Leaf chlorophyll parameters and photosynthetic characteristic variations with stand age in a typical desert species (Haloxylon ammodendron).

As a desert shrub, Haloxylon ammodendron combines ecological, economic, and social benefits and plays an important role in the ecological conservation of arid desert areas. Understanding its physiological characteristics and its mechanism of light energy utilization is important for the conservation and utilization of H. ammodendron. Therefore, we selected five stands (5-, 11-, 22-, 34-, and 46-year-old) of H. ammodendron as research objects in the study and measured their photosynthetic light response curves by a portable open photosynthesis system (Li-6400) with a red-blue light source (6400-02B). Then, we measured the leaf chlorophyll parameters in the laboratory, calculated the photosynthetic characteristics by using Ye Zipiao's photosynthetic model, analyzed their variation patterns across stand ages, and explored the relationships between leaf chlorophyll parameters and photosynthetic characteristics. The results showed that leaf chlorophyll parameters and photosynthetic characteristics of H. ammodendron at different stand ages were significantly different. Chl content, P nmax, and LUEmax of H. ammodendron were V-shaped with the increase of stand age. The 5-year-old H. ammodendron was in the rapid growth period, synthesized more Chl a+b content (8.47 mg g-1) only by using a narrower range of light, and the Pnmax and LUEmax were the highest with values of 36.21 µmol m-2 s-1 and 0.0344, respectively. For the 22-year-old H. ammodendron, due to environmental stress, the values of Chl a+b content, P nmax, and LUEmax were the smallest and were 2.64 mg g-1, 25.73 µmol m-2 s-1, and 0.0264, respectively. For the older H. ammodendron, its Chl content, P nmax, and LUEmax were not significantly different and tended to stabilize but were slightly higher than those of the middle-aged H. ammodendron. On the other hand, the other photosynthetic parameters did not show significant variation patterns with stand age, such as R d, AQE, LSP, LCP, and I L-sat. In addition, we found that the relationships between Chl a+b content and P nmax and between Chl a+b content and LUEmax were highly correlated, except for the older H. ammodendron. Thus, using leaf chlorophyll content as a proxy for photosynthetic capacity and light use efficiency should be considered with caution. This work will provide a scientific reference for the sustainable management of desert ecosystems and vegetation restoration in sandy areas.

A Comparison of Safety and Effectiveness Between Wingspan and Neuroform Stents in Patients With Middle Cerebral Artery Stenosis.

Background: Percutaneous transluminal angioplasty and stenting with the Wingspan stent has proven safe and effective in patients with middle cerebral artery stenosis (MCAS), but the off-label use of the Neuroform stent might be an alternative treatment. This study aimed to compare the safety and effectiveness of the above two intracranial stents in patients with MCAS. Methods: We retrospectively analyzed consecutive patients with symptomatic MCAS who had been treated with the Neuroform EZ or the Wingspan stent. A propensity score was generated to control for differences in baseline characteristics. The endpoints were the rate of peri-procedural complications within 30 days after stenting, the in-stent restenosis rate, and any target-vessel-related stroke or deaths during follow-up. Results: After matching for propensity score, the peri-procedural complication rate in the Wingspan group was 7.4% compared with 5.6% in the Neuroform group (p = 1.00), while the follow-up in-stent restenosis rates were 23.3 vs. 14.3%, respectively (p = 0.41). In the restenosis group, the patients tended to be younger (p < 0.01) and the degree of artery stenosis before stenting was higher (p < 0.01). Conclusion: This study indicated that in patients with symptomatic MCAS, Neuroform EZ stents are an alternative to Wingspan. Moreover, younger age and higher degree of artery stenosis before stenting might be a risk factor of in-stent restenosis.

Survival and pretreatment prognostic factors for extensive-stage small cell lung cancer: A comprehensive analysis of 358 patients.

