A Phase II Study of Neoadjuvant PLD/Cyclophosphamide and Sequential nab-Paclitaxel Plus Dual HER2 Blockade in HER2-Positive Breast Cancer.

BACKGROUND: Neoadjuvant trastuzumab/pertuzumab (HP) plus chemotherapy for HER2-positive breast cancer (BC) achieved promising efficacy. The additional cardiotoxicity still existed. Brecan study evaluated the efficacy and safety of neoadjuvant pegylated liposomal doxorubicin (PLD)/cyclophosphamide and sequential nab-paclitaxel based on HP (PLD/C/HP-nabP/HP). PATIENTS AND METHODS: Brecan was a single-arm phase II study. Eligible patients with stages IIA-IIIC HER2-positive BC received 4 cycles of PLD, cyclophosphamide, and HP, followed by 4 cycles of nab-paclitaxel and HP. Definitive surgery was scheduled after 21 days for patients completing treatment or experiencing intolerable toxicity. The primary endpoint was the pathological complete response (pCR). RESULTS: Between January 2020 and December 2021, 96 patients were enrolled. Ninety-five (99.0%) patients received 8 cycles of neoadjuvant therapy and all underwent surgery with 45 (46.9%) breast-conserving surgery and 51 (53.1%) mastectomy. The pCR was 80.2% (95%CI, 71.2%-87.0%). Four (4.2%) experienced left ventricular insufficiency with an absolute decline in LVEF (43%-49%). No congestive heart failure and ≥grade 3 cardiac toxicity occurred. The objective response rate was 85.4% (95%CI, 77.0%-91.1%), including 57 (59.4%) complete responses and 25 (26.0%) partial responses. The disease control rate was 99.0% (95%CI, 94.3%-99.8%). For overall safety, ≥grade 3 AEs occurred in 30 (31.3%) and mainly included neutropenia (30.2%) and asthenia (8.3%). No treatment-related deaths occurred. Notably, age of >30 (P = .01; OR = 5.086; 95%CI, 1.44-17.965) and HER2 IHC 3+ (P = .02; OR = 4.398; 95%CI, 1.286-15.002) were independent predictors for superior pCR (ClinicalTrials.gov Identifier NCT05346107). CONCLUSION: Brecan study demonstrated the encouraging safety and efficacy of neoadjuvant PLD/C/HP-nabP/HP, suggesting a potential therapeutic option in HER2-positive BC.

Association of the Verbal Rating Scale-Measured Dysmenorrhea with Nausea and Vomiting in Pregnancy: A Retrospective Cohort Study.

OBJECTIVES: Nausea and vomiting in pregnancy (NVP) is a common condition that reduces the quality of life by negatively affecting work and family life, physical and mental health, and economic well-being. However, its risk factors remain unclear. This study aimed to explore the association between NVP and verbal rating scale (VRS)-measured dysmenorrhea and to explore potential protective factors. METHODS: This retrospective cohort study was conducted from June 2018 to December 2020 at Tongji Hospital in Wuhan. Information on baseline characteristics, pregnancy-related history, periconceptional micronutrient supplementation, and obstetric outcomes were collected. The severity of dysmenorrhea was assessed using VRS. RESULTS: A total of 443 pregnant women were recruited and divided into the NVP group (n = 76) and the control group (n = 367). A significant association was observed between NVP and VRS-measured dysmenorrhea (c2=10.038, P = 0.007). After adjusting for covariates, the association between moderate/severe dysmenorrhea and NVP remained significant (OR 2.384; 95% CI 1.104-5.148, P = 0.004). First-trimester docosahexaenoic acid supplement (OR 0.443; 95% CI 0.205-0.960, P = 0.039) may be beneficial in reducing the risk of NVP. CONCLUSIONS: Women with moderate to severe dysmenorrhea have a higher risk of experiencing NVP during the first trimester. Periconceptional docosahexaenoic acid supplementation may play a protective role.

Combined inhibition of XIAP and autophagy induces apoptosis and differentiation in acute myeloid leukaemia.

