Clinical efficacy of etocoxib combined with low dose colchicine in the treatment of acute gouty arthritis in 37 patients / 中国基层医药

Objective:To investigate the clinical efficacy of etocoxib combined with low-dose colchicine in the treatment of acute gouty arthritis in 37 patients.Methods:A total of 74 patients with acute gouty arthritis who received treatment in The Second People's Hospital of Liaocheng from October 2019 to October 2021 were included in this study. They were randomly assigned to undergo treatment with etocoxib alone (control group, n = 37) or etocoxib combined with low-dose colchicine (observation group, n = 37). All patients were treated for 1 week. Clinical efficacy, Visual Analogue Scale score, laboratory indicators, incidence of adverse reactions, and Quality of Life Comprehensive Assessment Questionnaire-74 score were compared between the two groups. Results:The total response rate in the observation group was significantly higher than that in the control group [95% (35/37) vs. 65% (24/37)]. At 1, 3, and 6 days after treatment, the Visual Analogue Scale score in the observation group was significantly lower than that in the control group ( t = 19.77, 15.43, 29.01, all P < 0.001). After treatment, blood uric acid, C-reactive protein, and erythrocyte sedimentation rate in the observation group was (432.26 ± 31.26) μmol/L, (16.25 ± 1.62) mg/L, (31.26 ± 1.25) mm/h, respectively, which was significantly lower than (485.26 ± 39.62) μmol/L, (45.26 ± 3.88) mg/L, (46.52 ± 2.82) mm/h in the control group ( t = 6.39, 41.97, 30.09, all P < 0.001). Quality of Life Comprehensive Assessment Questionnaire-74 score in the observation group was significantly higher than that in the control group ( t = 13.41, 17.73, 16.09, 11.77, all P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Etocoxib combined with low-dose colchicine can effectively reduce pain and inflammatory reactions in patients with acute gouty arthritis and improve quality of life, with a low incidence of adverse reactions.

Prevalence of HEV infection markers in Chinese blood donors: a meta-analysis / 中国输血杂志

【Objective】 To analyze the serological markers and RNA prevalence of HEV infection in Chinese voluntary blood donors in different regions of China, so as to provide basis for the necessity of HEV screening and the formulation of screening strategies for voluntary blood donors. 【Methods】 Databases such as CNKI, Wanfang medicine and PubMed were searched for eligible literature, and the literature data meeting the inclusion criteria were extracted for meta-analysis using R4.1.3 software. 【Results】 A total of 26 studies were included, involving 97 928, 117 831 and 82 673 cases, respectively, for anti-HEV IgG, anti-HEV IgM and HEV RNA. The pooled estimated prevalence of anti-HEV IgG, anti-HEV IgM and HEV RNA among Chinese voluntary blood donors was 23.0% [95% CI (18%, 29%)] vs 1.13% [95% CI (0.94%, 1.36%)] vs 0.028%[95%CI(0.006%, 0.059%)], and there were significant differences among different cities and regions. 【Conclusion】 The past infection rate of HEV among voluntary blood donors in China was somewhat high and with significant regional differences. The current infection rate was relatively low and had decreased compared with that in the past decade, but there was still residual risk of blood transfusion. It is necessary to pay more attention to blood HEV screening of voluntary blood donors.

Research progress of caput femoris posterior tilt and its impact on prognosis in nondisplaced femoral neck fractures / 中国骨伤

There are still many unresolved problems in the treatment and prognosis of nondisplaced femoral neck fractures, such as nonunion and avascular necrosis of the caput femoris .In order to reduce the risk of various complications after non-displaced femoral neck fractures, the caput femoris posterior tilt of femoral neck fractures and its impact on prognosis have attracted more and more attention. A large number of scholars' studies have found that when the posterior tilt exceeds 20°, the risk of internal fixation failure increases significantly. Based on this concept, we can choose to use primary artificial joint replacement instead of three-screw internal fixation according to the different posterior tilt angles of patients to reduce the incidence of postoperative complications. At the same time, our analysis found that comminution of the posterior segment of the femoral neck would lead to an increase in the posterior inclination angles. The purpose of this review was to investigate the relationship between caput femoris posterior tilt of femoral neck fractures and surgical outcome, and to introduce a new method for measuring caput femoris posterior tilt of the femoral neck.