BACKGROUND: Extensive-stage small cell lung cancer (ES-SCLC) is deemed as a fatal malignancy with a poor prognosis. Although immunotherapy has gradually played an important role in the treatment of ES-SCLC since 2018, ES-SCLC treatment data and patient outcome before 2018, when chemotherapy served as a fundamental therapeutic strategy, is still meaningful as a summary of the situation regarding previous medical treatment and is a baseline for comparative data. In addition, the prognostic factors of ES-SCLC have failed to reach a consensus until now. Therefore, this study aimed to evaluate survival and identify the prognostic factors in an ES-SCLC population. METHODS: We retrospectively collected the detailed medical records of 358 patients with ES-SCLC from January 1, 2011 to December 31, 2018 in a Chinese top-level cancer hospital. The prognostic factors were evaluated by Cox univariate and multivariate analysis. RESULTS: The median overall survival (OS) of ES-SCLC patients (N = 358) was 14.0 months, the one- and two-year OS rates were 56.2% and 21.7%, respectively. Moreover, we identified two demographic characters (age ≥ 70, smoking index ≥ 400), one tumor burden factor (bone multimetastasis), two tumor biomarkers (cyfra211, CA125) and two laboratory indexes (decreased Na, PLR < 76) as independent prognostic factors for OS in this patient population. Progression-free survival (PFS) data of 238 patients was obtained for further analysis, and the median PFS was 6.2 months, and six-month and one-year PFS rates were 51.7% and 14.3%, respectively. Elevated cyfra211, decreased Hb and Na were identified as independent prognostic factors for PFS. CONCLUSIONS: This study provides real-world evidence of the survival and prognosis of ES-SCLC patients which will enable better evaluation and clinical decision-making in the future.

5-Hydroxymethylcytosine profiles of cfDNA are highly predictive of R-CHOP treatment response in diffuse large B cell lymphoma patients.

BACKGROUND: Although R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the standard chemotherapy regimen for diffuse large B cell lymphoma (DLBCL) patients, not all patients are responsive to the scheme, and there is no effective method to predict treatment response. METHODS: We utilized 5hmC-Seal to generate genome-wide 5hmC profiles in plasma cell-free DNA (cfDNA) from 86 DLBCL patients before they received R-CHOP chemotherapy. To investigate the correlation between 5hmC modifications and curative effectiveness, we separated patients into training (n = 56) and validation (n = 30) cohorts and developed a 5hmC-based logistic regression model from the training cohort to predict the treatment response in the validation cohort. RESULTS: In this study, we identified thirteen 5hmC markers associated with treatment response. The prediction performance of the logistic regression model, achieving 0.82 sensitivity and 0.75 specificity (AUC = 0.78), was superior to existing clinical indicators, such as LDH and stage. CONCLUSIONS: Our findings suggest that the 5hmC modifications in cfDNA at the time before R-CHOP treatment are associated with treatment response and that 5hmC-Seal may potentially serve as a clinical-applicable, minimally invasive approach to predict R-CHOP treatment response for DLBCL patients.

[Newest Reaserch Advance in treatment of Plasmablastic lymphoma--Review].

Plasmablastic lymphoma(PBL) shows a low incidence and poor prognosis, moreover, there is no standard treatment regimen for PBL. The treatment effect and value of CHOP regimen and radiotherapy are limited. Some studies showed that intensive chemotherapy alone or its combination with proteasome inhibitors or immune regulator can improve the overall survival of patients with PBL, which can be used as the first-line therapy for PBL patients. CAR-T and immunocheckpoint inhibitors showed treatment effect for the patients with refractory and relapsed plasmablastic lymphoma. The clinical value of potential targets in treating tumour worth to be studied further.

Actin-related protein Arp4 regulates euchromatic gene expression and development through H2A.Z deposition in blood-stage Plasmodium falciparum.

