[Effect of triple-induction regimen including all-trans retinoic acid, arsenic trioxide plus anthracyclines for adults with non-high-risk acute promyelocytic leukemia].

Objective: To analyze the effect of triple-induction regimen including all-trans retinoic acid(ATRA), arsenic trioxide(ATO) plus anthracyclines and double-induction regimen including ATRA and ATO for adults with non-high-risk acute promyelocytic leukemia(APL). Methods: The clinical data of adult patients with non-high-risk APL who were first diagnosed and admitted to the Henan Provincial People's Hospital from January 2009 to December 2019 were retrospectively analyzed. All patients were divided into triple-induction group and double-induction group according to the treatment. The general data of patients, blood routine, coagulation function changes and blood transfusions during the induction period were collected, and the complete remission rate, early mortality and prognosis of two groups were analyzed. Results: A total of 164 patients were enrolled, including 86 males and 78 females, and the M(Q1,Q3) of their age was 41(18, 70) years. Among them, 75 were in triple-induction group and 89 in double-induction group. The white blood cell(WBC) counts of triple-induction group on day 7th and 14th after induction were (9.49±6.10)×109/L and (5.43±3.97)×109/L, while those in double-induction group were (15.17±17.06)×109/L and (13.37±12.59)×109/L, the differences were statistically significant (both P<0.05). In addition, the peak of WBC in the triple-induction group was lower than that in the double-induction group [13.8(6.3,89.7)×109/L vs 19.2(3.8,112.8)×109/L, P=0.019]. On day 7th after induction, the platelet(PLT) counts in the triple-induction group was lower than that in the double-induction group [27(11,147)×109/L vs 45(8, 183)×109/L, P=0.014]. However, the difference was not statistically significant in PLT counts between the two groups on day 14th, 21st and 28th, or in PLT transfusions during induction (all P>0.05). After treatment, it was observed only in a few patients of two groups that the prothrombin time(PT) elongation ≥3 s and/or activated partial thromboplastin time(APTT) elongation ≥10 s, and the difference was not statistically significant (all P>0.05). The incidence of induced differentiation syndrome in the triple-induction group was lower than that in the double-induction group (2.7% vs 12.4%, P=0.022) The early mortality rate was lower than that in the double-induction group (1.3% vs 5.6%), but the difference was not statistically significant (P>0.05). There were no statistically significant differences in the early complete remission rate, genetic remission rate, molecular remission rate, relapse rate, overall survival (OS) rate and disease-free survival (DFS) rate between the two groups. Conclusion: For adults with non-high-risk APL, the triple-induction therapy can reduce the counts and peaks of WBC, and reduce the incidence of induced differentiation syndrome.

[Efficacy and safety of PD-1 inhibitor combined with chemotherapy in the primary treatment of phase â ¢/â £ extranodal nasal-type natural killer/T cell lymphoma].

The data of 9 patients with stage Ⅲ/Ⅳ extranodal nasal-type natural killer/T cell lymphoma from August 2019 to August 2020 in People's Hospital of Zhengzhou University was retrospectively analyzed. All the patients were treated with the programmed cell death-1 (PD-1) inhibitor combined with P-GemoX-DEX (gemcitabine+oxaliplatin+dexamethasone+peraspartase) regimen as the first-line treatment. After 4 cycles of treatment, positron emission tomography/computed tomography (PET/CT) was used to evaluate the curative effect, and adverse reactions were also observed. The median follow-up time was 7 months. The overall response rate, complete and partial remission rate was 9/9, 6/9 and 3/9, respectively. The main adverse event was hematological toxicity, with 6 cases of grade Ⅰ/Ⅱ neutropenia, and no immune-related adverse events were reported.

[Expression of PD-1, TIM-3, LAG-3 and BTLA in diffuse large B-cell lymphoma and its effect on prognosis].