Enhanced Vulnerability of LKB1-Deficient NSCLC to Disruption of ATP Pools and Redox Homeostasis by 8-Cl-Ado.

Loss-of-function somatic mutations of STK11, a tumor suppressor gene encoding LKB1 that contributes to the altered metabolic phenotype of cancer cells, is the second most common event in lung adenocarcinomas and often co-occurs with activating KRAS mutations. Tumor cells lacking LKB1 display an aggressive phenotype, with uncontrolled cell growth and higher energetic and redox stress due to its failure to balance ATP and NADPH levels in response to cellular stimulus. The identification of effective therapeutic regimens for patients with LKB1-deficient non-small cell lung cancer (NSCLC) remains a major clinical need. Here, we report that LKB1-deficient NSCLC tumor cells displayed reduced basal levels of ATP and to a lesser extent other nucleotides, and markedly enhanced sensitivity to 8-Cl-adenosine (8-Cl-Ado), an energy-depleting nucleoside analog. Treatment with 8-Cl-Ado depleted intracellular ATP levels, raised redox stress, and induced cell death leading to a compensatory suppression of mTOR signaling in LKB1-intact, but not LKB1-deficient, cells. Proteomic analysis revealed that the MAPK/MEK/ERK and PI3K/AKT pathways were activated in response to 8-Cl-Ado treatment and targeting these pathways enhanced the antitumor efficacy of 8-Cl-Ado. IMPLICATIONS: Together, our findings demonstrate that LKB1-deficient tumor cells are selectively sensitive to 8-Cl-Ado and suggest that therapeutic approaches targeting vulnerable energy stores combined with signaling pathway inhibitors merit further investigation for this patient population.

Research progress in research on platelets derived from induced pluripotent stem cells in vitro / 国际生物医学工程杂志

Currently, there are insufficient sources of platelets for clinical transfusion, and there are risks of alloimmune reactions and transfusion-transmitted infections (TTI) after transfusion. In recent years, platelets derived from human induced pluripotent stem cells (hiPSCs) have become one of the hottest research topics in the transfusion community, and studies have shown that they have the potential to address the limitations of platelet transfusion and alleviate the conflict between platelet supply and demand in clinical settings. However, the efficiency of hiPSCs in producing functional platelets in vitro is still low, and the yield and quality are still far below clinical transfusion standards. In this review, the basis and applications related to hiPSCs-derived platelets, studies related to human leukocyte antigen (HLA) gene-silenced hiPSC-derived platelets, and challenges faced by hiPSCs-derived platelet products were reviewed, providing references for in-depth research and future clinical applications of hiPSCs-derived platelets.

Detection ability of nucleic acid screen laboratory in blood bank based on NCCL external quality assessment data / 中国输血杂志

【Objective】 To evaluate the laboratory's NAT ability by analyzing the feedback reports of nucleic acid test (NAT) results of external quality assessment (EQA) of National Center for Clinic Laboratories (NCCL), so as to improve the laboratory management details and ensure blood safety. 【Methods】 The data of NCCL NAT EQA of blood screening laboratory of Tianjin Blood Center (a total of five occasions from Jan 2019 to Jun 2021) were statistically analyzed. 【Results】 From Jan 2019 to Jun 2021, the laboratory participated in EQA for five times and all the results were qualified. The test results of NAT EQA HIV RNA/HCV RNA/HBV DNA detected by R1, R2 and R4 were consistent with the reference results. R3 showed false positive results (CT value 40.46) in the single donation detection of sample No.1925 in HCV RNA. Unreported data of the laboratory was that in the first EQA in 2021, the R4 showed false positive results (CT value 35.8) in in the single donation detection of sample No.2113 in HIV RNA. 【Conclusion】 The performance of each NAT screening system in our laboratory is relatively stable except occasional false positive results influenced by every factor. Potential problems can be found and continuously improved by assaying EQA reports and the extended experimental results of EQA samples to further improve the detection ability.