BACKGROUND: Malaria caused by Plasmodium spp. is still a major threat to public health globally. The various approaches to developing new antimalarial agents rely on the understanding of the complex regulatory mechanisms of dynamic gene expression in the life-cycle of these malaria parasites. The nuclear members of the evolutionarily conserved actin-related protein nuclear (ARP) superfamily are the major components of nucleosome remodelling complexes. In the human malaria parasite Plasmodium falciparum, bioinformatics analysis has predicted three ARP orthologues: PfArp1, PfArp4 and PfArp6. However, little is known about the biological functions of putative PfArp4. In this study, we aimed to investigate the function and the underlying mechanisms of PfArp4 gene regulation. METHODS: A conditional gene knockdown approach was adopted by incorporating the glucosamine-inducible glmS ribozyme sequence into the 3' UTR of the PfArp4 and PfArp6 genes. The transgenic parasites PfArp4-Ty1-Ribo, PfArp6-Ty1-Ribo and pL6-PfArp4-Ty1::PfArp6-HA were generated by the CRISPR-Cas9 technique. The knockdown effect in the transgenic parasite was measured by growth curve assay and western blot (WB) analysis. The direct interaction between PfArp4 and PfArp6 was validated by co-IFA and co-IP assays. The euchromatic gene expression mediated through H2A.Z (histone H2A variant) deposition and H3K9ac modification at promoters and regulated by PfArp4, was determined by RNA-seq and ChIP-seq. RESULTS: The inducible knockdown of PfArp4 inhibited blood-stage development of P. falciparum. PfArp4 and PfArp6 were colocalized in the nucleus of P. falciparum parasites. PfArp4 gene knockdown altered the global transcriptome. PfArp4 protein colocalized with the histone variant H2A.Z and euchromatic marker H3K9ac in intergenic regions. The inducible downregulation of PfArp4 resulted in the depletion of H2A.Z and lower H3K9ac levels at the upstream regions of eukaryotic genes, thereby repressing the transcriptional abundance of H2A.Z-dependent genes. CONCLUSIONS: Our findings suggest that PfArp4 regulates the cell cycle by controlling H2A.Z deposition and affecting centromere function, contributing to the understanding the complex epigenetic regulation of gene expression and the development of P. falciparum.

[Effect of Jin's three-needle combined with MyoTrac biostimulation therapy on upper limb function in children with spastic hemiplegia].

OBJECTIVE: To compare the therapeutic effect among Jin 's three-needle combined with MyoTrac biostimulation therapy, simple Jin's three-needle and simple MyoTrac biostimulation therapy on upper limb function in children with spastic hemiplegia. METHODS: A total of 120 children with spastic hemiplegia were randomized into an observation group, a control group 1 and a control group 2, 40 cases in each group. Conventional occupational therapy was adopted in each group. Additionally, Jin's three-needle therapy was applied in the control group 1, scalp acupuncture and body acupuncture were sustained for 1 h and 30 min respectively, once a day, 5 times a week; MyoTrac biostimulation therapy was adopted in the control group 2, once a day, 15 min each time, 5 times a week; Jin 's three-needle combined with MyoTrac biostimulation therapy were given in the observation group. Two months were as one course, and totally 3 courses were required in the 3 groups. Before treatment and 2, 4, 6 months into treatment, the standard grasping score (sGr) and the standard visual-motor integration score (sVI) of Peabody developmental motor scales-2 (PDMS-2), the modified Ashworth scale (MAS) grade and active range of movement (AROM) of wrist joints were recorded in the 3 groups. RESULTS: Compared before treatment, sGr of 4, 6 months into treatment was increased in the observation group (P<0.05), sGr of 6 months into treatment was increased in the control group 1 and the control group 2 (P<0.05); sVI of 2, 4, 6 months into treatment was increased in the observation group (P<0.05), sVI of 6 months into treatment was increased in the control group 1 and the control group 2 (P<0.05). sGr and sVI of 6 months into treatment in the observation group were higher than those in the control group 1 and the control group 2 (P<0.05). Compared before treatment, the MAS grade of 6 months into treatment was improved in the 3 groups (P<0.05), and that in the observation group was superior to the control group 1 and the control group 2 (P<0.05). CONCLUSION: Jin 's three-needle combined with MyoTrac biostimulation therapy can effectively improve the fine function and muscle tone of upper limbs in children with spastic hemiplegia, and the improvement is superior to the simple Jin 's three-needle and the MyoTrac biostimulation therapy.

A retrospective analysis of real-world outcomes of elderly Chinese patients with diffuse large B-cell lymphoma.