Objective: To investigate the expression levels of programmed death protein 1 (PD-1)、T cell immunoglobulin domain and mucin domain 3(TIM-3)、lymphocyte activating gene 3 (LAG-3) and B and T lymphocyte attenuator (BTLA) in Diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) and their effects on prognosis. Methods: The paraffin specimens of 30 patients with DLBCL, NOS newly diagnosed in People's Hospital of Zhengzhou University were stained with immunohistochemistry. The effects of single positive and co-expression of the above molecules on progression-free survival (PFS) phase and overall survival (OS) phase were analyzed. Results: There was no significant difference in prognosis between PD-1, TIM-3, LAG3, BTLA single positive group and single negative group. The median PFS phase of PD-1 and TIM-3 co-expression group and TIM3 and BTLA co-expression group were 26 and 24 months respectively, which were both lower than the 54 months (P=0.021) and 47 months (P=0.037) in non-co-expression group. The median PFS phase and OS phase of PD-1, TIM-3 and LAG-3 co-expression group were 17 and 25 months respectively, which were significantly lower than the 41 months (P=0.024) and 60 months (P=0.015) of non-co-expression group. The median PFS phase and OS phase of PD-1, TIM-3, LAG-3 and BTLA co-expression group were 18 and 26 months respectively, which were significantly lower than the 40 months (P=0.038) and 57 months (P=0.041) of non-co-expression group. Conclusions: In patients with DLBCL, NOS, those with PD-1 and TIM-3 co-expression as well as those with TIM-3 and BTLA co-expression have poor PFS phase. Patients with PD-1, TIM-3 and LAG-3 co-expression and patients with PD-1, TIM-3, LAG-3 and BTLA co-expression have poor PFS and OS phase.

[The influence and clinical significance of proteasome inhibitor on serum bone metabolite markers in patients with myeloma bone disease].

Objective: To investigate the influence and clinical significance of proteasome inhibitor on serum bone metabolite markers including tartrate-resistant acid phosphatase 5b isoenzyme (TRACP-5b), type I collagen carboxy terminal peptide ß(ß-CTX), type I procollagen amino terminal prolongation peptide (PINP) and vitamin D3 in patients with myeloma bone disease (MBD). Methods: From April 2015 to June 2018, 68 patients with newly diagnosed MBD who admitted to our hospital were treated with proteasome inhibitor-based regimen. Serum concentration of TRACP-5b、ß-CTX、PINP and vitamin D3 were measured before treatment and after 4 and 8 cycles of chemotherapy, and imaging changes were observed. Results: After 4 and 8 cycles of chemotherapy, serum levels of TRACP-5b, ß-CTX and vitamin D3 were decreased significantly (P<0.05). The serum concentration of PINP was (78.1±44.9) ng/L before chemotherapy, while after 4 cycles, it turned to (94.5±56.1) ng/L without significant difference (t=-1.871, P=0.063). Moreover, it increased to (173.3±80.5) ng/L after 8 cycles of chemotherapy with significant difference (t=-8.272, P<0.001). The proportion of imaging classification ≥3 among all patients was 66.2%, and it decreased to 60.3% after 4 cycles of chemotherapy without significant difference (χ(2)=0.569, P=0.477). The proportion of imaging classification ≥3 after 8 cycles of chemotherapy decreased to 44.5%, which was significantly lower than that before treatment (χ(2)=6.260, P=0.012). After 8 cycles of chemotherapy, 63 patients were evaluable, of which 50 were effective and 13 were ineffective. Serum concentration of PINP in the effective group was higher than that in the ineffective group ((190.7±78.5) ng/L vs (106.5±47.3) ng/L,t=5.762, P<0.001), and the serum concentration of vitamin D3 in the effective group was lower than that in the ineffective group ((11.7±4.8) µg/L vs (15.6±5.5) µg/L, t=-2.478, P=0.016). The proportion of patients with more than grade 3 bone disease of the effective group was also significantly lower than that of the ineffective group (38.0% vs 69.2%, χ(2)=4.076, P=0.044). There was no significant difference in the serum concentration of TRACP-5b and ß-CTX between two groups. Conclusion: After treatment with the proteasome inhibitor -based regimen, the serum concentrations of TRACP-5b, ß-CTX and vitamin D3, which reflect osteoclast activity in MBD patients were decreased, the serum concentration of PINP indicating osteoblast activity was increased, and the grade of imaging of bone disease was decreased.

[Clinical study on factor â § inhibitor in children with hemophilia A].

