Pooled analysis of LAMP assay for the diagnosis of norovirus infection.

BACKGROUND: Rapid laboratory detection is essential to diagnose norovirus infection. LAMP has many advantages compared with RT-PCR for detecting norovirus, including high sensitivity, high specificity, rapidity, low cost, and intuitive results, which can be easily read with the naked eye with the help of color-based reporters. In this study, we intend to analyze the accuracy of LAMP methods for the diagnosis of norovirus infection. METHODS: Two researchers independently retrieved relevant literature up to January 2021 (PubMed, Web of Science, Cochrane Library, Embase, CNKI, Wan Fang, and VIP). The researchers screened all articles and extracted their research data for meta-analysis. QUADAS-2 tool was used to evaluate the quality of the included studies by Review Manager 5.3. Forest plots were performed by Meta-DiSc 1.4 to evaluate the accuracy of the test. Deeks' funnel plot symmetry tests were conducted by Stata 15.0 to check the potential publication bias. RESULTS: Eleven sets of data extracted from the eight included studies were included for meta-analysis. For the detection of norovirus, the pooled sensitivity, specificity, positive LR, negative LR, diagnostic OR, and their 95% CI were 0.96 (0.95-0.97), 0.99 (0.99-1.00), 91.14 (31.88-260.56), 0.06 (0.04-0.09), and 1473.68 (562.96-3857.70), respectively. Besides, AUC in the SROC curve was 0.9920. CONCLUSION: LAMP had high sensitivity and specificity in terms of the diagnosis of norovirus infection. However, further extension of this approach should be researched to ensure the accuracy and practicability of this hopeful test in the future.

Real-World Clinical Outcomes in Elderly Chinese Patients with Multiple Myeloma: A Single-Center Experience.

BACKGROUND Recently, improvement in overall survival (OS) was demonstrated in elderly patients with multiple myeloma (MM). Our aim here was to analyze treatment outcomes in elderly Chinese patients with MM in real-world practice. MATERIAL AND METHODS This retrospective study enrolled 122 newly diagnosed MM patients ages 65-84 between January 2007 and December 2015 in a single hematology department. RESULTS The median age of patients was 70.5 years. The median OS period of the entire cohort was 33 months; the 5-year OS estimate was 30.4%. The median OS of the 65-69, 70-74, and ≥75 years old groups were 43, 36, and 6 months, respectively. Female patients had better OS than male patients (40 and 28 months, P=0.026). Patients who received short-course bortezomib-containing regimens during their course of disease had a significantly longer median OS of 37 months compared with 28 months for patients without bortezomib treatment (P=0.029). Patients with age-adjusted Charlson comorbidity index (aaCCI) <5 showed longer median OS compared to those with aaCCI ³5 (45 months vs. 23 months, P<0.001). Multivariate analysis revealed that male sex, high aaCCI, and LDH were independent prognostic factor for OS. CONCLUSIONS The marked survival improvement in the elderly patients was associated with the increased use of short-course bortezomib. CCI and LDH are important clinical prognostic factors for survival in elderly MM patients.

Ganoderma lucidum polysaccharide exerts anti-tumor activity via MAPK pathways in HL-60 acute leukemia cells.

In this study, we investigated the anti-tumor activity both in vitro and in vivo of a polysaccharide obtained from Ganoderma lucidum on HL-60 acute myeloid leukemia cells, and focused on its targeting effect on mitogen-activated protein kinase (MAPK) pathways. It was found by the methods such as western blot and flow cytometry (FCM), that G. lucidum polysaccharide (GLP) blocked the extracellular signal-regulated kinase/MAPK signaling pathway, simultaneously activated p38 and JNK MAPK pathways, and therefore regulated their downstream genes and proteins, including p53, c-myc, c-fos, c-jun, Bcl-2, Bax, cleaved caspase-3 and cyclin D1. As a result, cycle arrest and apoptosis of HL-60 cells were induced. Therefore, GLP exerted anti-tumor activity via MAPK pathways in HL-60 acute leukemia cells.

Widely tunable quantum cascade laser-based terahertz source.