BACKGROUND: Elderly patients with diffuse large B-cell lymphoma (DLBCL) have a worse prognosis than younger patients, and the optimal treatment strategy for this group remains controversial. We conducted a retrospective analysis to investigate the clinical features and outcomes of elderly patients (>60 years) and to assess the impact of clinical and molecular factors on outcome in this age group. METHODS: From April 2006 to December 2012, a total of 349 elderly patients with DLBCL from the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College were included in this analysis. Patients were further divided into two age groups (61-69 years and ≥70 years). We compared clinical characteristics and outcomes between groups. RESULTS: Of 349 total patients, 204 (58.5%) were aged 61 to 69 years, and 145 (41.5%) patients were aged 70 years or older. Except for the Eastern Cooperative Oncology Group performance status, clinical characteristics were comparable between the two groups. With a median follow-up of 82 (range, 1-129) months, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 51.9% and 45.8%, respectively. The 5-year OS rates for patients aged 61 to 69 years and those over 70 years were 58.3% and 42.8% (P = 0.007), respectively, and the 5-year PFS rates were 51.0% and 38.6% (P = 0.034). Treatment regimens including rituximab provided a higher 5-year OS rate (63.1% vs. 37.1%, P < 0.001) and PFS rate (56.6% vs. 31.8%, P < 0.001) than chemotherapy alone. For patients aged 61 to 69 years, chemotherapy plus rituximab resulted in a higher 5-year OS rate (66.7% vs. 46.4%, P = 0.002) and PFS rate (60.0% vs. 38.1%, P = 0.002) than chemotherapy alone. For patients aged ≥70 years, there was a marked survival advantage in patients who received chemotherapy plus rituximab (5-year OS rate: 57.7% vs. 25.4%, P < 0.001; 5-year PFS rate: 51.3% vs. 23.9%, P < 0.001) compared with that seen in those who received chemotherapy alone. Multivariate analysis established that stage III/IV disease, elevated lactate dehydrogenase (LDH), initial treatment, and chemotherapy with rituximab were independent risk factors for 5-year OS, and stage III/IV disease, elevated LDH, and chemotherapy with rituximab were independent risk factors for 5-year PFS for elderly patients with DLBCL. CONCLUSIONS: In comparison to patients aged 61 to 69 years, those aged ≥70 years have poorer survival. Prolonged survival is obtainable with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-like in elderly Chinese patients in all age groups, indicating that the R-CHOP-like regimen should be considered for this population, even for those aged 70 years or older.

Phase 2 Study of First-line Intensity Modulated Radiation Therapy Followed by Gemcitabine, Dexamethasone, and Cisplatin for High-Risk, Early Stage Extranodal Nasal-Type NK/T-Cell Lymphoma: The GREEN Study.

PURPOSE: To investigate the efficacy and toxicity profile of sequential intensity modulated radiation therapy (IMRT) followed by gemcitabine, dexamethasone, and cisplatin (GDP) on previously untreated high-risk, early stage upper aerodigestive tract natural killer/T-cell lymphoma (UADT-NKTCL). METHODS AND MATERIALS: A phase 2 study was designed, and 40 high-risk patients with stage I(E)/II(E) UADT-NKTCL were enrolled between June 2010 and June 2014. High-risk patients were defined as those with at least 1 predefined risk factor: age >60 years, elevated serum lactate dehydrogenase, regional lymph node involvement, B symptoms, and primary tumor invasion. Patients received extended involved-site IMRT and GDP chemotherapy. The primary endpoint was the 2-year progression-free survival rate. Secondary endpoints were the 2-year overall survival rate, overall response rate, and toxicity. RESULTS: Median follow-up time was 60.1 months. The overall response rate and complete remission rate were 97.5% and 95.0%, respectively. The 2- and 5-year progression-free survival rates were 84.7% and 79.4%, and the corresponding overall survival rates were 89.9% and 82.1%, respectively. The most frequent radiation-induced toxicities were mild mucositis and skin reaction. Grade 3/4 neutropenia (12 of 40 patients), thrombocytopenia (7 of 40), and anemia (2 of 40) were observed during chemotherapy. CONCLUSIONS: First-line IMRT followed by GDP represents an effective and well-tolerated protocol for high-risk, early stage UADT-NKTCL.