Objective: To reveal the related factors of inhibitors and differences ofhemorrhage and joint disease before and after the production of inhibitors in children with hemophilia A (HA) . Methods: Retrospective analyses of the clinical data of 381 children with HA under the age of 16 registered in the Registration Management Center of Hemophilia in Henan Provincial from January 2015 to August 2018. Results: A total of the 381 children were enrolled with 116 (30.4%) mild, 196 (51.4%) moderate, and 69 (18.1%) severe cases; 54 patients (14.2%) had inhibitors, including 22 high and 32 low titer inhibitors. Positive family history was positively associated with inhibitors[P<0.001, OR=3.299 (95%CI 1.743-5.983) ], and high-intensity exposure was associated with inhibitors[P=0.002, OR=2.587 (95%CI 1.414-4.731) ]. High-intensity exposure was associated with high titer inhibitor production[P=0.001, OR=8.689 (95%CI 2.464-30.638) ], and high-intensity exposure increased the risk of high titer inhibitors in HA patients. After inhibitors occurred in 54 patients with HA, the rates of overall joint annual bleeding (z=-3.440, P=0.001) and traumatic annual bleeding (z=-2.232, P=0.026) increased, but the rates of the annual joint bleeding (z=-1.342, P=0.180) and spontaneous annual bleeding (z=-1.414, P=0.157) remained to be not statistically significant. The joint ultrasound score did not change significantly after the inhibitor information (z=-0.632, P=0.527) . Conclusions: Positive family history and high-intensity exposure could increase the risk of F Ⅷ inhibitors in HA patients, and high-intensity exposure increased the risk of high titer inhibitors. The rates of the overall joint annual bleeding and traumatic annual bleeding increased after the inhibitor information.

[Clinical significance of the ratio of serum beta-CTX/PINP in multiple myeloma bone diseases and bone metastases].

Objective: To explore the clinical significance of serum bone metabolites ß C-termianl telopeptide of type Ⅰ collagen(ß-CTX), Procollagen type Ⅰ N-terminal peptide(PINP) concentration and ratio of beta -CTX/PINP in multiple myeloma bone disease (MMBD) and bone metastases. Methods: A total of 31 cases of MM, 46 cases of bone metastases and 12 healthy controls were enrolled in the department of hematology, oncology and physical examination center of Henan Provincial People's Hospital respectively from October 2016 to October 2017. According to the imaging findings, MMBD was divided into 0-4 grades, group A included the patitents with grade 0-2 of osteopathy (n=8), and group B included the grade 3-4 (n=23). After two courses of chemotherapy, the curative effect was evaluated. MM group were divided into effective group (above partial remission , n=22) and uneffective group (unreached partial remission, n=9). ELISA method was used to detect the concentration of serum beta -CTX and PINP, and the ratio of beta -CTX/PINP was calculated. Results: The serum beta -CTX concentration in newly diagnosed MM, bone metastases and healthy control were (3 563 ± 544)ng/L, (6 690±343)ng/L, (2 726±1 026)ng/L (χ2=22.207, P<0.001), PINP concentration were (72 ± 14) ng/L, (112 ± 62) ng/L, (171 ± 62) ng/L (χ2=7.418, P=0.024) , and beta -CTX/PINP ratio were 93±19, 141±21, 17±8 (χ2=20.192, P<0.001), the differences were statistically significant. The ratio of initial MM beta -CTX/PINP was higher than that of healthy control (P=0.001). The concentration of beta -CTX (P=0.003) and the ratio of beta -CTX/PINP(P<0.001) in bone metastases were higher than those in healthy controls. The serum concentration of beta-CTX in newly diagnosed MM was lower than that in bone metastases (P<0.001). Before chemotherapy, the serum levels of beta -CTX and PINP in A and B groups were not statistically significant, but the ratio of serum beta -CTX/PINP in A group was lower than that in group B, and the difference was statistically significant. After two courses chemotherapy, the concentration of serum beta -CTX (P=0.023) and the ratio of beta -CTX/PINP (P<0.001) were decreased in MM group. There were no significant difference of serum beta -CTX, PINP concentration, and beta-CTX/PINP ratio before and after treatment in Group A. Patients in the group B, there was no significant difference in the changes of serum PINP concentration, but both serum beta -CTX concentration and beta-CTX/PINP ratio decreased after two courses[(4 027 ± 648)ng/L vs (2 370± 460) ng/L, P=0.043; 111± 23 vs 30± 6, P=0.002]. The ratio of serum beta-CTX/PINP decreased in the effective group, and the difference was statistically significant. There was no significant difference in serum beta-CTX, PINP concentration and beta-CTX/PINP ratio before and after treatment in the uneffective group. Conclusions: There is a difference between newly diagnosed MMBD and bone metastases in serum beta-CTX, which might be helpful for differential diagnosis, and the ratio of beta-CTX/PINP is positively correlated with the severity of MMBD, which might be used to evaluate the severity of bone disease and have a certain monitoring significance for the treatment of MM.