Perturbations in autophagy, apoptosis and differentiation have greatly affected the progression and therapy of acute myeloid leukaemia (AML). The role of X-linked inhibitor of apoptosis (XIAP)-related autophagy remains unclear in AML therapeutics. Here, we found that XIAP was highly expressed and associated with poor overall survival in patients with AML. Furthermore, pharmacologic inhibition of XIAP using birinapant or XIAP knockdown via siRNA impaired the proliferation and clonogenic capacity by inducing autophagy and apoptosis in AML cells. Intriguingly, birinapant-induced cell death was aggravated in combination with ATG5 siRNA or an autophagy inhibitor spautin-1, suggesting that autophagy may be a pro-survival signalling. Spautin-1 further enhanced the ROS level and myeloid differentiation in THP-1 cells treated with birinapant. The mechanism analysis showed that XIAP interacted with MDM2 and p53, and XIAP inhibition notably downregulated p53, substantially increased the AMPKα1 phosphorylation and downregulated the mTOR phosphorylation. Combined treatment using birinapant and chloroquine significantly retarded AML progression in both a subcutaneous xenograft model injected with HEL cells and an orthotopic xenograft model injected intravenously with C1498 cells. Collectively, our data suggested that XIAP inhibition can induce autophagy, apoptosis and differentiation, and combined inhibition of XIAP and autophagy may be a promising therapeutic strategy for AML.

MicroRNA-143 acts as a tumor suppressor through Musashi-2/DLL1/Notch1 and Musashi-2/Snail1/MMPs axes in acute myeloid leukemia.

BACKGROUND: The previous studies have revealed that abnormal RNA-binding protein Musashi-2 (MSI2) expression is associated with cancer progression through post-transcriptional mechanisms, however mechanistic details of this regulation in acute myeloid leukemia (AML) still remain unclear. Our study aimed to explore the relationship between microRNA-143 (miR-143) and MSI2 and to clarify their clinical significance, biological function and mechanism. METHODS: Abnormal expression of miR-143 and MSI2 were evaluated in bone marrow samples from AML patients by quantitative real time-PCR. Effects of miR-143 on regulating MSI2 expression were investigated using luciferase reporter assay. Functional roles of MSI2 and miR-143 on AML cell proliferation and migration were determined by CCK-8 assay, colony formation, and transwell assays in vitro and in mouse subcutaneous xenograft and orthotopic transplantation models in vivo. RNA immunoprecipitation, RNA stability measurement and Western blotting were performed to assess the effects of MSI2 on AML. RESULTS: We found that MSI2 was significantly overexpressed in AML and exerted its role of promoting AML cell growth by targeting DLL1 and thereby activating Notch signaling pathway. Moreover, we found that MSI2 bound to Snail1 transcript and inhibited its degradation, which in turn upregulated the expression of matrix metalloproteinases. We also found that MSI2 targeting miR-143 is downregulated in AML. In the AML xenograft mouse model, overexpression of MSI2 recapitulated its leukemia-promoting effects, and overexpression of miR-143 partially attenuated tumor growth and prevented metastasis. Notably, low expression of miR-143, and high expression of MSI2 were associated with poor prognosis in AML patients. CONCLUSIONS: Our data demonstrate that MSI2 exerts its malignant properties via DLL1/Notch1 cascade and the Snail1/MMPs axes in AML, and upregulation of miR-143 may be a potential therapeutic approach for AML.

dl-Methionine-Mediated Reversible Deactivation Radical Polymerization of Styrene and Methyl Methacrylate.

Reversible deactivation radical polymerization (RDRP) is a facile and highly efficient technique for the synthesis of well-defined polymer with precise structure. dl-Methionine (Met) as a RDRP control agent is described and assessed for RDRP of styrene (St) and methyl methacrylate (MMA) with AIBN as radical initiator at 75 °C, which enables excellent control of this polymerization. The addition of dl-Methionine significantly decreased the dispersity (D) of the polymers for both monomers and first-order linear kinetic plots of polymethyl methacrylate (PMMA) are observed in DMSO. Considering the heat resistance of dl-Methionine, kinetic studies indicate that polymerization develops at a faster rate at higher reaction temperature (100 °C) with the same dl-Methionine content. Well-defined polymethyl methacrylate-block-polystyrene (PMMA-block-PSt) is successfully achieved by the chain extension reaction that demonstrates the high end fidelities of this polymerization approach. The system allows the use of dl-Methionine, a rich source and easily synthesized agent, to mediate RDRP strategy.

