding leads various issues, such as chronic pain, arthritis and a serious complication during the surgery. Identifying this disease is mandatory to take the necessary treatment and maintains the normal clotting. It has been proved that the level of factor IX (FIX) is lesser with haemophilia patient and the attempt here is focused to quantify FIX level by interdigitated electrode (IDE) sensor. Single-walled carbon nanotube (SWCNT) was utilized to modify IDE sensing surface. On this surface, dual probing was evaluated with aptamer and antibody to bring the possible advantages. The detection limit with antibody was found to be 1 pM, while aptamer shows 100 fM. Further, a fine-tuning was attempted with sandwich pattern of aptamer-FIX-antibody and antibody-FIX-aptamer and compared. Specific elevation of detection with 10 folds was noticed and displayed the detection at 100 f. in both sandwich patterns. In addition, FIX was detected in the diluted human serum by aptamer-FIX-antibody sandwich, it was found that FIX detected from the dilution factor 1:640. A novel demonstration is with higher discrimination against other clotting factors, XI and VII.

PCR-based reverse genetics strategy for bluetongue virus recovery.

BACKGROUND: Bluetongue virus (BTV), an emerging insect vector mediated pathogen affecting both wild ruminants and livestock, has a genome consisting of 10 linear double-stranded RNA genome segments. BTV has a severe economic impact on agriculture in many parts of the world. Current reverse genetics (RG) strategy to rescue BTV mainly rely on in vitro synthesis of RNA transcripts from cloned complimentary DNA (cDNA) corresponding to viral genome segments with the aid of helper plasmids. RNA synthesis is a laborious job which is further complicated with a need for expensive reagents and a meticulous operational procedure. Additionally, the target genes must be cloned into a specific vector to prepare templates for RNA transcription. RESULT: In this study, we have developed a PCR based BTV RG system with easy two-step transfection. Viable viruses were recovered following a first transfection with the seven helper plasmids and a second transfection with the 10 PCR products on the BSR cells. Further, recovered viruses were characterized with indirect immunofluorescence assays (IFA) and gene sequencing. And the proliferation properties of these viruses were also compared with wild type BTV. Interestingly, we have identified that viruses containing the segment 2 of the genome from reassortant BTV, grew slightly slower than the others. CONCLUSION: In this study, a convenient PCR based RG platform for BTV is established, and this strategy could be an effective alternative to the original available BTV rescue methods. Furthermore, this RG strategy is likely applicable for other Orbiviruses.

Hydrocephaly Analysis Supported by Computerized Tomography and Nuclear Magnetic Resonance.

Hydrocephalus is widely known as "hydrocephaly" or "water in the brain," a building up of abnormal cerebrospinal fluid in the brain ventricles. Due to this abnormality, the size of the head becomes larger and increases the pressure in the skull. This pressure compresses the brain and causes damage to the brain. Identification by imaging techniques on the hydrocephalus is mandatory to treat the disease. Various methods and equipment have been used to image the hydrocephalus. Among them, computerized tomography (CT) scan and nuclear magnetic resonance (NMR) are the most considered methods and gives accurate result of imaging. Apart from imaging, cerebrospinal fluid-based biomarkers are also used to identify the condition of hydrocephalus. This review is discussed on "hydrocephalus" and its imaging captured by CT scan and NMR to support the biomarker analysis.

Free volume, gas permeation, and proton conductivity in MIL-101-SO3H/Nafion composite membranes.

A series of MIL-101-SO3H/Nafion composite membranes was synthesized. They show an improved proton conductivity, due to the abundance of SO3H groups, which fosters proton conduction by binding the water molecules and enabling a larger number of conducting sites. Gas (including water vapor, hydrogen, and oxygen) permeability, crystallinity, and free volumes of the MIL-101-SO3H/Nafion composite membranes were investigated, as well as their correlation. By increasing the MIL-101-SO3H content, the gas permeability of the membranes significantly decreases, since the crystalline region is larger and the water-bearing MIL-101-SO3H particles are efficient barriers for the gas molecules. The gas permeation in the composite membranes is a very complex process and the results indicate no simple linear relation between the gas permeability and the free volume size (VFV), or between the gas permeability and the crystallinity. Moreover, it is very interesting to observe that the influence of VFV on the gas permeability is closely related to the size of the particular gas molecules: the larger the size of the gas molecules, the larger the free volume needed to achieve their rapid diffusion in the membrane. The results suggest the presence of a threshold value for VFV, which depends on the size of the gas molecules: when VFV is lower than this value, the gas molecules cannot easily jump through neighboring free volumes to a neighboring site, and, as a result, the permeability drops quickly.

Exploiting the Surface-Enhanced IR Absorption Effect in the Photothermally Induced Resonance AFM-IR Technique toward Nanoscale Chemical Analysis.

The photothermally induced resonance AFM-IR technique (denoted as PTIR) is a promising and still developing analytical method that can provide nanoscale chemical and topographical information. Herein, by taking advantage of a customized PTIR system with either top-down or bottom-up incidence mode for a quantum cascade laser (QCL), we explore how the surface-enhanced IR absorption (SEIRA) effect due to the Au-coated AFM tip and/or substrate may affect the PTIR signals from 25 to 580 nm thick p-nitrobenzoic acid (PNBA) samples, as a function of sample thickness, incidence mode, laser polarization, and Au film morphology. By analysis of the νas(NO2) band intensity, it is revealed that the SEIRA effect may increase the PTIR signals by 1.5-8.3 times, with that from the Au-coated substrate being greater than that from the Au-coated tip. Nevertheless, the overall PTIR signal goes up monotonically over the entire thickness range for the top-down incidence mode, while it increases and then decreases with the sample thickness for the bottom-up incidence mode. The p-polarized laser enhances the PTIR signal more than does the s-polarized laser, especially on the Au-coated substrate. The significant loss of the PTIR signal of a PNBA sample corroborates the substantial loss of the SEIRA effect of an annealed Au film. The present work may promote the application of the SEIRA effect to the PTIR technique and provides hints for developing the PTIR technique into a more versatile analytical tool.