Decreased Prognostic Value of International Prognostic Score in Chinese Advanced Hodgkin Lymphoma Patients Treated in the Contemporary Era.

BACKGROUND: The International Prognostic Score (IPS) was developed based on the data of Western advanced Hodgkin lymphoma (HL) patients treated before 1992. Only a few studies ever evaluated the application value of IPS in Chinese population or in patients treated in the contemporary era whose outcomes has improved significantly than before. METHODS: We conducted a retrospective study involving 208 previously untreated Chinese advanced HL patients, who were admitted to Cancer Hospital Chinese Academy of Medical Sciences from January 1, 1999 to April 30, 2015 and received uniform first-line treatment. The prognostic value of both IPS and the seven IPS factors for freedom-from progression (FFP) and overall survival (OS) was assessed in this population. The statistical methods included Kaplan-Meier methodology, log-rank testing, and Cox proportional hazard regression analysis. RESULTS: With a median follow-up time of 79 months (range, 15-210 months), the 5-year FFP and OS were 78.8% and 86.0% respectively, which improved obviously compared with the original IPS study. The IPS remained prognostic for both FFP (P = 0.041) and OS (P = 0.013), but the range narrowed obviously, with 5-year FFP ranging from 87.2% to 61.5%, 5-year OS ranging from 94.1% to 69.2%, and the separation of survival curves was not as good as before. Only two of the seven IPS factors showed a significant independent prognostic value in the multivariate analysis: Stage IV (for FFP, hazard ratio [HR] = 2.219, 95% confidence interval [CI]: 1.148-3.948, P = 0.016; for OS, HR = 2.491, 95% CI: 1.159-5.355, P = 0.019) and hemoglobin <105 g/L (for FFP, HR = 2.136, 95% CI: 1.123-4.060, P = 0.021; for OS, HR = 2.345, 95% CI: 1.099-5.042, P = 0.028). A simple prognostic score calculated by adding one point each for any of the two factors was prognostic both for FFP (P < 0.001) and OS (P < 0.001) with the survival curves separating very well, but the range still narrowed. CONCLUSIONS: The IPS has decreased the prognostic value in Chinese advanced HL patients treated in the contemporary era. More prognostic factors are needed to supplement this original scoring system so as to identify different risk populations more accurately.

Dosimetric and Clinical Outcomes With Intensity Modulated Radiation Therapy After Chemotherapy for Patients With Early-Stage Diffuse Large B-cell Lymphoma of Waldeyer Ring.

PURPOSE: To assess the dosimetric benefit, prognosis, and toxicity of intensity modulated radiation therapy (IMRT) for early-stage, diffuse large B-cell lymphoma of Waldeyer ring (WR-DLBCL). METHODS AND MATERIALS: Sixty-one patients with early-stage WR-DLBCL who received chemotherapy followed by IMRT were retrospectively reviewed. Dosimetric parameters for the target volume and critical normal structures were evaluated, and survival was calculated. Linear regression analysis was used to assess the effect of the mean dose (Dmean) to the parotid glands on xerostomia. RESULTS: The median conformity index and homogeneity index of the planning target volume (PTV) were 0.83 and 0.90, respectively, demonstrating very good coverage of the target volume. The mean dose to the parotid glands was 24.9 Gy. The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) were 94.7%, 93.1%, and 98.3%, respectively. Early and late toxicities were mild, and no patient experienced late grade ≥3 toxicities. The Dmean to the parotid glands had a linear correlation with late grade ≥2 xerostomia. CONCLUSIONS: IMRT after chemotherapy can provide excellent dose conformity and achieve favorable survival and LRC with mild toxicities in patients with early-stage WR-DLBCL. Dose constraints for the parotid glands should be limited to <24 Gy for early-stage WR-DLBCL.

Clinical and prognostic differences between ALK-negative anaplastic large cell lymphoma and peripheral T cell lymphoma, not otherwise specified: a single institution experience.