[Comparison of different styles of allogeneic hematopoietic stem cell transplantation as first-line treatment treated with severe aplastic anemia in children and adolescents].

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from different donors as first-line treatment for children and adolescents with severe aplastic anemia (SAA) . Methods: The clinical data of 79 children and adolescents with SAA diagnosed from January 2013 to December 2016 in Henan Province were retrospectively analyzed. There were 50 males and 29 females, with a median age of 14(4-18) years. 40 cases received matched sibling transplantation (MSD-HSCT), 17 with unrelated donor transplantation (UD-HSCT), and 22 with haploidentical transplantation (haplo-HSCT). Results: The comparison of MSD-HSCT, UD-HSCT, haplo-HSCT groups was conducted and the median times of neutrophils engraftment were statistically significant [12(9-25) d, 14(10-22) d, 16(11-26) d, respectively (χ2=13.302, P=0.001)], but no difference in+30 d engraftment rate [97.3%(36/37), 100%(15/15), 100%(20/20), χ2=0.959, P=0.619]. The median times of PLT engraftment were not statistically significant [14(6-34)d, 16(7-32)d, 19(10-34)d, respectively, χ2=5.892, P=0.053], and the +30 d engraftment rate had no difference [97.3%(36/37), 100%(15/15), 100%(20/20), χ2=0.959, P=0.619]. The post-transplant infection rate showed no statistically significance [35.0% (14/40), 29.4% (5/17), 45.5% (10/22), χ2=1.158, P=0.560], as well as the incidences of aGVHD, grade III/IV aGVHD and cGVHD(χ2=0.230, P=0.891; χ2=2.628, P=0.269; χ2=3.187, P=0.203). The two-years OS rate was not statistically significant respectively [(77.1±6.7)%, (70.6±11.1)%, (77.3±8.9)%, χ2=0.330, P=0.845]. Severe post-transplant infection (RR=4.617, P=0.009), grade Ⅲ/Ⅳ aGVHD (RR=2.707, P=0.048) were independent risk factors for OS. Conclusion: The overall efficacy of MSD-HSCT, UD-HSCT and haplo-HSCT as first-line therapy for children and adolescents with SAA/VSAA is comparable.

[The analysis of prognosis-associated factors in adults with acute promyelocytic leukemia].

Objective: To explore the prognostic value of CD34, CD2, CD56 expressions and FLT3-ITD mutation in adults with acute promyelocytic leukemia (APL) . Methods: The immuno-phenotypic and molecular characteristics of 137 adult patients with APL (from January 2010 to March 2016, in Henan Provincial People's Hospital) were investigated. And the relationships between CD34, CD2, CD56 expressions, FLT3-ITD mutation and the outcomes of high WBC counts at onset, complete remission (CR) rate, early mortality, relapse rate (RR) , overall survival (OS) , disease free survival (DFS) were explored. Results: ①Among the 137 patients, the positive ratios of CD34, CD2, CD56 expressions and mutation rate of FLT3-ITD were 26.3%, 25.5%, 10.2% and 17.5%, respectively. The morbidities of positive CD34, CD2, CD56 expressions and FLT3-ITD mutation in the high-risk group were 43.2%, 47.7%, 18.2% and 27.3% respectively, while those in the low-/intermediate-risk groups were 18.3%, 15.1%, 6.5% and 12.9%, respectively (P<0.05) . ②At a median follow-up of 41 months, the total CR rate of the 137 adults APL patients was 96.9%, early mortality 6.6% and relapse rate 7.3% respectively. And RR of positive CD34 or CD2 expression patients was higher than negative CD34/CD2 expression ones (18.8% vs 3.3%, χ(2)=8.462, P=0.004; 16.1% vs 4.3%, χ(2)=4.382, P=0.028, respectively) . In addition, the early mortality of patients with positive CD56 expression or FLT3-ITD mutation was extremely higher than in negative ones (21.4% vs 4.9%, χ(2)=5.610, P=0.018; 16.7% vs 4.4%, χ(2)=4.833, P=0.028, respectively) . ③The whole OS and DFS were 88.3% and 84.7%, respectively. Wherein, OS and DFS in patients with CD34(+), CD56(+) or FLT3-ITD mutation were worse (P<0.05) . Conclusions: Positive CD34, CD2, CD56 expression and FLT3-ITD mutation were latent poor prognostic factors in adults with APL.