A compact, tunable, ultranarrowband terahertz source, Δν∼1 MHz, is demonstrated by upconversion of a 2.324 THz, free-running quantum cascade laser with a THz Schottky-diode-balanced mixer using a swept, synthesized microwave source to drive the nonlinearity. Continuously tunable radiation of 1 µW power is demonstrated in two frequency regions: ν(Laser) ± 0 to 50 GHz and ν(Laser) ± 70 to 115 GHz. The sideband spectra were characterized with a Fourier-transform spectrometer, and the radiation was tuned through CO, HDO, and D2O rotational transitions.

Diagnostic value of BinaxNOW antigen card for Severe Acute Respiratory Syndrome Coronavirus 2.

Rapid laboratory detection is remarkably crucial to diagnosing coronavirus disease 2019 (COVID-19) infection, due to whose outbreak causes to the world pandemic. The BinaxNOW antigen card (BinaxNOW) is a simple, effective, and cheap tool to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The meta-analysis in this study was conducted to evaluate the diagnostic performance of BinaxNOW for SARS-CoV-2. The researchers independently retrieved the related databases (PubMed, Embase, Web of Science, Cochrane Library) before May 1st, 2021, and extracted the relevant data based on the early inclusion/exclusion criterion. Quality Assessment of Diagnostic Accuracy Study-2 was used to evaluate the quality of the enrolled studies. Stata 16.0, Meta-DiSc 1.4, and Review Manager 5.3 were used to generate analytical data for the statistical analysis. 59 sets of data were identified from the seven studies included in this meta-analysis. The combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and their 95% confidence intervals were 0.77 (0.76 to 0.79), 0.99 (0.99 to 0.99), 65.72 (48.23 to 89.56), 0.23 (0.19 to 0.28), and 461.10 (281.55 to 755.13), respectively. The area under curve was 0.9910 in the summary receiver operating characteristic curve. BinaxNOW is beneficial for symptomatic patients' onset within 7 days. CT value and testing site may be the heterogeneity source of BinaxNOW accuracy. Moreover, this technology has an efficient performance for diagnosing COVID-19, especially in patients with heavy viral load. BinaxNOW may become a practical tool for large-scale or at-home use for COVID-19 in the post-pandemic era.Highlights● Pooled sensitivity with 0.77 and specificity with 0.99 in the BinaxNOW assay.● CT value and testing site may be the heterogeneity source of BinaxNOW accuracy.● BinaxNOW is beneficial for symptomatic patients' onset within 7 days.● BinaxNOW may become a practical tool for large-scale or at-home use for COVID-19.

2.32 THz quantum cascade laser frequency-locked to the harmonic of a microwave synthesizer source.

Frequency stabilization of a THz quantum cascade laser (QCL) to the harmonic of a microwave source has been accomplished using a Schottky diode waveguide mixer designed for harmonic mixing. The 2.32 THz, 1.0 milliwatt CW QCL is coupled into the signal port of the mixer and a 110 GHz signal, derived from a harmonic of a microwave synthesizer, is coupled into the IF port. The difference frequency between the 21st harmonic of 110 GHz and the QCL is used in a discriminator to adjust the QCL bias current to stabilize the frequency. The short-term frequency jitter is reduced from 550 kHz to 4.5 kHz (FWHM) and the long-term frequency drift is eliminated. This performance is compared to that of several other THz QCL frequency stabilization techniques.

A Novel Insight into Paraptosis-Related Classification and Signature in Lower-Grade Gliomas.

Lower-grade gliomas (LGG) are the most common intracranial malignancies that readily evolve to high-grade gliomas and increase drug resistance. Paraptosis is defined as a nonapoptotic form of programmed cell death, which is gradually focused on patients with gliomas to develop treatment options. However, the specific role of paraptosis in LGG and its correlation is still vague. In this study, we first establish the novel paraptosis-based prognostic model for LGG patients. The relevant data of LGG patients were acquired from The Cancer Genome Atlas database, and we found that LGG patients could be divided into three different clusters based on paraptosis via consensus cluster analysis. Through least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis, 10-paraptosis-related gene (PRG) signatures (CDK4, TNK2, DSTYK, CDKN3, CCR4, CASP9, HSPA5, RGR, LPAR1, and PDCD6IP) were identified to separate LGG patients into high- and low-risk subgroups successfully. The Kaplan-Meier analysis and time-dependent receiver-operating characteristic showed that the performances of predicting overall survival (OS) were dramatically high. The parallel results were reappeared and verified by using the Chinese Glioma Genome Atlas and Gene Expression Omnibus databases. Independent prognostic analysis and nomogram construction implied that risk scores could be considered the independent factor to predict OS. Enrichment analysis indicated that immune-related biological processes were generally enriched, and different immune statuses were highly infiltrated in high-risk group. We also confirmed the potential relationship of 10-PRG signatures and drug sensitivity of Food and Drug Administration-approved drugs. In summary, our findings provide a novel knowledge of paraptosis status and crucial direction to further explore the role of PRG signatures in LGG.