Inorganic-Organic Hybrid Phototransistor Array with Enhanced Photogating Effect for Dynamic Near-Infrared Light Sensing and Image Preprocessing.

Narrow-band-gap organic semiconductors have emerged as appealing near-infrared (NIR) sensing materials by virtue of their unique optoelectronic properties. However, their limited carrier mobility impedes the implementation of large-area, dynamic NIR sensor arrays. In this work, high-performance inorganic-organic hybrid phototransistor arrays are achieved for NIR sensing, by taking advantage of the high electron mobility of In2O3 and the strong NIR absorption of a BTPV-4F:PTB7-Th bulk heterojunction (BHJ) with an enhanced photogating effect. As a result, the hybrid phototransistors reach a high responsivity of 1393.0 A W-1, a high specific detectivity of 4.8 × 1012 jones, and a fast response of 0.72 ms to NIR light (900 nm). Meanwhile, an integrated 16 × 16 phototransistor array with a one-transistor-one-phototransistor (1T1PT) architecture is achieved. On the basis of the enhanced photogating effect, the phototransistor array can not only achieve real-time, dynamic NIR light mapping but also implement image preprocessing, which is promising for advanced NIR image sensors.

Smartphone-based infrared thermography to assess progress in thoracic surgical incision healing: A preliminary study.

Immediate assessment of surgical incisions is an important component of wound management, and the development of relevant technologies has the potential to address these challenges. Smartphone-based handheld thermal imagers can collect infrared radiation from the skin to monitor local blood perfusion and metabolic levels in incisions. Here, we used this imaging technology for early assessment of healing progress and potential for predicting the healing status of thoracic surgical incisions. Thermal image acquisition and temperature extraction were performed on 40 patients for 7 consecutive days postoperatively, and visualised early warning information was observed, with temperature and temperature readings showing non-linear trajectory changes during the measurement period, and temperature readings on day 4 achieving high prediction of healing status at 1-2 months capability with sensitivities and specificities of 91.67% and 85.71%, respectively, suggesting a promising clinical application of portable thermography for assessing incision healing dynamics and providing a scientific basis for later artificial intelligence-driven decision algorithms.

TNFα antagonist in combination with PD-1 blocker to prevent or retard malignant transformation of B[a]P-induced chronic lung inflammation.

Benzo[a]pyrene (B[a]P) is a typical complete carcinogen in tobacco, but its mechanism of inducing the development of chronic pneumonia and consequent lung cancer is unclear. Here we elucidated the role of myeloid-derived suppressor cells (MDSCs) in developing B[a]P-induced chronic lung inflammation and efficacy of immunotherapy in preventing subsequent malignant transformation. Our study showed that as B[a]P could induce the accumulation of MDSCs in lung tissues and enhance the immunosuppressive effect regulated by cytokines and metabolites, thereby promoting the formation of immunosuppressive microenvironment, where effector T cells were exhausted, NK cells were dysfunctional, regulatory T (Treg) cells were expanded, polarized alveolar macrophages were transformed from M1 to M2. Subsequently, we performed the immunotherapy to block TNFɑ only or both TNFɑ and PD-1 at the early- or middle-stage of B[a]P-induced chronic lung inflammation to ameliorate the immunosuppressive microenvironment. We found that TNFɑ antagonist alone or with PD-1 blocker was shown to exert therapeutic effects on malignant transformation at the early stage of B[a]P-induced chronic lung inflammation. Taken together, our findings demonstrated that B[a]P-induced chronic lung inflammation resulted in the accumulation of MDSCs in lung tissues and exercise their immunosuppressive functions, thereby developing an immunosuppressive microenvironment, thus TNFɑ antagonist alone or with PD-1 blocker could prevent or retard the malignant transformation of B[a]P-induced chronic lung inflammation.