Status and characteristics of blood donor deferrals: a retrospective analysis in Tianjin from 2016 to 2020 / 中国输血杂志

【Objective】 To analyze the profile, preliminary screening and laboratory test results of voluntary blood donors in the past five years, so as to provide basis for formulating the recruitment strategy, ensuring clinical blood use and improving blood safety and quality. 【Methods】 789 570 voluntary blood donors from 2016 to 2020 were classified according to the category, and the positive rate of blood testing results was statistically analyzed. 【Results】 The proportion of transfusion-transmitted infections (TTI), including HBsAg, anti-HCV, anti-T, and anti-HIV, was led by HBsAg, except for anti-TP leading in 2018. The positive rate of ELISA items and ALT tests showed statistical significance by age groups(P0.05). The positive rate of preliminary screening and laboratory testing showed differences among occupation and educational background(P0.05). The number of HIV positive males (n=228) was higher than that of females(n=3), and the proportion of workers (23.08%~40.74%) and staff (16.67%~46.67%) were large. In 2020, however, the proportion of HIV infected students increased sharply to 21.62%. Sole HBV DNA positive cases was the most (n=460), while the number of sole HIV RNA(n=3) and HCV RNA positive cases (n=6) were rather low. 【Conclusion】 Targeted recruitment strategies should be formulated according to the profile and test results of voluntary blood donors to further improve blood test ability and ensure blood safety.

HBV serologic and virus characteristics of HBsAg negative and NAT non-discriminated samples from blood donors / 中国输血杂志

【Objective】 To investigate the HBV infection of TMA initially reactive but discriminatory test non-reactive samples(NDR) after the individual donation nucleic acid detection(ID-NAT)of TMA, and analyze its serological and molecular biological characteristics, so as to improve the safety of blood transfusion. 【Methods】 121 970 samples of blood donors in the center from January 1, 2021 to December 31, 2021 were routinely tested by serology and nucleic acid of ID NAT, and 21 HBsAg(-)/ NDR samples were random collected. After the plasma samples were concentrated by ultra-high speed centrifugation, the gene sequences of BCP/PC, pre-S/S and S region were amplified by Nested PCR. The S region sequence was also sequenced to analyze the viral genotype and amino acid variation. At the same time, the original TMA retest discriminatory test was adopted, and Roche MPX 2.0 was used for ID-NAT, and the samples was not virus-concentrated.NDR samples were supplemented with electrochemiluminescence for anti-HBc and anti-HBs quantitative detection. 【Results】 Of the 121 970 samples screened, 117(0.096%) were found to be HBsAg(-)/NDR samples, of which 21 samples underwent a confirmation test. Sixteen(76.2%) cases were positive for HBV DNA by TMA retest, 7(33.3%) positive for HBV DNA by Roche MPX 2.0 ID-NAT, 9(42.9%) confirmed by Nested PCR, and 8(38.1%) positive by any two methods. Test results of serological markers were as follows: 17(80.9%) positive anti-HBc and 8(38.1%) positive anti-HBs. Eight infected cases were confirmed to have occult hepatitis B infection(OBI). The gene sequence of S region was successfully amplified and sequenced in 3 cases, all of which belonged to C type. Two mutations occurred in specimen S-2, all of which were outside MHR. There were 13 mutations in sample S-6, 6 mutations outside MHR and 7 mutations inside MHR. 【Conclusion】 Nearly 40% of NDR samples can still be detected as HBV DNA positive after virus concentration. Anti-HBc has a high detection rate, and there may be a potential risk of HBV transmission. The current NAT detection sensitivity should be improved. The amino acid mutation of S gene sequence may be related to OBI formation.

Establish deferral criterion for HIV serological testing in blood donors / 中国输血杂志

