Resveratrol as a cardioprotective adjuvant for 5-fluorouracil in the treatment of gastric cancer cells

The clinical application of 5-fluorouracil (5-Fu), a potent chemotherapeutic agent, is often hindered by its well-documented cardiotoxic effects. Nevertheless, natural polyphenolic compounds like resveratrol (RES), known for their dual anti-tumor and cardioprotective properties, are potential adjunct therapeutic agents. In this investigation, we examined the combined utilization of RES and 5-Fu for the inhibition of gastric cancer using both in vitro and in vivo models, as well as their combined impact on cardiac cytotoxicity. Our study revealed that the co-administration of RES and 5-Fu effectively suppressed MFC cell viability, migration, and invasion, while also reducing tumor weight and volume. Mechanistically, the combined treatment prompted p53-mediated apoptosis and autophagy, leading to a considerable anti-tumor effect. Notably, RES mitigated the heightened oxidative stress induced by 5-Fu in cardiomyocytes, suppressed p53 and Bax expression, and elevated Bcl-2 levels. This favorable influence enhanced primary cardiomyocyte viability, decreased apoptosis and autophagy, and mitigated 5-Fu-induced cardiotoxicity. In summary, our findings suggested that RES holds promise as an adjunct therapy to enhance the efficacy of gastric cancer treatment in combination with 5-Fu, while simultaneously mitigating cardiotoxicity.

Comparison of two types of flaps based on dorsal cutaneous branch of proper palmar digital artery for repair of wound of fingertip or finger-pulp / 中华显微外科杂志

Objective:To compare the clinical effectiveness of propeller flap and vascular chain flap based on dorsal cutaneous branch of proper palmar digital artery for repair of wounds of fingertip or finger-pulp.Methods:From April 2018 to May 2021, a total of 55 patients (55 fingers) with wounds of fingertip or finger-pulp in the 2nd-5th fingers were treated in emergency surgery in the Department of Hand Surgery, the Second Hospital of Tangshan. The patients were randomly divided into 2 groups by the method of drawing lots. The wounds of 29 patients (29 fingers) were repaired by propeller flaps based on dorsal cutaneous branch of proper palmar digital artery (propeller group) and that of 26 patients(26 fingers) were treated by vascular chain flaps based on dorsal cutaneous branch of proper palmar digital artery(vascular chain group). Survival of the flaps and the skin grafts at donor sites were observed between the 2 groups. The operation and follow-up time in both groups were recorded. Postoperative follow-up included outpatient clinic visits, telephone reviews and WeChat video-clips. At final follow-up, the static TPD of the flaps, patient satisfaction with the appearance of flaps and donor sites and the Range of motion(ROM) of the injured fingers were recorded. The measurement and count data of both groups were compared by independent sample t-test, χ2 tests or Fisher's exact test, respectively. P<0.05 was considered a statistically significant. Results:All the flaps and skin grafts survived primarily in both groups. The operation time in propeller group was 57.55 minutes±4.35 minutes. It was less than what in the vascular chain group (61.12 minutes±4.58 minutes) and with statistically significant difference( P<0.05). The follow-up period was 14.55 months±2.89 months in propeller group and 15.15 months±3.78 months in the vascular chain group. There was no significant difference between the 2 groups( P>0.05). At final follow-up, the static TPD and patient satisfaction with the appearance of flaps in propeller group were 6.55 mm±1.24 mm and 4.59±0.50, which were better than 7.46 mm±1.27 mm and 4.31±0.47 in the vascular chain group with a statistically significant difference( P<0.05). The patient satisfaction with the appearance of donor sites and ROM of the injured digital joints in propeller group were 4.45±0.57 and 190.86°±8.56°, while what in the vascular chain group were 4.35±0.56 and 185.96°±10.58°. There was no significant difference between the 2 groups( P>0.05). Conclusion:The propeller flap and vascular chain flap are both based on dorsal cutaneous branch of proper palmar digital artery and are both suitable for repair of wounds of fingertip or finger-pulp. Compared with the vascular chain flap, the propeller flap has the advantages in shorter operation time, better flap sensation and appearance.

Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience / 中华血液学杂志

Objective: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. Methods: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven+ AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3-28; azacitidine, 75 mg/m(2) D1- 7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR) /CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) , and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. Results: The median age of the patients was 54 (18-77) years, 33 (55.0%) were males, and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0%) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1-5) . According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) achieved partial remission (PR) , and the ORR was 83.3%. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1%) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3%) cases achieved CR/CRi (7/21 achieved MRD negativity) , 3 achieved PR, and the ORR was 66.7%. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7%) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence<18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy) . Eleven of 24 (45.8%) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3%) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P=0.031) . After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8%. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+ AZA was tolerable for AML patients. Conclusion: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.

The Application of the Mosoteach-based Mobile Interactive Teaching Modein Literature Reading and Discussion of the Molecular Biology Course / 中国生物化学与分子生物学报

Graduate education emphasizes the development of students’ scientific research andinnovation abilities. Literature reading and discussion (LRD) plays an active role in the development ofinnovative thinking and critical thinking for graduate students. However, in traditional, large molecularbiology classes, the effective implementation of large-scale, collective LRD presents a great challenge. Mosoteach is a cloud-based free app designed specifically for education with powerful human-computerinteraction and human-human interaction functions. In the present study, LRD was introduced into amolecular biology course for graduate students and was conducted via the Mosoteach app. The onlinediscussion board in the Mosoteach cloud class was restricted to enrolled students and was designated theprivate online discussion board (PODB). The PODB built a sense of community for students and was aneffective approach for organizing and facilitating discussion in large classes. Small-group learning in LRDwas helpful to understand the literature and foster collaboration and discussion. Overall, we demonstratedthat Mosoteach-based LRD was helpful in improving student learning outcomes. The relationship betweenstudent learning style and engagement, satisfaction and academic performance in cloud classes meritsfurther investigation.