Bio-Inspired In-Sensor Compression and Computing Based on Phototransistors.

The biological nervous system possesses a powerful information processing capability, and only needs a partial signal stimulation to perceive the entire signal. Likewise, the hardware implementation of an information processing system with similar capabilities is of great significance, for reducing the dimensions of data from sensors and improving the processing efficiency. Here, it is reported that indium-gallium-zinc-oxide thin film phototransistors exhibit the optoelectronic switching and light-tunable synaptic characteristics for in-sensor compression and computing. Phototransistor arrays can compress the signal while sensing, to realize in-sensor compression. Additionally, a reservoir computing network can also be implemented via phototransistors for in-sensor computing. By integrating these two systems, a neuromorphic system for high-efficiency in-sensor compression and computing is demonstrated. The results reveal that even for cases where the signal is compressed by 50%, the recognition accuracy of reconstructed signal still reaches ≈96%. The work paves the way for efficient information processing of human-computer interactions and the Internet of Things.

Highly Linear and Symmetric Synaptic Memtransistors Based on Polarization Switching in Two-Dimensional Ferroelectric Semiconductors.

Brain-inspired neuromorphic computing hardware based on artificial synapses offers efficient solutions to perform computational tasks. However, the nonlinearity and asymmetry of synaptic weight updates in reported artificial synapses have impeded achieving high accuracy in neural networks. Here, this work develops a synaptic memtransistor based on polarization switching in a two-dimensional (2D) ferroelectric semiconductor (FES) of α-In2 Se3 for neuromorphic computing. The α-In2 Se3 memtransistor exhibits outstanding synaptic characteristics, including near-ideal linearity and symmetry and a large number of programmable conductance states, by taking the advantages of both memtransistor configuration and electrically configurable polarization states in the FES channel. As a result, the α-In2 Se3 memtransistor-type synapse reaches high accuracy of 97.76% for digit patterns recognition task in simulated artificial neural networks. This work opens new opportunities for using multiterminal FES memtransistors in advanced neuromorphic electronics.

Integrated analysis of multiple microarray studies to identify potential pathogenic gene modules in preeclampsia.

BACKGROUND: Preeclampsia is a life-threatening hypertensive disorder during pregnancy, while underlying pathogenesis and its diagnosis are incomplete. METHODS: In this study, we utilized the Robust Rank Aggregation method to integrate 6 eligible preeclampsia microarray datasets from Gene Expression Omnibus database. We used linear regression to assess the associations between significant differentially expressed genes (DEGs) and blood pressure. Functional annotation, protein-protein interaction, Gene Set Enrichment Analysis (GSEA) and single sample GSEA were employed for investigating underlying pathogenesis in preeclampsia. RESULTS: We filtered 52 DEGs and further screened for 5 hub genes (leptin, pappalysin 2, endoglin, fms related receptor tyrosine kinase 1, tripartite motif containing 24) that were positively correlated with both systolic blood pressure and diastolic blood pressure. Receiver operating characteristic indicated that hub genes were potential biomarkers for diagnosis and prognosis in preeclampsia. GSEA for single hub gene revealed that they were all closely related to angiogenesis and estrogen response in preeclampsia. Moreover, single sample GSEA showed that the expression levels of 5 hub genes were correlated with those of immune cells in immunologic microenvironment at maternal-fetal interface. CONCLUSIONS: These findings provide new insights into underlying pathogenesis in preeclampsia; 5 hub genes were identified as biomarkers for diagnosis and prognosis in preeclampsia.

The role of prepotent response inhibition and interference control in depression.