【Objective】 To establish deferral criterion of HIV ELISA (enzyme-linked immunosorbent assay) and electrochemiluminescence immunoassay(ECLIA) by using receiver operating characteristic curve(ROC) method to screen HIV reactive blood donors suitable for entering the re-entry process and improve the management efficiency of reactive blood donors. 【Methods】 The test results of 92 001 blood donors from February to September 2019 were analyzed, and 177 reactive samples were screened by conventional screening mode (twice ELISA and once nucleic acid), supplemented with electrochemiluminescence immunoassay assay (ECLIA), and confirmed by Western blotting (WB). Screening reactive samples were divided into three groups: group A was both serological and nucleic acid reactivity, group B was only serological reactive, and group C was only nucleic acid reactivity. Its efficacy in blood donor classification was assessed by drawing ROC curves with 99% specific corresponding S/CO low values as the deferral criterion of the corresponding serological method. 【Results】 1) A total of 177 HIV reactive samples were detected in conventional mode, including 34 in group A, 142 in Group B and 1 in Group C. The positive predictive value (PPV) was 100%, 0.75% and 100%, respectively. ECLIA detection mode (once ECLIA and once NAT), a total of 67 HIV reactive samples including 34 in group A, 32 in group B and 1 in group C, with positive predictive values of 100%, 3.7% and 100%, respectively.2) The HIV test results showed diversity, with 36 true positive samples including 1 HIV elite controller and 3 early HIV infections (1 HIV ELISA antigen/antibody window and 2 ELISA HIV antibody window), and 32 serological and NAT cases were reactive infections.3) The deferral limit of ELISA 1 and ELISA 2 in conventional screening mode were 20.25 and 9.85, respectively, can screen 97.14% (34/35) of all true positive samples in group A and B, except for one ELISA HIV antibody window (ELISA 2 reactivity). The positive predictive values were 93.94% and 92.85%, respectively. The ECLIA deferral limit of 7.83 can screens all true positive samples in Groups A and B (35/35)in ECLIA mode. The positive predictive value was 94.59%. 【Conclusion】 The establishment of deferral limits in this study can effectively screen HIV-positive blood donors, and the number of screened blood donors is greatly reduced, which is helpful to fine and scientific management of HIV-reactive blood donors. The deferral limit values of different testing reagents are quite different, so each laboratory should choose appropriate testing methods to establish the deferral limit values suitable for the laboratory according to its own testing ability, so as to provide technical support for optimizing the process of returning blood donors to the team.

Study on the hepatitis B virus infection in blood donors reactive to jointed NAT but non-reactive to primary discriminatory test / 中国输血杂志

【Objective】 To analyze the status of HBV infection in blood donors reactive to jointed NAT but non-reactive to primary discriminatory tests (NRR), so as to provide suggestions and data support for subsequent studies on NRR samples. 【Methods】 HCV RNA and HIV RNA repeat differential detection, HBV DNA viral load detection and HBV pgRNA copy volume detection were performed in the plasma of 60 blood donors with negative ELISA results in routine blood screening and NRR in NAT. HBsAg, HBsAb, HBcAb, HBeAg and HBeAb serological tests were performed on the NRR samples with positivity in HBV DNA viral load and HBV pgRNA virus copy detection, so as to analyze the serological infection status and occult hepatitis B (OBI) infection. 【Results】 The HCV RNA and HIV RNA repeat discrimination results of 60 NRR samples were negative. The quantitative detection results of HBV DNA in 60 NRR samples were positive in 9 cases (15%), and the HBV DNA concentration was less than 10IU/mL. Nine cases (15%) were positive for HBV pgRNA quantitative detection, and the virus copy volume ±SD was (289±58.25) copies/mL. Two NRR samples (3.33%) were HBV DNA positive and HBV pgRNA positive. Among the 9 HBV-DNA positive samples, the highest positive rate of HBcAb was 66.67%, and 7 (77.78%) of them were confirmed to be seropositive for OBI. Among the 9 HBV pgRNA positive samples, the copy amount of pgRNA in HBcAb positive samples was slightly higher than that in negative samples, while the copy amount of pgRNA in HBsAb and HBeAb positive samples was lower than that in corresponding negative samples. In recent 6 years, the proportion of NRR samples in the single NAT system of the center fluctuated from 0.09% to 0.13%. 【Conclusion】 HBV DNA and HBV pgRNA exist in NRR samples. HBV DNA and/or HBV pgRNA positive samples can be detected in the relevant serological infectious markers. NRR samples have a certain potential risk of OBI infection. HBV DNA detection plus HBV pgRNA can better confirm the status of virus infection in NRR and improve the safety of blood transfusion.

