Common ABCB1 SNP, C3435T could affect systemic exposure of dapagliflozin in healthy subject

P-glycoprotein (P-gp) is a transporter that plays an excretory role in epithelial cells. It is encoded by ABCB1, and single nucleotide polymorphisms (SNPs) in this gene can affect systemic drug exposure. Dapagliflozin and sitagliptin, used in type 2 diabetes treatment, are P-gp substrates. Here, we aimed to investigate whether ABCB1 polymorphisms affect dapagliflozin and sitagliptin pharmacokinetics (PK) in healthy Korean subjects.The study population consisted of 100 healthy Korean subjects (94 men and 6 women) who participated in four different clinical trials and received dapagliflozin and sitagliptin doses of 10 and 100 mg, respectively. We determined ABCB1 genotypes for the C3435T, C1236T, and G2677T/A SNPs. The relationship between the genotypes and dapagliflozin PKs was examined.Dapagliflozin and sitagliptin PK parameters were not statistically significantly affected by ABCB1 SNP genotypes. However, homozygous 3435TT subjects showed higher dapagliflozin PK parameters than CT and CC subjects. In subjects with the 3435TT and those with 3435CC and 3435CT genotypes, mean Cmax, AUCinf, and AUC0-1 values of dapagliflozin were 223.06 ng/mL and 194.81 ng /mL (p = 0.2767), 673.58 ng*h/mL and 573.96 ng*h/mL (p = 0.0492), and 128.53 ng*h/mL and 104.61 ng*h/mL (p = 0.2678), respectively.In summary, dapagliflozin and sitagliptin PK parameters were not significantly different between individuals with C1236T and C2677T/A ABCB1 genetic polymorphisms. Dapagliflozin exhibited higher systemic exposure in 3435TT subjects than in CC/CT subjects.

Impact of Coronavirus Disease 2019 on Prognosis and Treatment Strategies in Patients with Hematological Malignancy--Review / 中国实验血液学杂志

Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide since outbreak in December 2019, and become a global public health crisis. Patients with hematological malignancy concurrently infected with COVID-19 are often associated with severe even fatal complications, due to low basic immune function, high intensity of chemotherapy and radiotherapy, and slow immune reconstruction post hematopoietic stem cell transplantation, and their treatment strategies, such as anti-infective therapy, blood transfusion, and the use of granulocyte colony stimulating factor need to be adjusted. The characteristics of patients, chemotherapy, hematopoietic stem cell transplantation, and other clinical factors may affect the prognosis of patients with hematological malignancy concurrently infected with COVID-19. Herein, the latest research progress is reviewed.

Analysis on exercise capacity of patients with pneumoconiosis and different degrees of pulmonary dysfunction / 中国职业医学

OBJECTIVE: To explore the exercise capacity of patients with occupational pneumoconiosis with varying degrees of pulmonary dysfunction. METHODS: A total of 488 hospitalized occupational pneumoconiosis patients were selected as study subjects using the judgment sampling method and examined for pulmonary function test and cardiopulmonary exercise test(CPET). Among them, 272 patients with normal lung function were assigned as the control group, and 216 patients with abnormal lung function as the case group. The case group was divided into mild, moderate and severe pulmonary dysfunction subgroups according to the forced expiratory volume in one second/predicted value ratio(FEV_1%pred).RESULTS: The FEV_1%pred, maximal voluntary ventilation(MVV), maximum exercise tidal volume(VT_(max)), breathing reserve(BR), maximal Watt(W_(max)), maximum oxygen uptake(VO_(2max)) and anaerobic threshold(AT) in patients of the case group were lower than that in the control group(all P<0.05). The FEV_1%pred, MVV, VT_(max), W_(max), and VO_(2max) in patients in the 3 subgroups of abnormal lung function were decreased(all P<0.05) compared with the control group. The VO_(2max) and AT decreased in the case group with the increase of the degree of pulmonary dysfunction(P<0.05). The FEV1%pred, MVV, maximal exercise minute ventilation and VT_(max) of the study subjects were positively correlated with VO_(2max) and AT(all P<0.01), but the BR had no correlation with VO_(2max) and AT(all P>0.05). CONCLUSION: The more serious the abnormal degree of pulmonary function in the patients with occupational pneumoconiosis, the more obvious the decline of their exercise ability, showing a dose-effect relationship.