INTRODUCTION: The ability to suppress inappropriate prepotent response and to overcome the interference of irrelevant information are two important components of inhibitory control. Little is known, however, about the relevant contributions in these two components of inhibitory control to depression. The aim of the present study was to assess the prepotent response inhibition and interference control simultaneously in a group of patients diagnosed with major depression disorder (MDD). METHODS: A clinical group of patients with MDD (n = 41) and a control group of healthy volunteers (n = 39) were recruited and assessed using the stop-signal task and the Flanker task respectively. RESULTS: The results showed longer stop-signal reaction time in patients with MDD in the stop-signal task. Regarding the interference control function, the analysis showed the response accuracy under the incongruent condition was significantly lower in patients with MDD than healthy individuals. CONCLUSIONS: In conclusion, patients with MDD showed impairments both in prepotent response inhibition and interference control. The present findings provide a better understanding of the mechanism of depression-related deficits in inhibition and have great implications for the development of cognitive training programmes to remediate cognitive dysfunction in depression.

Predictive and prognostic values of preoperative platelet parameters in patients with gynecological tumors.

BACKGROUND: Platelets play a role in tumor cell growth, metastasis, and angiogenesis, and the present study aimed to evaluate diagnostic and prognostic values of platelet parameters in patients with gynecological tumors. METHODS: A total of 1062 women were included. Differences of platelet parameters (platelet count [PLT], plateletcrit [PCT], mean platelet volume [MPV], platelet-large cell rate [P-LCR], and platelet distribution width [PDW]) between different categories were analyzed by nonparametric test. The optimal cutoff value was calculated with receiver operating characteristic analysis. Overall survivals were analyzed with Kaplan-Meier method and log-rank tests for univariate analysis. RESULTS: Platelet count and PCT were significantly increased, and MPV and P-LCR were significantly reduced in malign and benign gynecological tumor groups compared with the controls (P < .001); PDW had no significant differences. There were no significant differences in PLT, PCT, MPV, P-LCR, and PDW between different tumor locations and pathologic types. The optimal cutoff values of PLT, PCT, MPV and P-LCR were 274, 0.26, 10.08, and 24.8 (AUC: 0.661, 0.643, 0.593, 0.562), and PCT had preferable sensibility and specificity (50.84% and 70.42%) in predicting the presence of gynecological tumors. According to survival analysis, increased PLT (≥274 × 109 /L) and PCT (≥0.26), and induced MPV (<10.08 fL) and P-LCR (<24.8%) were associated with shorter overall survival. CONCLUSIONS: Platelet count, PCT, MPV, and P-LCR can be used as preferable auxiliary parameters for predicting the presence of gynecological tumors. Increased PLT and PCT, or decreased MPV and P-LCR indicated a heavier tumor burden and shorter overall survival.

[A case of inherited afibrinogenemia caused by an IVS7-12A>G splice mutation of FGG gene].

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with inherited afibrinogenemia. METHODS: For the proband and his family members, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), Fibrin(ogen) degradation products (FDPs), D-dimer (D-D), plasminogen activity (PLG:A) and the TT mixed experiment with protamine sulfate were determined with a STAGO-R automatic coagulation analyzer. The activity and antigen of fibrinogen (Fg) in plasma were measured with the Clauss method and immunonephelometry method, respectively. All exons and flanking regions of the fibrinogen genes (FGA, FGB and FGG) were amplified by PCR and directly sequenced. Human Splicing Finder software was used to predict and score the change of splicing site caused by the mutation. RESULTS: The proband showed normal FDPs and D-D but significantly prolonged TT, PT and APTT. The activity and antigen of fibrinogen in plasma were significantly decreased (<0.1 g/L). His young sister and parents showed slightly prolonged TT (18.20-18.50 s) and decreased fibrinogen activity (1.27-1.54 g/L) and fibrinogen antigenic content (1.34-1.56 g/L). Genetic testing revealed that the proband has carried homozygous IVS7-12A>G (g.4147A>G) mutations of the FGG gene, for which his parents and young sister were heterozygous. As predicted by Human Splicing Finder and Mutation Taster software, the variant may generate a new splicing site which can extend the sequence of exon 7 by 11 bp, with alteration of the coding sequence. PROVEAN suggested the variant to be deleterious. CONCLUSION: The afibrinogenemia of the proband may be attributed to the FGG IVS7-12A>G variant, which was unreported previously.