Clinical differences between anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALK(-) ALCL) and peripheral T cell lymphoma, not otherwise specified (PTCL-NOS), remain unclear. The aim of this study was to compare the clinical and prognostic features of these two lymphoma types. We retrospectively analyzed 167 patients with ALK(-) ALCL (n = 48) and PTCL-NOS (n = 119). Compared with ALK(-) ALCL patients, PTCL-NOS patients exhibited distinct differences in clinical features with a propensity for more advanced stages, frequent extranodal involvement, and a poor performance status, leading to a higher risk group according to the International Prognostic Index or Prognostic Index for PTCL-NOS. Patients with ALK(-) ALCL were associated with a higher complete response rate (47.9 vs. 31.0 %; P = 0.041) after initial chemotherapy than patients with PTCL-NOS. The prognosis was significantly different between two subtypes, with a 5-year overall survival (OS) rate of 57.9 % for ALK(-) ALCL and 23.9 % for PTCL-NOS (P = 0.002). The subgroup analysis showed significant differences in OS and progression-free survival between the two subtypes in early-stage diseases, but not in advanced-stage diseases. We conclude that patients with ALK(-) ALCL showed favorable clinical features, higher chemosensitivity, and a superior outcome than those with PTCL-NOS.

Intensity Modulated Radiation Therapy for Early-Stage Primary Gastric Diffuse Large B-Cell Lymphoma: Dosimetric Analysis, Clinical Outcome, and Quality of Life.

PURPOSE: To evaluate the dosimetric superiority, efficacy, toxicity, and quality of life (QOL) data of intensity modulated radiation therapy (IMRT) in patients with primary gastric diffuse large B-cell lymphoma (PG-DLBCL). METHODS AND MATERIALS: Forty-six consecutive patients with early-stage PG-DLBCL underwent IMRT after chemotherapy. The majority of patients (61.5%) were subclassified as the non-germinal center B cell-like subtype. Dosimetric parameters of the planning target volume (PTV) and organs at risk were assessed. Survival rates were depicted with the Kaplan-Meier method and compared with the log-rank test. Quality of life was evaluated using the QLQ-C30-STO22 questionnaires at the last follow-up contact. RESULTS: The median PTV mean dose was 41.6 Gy. Only 0.73% of the PTV received <95% of the prescribed dose, indicating excellent target coverage. The median kidney V20 and liver V30 were 14.1% and 16.1%, respectively. The 5-year overall survival (OS), progression-free survival, and locoregional control rates for all patients were 80.4%, 75.0%, and 93.2%, respectively. Stage, lactate dehydrogenase level, and immunophenotype were significant prognostic factors for OS, and only stage was a significant factor for locoregional control. Consolidation IMRT in patients with complete response after chemotherapy resulted in significantly better OS and progression-free survival than salvage IMRT in patients with non-complete response. Two of 8 patients who had chronic liver disease experienced grade 4 or grade 5 acute hepatic failure after 4 to 5 cycles of rituximab-based chemotherapy and IMRT (40 Gy). No other serious acute or late toxicity was observed. The long-term global and functional QOL scales were excellent, with negligible symptom scales. CONCLUSIONS: Intensity modulated radiation therapy yielded excellent target coverage and critical tissue sparing and achieved favorable outcomes with acceptable toxicity and good long-term QOL in early-stage PG-DLBCL.

GDP (Gemcitabine, Dexamethasone, and Cisplatin) Is Highly Effective and Well-Tolerated for Newly Diagnosed Stage IV and Relapsed/Refractory Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type.

This study was conducted to evaluate the effectiveness and tolerance of GDP (gemcitabine, dexamethasone, and cisplatin) regimen in patients with newly diagnosed stage IV and relapsed/refractory extranodal natural killer/T-cell lymphoma, nasal type (ENKTL).The study enrolled 41 ENKTL patients who received GDP regimen at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2008 and January 2015.The disease status was newly diagnosed stage IV in 15 patients and relapsed/refractory in 26 patients. The median number of cycles of chemotherapy per patient was 6 (range, 2-8 cycles). The overall response rate and complete-remission rate were 83.0% (34/41) and 41.5% (17/41), respectively. After a median follow-up of 16.2 months, 1-year progression-free survival rate and 1-year overall survival rate for the whole cohort were 54.5% and 72.7%. Grade 3 to 4 adverse events included neutropenia (34.1%), thrombocytopenia (19.5%), and anemia (14.6%).Our study has suggested high efficacy and low toxicity profile of GDP regimen in patients with newly diagnosed stage IV and relapsed/refractory ENKTL.