Professor -' clinical experiences in the identification and treatment of cranial tinnitus / 中国针灸

On the base of the relevant theories on disease identification of western medicine and traditional Chinese medicine, professor - has made the differentiation of cranial tinnitus and proposes the intervention measures. The location of disease is identified firstly. Secondly, the deficiency is distinguished from the excess, and the involved organs are determined as well. In view of the holistic idea and in combination of meridian differentiation of acupuncture-moxibustion, the principle of treatment is proposed, named "regulating , harmonizing blood circulation, clearing office and tranquilizing the mind". In treatment, the disease is treated individually. According to the involved location of onset and the related meridian running course, acupuncture-moxibustion therapy is exerted, in which, the local acupoints are combined with the distal ones. Additionally, electroacupuncture is used flexibly. The appropriate electric wave and frequency are selected in consideration of the syndromes/patterns of disease so as to optimize the regimen of acupuncture-moxibustion therapy. All of the approaches aforementioned provide the reference to clinical treatment of traditional Chinese medicine.

Analysis of induction efficacy and prognostic factors in FLT3-ITD positive acute myeloid leukemia in the real world / 中华血液学杂志

Objective: To investigate the efficacy and prognostic factors of induction therapy in FLT3-ITD(+) acute myeloid leukemia (AML) in the real world data. Methods: From January 2013 to December 2016, 114 de novo patients with FLT3-ITD(+)AML were enrolled in this study. Out of 114 cases, 75 were male, and 39 were female. The median age was 42 years old (ranged from 14 to 72 years old) . The chemotherapy regimens were used for induction therapy and all cases were followed up. The treatment response was evaluated by MICM and the comparison of the ratio were analyzed by chi-square test and the survival was estimated by Kaplan-Meier analysis and Cox proportional hazards model was used to identify independent prognostic factors. Results: There were 52 FLT3-ITD(+)AML patients with favorable prognosis genes (46 cases with NPM1, 5 cases with RUNX1-RUNX1T1, 1 case with CEBPA double mutation) and 62 patients with other types of FLT3-ITD(+)AML at diagnosis. All patients completed at least one cycle of induction therapy and the clinical curative effect was evaluated, complete remission (CR) rate was 50.0% (57/114) in one cycle and total CR rate was 72.5% (74/104) in two cycles. The CR rate of the FLT3-ITD(+) AML patients with favorable prognosis genes was 67.3% (35/52) in one cycle and 83.3% (40/48) in two cycles; for the other types FLT3-ITD(+)AML patients, the CR rate was 35.5% (22/62) in one cycle and 64.8% (35/54) in two cycles. There was a significant difference in CR rate between the FLT3-ITD(+)AML patients with and without favorable prognosis genes (P<0.05) . This indicates that the FLT3-ITD(+)AML patients with favorable prognosis gene had relatively good therapeutic effect. Among other types of FLT3-ITD(+)AML patients who did not achieve remission from one cycle of chemotherapy, 9 patients were given sorafenib plus chemotherapy and 6 cases (66.7%) achieved CR; 23 patients were given conventional chemotherapy and 7 cases (30.4%) achieved CR. There was a significant difference between sorafenib plus chemotherapy and conventional chemotherapy groups (χ(2)=4.47, P<0.05) and this indicates that sorafenib plus chemotherapy can significantly improve the CR rate of FLT3-ITD(+)AML patients. Comparing overall survival (OS) and disease free survival (DFS) , there was no significant difference between sorafenib plus chemotherapy and conventional chemotherapy groups (P values were 0.641 and 0.517, respectively) . Conclusion: The overall prognosis of FLT3-ITD(+)AML patients is poor, and the stratification therapeutic efficacy of FLT3-ITD(+)AML without favorable prognosis gene can be improved by sorafenib combined with chemotherapy.

Observation on the efficacy of consolidation chemotherapy combined with allogeneic natural killer cell infusion in the treatment of low and moderate risk acute myeloid leukemia / 中华血液学杂志