Terahertz inverse synthetic aperture radar (ISAR) imaging with a quantum cascade laser transmitter.

A coherent transceiver using a THz quantum cascade (TQCL) laser as the transmitter and an optically pumped molecular laser as the local oscillator has been used, with a pair of Schottky diode mixers in the receiver and reference channels, to acquire high-resolution images of fully illuminated targets, including scale models and concealed objects. Phase stability of the received signal, sufficient to allow coherent image processing of the rotating target (in azimuth and elevation), was obtained by frequency-locking the TQCL to the free-running, highly stable optically pumped molecular laser. While the range to the target was limited by the available TQCL power (several hundred microwatts) and reasonably strong indoor atmospheric attenuation at 2.408 THz, the coherence length of the TQCL transmitter will allow coherent imaging over distances up to several hundred meters. Image data obtained with the system is presented.

Bortezomib plus intermediate-dose dexamethasone and thalidomide in elderly untreated patients with multiple myeloma: a Chinese experience.

Bortezomib has proven to be active in patients with multiple myeloma (MM), including elderly patients. The aim of this study was to evaluate the efficacy and toxicity of bortezomib in combination with intermediate-dose dexamethasone (Dex) and thalidomide in untreated MM patients aged > or =65 years in a Chinese single center. In this study, 18 patients were treated with bortezomib at 1.3 mg/m(2) IV on Days 1, 4, 8, and 11 and Dex at 20 mg/day IV on Days 1-4 and 8-11 simultaneously. Thalidomide at dose of 100 mg/day was given everyday. The mean number of cycles of bortezomib treatment was 2.06. Three patients (17%) achieved a complete response (CR), four (22%) a very good partial response (VGPR), and nine (50%) a PR, resulting in an overall response rate of 89%. The median time to response was 22 days (range 14-50 days). The duration of response was significantly longer in patients achieving a CR/VGPR with respect to those achieving only a PR (8.5 vs. 4.2 months, P = 0.03). Grade 3-4 toxicities occurring in patients comprised weakness, thrombocytopenia, diarrhea, infection, and neuropathy. Only one patient suffered from deep vein thrombosis. This preliminary experience in Chinese patients indicated that bortezomib-Dex-thalidomide is highly effective in elderly untreated patients with MM, even in patients with poor prognostic features.

Clinical applications of adoptive natural killer cell immunotherapy for cancer: current status and future prospects.

Natural killer (NK) cells are cytotoxic and cytokine-producing lymphocytes involved in the immune defense against viral infections and tumors. NK cells activated with cytokines, such as interleukin-2, have been used since the 1980s as adoptive immunotherapy against cancer. NK cell alloreactivity has been demonstrated to enhance control of acute myeloid leukemia relapse and greatly reduce the risk of graft-versus-host disease in HLA haplotype-mismatched hematopoietic transplantation, and has been explored as a tool for adoptive immunotherapy for cancer patients. Future manipulation to improve NK cell adoptive immunotherapy by means of increasing target recognition and reducing inhibitory signaling is being explored.

Genetic variants in HLA-DP/DQ contribute to risk of acute myeloid leukemia: A case-control study in Chinese.