Optimization of Ultrafiltration Technology of Enzymatic Hydrolysate from Eucommia ulmoides Peel / 中国药房

OBJECTIVE：To optim ize the ultrafiltration technology of enzymatic hydrolysate from Eucommia ulmoides peel. METHODS：The single factor test was adopted to investigate the effects of molecular weight of ultrafiltration membrane ，liquid temperature，operating pressure ，operating frequency ，membrane filtration time ，liquid concentration and pH on transfer rates of aucubin，geniposide and chlorogenic acid as well as solid removal rate in enzymatic hydrolysate from E. ulmoides peel. Setting the molecular cut off of fixed ultrafiltration membrane of 100 000，liquid concentration of 7 g/L，and pH value of 7，the ultrafiltration technology was optimized by Box-Behnken design response-surface methodology and validated with liquid temperature ，operating pressure，operating frequency and membrane passing time as factors ，using comprehensive scores calculated from transfer rates of aucubin，geniposide and chlorogenic acid as well as solid removal rate as indexes. RESULTS ：The optimal ultrafiltration technology of enzymatic hydrolysate from E. ulmoides peel was as follows as liquid temperature of 35 ℃，operating pressure of 0.5 MPa，operating frequency of 35 Hz and membrane passing time of 42 min. Results of validation tests showed that the comprehensive scores of the transfer rates of aucubin ，geniposide and chlorogenic acid as well as solid removal rate in enzymatic hydrolysate from E. ulmoides peel was 78.06％（RSD＝1.43％，n＝3），and its relative error with the predicted value （77.18％） was 1.14％. CONCLUSIONS ：The optimized ultrafiltration technology is stable and reliable ，and can be used for the ultrafiltration purification of enzymatic hydrolysate from E. ulmoides peel.

Effect of the course of treatment with broad-spectrum antibiotics on intestinal flora and short-chain fatty acids in feces of very low birth weight infants: a prospective study / 中国当代儿科杂志

OBJECTIVES@#To study the effect of the course of treatment with broad-spectrum antibiotics on intestinal flora and short-chain fatty acids (SCFAs) in feces of very low birth weight (VLBW) infants.@*METHODS@#A total of 29 VLBW infants who were admitted to the Neonatal Diagnosis and Treatment Center of Children's Hospital Affiliated to Chongqing Medical University from June to December 2020 were enrolled as subjects for this prospective study. According to the course of treatment with broad-spectrum antibiotics, they were divided into two groups: ≤7 days (@*RESULTS@#There was a significant reduction in Chao index of the intestinal flora in the ≤7 days group and the >7 days group from week 2 to week 4 (@*CONCLUSIONS@#The course of treatment with broad-spectrum antibiotics can affect the abundance, colonization, and evolution of intestinal flora and the content of their metabolites SCFAs in VLBW infants. The indication and treatment course for broad-spectrum antibiotics should be strictly controlled in clinical practice.

Research Advances on Clinical Application of Umbilical Cord Blood Transplantation in the Treatment of Hematological Diseases--Review / 中国实验血液学杂志

Abstract　　Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells (HSCs) for patients who were lack of HLA match related or unrelated donors. Compared with bone marrow and mobilized peripheral blood, UCB has the advantages of easy availability, safety for donors, and low requirement for HLA match between donors and recipients. However, the cell amount in UCB is relatively less, which was associated with increased graft failure, delayed hematologic recovery, immune reconstitution, and higher transplant related mortality after UCB transplantation (UCBT). Double-unit UCB is a straightforward method to augment cell amount in UCB. Compared with single-unit UCBT, double-unit CBT associated with less risk of primary disease relapse and increased incidence rate of graft-versus-host disease (GVHD), but the hematologic recovery and overall survival of recipients were no significantly difference between single and double-unit UCBT. Novel strategies for UCB expansion significantly increased the cell amount in UCB, single-unit expanded UCBT not only increased the sources of UCB, but also decreased the high cost of double-unit UCB. ATG can decrease the risk of graft failure and GVHD rate, but the role of ATG in UCBT is still controversial. Herein, the recent clinical advances on UCBT in the treatment of hematologic diseases are systematically reviewed.