Generation, identification, and functional analysis of monoclonal antibodies against porcine epidemic diarrhea virus nucleocapsid.

The variant strains of porcine epidemic diarrhea virus (PEDV) severely threaten the pig industry worldwide and cause up to 100% mortality in suckling piglets. It is critically important and urgent to develop tools for detection of PEDV infection. In this study, we developed six monoclonal antibodies (mAbs) targeting N protein of PEDV and analyzed their applications on enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence assay (IFA), western blot assay, and flow cytometry assay. The results demonstrated that all these six mAbs were IgG1 isotype and κ chain. Among these six mAbs, 3F12 recognizes a linear epitope (VAAVKDALKSLGI) while the other five mAbs recognize different conformational epitopes formed by a specific peptide fragment or the full length of N protein. The functional analysis showed that all these six mAbs were applicable to ELISA, western blot, IFA, and flow cytometry assay. In conclusion, we developed six mAbs against PEDV-N protein to facilitate the early detection of PEDV infection using ELISA, western blot, IFA, and flow cytometry.

Enhancement in Proton Conductivity and Thermal Stability in Nafion Membranes Induced by Incorporation of Sulfonated Carbon Nanotubes.

Proton exchange membrane fuel cell (PEMFC) is one of the most promising green power sources, in which perfluorinated sulfonic acid ionomer-based membranes (e.g., Nafion) are widely used. However, the widespread application of PEMFCs is greatly limited by the sharp degradation in electrochemical properties of the proton exchange membranes under high temperature and low humidity conditions. In this work, the high-performance sulfonated carbon nanotubes/Nafion composite membranes (Su-CNTs/Nafion) for the PEMFCs were prepared and the mechanism of the microstructures on the macroscopic properties of membranes was intensively studied. Microstructure evolution in Nafion membranes during water uptake was investigated by positron annihilation lifetime spectroscopy, and results strongly showed that the Su-CNTs or CNTs in Nafion composite membranes significantly reinforced Nafion matrices, which influenced the development of ionic-water clusters in them. Proton conductivities in Su-CNTs/Nafion composite membranes were remarkably enhanced due to the mass formation of proton-conducting pathways (water channels) along the Su-CNTs. In particular, these pathways along Su-CNTs in Su-CNTs/Nafion membranes interconnected the isolated ionic-water clusters at low humidity and resulted in less tortuosity of the water channel network for proton transportation at high humidity. At a high temperature of 135 °C, Su-CNTs/Nafion membranes maintained high proton conductivity because the reinforcement of Su-CNTs on Nafion matrices reduced the evaporation of water molecules from membranes as well as the hydrophilic Su-CNTs were helpful for binding water molecules.

Characterization of the Apelin/Elabela Receptors (APLNR) in Chickens, Turtles, and Zebrafish: Identification of a Novel Apelin-Specific Receptor in Teleosts.

Apelin receptor(s) (APLNR) are suggested to mediate the actions of apelin and Elabela (ELA) peptides in many physiological processes, including cardiovascular development and food intake in vertebrates. However, the functionality of APLNR has not been examined in most vertebrate groups. Here, we characterized two APLNRs APLNR1, APLNR2) in chickens and red-eared sliders, and three APLNRs in zebrafish (APLNR2a, APLNR2b, APLNR3a), which are homologous to human APLNR. Using luciferase-reporter assays or Western blot, we demonstrated that in chickens, APLNR1 (not APLNR2) expressed in HEK293 cells was potently activated by chicken apelin-36 and ELA-32 and coupled to Gi-cAMP and MAPK/ERK signaling pathways, indicating a crucial role of APLNR1 in mediating apelin/ELA actions; in red-eared sliders, APLNR2 (not APLNR1) was potently activated by apelin-36/ELA-32, suggesting that APLNR2 may mediate apelin/ELA actions; in zebrafish, both APLNR2a and APLNR2b were potently activated by apelin-36/ELA-32 and coupled to Gi-cAMP signaling pathway, as previously proposed, whereas the novel APLNR3a was specifically and potently activated by apelin. Similarly, an apelin-specific receptor (APLNR3b) sharing 57% sequence identity with zebrafish APLNR3a was identified in Nile tilapia. Collectively, our data facilitates the uncovering of the roles of APLNR signaling in different vertebrate groups and suggests a key functional switch between APLNR1 and APLNR2/3 in mediating the actions of ELA and apelin during vertebrate evolution.

Bone marrow PD-1 positive T cells reflect tumor mass and prognosis in multiple myeloma.

Programmed cell death protein 1 (PD-1) negatively regulates T cell effector mechanisms and contributes to tumor cell escape from immune surveillance. To evaluate potential clinical significance of PD-1 in multiple myeloma (MM), we quantified PD-1 expressing T cells in bone marrow (BM) of MM patients using flow cytometry. Our results showed that PD-1 positive T cells in BM from relapsed/refractory patients were significantly higher than those in the newly diagnosed, partial/complete remission MM, and controls, respectively. Additionally, high-risk MM patients had more PD-1 positive T cells in BM than low-risk patients. Moreover, PD-1 positive T cells in relapsed/refractory MM patients were positively associated with myeloma cell counts in BM and clinical stages. PD-1 positive T cells in BM of all MM and relapsed/refractory MM patients were positively correlated with their serum ß2-microglobulin concentrations. Our results strongly suggest that PD-1 expressing T cells in BM may be applied as a biomarker to reflect tumor mass and prognosis.