Discriminatory positive rate of individual donor-nucleic acid test mode of blood station laboratories in the Beijing-Tianjin-Hebei Region / 中国输血杂志

【Objective】 To analyze the discriminatory positive rate(DPR)of individual donor-nucleic acid test (ID-NAT)mode of blood screening laboratories in the Beijing-Tianjin-Hebei Region, explore the possible reasons for DPR differences among blood station laboratories and the measures to lesson the differences, in order to lay a foundation for realizing the homogenization of detection quality of blood screening laboratories in Beijing-Tianjin-Hebei Region. 【Methods】 The number of triplex-positive samples and discriminatory -positive samples of A, B, C, and D blood station laboratories, which submitted to ID-NAT system, in Beijing-Tianjin-Hebei Region from January to December 2018 were collected by a questionnaire of Quality Supervise Index of Blood Station Laboratories in Beijing-Tianjin-Hebei Region. The triplex-positive samples were divided into solo-positive samples(NAT+ ELISA-) and dual-positive samples(NAT+ ELISA+ ). The changes of total DPR of A, B and C blood screening laboratories in different months was analyzed and compared respectively. The differences of total DPR of ID-NAT, DPR of NAT+ ELISA+ samples, and DPR between NAT+ ELISA-samples and NAT+ ELISA+ samples of A, B, and C blood screening laboratories during January 2018 to December 2018 was analyzed and compared. The difference of DPR of NAT+ ELISA-samples among A, B, C, and D blood station laboratories was also compared. 【Results】 Significant difference in total DPR was noticed in different months of A, B, and C blood station laboratories from January to December 2018(P<0.05), with the highest DPRs of A, B and C laboratory at 91.67%, 72.73%. and 80.39%, the lowest DPRs at 65.88%, 21.05%, and 7.69%, respectively. Significant statistical differences in the total DPR and the DPR of NAT+ ELISA+ samples were found among A, B, and C blood station laboratories(P<0.05). Significant statistical differences in the DPR of NAT+ ELISA- samples were found among A, B, C, and D laboratories(P<0.05). The DPR of NAT+ ELISA+ samples of A and B blood station laboratories (95.97% and 85.25%) were significantly higher than those of NAT+ ELISA-samples (36.36% and 30.71%)(P<0.05). However, the DPR of NAT+ ELISA+ samples of C blood station laboratory (32.63%) was significantly lower than that of NAT+ ELISA-samples (44.39%)(P <0.05). 【Conclusion】 There were significant differences in the total DPR, the DPR of NAT+ ELISA-samples and NAT+ ELISA+ samples that were detected by ID-NAT system in 2018 among blood station laboratories in the Beijing-Tianjin-Hebei Region, and the total discriminatory positive rate in different months was also different for the same blood station. It is necessary to explore the reasons leading to the differences and seek solutions in order to achieve the homogenization of detection quality of blood screening laboratories in Beijing-Tianjin-Hebei Region.

ECLIA and confirmation results of HIV reactive samples in blood screening / 中国输血杂志

【Objective】 To perform electrochemiluminescence immunoassay (ECLIA) and Western blotting (WB) confirmation tests for HIV reactive samples in blood screening, and analyze the correlation between ELISA (enzyme-linked immunosorbent assay), ECLIA results and confirmed infection, so as to provide data support for the application of ECLIA in blood screening. 【Methods】 177 HIV reactive samples in blood screening testing detected by our laboratory from February to October 2019 were collected, of which 137 were reactiv to isolated ELISA reagent e, 39 to dual ELISA reagent, and 1 in window period. Ten maker-negative samples were randomly selected to undergo ECLIA with the above 177 samples. HIV reactive samples were sent to Centers for Disease Control and Prevention (CDC) for confirmation tests, and the results were analyzed and compared. 【Results】 Among the 177 HIV reactive samples, 66 were ECLIA reactive, 111 negative, and the 10 maker-negative samples remained negative. The sensitivity, specificity, positive predictive value, negative predictive value and total concordance rate of ECLIA were 97.1%, 81.1%, 55%, 99.1% and 84.2%, respectively, showing better performance than that of two ELISA reagents(P0.05). The positive predictive value and specificity were tested by chi-square test, and the difference between ECLIA and reagent 2 was statistically significant (P<0.05). The ECLIA results showed significant correlation with the confirmation results with good consistency(examed by Kappa test). Among the three reagents, ECLIA presented highest accuracy and largest Youden index. 【Conclusion】 ECLIA presents high detection sensitivity, which can improve the detection ability of early HIV infection and shorten the window period of HIV detection, therefore should be popularized in blood screening.