[Efficacy of combination of ATRA, ATO and anthracyclines induction therapy in patients with acute promyelocytic leukemia].

Objective: To explore the efficacies of regimens of three-drug induction therapy (ATRA+ATO+anthracyclines) versus two-drug induction therapy (ATRA+ATO) in patients with acute promyelocytic leukemia (APL). Methods: Of 184 patients diagnosed with APL from January 2009 to March 2016, 58 patients underwent three-drug induction therapy, while the rest were treated with two-drug induction therapy. Three-drug induction therapy was of ATRA (20 mg·m(-2)·d(-1), d(1-28)) + ATO (0.16 mg·kg(-1)·d(-1), d(1-28)) + Idarubicin (8 mg·m(-2)·d(-1), d(3-5)) /daunorubicin (40 mg·m(-2)·d(-1), d(3-5)) , while two-drug induction therapy ATRA+ATO with the same doses and methods as above. Of 184 cases, 69 cases accompanied with WBC counts>10×10(9)/L, 115 cases with WBC counts≤10×10(9)/L at onset. Results: ①Short-term efficacy: After one cycle induction therapy, the rates of hematologic remission, genetic remission, molecular remission and induced differentiation syndrome (DS) in three-drug regimen group were 98.3%, 87.9%, 72.4% and 0 respectively, while those in two-drug regimen group were 87.3%, 65.9%, 51.6% and 12.7% respectively. In patients with WBC >10×10(9)/L, DS rate and early mortality in three-drug regimen group were lower than in two-drug regimen group (0 vs 15.6%, 4.2% vs 15.6%, respectively). In patients with WBC≤10×10(9)/L, DS rate in three-drug regimen group was also lower than in two-drug regimen group (0 vs 12.3%) , but there were no statistical differences in terms of relapse and early mortality. ② Long-term efficacy: The relapse rate, overall survival (OS) and disease free survival (DFS) in three-drug regimen group were 0, 98.5%, 96.6% respectively, while those in two-drug regimen group were 8.6%, 86.5% and 84.1% respectively; the advantages of three-drug over two-drug regimen, especially in cases of WBC >10×10(9)/L were observed. ③ Side effects: the incidences of gastrointestinal reaction, liver dysfunction, myocardial damage and headache in three-drug regimen group hardly increased. Conclusion: The efficacies of three-drug induction therapy were superior to two-drug one.

Cloning and bioinformatic analysis of transcription factor MYB10 from the red-leaf peach.

In higher plants, the transcription factor MYB10 is an important regulator of anthocyanin biosynthesis. In order to study its role in the development of red coloration in peach leaves, the full-length MYB10 complementary DNA sequence of the red-leaf peach cultivar 'Tsukuba No. 5' (Prunus persica f. atropurpurea) was successfully cloned using reverse transcription-polymerase chain reaction. The sequence was assigned the GenBank accession No. KP315904. Bioinformatic analysis identified the complete MYB10 open reading frame, consisting of 678 bp encoding 225 amino acids. The predicted protein has a molecular weight of 26.56 kDa and a theoretical isoelectric point of 8.97. The secondary structure was found to comprise approximately 34.22% alpha helix, 15.11% extended strand, 10.67% beta turn, and 40% random coil. Subcellular analysis indicated that MYB10 may function in the cytoplasm. Assessment of the amino acid sequence suggested the presence of one serine and two threonine phosphorylation sites. Quantitative real-time polymerase chain reaction revealed that MYB10 expression positively correlated with anthocyanin content in red-leaf peach, indicating that this transcription factor plays a role in the biosynthesis of this pigment in peach trees.