Ressarch Advances of Prevantive and Therapeatic Effect of Mesenchymal Stromal Cells on Graft-Versus-Host Disease--Review / 中国实验血液学杂志

Graft-versus-host disease (GVHD) is a frequently encountered serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), it limits the success and widespread use of allo-HSCT. Mesenchymal stem cells (MSCs) are selected as ideal prophylactic and treatment means for GVHD during allo-HSCT due to their unique immunomodulatory and regenerative properties. Herein, the recent research progress about the prevantive and therapeutic effects of MSCs on GVHD and several issues related with the applications of MSC, including whether MSCs increasing risk of primary disease relapse and infection, impact of several clinical parameters on the clinical response to MSCs, and the prevantive and therapeutic effect of MSC-derived extracellular vesicles on GVHD are systematically reviewed.

Analysis of Clinical Pathological Features and Prognosis in Young Patients with Diffuse Large B Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical pathological features of the patients with diffuse large B cell lymphoma (DLBCL) and their prognostic factors.@*METHODS@#The prognosis of the clinical pathological features and their influence on prognosis of 177 patients diagnosed as DLBCL at the first visit from January 2013 to May 2017 in our hospital were analyzed retrospectively.@*RESULTS@#The univariate analysis showed that overall survival (OS) and progression-free survival (PFS) were associated with later Ann Arbor stage (Ⅲ-Ⅳ) ( P＜0.01, P＜0.05), high performance status (ECOG score 2-4) (P＜0.01, P＜0.05), extranodal involvement ＞1 (P＜0.01, P＜0.05), elevated LDH level (P＜0.01, P＜0.05). B symptom (P＜0.05) and elevated β2-MG level (P＜0.05) also influenced OS. COX multivariate analysis showed that the elevated β2-MG level (P＜0.05) and later stage (Ⅲ-Ⅳ) (P＜0.05) have an independent influence on OS, later stage (Ⅲ-Ⅳ) (P＜0.05) also independently influenced PFS. The patients with high aaIPI score (2-3) and bone marrow involvement before treatment had poor OS (P＜0.01, P＜0.01) and PFS (P＜0.05, P＜0.01).@*CONCLUSION@#Elevated β2-MG level can independently influence OS, and later stage (Ⅲ-Ⅳ) can independently influence both OS and PFS. High aaIPI score (2-3) and bone marrow involvement before treatment have an inferior influence on OS and PFS.

Analysis on academic characteristics and medication rules of traditional Chinese medical master Liu Zu-yi for treating insomnia / 中国中药杂志