Objective: To evaluate the efficacy of consolidation chemotherapy combined with allogeneic natural killer (NK) cell infusion in the treatment of low or intermediate-risk (LIR) acute myeloid leukemia (AML) . Methods: A cohort of 23 LIR AML patients at hematologic complete remission (CR) received NK cell transfusion combined with consolidation chemotherapy after 3 consolidation courses from January 2014 to June 2019 were reviewed. Control group cases were concurrent patients from Department of Hematology, and their gender, age, diagnosis, risk stratification of prognosis, CR and the number of courses of consolidate chemotherapy before NK cell transfusion were matched with LIR AML patients. Results: A total of 45 times of NK cells were injected into 23 LIR AML patients during 4 to 7 courses of chemotherapy. The median NK cell infusion quantity was 7.5 (6.6-8.6) ×10(9)/L, and the median survival rate of NK cells was 95.4% (93.9%-96.9%) . Among them, the median CD3(-)CD56(+) cell number was 5.0 (1.4-6.4) ×10(9)/L, accounting for 76.8% (30.8%-82.9%) ; The number of CD3(+) CD56(+) cells was 0.55 (0.24-1.74) ×10(9)/L, accounting for 8.8% (4.9%-20.9%) . Before NK cell infusion, the number of patients with positive MRD in the treatment and control groups were 9/23 (39.1%) and 19/46 (41.3%) (χ(2)=0.030, P=0.862) respectively. After NK infusion, There was no significant difference in terms of MRD that went from negative to positive between the treatment and the control groups (14.3% vs 22.2%, χ(2)=0.037, P=0.847) . In the treatment group, 66.7% (6/9) of the MRD were converted from positive to negative, which was significantly higher than that in the control group (10.5%, 2/19) (χ(2)=6.811, P=0.009) . Morphological recurrence occurred in 1 case of MRD negative in the treatment group and 2 cases of MRD positive in the control group. By the end of follow-up, the median follow-up was 35 (10-59) months, the number of patients with morphological recurrence in the treatment group was 30.4% (7/23) , which was significantly lower than that in the control group (50.2%, 24/46) (χ(2)=2.929, P=0.087) , although there was no statistically significant difference between the two groups. There was no significant difference on MRD-negative between the treatment and the control groups (43.5% vs 43.5%, χ(2)=1.045, P=0.307) . The 3-year leukemia-free survival was better in the treatment group [ (65.1±11.1) %] than that in the control group [ (50.0±7.4) %] (P=0.047) . The 3-year overall survival in the treatment and control groups were (78.1±10.2) % and (65.8±8.0) % (P=0.212) , respectively. Conclusion: The consolidation of chemotherapy combined with allogeneic NK cell infusion contributed to the further remission of patients with LMR AML and the reduction of long-term recurrence.

Minimal residual disease in adults with Philadelphia chromosome negative acute lymphoblastic leukemia in high-risk / 中华血液学杂志

Objective: To explore the significance of minimal residual disease (MRD) in predicting prognosis and guiding therapy of adults with Philadelphia-chromosome negative acute lymphoblastic leukemia (Ph(-) ALL) in high-risk. Methods: Data of newly diagnosed adults with Ph(-) ALL in high-risk who achieved CR were reviewed. Variables associated with outcome were identified by COX regression model and Landmark analysis. Results: A total of 177 patients, 99 (56%) cases male with a median age of 40 years (range, 16-65 years) were included in this study. Of them, 95 (54%) patients received allo-HSCT in CR(1). Multivariate analyses showed that MRD negativity after the first cycle of consolidation (HR=0.52, 95%CI 0.30-0.89, P=0.017) and achieving CR within 4 weeks (HR=0.43, 95%CI 0.24-0.79, P=0.006) were the factors significantly-associated with longer DFS, and allo-HSCT was associated with both longer DFS (HR=0.13, 95%CI 0.08-0.22, P<0.001) and OS (HR=0.24, 95%CI 0.15-0.41, P<0.001) . Landmark analysis was performed on 121 patients, of 85 patients achieving MRD negativity after the first cycle of consolidation, multivariate analyses showed that MRD negativity after the third cycle of consolidation was significantly-associated with longer DFS (HR=0.18, 95%CI 0.05-0.64, P=0.008) and OS (HR=0.14, 95%CI 0.04-0.50, P=0.003) . For the patients achieving MRD negativity after both the first and the third cycles of consolidation, the 3-year DFS rate in the allo-HSCT cohort had a higher trend compared with that in the chemotherapy cohort (75.2% vs 51.3%, P=0.082) , however, the 3-year OS rates in the 2 cohorts were similar (72.7% vs 68.7%, P=0.992) . In those with MRD positivity after the first and/or the third cycle of consolidation, 3-year DFS (64.8% vs 33.3%, P=0.006) and OS (77.0% vs 33.3%, P=0.028) rates in the allo-HSCT cohort were significantly higher than those in the chemotherapy cohort, and similar to those in the cohort achieving MRD negativity after both the first and the third cycles of consolidation and receiving allo-HSCT. Conclusions: MRD negativity after the first cycle of consolidation was a predictor for better outcome in adults with Ph(-) ALL in high-risk. The survival advantage of the allo-HSCT cohort was not pronounced compared with that in the chemotherapy cohort even in those with high-risk features but achieving MDR negativity after both the first and third cycles of consolidation. However, allo-HSCT could be a good option for the patients with MRD positivity after the first and/or the third cycle of consolidation.

Application of Ilizarov technique for thumb shortening or bone defects after trauma / 中华骨科杂志