Human leukocyte antigens (HLA) are heterodimeric cell surface molecules that bind short peptides derived from non-self and self proteins. Accumulative evidence showed that specific alleles of HLA class II were associated with the susceptibility to malignant tumors including acute leukemia. In this study, we investigated the association between four single nucleotide polymorphisms (SNPs) at HLA-DP/DQ and acute myeloid leukemia (AML) risk. We genotyped four SNPs in HLA-DP (rs3077 G > A and rs9277535 G > A) and HLA-DQ (rs2856718 A > G and rs7453920 G > A) in a case-control study of 545 AML cases and 1034 cancer-free controls using Taqman allelic discrimination assay. The associations between these SNPs and AML risk were estimated by computing the odds ratios (ORs) and their 95% confidence intervals (CIs) from multivariate logistic regression analysis. We found significant associations of the variant alleles in HLA-DP (rs3077 and rs9277535) and HLA-DQ rs7453920 with increased AML risk (adjusted OR = 1.29, 95%CI = 1.10-1.51for rs3077 in additive model; adjusted OR = 1.29, 95%CI = 1.11-1.51 for rs9277535 in additive model; adjusted OR = 3.18, 95%CI = 1.86-5.46 for rs7453920 in recessive model). When combining the effects of rs3077, rs9277535 and rs7453920, we found that AML risk was significantly increased with the increasing number of variant alleles of the three SNPs in a dose-dependent manner (P for trend < 0.001). Besides, we found multiplicative interaction between rs3077 and age (≤45 years old and > 45 years old; P = 0.046). In conclusion, HLA-DP and HLA-DQ loci are candidate susceptibility regions for AML in Han Chinese.

Frequency stabilization of a single mode terahertz quantum cascade laser to the kilohertz level.

A simple analog locking circuit was shown to stabilize the beat signal between a 2.408 THz quantum cascade laser and a CH(2)DOH THz CO(2) optically pumped molecular laser to 3-4 kHz (FWHM). This is approximately a tenth of the observed long-term (t approximately sec) linewidth of the optically pumped laser showing that the feedback loop corrects for much of the mechanical and acoustic-induced frequency jitter of the gas laser. The achieved stability should be sufficient to enable the use of THz quantum cascade lasers as transmitters in short-range coherent transceivers.

The functional polymorphisms of ARID5B and IKZF1 are associated with acute myeloid leukemia risk in a Han Chinese population.

Since two genome-wide association studies identified the same susceptible region at ARID5B and IKZF1 for acute leukemia in Caucasians in the same time, several research groups have confirmed the similar results in different ethnicities and of different acute leukemia subtypes (ALL and AML). However, the causal variants of these two genes were not identified. In this study, we systematically screened 6 potentially functional SNPs in ARID5B and IKZF1 genes, and conducted a case-control study including 660 AML cases and 1034 cancer-free controls to investigate the associations between these SNPs and AML risk. We found that the variant alleles of rs4509706 and rs11761922 could significantly increase the risk of AML (rs4509706: OR=1.35, 95%CI=1.12-1.62 in additive model; rs11761922: OR=1.29, 95%CI=1.02-1.62 in recessive model). Luciferase reporter assay showed that both rs11761922-G and rs4509706-C significantly increased the luciferase levels as compared with rs11761922-C and rs4509706-T in K562 cells (P<0.05 for rs11761922 and P<0.001 for rs4509706). Our results indicated that rs4509706 and rs11761922 may play important roles in AML development in Chinese population.

The functional polymorphisms of LIS1 are associated with acute myeloid leukemia risk in a Han Chinese population.

There is increasing evidence that the human lissencephaly-1 gene, LIS1, plays an important role in carcinogenesis of several malignancies including leukemia. However, little is known about the relationship between single nucleotide polymorphisms (SNPs) in LIS1 and the susceptibility to myeloid leukemia. In the present study, we systematically screened 5 potentially functional polymorphisms in LIS1, and conducted a case-control study including 660 acute myeloid leukemia (AML) patients and 1034 cancer-free controls in a Chinese population, to assess the association between these SNPs and AML risk. We found that the variant alleles of rs4790348, rs4790353, and rs7209748 could significantly increase the AML risk (rs4790348: adjusted OR=1.31, 95%CI=1.13-1.53 in additive model; rs4790353: adjusted OR=4.97, 95%CI=1.59-15.50 in recessive model; rs7209748: adjusted OR=2.34, 95%CI=1.11-4.94 in recessive model). These findings indicated that genetic variants in LIS1 may contribute to AML risk in Chinese population.

Evaluation of pretreatment red cell distribution width in patients with multiple myeloma.