Inhibition of nonsense-mediated decay rescues p53ß/γ isoform expression and activates the p53 pathway in MDM2-overexpressing and select p53-mutant cancers.

Inactivation of p53 is present in almost every tumor, and hence, p53-reactivation strategies are an important aspect of cancer therapy. Common mechanisms for p53 loss in cancer include expression of p53-negative regulators such as MDM2, which mediate the degradation of wildtype p53 (p53α), and inactivating mutations in the TP53 gene. Currently, approaches to overcome p53 deficiency in these cancers are limited. Here, using non-small cell lung cancer and glioblastoma multiforme cell line models, we show that two alternatively spliced, functional truncated isoforms of p53 (p53ß and p53γ, comprising exons 1 to 9ß or 9γ, respectively) and that lack the C-terminal MDM2-binding domain have markedly reduced susceptibility to MDM2-mediated degradation but are highly susceptible to nonsense-mediated decay (NMD), a regulator of aberrant mRNA stability. In cancer cells harboring MDM2 overexpression or TP53 mutations downstream of exon 9, NMD inhibition markedly upregulates p53ß and p53γ and restores activation of the p53 pathway. Consistent with p53 pathway activation, NMD inhibition induces tumor suppressive activities such as apoptosis, reduced cell viability, and enhanced tumor radiosensitivity, in a relatively p53-dependent manner. In addition, NMD inhibition also inhibits tumor growth in a MDM2-overexpressing xenograft tumor model. These results identify NMD inhibition as a novel therapeutic strategy for restoration of p53 function in p53-deficient tumors bearing MDM2 overexpression or p53 mutations downstream of exon 9, subgroups that comprise approximately 6% of all cancers.

Phospholipase Dα6 and phosphatidic acid regulate gibberellin signaling in rice.

Phospholipase D (PLD) hydrolyzes membrane lipids to produce phosphatidic acid (PA), a lipid mediator involved in various cellular and physiological processes. Here, we show that PLDα6 and PA regulate the distribution of GIBBERELLIN (GA)-INSENSITIVE DWARF1 (GID1), a soluble gibberellin receptor in rice. PLDα6-knockout (KO) plants display less sensitivity to GA than WT, and PA restores the mutant to a normal GA response. PA binds to GID1, as documented by liposome binding, fat immunoblotting, and surface plasmon resonance. Arginines 79 and 82 of GID1 are two key amino acid residues required for PA binding and also for GID1's nuclear localization. The loss of PLDα6 impedes GA-induced nuclear localization of GID1. In addition, PLDα6-KO plants attenuated GA-induced degradation of the DELLA protein SLENDER RICE1 (SLR1). These data suggest that PLDα6 and PA positively mediate GA signaling in rice via PA binding to GID1 and promotion of its nuclear translocation.

Unqualified rate of anti-HIV detection in the laboratories from blood banks in Beijing-Tianjin-Hebei region / 中国输血杂志