Objective To study the effect of Ilizarov technique on thumb shortening and bone defect after trauma.Methods The clinical data of 20 patients with thumb shortening or bone defect treated by Ilizarov technique from April 2010 to January 2018 were retrospectively analyzed.There were 19 males and 1 female including 15 left fingers and 5 right fingers.The age ranged from 20 to 56 years,with an average of 33.1 years.The osteotomy plane included 9 cases at distal part of the metacarpal,6 cases proximal phalanx base,1 case interphalangeal joint and 1 case distal part of proximal phalanx.Two cases were osteomyelitis after proximal and distal phalanges trauma,which resulted in interphalangeal joint defects after lesion clearance,and the length of the joint defect was 0.5 cm and 0.7 cm respectively.One case was emergency finger shortening fusion,which resulted in metacarpophalangeal joint defect due to nonunion of fusion site,and the length of the joint defect was 0.5 cm.Causes of injury included mechanical strangulation (12 cases),crush injury (6 cases) and traffic injury (2 cases).Semi-ring external fixator was used to extend the extension.There were 15 cases of metacarpal bone osteotomy and 5 cases of proximal phalanx osteotomy,prolonged from the 5th day after surgery.The osteotomy was prolonged by 0.5 mm every day,once every 6 hours.Results The follow-up time ranged from 184 to 446 days with an average of 244.6 days.The average extension period was 62.2 days (26-118 days),and the average extension length was 3.1 cm (1.3-5.9 cm).The healing index was 43.7-84.1 d/cm and the average healing index was 64.8 d/cm.The external fixed extender was used for 114-376 days with an average of 206.3 days.The distraction index was 20.1 c/cm (range,19.5-21.4 d/cm) and the maturity index was 46.5 d/cm (range,39.4-110.1 d/cm) and the external fixation index was 66.5 d/cm (range,60-130.8 d/cm).The finger pointing function and sensory function of thumb were restored after operation.According to the trial criteria of thumb and finger reconstruction function evaluation in the upper limb part evaluation criteria of Hand Surgery Society of Chinese Medical Association,11 cases were excellent,9 cases good,and the excellent and good rate was 100％(20/20).The two-point discrimination was 4-9 mm.The patients were satisfied with the function and appearance.Conclusion Ilizarov technique is a good method to treat thumb shortening and bone defect after trauma.

Effect of CPEB4 on Proliferation and Apoptosis of Chronic Myeloid Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To explore the expression of CPEB4 in K562 cells, the biological activity and its possible molecular mechanisms.@*METHODS@#Western blot was used to detect the expression of CPEB4 in normal leukocytes and K562 cells. The overexpression plasmid pcDNA3.1(+)-His-CPEB4 and the silencing plasmid pPLK+Puro-CPEB4 shRNA were transfected into K562 cells to change the expression of CPEB4 in K562 cells, and the transfection efficiency was detected by Western blot. Finally, CCK-8 and flow cytometry were used to detect the proliferation and apoptosis of differently treated cells, and the expression changes of proliferation and apoptosis marker proteins (AKT, p-AKT, caspase-3, BCL-2) were detected by Western blot.@*RESULTS@#Compared with normal leukocytes, the expression of CPEB4 protein in K562 cells was higher (P＜0.01). Compared with the control group, the proliferation of CPEB4-silenced K562 cells significantly increased (P＜0.01), the number of apoptotic cell significantly decreased, and expression of AKT, p-AKT and BCL-2 was significantly increased, the protein expression of caspase-3 was significantly reduced. The proliferation of K562 cells after CPEB4 overexpression was slowed down (P＜0.05), the number of apoptotic cells significantly increased,the expressions of AKT, p-AKT and BCL-2 were significantly down-regulated, and the expression of caspase-3 was up-regulated.@*CONCLUSION@#CPEB4 can inhibit the proliferation and promote the apoptosis of K562 cells, the AKT, p-AKT, BCL-2 and caspase-3 are involved in the regulation mechanism.

Outcomes of adult patients with de novo acute myeloid leukemia received idarubicin plus cytarabine regimen as induction chemotherapy / 中华血液学杂志

Objective: To explore outcomes in adult with de novo acute myeloid leukemia (AML) received IA10 (10 mg/m(2) d1-3 idarubicin plus cytarabine 100 mg/m(2) d1-7) regimen as induction chemotherapy. Methods: From January 2008 to February 2016, data of consecutive newly-diagnosed AML (non-M(3)) adults treated with IA10 who achieved morphologic leukemia-free state (MLFS) but not accepted allogeneic hematopoietic stem cell transplantation (allo-HSCT) were assessed retrospectively. Results: A total of 198 patients were included in this study with 96 (48.5%) male and a median age of 42 years old (range, 18-62 years old). Using the SWOG cytogenetic classification, 45 (22.7%), 104 (52.5%), 24 (12.1%) and 25 (12.6%) patients belonged to favorable, intermediate, unfavorable and unknown categories, respectively. 6 (3.0%) patients had monosomal karyotype, and 28 (14.1%) positive FLT3-ITD mutation. A complete remission (CR, defined as MLFS with ANC ≥ 1×10(9)/L and PLT ≥ 100×10(9)/L) achieved in 168 (84.8%) patients, a CRp (defined as MLFS with incomplete PLT recovery) in 16 (8.1%) and a CRi (defined as MLFS with incomplete ANC and PLT recovery) in 14 (7.1%). With a median follow-up period of 15 months (range, 1 to 70 months) in survivors, the probabilities of cumulative incident of relapse (CIR), disease free survival (DFS) and overall survival (OS) rates at 2-year were 45.2%, 46.9% and 62.9%, respectively; the median durations of relapse, DFS and OS were 34, 20 and 37 months respectively. At the time of achieving first MLFS, multivariate analyses showed that positive FLT3-ITD mutation and CRi were common adverse factors affecting CIR, DFS and OS; unfavorable-risk of SWOG criteria was an adverse factor affecting CIR and DFS; monosomal karyotype was associated with shorter OS. After first consolidation therapy, FLT3-ITD mutation positive and unfavorable-risk of SWOG criteria had negatively impact on CIR, DFS and OS; peripheral blasts ≥ 0.50 and positive MRD (defined as RQ-PCR WT1 mRNA ≥ 0.6% or any level of abnormal blast population detected by flow cytometry) after first consolidation therapy were common adverse factors affecting CIR and DFS; CRi was an adverse factor affecting DFS and OS. Conclusions: In adult with de novo AML received IA10 regimen as induction regimen, unfavorable molecular markers or cytogenetics at diagnosis and CRi independently predicted poor outcome. In addition, a higher percentage of peripheral blasts, monosomal karyotype and positive MRD after first consolidation therapy had negatively impact on outcomes.