Whole Blood PCR Amplification with Pfu DNA Polymerase and Its Application in Single-Nucleotide Polymorphism Analysis.

AIMS: Point-of-care genetic analysis may require polymerase chain reaction (PCR) to be carried out on whole blood. However, human blood contains natural inhibitors of PCR such as hemoglobin, immunoglobulin G, lactoferrin, and proteases, as well as anticoagulant agents, including EDTA and heparin that can reduce whole blood PCR efficiency. Our purpose was to develop a highly specific, direct whole blood single-nucleotide polymorphism (SNP) analysis method based on allele-specific (AS) PCR that is mediated by Pfu DNA polymerase and phosphorothioate-modified AS primers. RESULTS: At high Mg(2+) concentrations, Pfu DNA polymerase efficiently amplified genomic DNA in a reaction solution containing up to 14% whole blood. Among the three anticoagulants tested, Pfu DNA polymerase showed the highest activity with sodium citrate. Meanwhile, Triton X-100 and betaine inhibited Pfu DNA polymerase activity in whole blood PCR, whereas trehalose had virtually no effect. These findings provided for the development of a low-cost, simple, and fast direct whole blood genotyping method that uses Pfu DNA polymerase combined with phosphorothioate AS primers for CYP2C9*3 and VKORC1(-1639) loci. CONCLUSIONS: With its high DNA amplification efficiency and tolerance of various blood conditions, Pfu DNA polymerase can be used in clinical laboratories to analyze SNPs in whole blood samples.

Ifosfamide, Cisplatin or Carboplatin, and Etoposide (ICE)-based Chemotherapy for Mobilization of Autologous Peripheral Blood Stem Cells in Patients with Lymphomas.

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a promising approach for lymphomas. This study aimed to evaluate the effect of ifosfamide, cisplatin or carboplatin, and etoposide (ICE)-based regimen as a mobilization regimen on relapsed, refractory, or high-risk aggressive lymphoma. METHODS: From June 2001 to May 2013, patients with lymphomas who mobilized by ICE-based regimen for ASCT were analyzed in this retrospective study. The results of the autologous peripheral blood stem cells collection, toxicity, engraftment after ICE-based mobilization regimen were analyzed in this study. Furthermore, risk factors for overall survival (OS) and progression free survival (PFS) were evaluated by univariate analysis. RESULTS: The stem cells were mobilized using ICE-based regimen plus rituximab or ICE-based regimen alone in 12 patients and 54 patients, respectively. The results of stem cell mobilization were excellent. Ninety-seven percentages of the patients had the stem cell collection of at least 2.0 × 10 6 CD34 + cells/kg and 68% had at least 5 × 10 6 CD34 + cells/kg. Fifty-eight percentage of the patients experienced Grade 4 neutropenia, 20% developed febrile neutropenia, and only 12% had Grade 4 thrombocytopenia. At a median follow-up of 63.8 months, the 5-year PFS and OS were 64.4% and 75.3%, respectively. CONCLUSION: ICE is a powerful regimen for stem cell mobilization in patients with lymphomas.

Systemic chemotherapy followed by locoregional definitive intensity-modulated radiation therapy yields prolonged survival in nasopharyngeal carcinoma patients with distant metastasis at initial diagnosis.