[Clinical and genetic analysis of a pedigree affected with type I hereditary antithrombin deficiency due to a g.2736dupT variant of the AT gene].

OBJECTIVE: To analyze the phenotype and genotype of a patient affected with inherited antithrombin deficiency. METHODS: All exons and exon-intron boundaries of the AT genes were subjected to PCR amplification and Sanger sequencing. The influence of variants on the disease was predicted using bioinformatic software (MutationTaster). RESULTS: The results of all coagulation tests were normal, though the antithrombin activity and antigen content of the proband and his father have decreased significantly (34%, 48% and 12.97 mg/dL, 15.60 mg/dL, respectively). His mother was normal. Genetic analysis revealed that the proband and his father both carried a heterozygous g.2736dupT variant of the AT gene. Bioinformatic analysis suggested that the variant may be pathogenic. CONCLUSION: The proband and his father both had type I hereditary antithrombin deficiency caused by a g.2736dupT variant of the AT gene. The variant was unreported previously.

A Single Multiplex crRNA Array for FnCpf1-Mediated Human Genome Editing.

Cpf1 has been harnessed as a tool for genome manipulation in various species because of its simplicity and high efficiency. Our recent study demonstrated that FnCpf1 could be utilized for human genome editing with notable advantages for target sequence selection due to the flexibility of the protospacer adjacent motif (PAM) sequence. Multiplex genome editing provides a powerful tool for targeting members of multigene families, dissecting gene networks, modeling multigenic disorders in vivo, and applying gene therapy. However, there are no reports at present that show FnCpf1-mediated multiplex genome editing via a single customized CRISPR RNA (crRNA) array. In the present study, we utilize a single customized crRNA array to simultaneously target multiple genes in human cells. In addition, we also demonstrate that a single customized crRNA array to target multiple sites in one gene could be achieved. Collectively, FnCpf1, a powerful genome-editing tool for multiple genomic targets, can be harnessed for effective manipulation of the human genome.

[Analysis of a pedigree affected with congenital dysfibrinogenemia due to a novel Gly31Glu mutation of FGA gene].

OBJECTIVE: To analyze the phenotype and genotype of a pedigree affected with congenital dysfibrinogenemia. METHODS: Liver and kidney functions of the proband and her relatives were determined. Coagulation tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time(TT), fibrin(ogen) degradation products (FDPs), D-dimer(D-D) and the calibration experiment of protamine sulfate of against plasma TT were detected in the proband and her predigree members. The activity and antigen of fibrinogen (Fg) in plasma were measured by Clauss method and immunonephelometry method, respectively. All of the exons and exons-intron boundaries of the three fibrinogen genes (FGA, FGB and FGG) were subjected to PCR amplification and Sanger sequencing. Potential influence of the suspected mutations were analyzed with bioinformatics software including PolyPhen-2, SIFT and Mutation Taster. RESULTS: The proband had normal PT, APTT, FDPs, D-D and prolonged TT (31.8 s). The activity of fibrinogen (Fg) in plasma was significantly decreased but the antigen was normal. Genetic analysis revealed a heterozygous c.92G>A (p.Gly31Glu) mutation in exon 2 of the FGA gene. Family studies revealed that the mother carried the same mutation. Bioinformatic analysis suggested that the mutation may affect the function of Fg Protein. CONCLUSION: The dysfibrinogenemia was probably caused by the novel Gly31Glu mutation of the FGA gene.

[Clinical and genotypic analysis of two Chinese pedigrees affected with hereditary coagulable factor VII deficiency].