Efficacy and safety of decitabine in combination with G-CSF, low-dose cytarabine and aclarubicin in MDS-EB and AML-MRC / 中华血液学杂志

Objective: To evaluate the clinical efficacy and safety of decitabine in combination with lower-dose CAG regimen (G-CSF, cytarabine and aclarubicin; D-CAG regimen) in the treatment of myelodysplastic syndromes with excess blasts (MDS-EB) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), compared to standard CAG regimen. Methods: A total of 42 patients with newly diagnosed MDS-EB and AML-MRC from May 2011 to March 2017 were included in the retrospective study. 21 cases were initially treated with G-CSF for priming, in combination with cytarabine of 10 mg/m(2) q12h for 14 days and aclarubicin of 20 mg/d for 4 days (CAG regimen) and the other 21 cases were initially treated with decitabine of 20 mg/m(2) for 5 days and lower-dose CAG regimen (cytarabine of 10 mg/m(2) q12h for 7 days, aclarubicin of 10 mg/d for 4 days, and G-CSF for priming (D-CAG regimen). After two cycles of induction chemotherapy, the patients who obtained complete remission(CR) received consolidation chemotherapy or hematopoietic stem cell transplantation (HSCT). Results: Among a total of 42 patients, the median age was 52.5 years (18-65 years) and 64.3% of them were male. Baseline characteristics of patients between D-CAG group and CAG group showed no significant differences. The CR for patients in D-CAG group was 81.0% (17/21), compared to 52.4% (11/21) in CAG group after 2 cycles of therapy (χ(2)=3.857, P=0.050). The overall response rate (ORR) for patients in D-CAG group and CAG group was 85.7% (18/21) and 76.2% (15/21) respectively, without significant difference (χ(2)=1.273, P=0.259). By December 2017, the median follow-up of D-CAG group and CAG group was 13(6-32) months and 15(2-36) months respectively. Finally, 10 patients in D-CAG group and 7 patients in CAG group received HSCT respectively. Except patients receiving HSCT, the median leukemia-free survival (LFS) time for patients in D-CAG group and CAG group was 18.0 (95%CI 6.6-29.4) months and 11.0 (95%CI 0-23.9) months respectively. Probabilities of 12 months LFS for D-CAG group and CAG group were (63.6±14.5)% and (50.0±13.4)% respectively, without difference (χ(2)=0.049, P=0.824). Except patients receiving HSCT, there were 2 deaths in D-CAG group and 7 deaths in CAG group respectively. The cumulative probabilities of 12 months OS for non-HSCT patients in D-CAG group and CAG group were (90.9±8.7)% and (61.5±13.5)% respectively, without significant difference (χ(2)=1.840, P=0.175). The incidences of side effects between D-CAG group and CAG group did not show significant differences (P=0.479), and the main side effects included cytopenias, pneumonia, infections of skin and soft tissues, neutropenic patients with fever, liver dysfunction. Conclusion: The decitabine in combination with lower-dose CAG regimen improved CR for patients with MDS-EB and AML-MRC, and was a promising choice.

Age-related clinical characteristics and prognosis in non-senile adults with acute myeloid leukemia / 中华血液学杂志

Objective: To explore age-related clinical characteristics, early responses and outcomes in non-senile adults with de novo acute myeloid leukemia (AML). Methods: Data of consecutive cases of 18-65 years adults with de novo AML (non-acute promyelocytic leukemia) were reviewed retrospectively. Clinical characteristics at diagnosis, early responses and outcomes across different age groups of patients were analyzed. Results: 1 097 patients were enrolled. 591 (53.9%) were male. Median age was 42 years. Increasing age was significantly associated with decreasing WBC count (P=0.003), increasing PLT count (P=0.034), lower blast proportions in bone marrow (P=0.021). The incidence of NPM1(+)/FLT3-ITD(-) increased with age (P<0.001). Multivariate analyses showed that increasing age was associated with low probabilities of achieving morphologic leukemia free state (MLFS) (P=0.053) and complete remission (CR) (P=0.004) and poor overall survival (OS) (P=0.070) in the whole patients population. However, increasing age was not associated with low MLFS rate and poor OS, except low CR rate (P=0.075) in those receiving standard induction regimen instead of low-intensity regimen. Conclusions: There were significant differences on clinical characteristics, cytogenetics and molecular genetics across different age groups in non-senile adults with de novo AML. In the patients receiving standard induction regimen, age was not associated with MLFS rate and OS.