Isolation and expression analysis of four HD-ZIP III family genes targeted by microRNA166 in peach.

MicroRNA166 (miR166) is known to have highly conserved targets that encode proteins of the class III homeodomain-leucine zipper (HD-ZIP III) family, in a broad range of plant species. To further understand the relationship between HD-ZIP III genes and miR166, four HD-ZIP III family genes (PpHB14, PpHB15, PpHB8, and PpREV) were isolated from peach (Prunus persica) tissue and characterized. Spatio-temporal expression profiles of the genes were analyzed. Genes of the peach HD-ZIP III family were predicted to encode five conserved domains. Deduced amino acid sequences and tertiary structures of the four peach HD-ZIP III genes were highly conserved, with corresponding genes in Arabidopsis thaliana. The expression level of four targets displayed the opposite trend to that of miR166 throughout fruit development, with the exception of PpHB14 from 35 to 55 days after full bloom (DAFB). This finding indicates that miR166 may negatively regulate its four targets throughout fruit development. As for leaf and phloem, the same trend in expression level was observed between four targets and miR166 from 75 to 105 DAFB. However, the opposite trend was observed for the transcript level between four targets and miR166 from 35 to 55 DAFB. miRNA166 may negatively regulate four targets in some but not all developmental stages for a given tissue. The four genes studied were observed to have, exactly or generally, the same change tendency as individual tissue development, a finding that suggests genes of the HD-ZIP III family in peach may have complementary or cooperative functions in various tissues.

Potassium contributes to zinc stress tolerance in peach (Prunus persica) seedlings by enhancing photosynthesis and the antioxidant defense system.

Zinc (Zn) is considered to be a major industrial pollutant because excessive amounts can impair plant growth. In this paper, we found that peach 'Yoshihime' seedlings are promising Zn tolerant plants. However, heavy Zn toxicity (2 mM) damaged plant performance by disrupting biochemical processes, including photosynthesis, proline production, and K(+) nutrition. Notably, elevated external K(+) supply (10 mM) alleviated peach seedlings from Zn toxicity, evidenced by enhanced photosynthesis, antioxidant defense systems, and plant K(+) nutritional status. Moreover, the transcript levels of KUP (K(+) uptake) genes involved in K(+) acquisition, transport, and homeostasis were significantly upregulated following supply of sufficient K(+) upon Zn toxicity. In general, K(+) favorably contributes to improvements in internal K(+) homeostasis, via the help of K(+) transporters, further protecting plant photosynthesis and the antioxidative defense system. Our findings further benefit the study of the mechanisms underpinning heavy metal tolerance in woody plants.

Diversity, population structure, and evolution of local peach cultivars in China identified by simple sequence repeats.

The fruit peach originated in China and has a history of domestication of more than 4000 years. Numerous local cultivars were selected during the long course of cultivation, and a great morphological diversity exists. To study the diversity and genetic background of local peach cultivars in China, a set of 158 accessions from different ecological regions, together with 27 modern varieties and 10 wild accessions, were evaluated using 49 simple sequence repeats (SSRs) covering the peach genome. Broad diversity was also observed in local cultivars at the SSR level. A total of 648 alleles were amplified with an average of 13.22 observed alleles per locus. The number of genotypes detected ranged from 9 (UDP96015) to 58 (BPPCT008) with an average of 27.00 genotypes per marker. Eight subpopulations divided by STRUCTURE basically coincided with the dendrogram of genetic relationships and could be explained by the traditional groups. The 8 subpopulations were juicy honey peach, southwestern peach I, wild peach, Buddha peach + southwestern peach II, northern peach, southern crisp peach, ornamental peach, and Prunus davidiana + P. kansuensis. Most modern varieties carried the genetic backgrounds of juicy honey peach and southwestern peach I, while others carried diverse genetic backgrounds, indicating that local cultivars were partly used in modern breeding programs. Based on the traditional evolution pathway, a modified pathway for the development of local peach cultivars in China was proposed using the genetic background of subpopulations that were identified by SSRs. Current status and prospects of utilization of Chinese local peach cultivars were also discussed according to the SSR information.