Chemotherapy is the current mainstay of treatment for patients with newly diagnosed metastatic nasopharyngeal carcinoma (NPC), whereas the role of locoregional radiotherapy remains to be defined. In this study, we retrospectively evaluated the outcome of systemic chemotherapy followed by locoregional definitive intensity-modulated radiation therapy (IMRT) as first-line treatment for these patients. Forty-one patients with pathologically confirmed NPC with distant metastasis at initial diagnosis seen between March 2005 and February 2014 were included. All the patients were treated with platinum-based systemic chemotherapy followed by definitive IMRT to the primary head and neck region with or without concurrent chemotherapy. In addition, local treatment to metastatic lesions was given in 19 patients. With a median follow-up time of 25 months, 24 patients had died, and the estimated median overall survival time was 31.2 months. The 1-, 2-, 3- and 5-year estimated OS rates were 89.9, 67.4, 41.1 and 22.5%, respectively. Prognostic analyses showed that serum lactate dehydrogenase level (P = 0.021) and number of metastatic sites (single vs. multiple; P = 0.016) were significant prognostic factors. Five patients are still alive without evidence of disease after 52 to >101 months. All of them had a single metastatic lesion and received local treatment to metastatic sites. These results suggest that the use of definitive IMRT to treat the locoregional tumor in combination with systemic chemotherapy may prolong survival in patients with newly diagnosed metastatic NPC, making curability a possible consideration in selected patients with single metastasis. Further prospective clinical trials are warranted.

High levels of BCOX1 expression are associated with poor prognosis in patients with invasive ductal carcinomas of the breast.

This study was to examine the breast cancer-overexpressed gene 1 (BCOX1) expression in invasive ductal carcinomas (IDC) of the breast and its value in the prognosis of the disease. The levels of BCOX1 expression in 491 paired IDC and surrounding non-tumor breast tissues as well as 40 paired fresh specimens were evaluated by tissue microarray, immunohistochemistry and quantitative RT-PCR. The potential associations of high BCOX1 expression with clinicopathological variables and the overall survival of these patients were analyzed. The relative levels of BCOX1 mRNA transcripts in the IDC breast tissues were significantly higher than that in the corresponding non-tumor tissues (P = 0.005). The anti-BCOX1 was predominantly stained in the cytoplasm of breast tissue cells and the levels of BCOX1 expression in the majority of breast cancer tissues were obviously higher than that in the corresponding non-tumor breast tissues. High levels of BCOX1 expression were found in 59.5% (292/491) of breast cancer tissues. The high BCOX1 expression was significantly associated with high histological grade (P = 0.037), positive expression of human epidermal growth factor receptor 2 (HER2, P = 0.031) and triple negative breast cancer (P = 0.027). The high BCOX1 expression in breast cancers was significantly associated with a shorter overall survival of these patients (P = 0.023), particularly in patients with triple negative breast cancer (P = 0.005). Therefore, the high BCOX1 expression may serve as a novel marker of poor prognosis and a potential therapeutic target for patients with IDC of the breast.

High-dose therapy and autologous stem cell transplantation in peripheral T-cell lymphoma: treatment outcome and prognostic factor analysis.

Peripheral T-cell lymphoma (PTCL) carries a poor prognosis with conventional treatment. We retrospectively analyzed data from 45 patients with PTCL who received high-dose therapy and autologous stem cell transplantation (HDT/ASCT) from 1990 to 2008 in our center. Eighteen patients underwent HDT/ASCT in complete remission to induction chemotherapy (CR1), and 27 patients underwent HDT/ASCT in other disease statuses. The median follow-up was 113.5 months (range 52.6-261.0) for surviving patients. The 5-year overall survival (OS) and progression-free survival (PFS) were 64 and 60 %, respectively. The 5-year OS for patients in CR1 and in other disease statuses was 89 and 47 %, respectively (P = 0.002), and 5-year PFS was 83 and 43 % (P = 0.007). In the subgroup excluding anaplastic large cell lymphoma, patients transplanted in CR1 also had significantly better 5-year OS (82 vs. 37 %, P = 0.009) and PFS (82 vs. 33 %, P = 0.008) than those transplanted in other disease statuses. Multivariate analysis showed that CR1 status was the only significant prognostic factor for OS (P = 0.040) and PFS (P = 0.040). These results support the use of HDT/ASCT consolidation in CR1 for PTCL patients. Prospective randomized trials are necessary to confirm the efficacy of this approach.