Effect of Bryan cervical disc replacement on cervical curvature and replacement segment in treating cervical spondylosis / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the effect of Bryan cervical disc replacement on cervical curvature and replacement segment in the treatment of cervical spondylosis, and analyze its clinical efficacy.</p><p><b>METHODS</b>Forty-nine patients underwent Bryan artificial cervical disc replacement from August 2010 to August 2013 were retrospectively analyzed. There were 26 males and 23 females, aged from 27 to 66 years old with an average of 48.5 years. Including 21 cases of nerve root type, 16 cases of spinal cord type, 12 cases of mixed type. And 21 cases were single segment replacement, 28 cases were double segments replacement. Preoperative and postoperative pain was compared using visual analogue scale(VAS);cervical function was observed by Japanese Orthopedic Association Scores (JOA) and Neck Disability Index (NDI);cervical lordosis curvature, function spinal unit(FSU) curvature, activities of replacement and adjacent segment, FSU activity were measured by cervical X-rays. Clinical effects were evaluated by the Odom method.</p><p><b>RESULTS</b>All the patients were followed up for 18.5 to 37.3 months with an average of 33.1 months. Pvoperative VAS, JOA, NDI scores were 7.08±1.55, 5.2±1.9, 39.96±7.06 before operation, 3.76±2.33, 13.20±1.20, 25.20±6.64 at 3 months after operation, and 2.80±1.50, 14.3±1.6, 24.24±7.89 at the last follow-up. Patients at three months and the last follow-up after operation were obviously improved in their VAS, JOA, and NDI scores (<0.05). There was no significant difference between the scores at last follow-up and 3 months after operation. Cervical lordosis changed from (10.64±4.26)° preoperatively to (13.68±4.56) ° at the last follow-up;the FSU curvature from (5.40±0.41) °to (9.92±2.00) °at the last follow-up (<0.05). The range of motion of the cervical spine preoperatively, 3 month postoperatively, and at the last follow-up were(70.84±6.17)°, (60.00±6.58)°, (71.48±4.61)°; FSU activities were(12.00±0.49)°, (9.36±0.26)°, (12.52±0.33)°;the activities of replacement segment were (10.48±0.67)°, (7.24±0.34)°, (9.28±0.36)°;the activities of upper segment of replacement were (10.52±0.60)°, (8.60±0.30)°, (10.44±0.43)°;the activities of lower segment of replacement were (8.48±0.40)°, (6.56±0.36)°, (9.60±0.39)°;there were significant differences in above items preoperatively and 3 months postoperatively(<0.05); and there were no significant difference preoperatively and at the last follow-up(>0.05). Pharyngeal discomfort and hoarseness occurred in 5 cases, and were recovered within 2 weeks after operation;heterotopic ossification occurred in 1 case at 6 months after operation;displacement of prosthesis occurred in 1 case at 12 months after operation. Based on Odom standard to evaluate the clinical outcome, 20 cases obtained excellent results, with 27 good, 2 general.</p><p><b>CONCLUSIONS</b>Bryan artificial cervical disc replacement not only generate good clinical effects, but may also restore the cervical lordosis and FSU curvature, while retaining the activities of replacement segment, and restoring overall cervical biomechanical functions.</p>

Analgesic effects of Marasmius androsaceus mycelia ethanol extract and possible mechanisms in mice

Marasmius androsaceus is a medicinal fungus mainly used to treat various forms of pain in China. This study investigated the analgesic effects of an ethanol extract of M. androsaceus (MAE) and its potential molecular mechanisms. Oral administration of MAE (50, 200, and 1000 mg/kg) had significant analgesic effects in an acid-induced writhing test, a formalin test, and a hot-plate test, with effectiveness similar to tramadol (the positive control drug). The autonomic activity test showed that MAE had no harmful effects on the central nervous system in mice. MAE resulted in significantly enhanced levels of noradrenalin and 5-hydroxytryptamine in serum but suppressed both of these neurotransmitters in the hypothalamus after 30 s of hot-plate stimulation. Co-administration with nimodipine (10 mg/kg; a Ca2+ channel blocker) strongly enhanced the analgesic effect in the hot-plate test compared to MAE alone. Moreover, MAE down-regulated the expression of calmodulin-dependent protein kinase II (CaMKII) in the hypothalamus after a 30-s thermal stimulus. These results suggested that the analgesic ability of MAE is related to the regulation of metabolism by monoamine neurotransmitters and Ca2+/CaMKII-mediated signaling, which can potentially aid the development of peripheral neuropathic pain treatments obtained from M. androsaceus.

Effects of Cyclin A1 on the Proliferation of SKM-1 Cells and Its Potential Role in Myelodysplastic Syndrome / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Cyclin A1 on the proliferation of SKM-1 cells and its underlying role in myelodysplastic syndrome (MDS).</p><p><b>METHODS</b>Cyclin A1 was knocked down with its small interfering RNA (siRNA). The efficiency of siRNA transfection was measured by Western blot and RT-PCR. Then the proliferation of SKM-1 cells and the expression of CDK2,RUNX1 and SRSF2 with and without knockdown of Cyclin A1 recorded and analysed respectively.</p><p><b>RESULTS</b>Cyclin A1 was knocked down by siRNA after transfected for 48 h. The kncokdown of Cyclin A1 inhibited the proliferation of SKM-1 cells and down-regulated the expression of CDK2, RUNX1 and SRSF2, and these effects were at least partially mediated through RUNX1 and SRSF2 signaling pathway.</p><p><b>CONCLUSION</b>Cyclin A1 plays an important role in the proliferation of SKM-1 cells. These findings provide new insights into the pathogenesis of MDS, and it may be a potential target in the treatment of MDS.</p>