BACKGROUND: Red blood cell distribution width (RDW) has been reported as an inflammatory biomarker and a predictor of prognosis in different types of cancer. However, the role of RDW at diagnosis in patients with multiple myeloma (MM) has been less explored. OBJECTIVE: We aimed to investigate the association between RDW and the response to treatment and overall survival (OS) in patients with MM. METHODS: We retrospectively analyzed the data for 196 MM patients between January 1, 2007 and December 31, 2015. Kaplan-Meier analysis and Cox regression model were used. RESULTS: High RDW values were associated with lower platelet count, lower hemoglobin levels, lower albumin levels, and higher lactate dehydrogenase (LDH) level. Among the entire cohort, the overall response rates (ORR) and complete response (CR) rate of initial therapy were markedly higher in the low-RDW group compared to the high-RDW group. RDW was significant lower in CR in comparison to Non-CR groups in patients treated with bortezomib-based regimens as induction therapy. The patients with low-RDW at diagnosis had better OS when compared to those with high-RDW. CONCLUSIONS: Elevated RDW was associated with worse survival in patients with MM and could predict treatment responses. Further larger and prospective studies are required.

Real-world outcome and healthcare costs of relapsed or refractory multiple myeloma: A retrospective analysis from the Chinese experience.

OBJECTIVES: Our aim was to retrospectively investigate the real-world outcome and healthcare costs associated with the treatment of patients with relapsed or refractory multiple myeloma (RRMM) in a Chinese single center. METHODS: A retrospective study was conducted for 93 patients between January 2008 and December 2013 in a Chinese hematology department. Total monthly costs attributable to each cost component were described across all regimens and for bortezomib-based treatment regimens. RESULTS: Mean total cost per patient-month ($1139.85) varied depending on the sequence of therapy (range: mean $51.63-$6600.96). Drugs and hospital visit were the most and the least consumed resource (65.48% and 2.87%, respectively). Mean total monthly costs were $2071.96 (range: $679.73-$6600.96) and $551.14 (range: $51.63-$1698.59) for patients receiving bortezomib and patients not receiving bortezomib, respectively. Differences between the two groups were significant for drugs; drugs costs were higher for patients treated with bortezomib. Kaplan-Meier curves showed a longer overall survival (mean [median] 31.43 [25] vs. 21.93 [18] months) for patients treated with bortezomib. CONCLUSION: Real-world costs during treatment of RRMM varied greatly. Total costs during bortezomib-based regimens are significantly higher compared with non-bortezomib regimens. Further multi-center studies are needed to assess the cost-effectiveness of bortezomib for the treatment of RRMM in China.

Replication analysis confirms the association of several variants with acute myeloid leukemia in Chinese population.

PURPOSE: Two genome-wide association studies (GWASs) have identified several new acute leukemia susceptibility loci in populations of European descent. However, the roles of these loci in the development of acute leukemia in other populations are largely unknown. METHODS: We genotyped 16 single-nucleotide polymorphisms selected from published GWASs in an independent case-control study with a total of 545 acute myeloid leukemia (AML) cases and 1034 cancer-free controls in a Chinese population. Multivariate logistic regression was used to analyze the associations between these variants and AML risk. RESULTS: We found that with the similar effect to GWASs, risk alleles of rs2191566, rs9290663, rs11155133, rs2239633, rs10821936, and rs2242041 significantly increased the risk of AML in at least one genetic model [odds ratios (ORs) range from 1.26 to 4.34, P values range from <0.001 to 0.043]. However, the variant T allele of rs10873876 decreased the AML risk, which was in the opposite effect direction (OR 0.62, P < 0.001 in additive model). Besides, we found significant multiplicative interaction between rs9290663 and age (≤45 years old and >45 years old; P = 0.009). CONCLUSION: Our results indicated that genetic variants associated with acute leukemia risk in European populations may also play important roles in AML development in Chinese population.

[Relationship between RAD51-G135C and XRCC3-C241T Single Nucleotide Polymorphisms and Onset of Acute Myeloid Leukemia].