【Objective】 To investigate the unqualified rate of anti-HIV detection of blood screening laboratories in Beijing-Tianjin-Hebei region, and explore the differences in anti-HIV detection ability and influencing factors in each laboratory. 【Methods】 Through filling questionnaires via e-mail, the anti-HIV ELISA unqualified rate and confirmed (WB) positive results (data) from January to December 2018 from 15 blood screening laboratories in Beijing-Tianjin-Hebei region were collected. Our laboratory was responsible for data collection and confirmation, and statistics software SPSS22.0 was used for analysis. 【Results】 1) There was a statistically significant difference among the unqualified rate of anti-HIV ELISA(6.77‱~35.71‱) and confirmed positive rate(0.60‱~3.56‱) in 15 blood screening laboratories in Beijing-Tianjin-Hebei region (P<0.05); 2) There were significant differencse among the ELISA unqualified rate and the confirmed positive rate of 8 reagents for anti-HIV detection(P<0.01), and the sensitivity of the 4th generation detection reagent and the imported reagent was higher than that of the 3rd generation reagent and the domestic reagent. The anti-HIV ELISA unqualified rate of R5 was the highest (19.08‱). 3)There were significant differences in the anti-HIV ELISA unqualified rate of R1, R2, R3, R5 and R7 reagents among different blood station laboratories(P<0.05), and there were no significant differences in the anti-HIV ELISA unqualified rate of R4, R6 and R8 reagents among different blood station laboratories(P>0.05). 4)The unqualified rate of anti-HIV ELISA of laboratories using different regents showed significant differences(P<0.05), except H, J, M. The unqualified rate of imported reagent was significantly higher than that of domestic reagents of laboratories using imported and domestic reagents combinations(P<0.05), except O. 62.5% (5/8) laboratories using domestic 3rd and 4th generation reagent combination showed significant differences in the unqualified rates among different reagents(P<0.05); 5) The positive rate of single-reagent(62.02%~95.45%)in 15 blood screening laboratories showed significant difference(P<0.001), and A was the lowest (62.02%). 【Conclusion】 The anti-HIV detection ability among 15 blood screening laboratories in Beijing-Tianjin-Hebei region is quite different. The application of different reagents is the main factor for the difference, and other factors such as personnel, instruments and test strategies also has a great impact on the detection of anti-HIV. It is still necessary to promote the process of homogenization of blood testing quality among blood screening laboratories in Beijing-Tianjin-Hebei region.

Performance verification of four nucleic acid detection systems: A comparitve study / 中国输血杂志

【Objective】 To compare the analytical performance of Tigris, Panther, ChiTaS BSS1200 and cobas S201 system to see if they satisfy the requirements of blood screening and to know the concordance of the results presented by these four systems. 【Methods】 According to the relevant documents of ISO15189 and Standard Operating Procedure of Blood Station(2019), the parameters needed to be verified for nucleic acid tests(NAT) included: analytical sensitivity verification, system compare test, anti-jamming capability and anti-cross-contamination ability. 【Results】 The 95% detection limits of Tigris, Panther, ChiTaS BSS1200 and Cobas S201 for HBV-DNA(IU/mL), HIV-RNA(IU/mL) and HCV-RNA(IU/mL) were 2.013 vs 4 vs 2.995 vs 0.99, 13.039 vs 10.21 vs 30.952 vs 32.24, and 2.278 vs 2.077 vs 12.008 vs 3.39, respectively. In the performance comparison verification between NAT systems, the results of the two sets of Tigris systems were in full accordance with serum plate, with a concordance rate of 100%, Kappa value of 1, and none cross-contamination.The concordance rate of No.1 Panther system was 100%, and No.2 98%, with Kappa value of 0.961 and none cross-contamination. Hemolytic samples (5g/L Hb concentration) and lipemic blood samples (13.81 mmol/L TG concentration) had no significant effect on the detection of low-concentration samples. 【Conclusion】 No significant differences in the performance of NAT systems were notable by devices, as the four systems were fully automated with high sensitivity, which can fully satisfy the blood screening requirements. Panther system demonstrates superior analysis sensitivity in HCV-RNA/HIV-RNA and lower in HBV DNA, but also in required criteria, as compared to Tigris system. Neither hemolysis nor lipemic blood had any significant effect on the test results.

A Synthetic Photorespiratory Shortcut Enhances Photosynthesis to Boost Biomass and Grain Yield in Rice.

Several photorespiratory bypasses have been introduced into plants and shown to improve photosynthesis by increasing chloroplastic CO2 concentrations or optimizing energy balance. We recently reported that an engineered GOC bypass could increase photosynthesis and productivity in rice. However, the grain yield of GOC plants was unstable, fluctuating in different cultivation seasons because of varying seed setting rates. In this study, we designed a synthetic photorespiratory shortcut (the GCGT bypass) consisting of genes encoding Oryza sativa glycolate oxidase and Escherichia coli catalase, glyoxylate carboligase, and tartronic semialdehyde reductase. The GCGT bypass was guided by an optimized chloroplast transit peptide that targeted rice chloroplasts and redirected 75% of carbon from glycolate metabolism to the Calvin cycle, identical to the native photorespiration pathway. GCGT transgenic plants exhibited significantly increased biomass production and grain yield, which were mainly attributed to enhanced photosynthesis due to increased chloroplastic CO2 concentrations. Despite the increases in biomass production and grain yield, GCGT transgenic plants showed a reduced seed setting rate, a phenotype previously reported for the GOC plants. Integrative transcriptomic, physiological, and biochemical assays revealed that photosynthetic carbohydrates were not transported to grains in an efficient manner, thereby reducing the seed setting rate. Taken together, our results demonstrate that the GCGT photorespiratory shortcut confers higher yield by promoting photosynthesis in rice, mainly through increasing chloroplastic CO2 concentrations.