Effects and cost of four formulations of niclosamide ethanolamine salt in On-comelania hupensis snail control in field / 中国血吸虫病防治杂志

Objective To investigate the effects and cost of four formulations of niclosamide ethanolamine salt in Oncomela-nia hupensis snail control in the field in marshland and lake regions,so as to provide the evidence for drawing up the plan of mol-luscicide using in schistosomiasis endemic areas. Methods One drainage channel and one channel without water in the same area with snails in Jiangling County,Jingzhou City were selected as the research fields. The drainage channel was divided into 9 sections,except one section as a blank control group where the natural death rate of snails was observed only,and the remaining 8 sections were taken as the observation groups,where different dosages of 4％niclosamide ethanolamine salt powder,5％ni-closamide ethanolamine salt granules,25％ niclosamide ethanolamine salt suspending agent,26％ metaldehyde and ni-closamide ethanolamine salt suspending agent,and 50％niclosamide ethanolamine salt wettable powder were used re-spectively. The channel without water were divided into 4 sections,except one section as a blank control group,the oth-er 3 segments were taken as the observation groups,where 4％niclosamide ethanolamine salt powder,5％niclosamide ethanolamine salt granules,and 50％ niclosamide ethanolamine salt wettable powder were used respectively. Before and after spraying molluscicide for 7 days and 15 days,the system sampling method was used to observe the effects of snail control. Meanwhile,the unit cost method was used to calculate the costs of the different mulluscicide formulations abovementioned in unit area(1 m2). Results In the field at the drainage channel,the snail mortality rates of the groups spraying 4％niclosamide ethanolamine salt powder(50 g/m2),5％niclosamide ethanolamine salt granules(40 g/m2),25％ niclosamide ethanolamine suspending agent,26％ metaldehyde and niclosamide ethanolamine salt sus-pending agent,and 50％niclosamide ethanolamine salt wettable powder(2 g/m2 and 4 g/m2)for 7 days were 79.52％-97.87％,while the rates after spraying for 15 days were 71.00％-96.30％,and compared with those before spraying, the differences were statistically significant(all P<0.01). For the groups spraying with 2 g/m2 or 4 g/m2 suspending agent as well as wettable powder for 7 days,the snail mortality rates were significantly different(both P<0.05). In the field at the channel without water,the snail mortality rates of the 3 observation groups after spraying molluscicide for 7 days were 97.14％-100％,while for 15 days were 94.32％-100％,and compared with the rates before spraying,all the differences were statistically significant(all P<0.01). The unit costs per 1 m2 of the molluscicide abovementioned were ranged from 0.280 Yuan to 0.416 Yuan. Conclusions In marshland area inside embankment,the molluscicide formulations of the powder and granule are suitable for the environments without water or with instability water level , while the molluscicide formulations of the suspended agents and wettable powder are suitable for the water environment. Though the unit cost of powder is the lowest,the molluscicide in this formulation flies away seriously.

Clinical and Prognostic analysis of 43 Children with Mature B-cell Non-Hodgkin's Lymphoma/Acute Lymphoblastic Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the clinical and prognostic features as well as treatment response of childhood B-cell non-Hodgkin's lymphoma/acute lymphoblastic leukemia (B-NHL/B-ALL), so as to better modify the treatment for further improving the prognosis.</p><p><b>METHODS</b>The clinical data of 43 patients with newly-diagnosed childhood B-NHL/B-ALL from July 2005 to December 2013 in West China Second Hospital of Sichuan University were retrospectively analyzed with particular focus on clinical presentations, laboratory findings and histology. Among them 26 patients received B-NHL-2010 protocol and 17 patients received LMB-89 protocol treatment. Kaplan-Meier method was used to compare the survival rates between groups, while multiple factor logistic regression was used to identify the prognostic factors.</p><p><b>RESULTS</b>(1) The median age at diagnosis was 7.58 (2.42-13.67) years. The male-to-female ratio was 2.9 : 1. No significant difference was found in the median age at diagnosis between male and female children with B-NHL/B-ALL (P = 0.837). (2) Burkitt's lymphoma was the most common (34/43, 79.07%), followed by diffuse large B cell lymphoma (4/43, 9.3%), ALL-L3 (3/43, 6.98%) and others (2/43, 4.65%) in decreasing frequency. (3) According to St. Jude staging classification, 4 patients (9.30%) were divided into stage I, 9 patients (20.93%) into stage II, 23 patients (53.49%) into stage III and 7 patients (16.28%) into stage IV; (4) Clinically, the common predilection sites were as following: ileocecus (11/43, 25.58%), nasopharynx (10/43, 23.26%), faciomaxillary (9/43, 20.93%), superficial lymphadenopathy (8/43, 18.60%), other sites such as mediastinum and bone marrow (5/43, 11.63%). (5) With a median follow up of 24 months (0.7-105 months), the 2-year overall survival (OS) rate and event-free survival (EFS) rate were 79.8% ± 6.5%% and 71.0% ± 7.2%, respectively. The 2-year OS and EFS rates in patients treated with B-NHL-2010 protocol were 79.1% ± 8.4% and 74.1% ± 8.4%, while those in patients treated with LMB-89 protocol were 87.5% ± 8.3% and 66.7% ± 12.4%, respectively, but there was no significant difference between them (P > 0.05). The 2-year EFS rate in patients with LDH > 2N and bone marrow infiltration were significantly lower than that of other groups (P < 0.05). (6) 8 patients (18.6%) relapsed. The median relapsed time was 6 months (2-9 months). 1 patient suffered progressive disease. Male, systemic symptom, elevated LDH, bone marrow and CNS infiltration and advanced stage (stage III and stage IV) were associated with relapse /progressive disease. Logistic regression analysis showed that LDH > 2N was an independent unfavorable prognostic factors (OR = 31.129, P = 0.02).</p><p><b>CONCLUSION</b>Outcome of B-NHL/B-ALL is greatly improved by current intensive and short-time chemotherapy regimen. The 2-year event-free survival (EFS) rate is 71.0% ± 7.2%. There is no significant difference in EFS rate between patients treated with B-NHL-2010 protocol and LMB89 protocol. The long-term survival rate in patient with advanced disease need to be further improved.</p>