OBJECTIVE: To investigate the relationship between RAD51-G135C and XRCC3-C241T single nucleotide polymorphisms and onset of acute myeloid leukemia (AML). METHODS: The study was performed in 2 groups: AML patient group and normal person group as control group. Genomic DNA was extracted from peripheral blood cells of 545 AML patients and 1 034 normal persons. Genotypes of RAD51-G135C and XRCC3-C241T were analyzed by TaqMan probe technology and the ralatienship between RAD51-G135C/XRCC3-C241T polymorphisms and onset of acute myeloid leukemia was investigated. RESULTS: Compared with the control group, RAD51-G135C homozygous mutant (CC) could significantly increase the risk of AML patients (OR=3.07), and there was no statistical relationship between heterozygous mutant (GC) of RAD51-G135C and onset of AML. There was no statistical relationship between homozygous mutant (TT) of XRCC3-C241T and onset of AML, and the XRCC3-C241T heterozygous mutation type (CT) increased the risk of AML patients (OR=0.66). CONCLUSION: RAD51-G135C homozygous mutant and XRCC3-C241T heterozygous mutation significantly increase the risk of the AML onset, which can provide more predictive value for incidence of AML.

Contributions of T lymphocyte abnormalities to therapeutic outcomes in newly diagnosed patients with immune thrombocytopenia.

T cell abnormalities have been reported to play an important role in pathogenesis of immune thrombocytopenia (ITP) besides specific autoantibodies towards platelet. The aim of this study was to explore the clinical importance of T lymphocyte subsets in adult patients with newly diagnosed ITP before and after first-line treatment. Elderly ITP patients were also studied and we tried to analyze the relationships between these items and therapeutic outcomes. The patients were treated with intravenous immunoglobulin (IVIG) plus corticosteroids and therapeutic responses were evaluated. As a result, compared with the controls, absolute lymphocyte counts in ITP patients decreased significantly before treatment. After treatment, lymphocyte counts restored to control level regardless of their treatment outcomes. In addition, we observed increased IgG and CD19+ cell expression and decreased CD4+/CD8+ cell ratio in both whole ITP group and elderly group before treatment. After treatment, the increased IgG and CD19+ cell expression could be reduced in both respond and non-respond group regardless of patient age, while CD4+/CD8+ cell ratio could not be corrected in non-respond ITP patients. In non-respond ITP patients, increased CD8+ cell expression was noticed and could not be corrected by first-line treatment. Furthermore, even lower NK cell expression was found in non-respond elderly patients after treatment when compared with that in controls. Our findings suggest that ITP patients usually had less numbers of peripheral lymphocytes and patients with higher levels of CD8+ cells or lower levels of CD4+/CD8+ cell ratio were less likely to respond to first-line treatment. Lower levels of NK cells made therapies in elderly ITP patients even more difficult.

[FcγRIII a polymorphisms and efficacy of Rituximab combined chemotherapy for diffuse large B-cell lymphoma in Chinese patients].

OBJECTIVE: To evaluate the impact of Fc gamma receptor IIIa (FcγR IIIa) polymorphisms on the efficacy of rituximab (RTX) combined chemotherapy for patients with diffuse large B-cell lymphoma (DLBCL). METHODS: FcγRIIIa polymorphisms were analyzed by PCR in 122 patients and 100 healthy controls. All patients received 8(4-12) cycles of RTX combined chemotherapy. RESULTS: 78(63.93%) patients with F/F, 5(4.10%) with V/V, and 39(31.97%) with V/F were identified, which were not different compared to controls. Patients with different FcγRIIIa genotypes did not have any difference in terms of gender, age, molecular subtypes, lactate dehydrogenase (LDH) or international prognostic index (IPI). The overall response rate (ORR) was 89.35% with a complete response (CR) of 80.33% and a partial response (PR) of 9.02%. The ORR was 83.33%, 100.00% and 100.00% in F/F, V/V and V/F, respectively. A higher response rate was observed in V/V and V/F as compared with F/F (P<0.05). With a median follow-up of 35 months (range: 12-62 months), 46(37.71%) patients had relapsed and 40 (32.79%) cases progressed and ended in death. The 3-year progress-free survival (PFS) rate was 41.03%, 100.00%, 100.00% in F/F, V/V and V/F, respectively. The 3-year overall survival (OS) rate was 48.72%, 100.00% and 100.00% in patients with three genotypes. The PFS and OS rate were significantly higher in V/V and V/F as compared with F/F (P<0.05). CONCLUSION: FcγR III a polymorphisms could predict response and prognosis of RTX combined chemotherapy for patients with DLBCL.