OBJECTIVE: To explore molecular etiology and clinical characteristics of two pedigrees affected with hereditary factor VII(FVII) deficiency. METHODS: The nine exons and flanking sequences of the F7 gene of the probands were amplified by PCR. The amplicons were analyzed by direct sequencing. Suspected mutations were subjected to SWISS-MODEL modeling and analysis of protein structure change by Pymol software and conservation of amino acids across various species. RESULTS: For proband of pedigree 1, the prothrombin time (PT), FVII activity (FVII:C) and FVII antigen (FVII:Ag) were 36.3 s, 3%, 53.56%, respectively. Sequencing revealed a compound heterozygous variants of c.80_81delCT and c.1371G>T(p.Arg439Ser). His son carried a heterozygous c.1371G>T (p.Arg439Ser) variant. For proband of pedigree 2, the PT, FVII:C and FVII:Ag were 22.3 s, 4%, 1.58%, respectively. Sequencing has revealed a compound heterozygous c.278G>T(p.Arg75Met) missense variant in exon 3 and c.1278T>G (p.His408Gln) in exon 9 of the F7 gene. His mother and son both carried a heterozygous c.278G>T(p.Arg75Met) variant. Three-dimensional simulation and homology analysis revealed that the p.Arg439Ser and p.Arg75Met can respectively alter part of hydrogen bonds and two highly conserved amino acids. CONCLUSION: Two novel heterozygous missense variants of the F7 gene [c.1371G>T(p.Arg439Ser) and c.278G>T(p.Arg75Met)] probably account for the decrease of factor VII in the two pedigrees.

The analysis of false prolongation of the activated partial thromboplastin time (activator: silica): Interference of C-reactive protein.

BACKGROUND: To investigate the effect of C-reactive protein on the activated partial thromboplastin time (APTT) (different activators) in different detecting systems. METHODS: The C-reactive protein and coagulation test of 112 patients with the infectious disease were determined by automation protein analyzer IMMAG 800 and automation coagulation analyzer STA-R Evolution, respectively. The pooled plasma APTT with different concentrations of C-reactive protein was measured by different detecting system: STA-R Evolution (activator: silica, kaolin), Sysmex CS-2000i (activator: ellagic acid), and ACL TOP 700 (activator: colloidal silica). In addition, the self-made platelet lysate (phospholipid) was added to correct the APTT prolonged by C-reactive protein (150 mg/L) on STA-R Evolution (activator: silica) system. RESULTS: The good correlation between C-reactive protein and APTT was found on the STA-R Evolution (activator: silica) system. The APTT on the STA-R Evolution (activator: silica) system was prolonged by 24.6 second, along with increasing C-reactive protein concentration. And the APTT of plasma containing 150 mg/L C-reactive protein was shortened by 3.4-6.9 second when the plasma was mixed with self-made platelet lysate. However, the APTT was prolonged unobviously on other detecting systems including STA-R Evolution (activator: kaolin), Sysmex CS-2000i, and ACL TOP 700. CONCLUSION: C-reactive protein interferes with the detection of APTT, especially in STA-R Evolution (activator: silica) system. The increasing in C-reactive protein results in a false prolongation of the APTT (activator: silica), and it is most likely that C-reactive protein interferes the coagulable factor binding of phospholipid.

[Phenotypic and genetic analysis of two pedigrees affected with hereditary coagulation FXII deficiency].

OBJECTIVE: To carry out phenotypic and genotypic analysis for two Chinese pedigrees affected with coagulation factor XII (F XII) deficiency. METHODS: Plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), and blood coagulation factor VIII, IX, XI, XII activity (FVIII:C, FIX:C, FXI:C, FXII:C) were determined with one stage clotting assay on a STAGO coagulation analyzer. FXII antigen was determined with an enzyme linked immunosorbent assay (ELISA). The 14 exons and their flanking sequences of the F12 gene were subjected to PCR amplification and Sanger sequencing. The conservation and structure of mutant protein were analyzed with MegAlign software and PYMOL software. RESULTS: The APTT of the probands was significantly prolonged, while their FXII:C and FXII:Ag were significantly reduced. Genetic analysis of the proband has revealed three novel mutations in the F12 gene, including g.5972G>A splice site mutation in intron 5, g.8810_8814delGTCTA in exon 14, and g.6259G>A (p.Pro182Leu) in exon 7. In addition, a previously known mutation IVS13-1G>A has been found. CONCLUSION: Four mutations have been identified in the two Chinese pedigrees, among which three were novel. Above mutations probably played a role in the defect of FXII in the two pedigrees.