Clinical study of a cervical anterior Hybrid technique with posterior longitudinal ligament retained for cervical spondylosis / 中国骨伤

<p><b>OBJECTIVE</b>To explore the clinical effects and significances of a cervical anterior Hybrid technique with posterior longitudinal ligament retained in treating cervical spondylosis.</p><p><b>METHODS</b>The clinical data of 138 patients with cervical spondylosis underwent cervical anterior Hybrid surgery were retrospectively analyzed from March 2009 to March 2013. There were 52 males and 86 females,the age ranged from 36 to 58 years old with an average of 45.3 years. Course of disease was from 3 to 16 months. Cervical spondylosis classification included 22 cases with nerve root type, 68 cases with myelopathic type, 48 cases with mixed type. All patients were treated with the primary Hybrid surgery and their cervical posterior longitudinal ligaments were retained in anterior decompression. JOA score and image examination were used to evaluate clinical effect, and image examination included range of motion of the replacement segment, range of motion of the whole cervical spine, the sagittal diameter of the spinal cord before and after operation.</p><p><b>RESULTS</b>All operations were successful and operation time was 60 to 125 min (averaged 90.6 min), perioperative bleeding was 10 to 60 ml (averaged 30.1 ml). All patients were followed up from 12 to 48 months with an average of 22.2 months. All pathological segments obtained fully decompression, reserved posterior longitudinal ligament had no obvious hypertrophy, proliferation and calcification. The prosthesis had good location and the incision healed well without complications. Upper limbs root symptoms were completely relieved in the patients with cervical spondylotic radiculopathy, muscle strengths and sensations got different recovery in the patients with cervical spondylotic myelopathy. JOA score was increased from preoperative 8.62±1.22 to final follow-up 14.26±1.47 (P<0.05). Artificial intervertebral discs were stabilized in the patients, the replacement segment and range of motion of whole cervical spine were respectively (14.2± 5.6)° and (33.8±10.3)°, there was no significant differences between preoperative and postoperative (P>0.05). Spinal cord sagittal diameter was increased from preoperative (5.2±1.3) mm to postoperative (8.8±0.5) mm (P<0.05).</p><p><b>CONCLUSION</b>Anterior cervical Hybrid surgery with posterior longitudinal ligament retained can achieve fully decompression and good clinical efficacy, we recommend retaining the normal posterior longitudinal ligament in surgery as complete as possible.</p>

Methylation of CpG island in promoter region of RUNX2 gene and its expression in HOX11(+) acute T lymphoblastic leukemia / 中国实验血液学杂志

This study was purposed to detect the methylation status in promoter region of RUNX2 gene and its expression in cell lines and patients with HOX11(+) T-cell acute lymphoblastic leukemia (T-ALL) and to explore the relationship between the expression level of RUNX2 gene and methylation of CpG island in its promoter region. The methylation pattem in promoter region of RUNX2 gene was detected with bisulfite sequencing PCR, DNA methylation immunoprecipitation technique and promoter oligonucleotide microarray analysis and the expression levels of RUNX2 mRNA was detected with RT-PCR in 3 T-ALL cell lines (sil-ALL, DND41 and RPMI), as well as in 75 clinic bone marrow samples including 38 de novo T-ALL patients, 29 complete remission T-ALL patients and 8 normal samples. The results showed that there were hypermethylation of CpG island in promoter region of RUNX2 gene in patients with highly expressing HOX11(+) T-ALL. The methylation rate of the promoter CpG islands of RUNX2 gene in HOX11(+) T-ALL (78.9%) was significantly higher than that in HOX11(-) T-ALL (36.8%) (P < 0.01). The expression of RUNX2 in HOX11(+) cell lines was significantly lower than that in HOX11(-) cell lines, and the expression level of RUNX2 in the HOX11(+) T-ALL patients (0.581 ± 0.257) was significantly lower than that in HOX11(-) T-ALL patients (0.835 ± 0.317). The relationship between RUNX2 and HOX11 mRNA expression level showed a negative correlation (rs = -0.378, P < 0.01). The expression levels of RUNX2 gene negatively correlated with the methylation of CpG island in its promoter region (rs = -0.419, P < 0.01). It is concluded that HOX11 is a negative regulator of RUNX2 gene and the expression of RUNX2 is down regulated or even lost by promoter methylation in T-ALL, which demonstrate a better event-free survival and a marked trend for longer overall survival for HOX11-high T-ALLs. The expression and methylation level of RUNX2 gene may have some significance in evaluating the curative effect of T-ALL. The abnormal expression of RUNX2 may be a prognostic marker in T-ALL patients.