A YAP/FOXM1 axis mediates EMT-associated EGFR inhibitor resistance and increased expression of spindle assembly checkpoint components.

Acquired resistance to tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) remains a clinical challenge. Especially challenging are cases in which resistance emerges through EGFR-independent mechanisms, such as through pathways that promote epithelial-to-mesenchymal transition (EMT). Through an integrated transcriptomic, proteomic, and drug screening approach, we identified activation of the yes-associated protein (YAP) and forkhead box protein M1 (FOXM1) axis as a driver of EMT-associated EGFR TKI resistance. EGFR inhibitor resistance was associated with broad multidrug resistance that extended across multiple chemotherapeutic and targeted agents, consistent with the difficulty of effectively treating resistant disease. EGFR TKI-resistant cells displayed increased abundance of spindle assembly checkpoint (SAC) proteins, including polo-like kinase 1 (PLK1), Aurora kinases, survivin, and kinesin spindle protein (KSP). Moreover, EGFR TKI-resistant cells exhibited vulnerability to SAC inhibitors. Increased activation of the YAP/FOXM1 axis mediated an increase in the abundance of SAC components in resistant cells. The clinical relevance of these finding was indicated by evaluation of specimens from patients with EGFR mutant lung cancer, which showed that high FOXM1 expression correlated with expression of genes encoding SAC proteins and was associated with a worse clinical outcome. These data revealed the YAP/FOXM1 axis as a central regulator of EMT-associated EGFR TKI resistance and that this pathway, along with SAC components, are therapeutic vulnerabilities for targeting this multidrug-resistant phenotype.

Synergistic effects of low­dose chemotherapy and T cells in renal cell carcinoma.

Renal cell carcinoma (RCC) is not sensitive to conventional radiotherapy and chemotherapy, and the effectiveness rate of molecular targeted therapy is low. Therefore, it is urgent to identify new treatment methods. Recently, adoptive T­cell therapy has provided a new option for cancer treatment. Furthermore, low­dose chemotherapy not only has no evident side effects and inhibitory effects on the human immune system, but can also enhance the immune activity of some effector cells. Therefore, it is surmised that the combination of different mechanisms of chemotherapy and immunotherapy could be a new treatment concept. In the present study, the effects of low­dose chemotherapy combined with T cells in the treatment of renal cell carcinoma were explored using cytotoxicity assays, enzyme­linked immunosorbent assay (ELISA), western blot analysis and flow cytometric analysis. The results revealed that low­dose chemotherapy and T cells had synergistic effects on tumor cell elimination in vitro. The transforming growth factor (TGF)­ß signaling pathway may be involved in the inhibition of T­cell functions. The targeted inhibition of TGF­ß signals may be a promising therapeutic strategy for the treatment of renal cancer. The present results provided a novel strategy for the combination of low­dose chemotherapy and T cells to enhance the therapeutic efficacy of RCC treatment.

A pseudolikelihood approach for assessing genetic association in case-control studies with unmeasured population structure.

The case-control study design is one of the main tools for detecting associations between genetic markers and diseases. It is well known that population substructure can lead to spurious association between disease status and a genetic marker if the prevalence of disease and the marker allele frequency vary across subpopulations. In this paper, we propose a novel statistical method to estimate the association in case-control studies with unmeasured population substructure. The proposed method takes two steps. First, the information on genomic markers and disease status is used to infer the population substructure; second, the association between the disease and the test marker adjusting for the population substructure is modeled and estimated parametrically through polytomous logistic regression. The performance of the proposed method, relative to the existing methods, on bias, coverage probability and computational time, is assessed through simulations. The method is applied to an end-stage renal disease study in African Americans population.