To analyze the academic characteristics and medication rules of traditional Chinese medical master Liu Zu-yi for treating insomnia. Totally 178 cases of insomnia treated by Professor Liu were collected,and the treatment data were input into traditional Chinese medicine inheritance support system( TCMISS) by using data mining methods,such as essential information,frequency statistics of symptoms,syndrome type statistics,extraction of syndrome elements,frequency statistics of drugs; and four properties and five tastes of drugs,distribution of meridians,regularity of prescriptions,new prescription analysis were mined. It was found that the most commonly used drugs( over 100 times) were Albiziae Cortex,Longgu,Polygoni Multiflori Caulis,Ostreae Concha,Ziziphi Spinosae Semen,Crataegi Fructus; the commonly used couplet medicines were Longgu-Ostreae Concha,Ziziphi Spinosae Semen-Polygoni Multiflori Caulis,Ziziphi Spinosae Semen-Albiziae Cortex-Polygoni Multiflori Caulis; and seven new prescriptions in treating insomnia were explored,such as prescriptions containing Hordei Fructus Germinatus,Ziziphi Spinosae Semen,Galli Gigerii Endothelium Corneum,Rehmanniae Radix,Lilii Bulbus. Based on the introduction and discussion of Professor Liu's academic views and characteristics on insomnia treatment and the illustrative evidences added to the typical case list,this paper combines the academic characteristics,data support and typical medical records to verify each other,and objectively summarizes his academic experience for treating insomnia. Treatment shall focus on the primary cause of disease in three aspects; syndrome differentiation shall distinguish between excessive disease and deficient disease; therapy shall reinforce deficiency and reduce diarrhea,regulate the five internal organs,and emphasizes the heart and liver,particularly the liver; medication shall focus on the drugs for calming the mind and protecting the stomach and spleen,which are commonly combined with three types of traditional Chinese medicine with effect in introducing Yangqi( Pinelliae Rhizoma Praeparatum,Prunellae Spica,Polygoni Multiflori Caulis) and restraining Yangqi( Longgu,Ostreae Concha,Ziziphi Spinosae Semen); nursing care focuses on preserving the body and tranquilizing the mind by means of three methods for tranquilizing the mind and three methods for preserving the body.

Application of hypobaric ropivacaine spinal anesthesia and nerve block anesthesia in hip surgery ofelderly patients / 中国组织工程研究

BACKGROUND: The rational choice of anesthesia for the elderly patients with hip surgery not only ensures the smooth operation, but also significantly reduces the incidence of postoperative complications. OBJECTIVE: To compare the clinical anesthetic effects between combined lumbar plexus-sciatic nerve block and hypobaric ropivacaine spinal anesthesia in hip joint surgery of elderly patients. METHODS: Forty patients who were scheduled for hip joint surgery, at the age of 65-99 years old, American Society of Anesthesiologists grades II-III, were enrolled and randomly allocated to two groups: nerve block (n=20) and spinal anesthesia (n=20). In nerve block group, combined lumber plexus-sciatic nerve block was performed directed by a nerve stimulator under the guidance of ultrasound. In spinal anesthesia group, patients received single-dose hypobaric ropivacaine spinal anesthesia at L3-4interspace. Hemodynamic changes, anesthetic effects and perioperative adverse effects were recorded in both groups before and after anesthesia. RESULTS AND CONCLUSION: (1) The patients' heart rate and mean artery pressure in each group did not change significantly before and after anesthesia in the nerve block and spinal anesthesia groups (P > 0.05). (2) The onset time of anesthesia in spinal anesthesia group was significantly faster than that in nerve block group (P < 0.01). Hypobaric ropivacaine spinal anesthesia had a better analgesic effect during the surgery, which did not need extra intravenous anesthetics. The duration of motor and sense block was significantly longer in nerve block group than in spinal anesthesia group (P < 0.01). However, five patients in spinal anesthesia group needed extra intravenous anesthetics to finish the surgery. (3) No side effects were found in both nerve block and spinal anesthesia groups. (4) These indicated that compared to combined lumbar plexus-sciatic nerve block, hypobaric ropivacaine spinal anesthesia can provide a better analgesic effect during the hip joint surgery with stable hemodynamics. Moreover, hypobaric ropivacaine spinal anesthesia dose not increase the incidence of complications and has very good clinical application prospects.

Clinical Characteristics, Treatment and Prognosis of PTLD after allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the clinical characteristics of patients with post-transplantation lymphoproliferative disease (PTLD) after allogeneic peripheral blood hematopoietic stem cell transplantation, and to improve the understanding and diagnosis of PTLD.</p><p><b>METHODS</b>The clinical data of 244 patients underwent allogeneic hematopoietic stem cell transplantation in the General Hospital of PLA from May 2014 to April 2017 were analyzed retrospectively. The follow-up time was up to November 30, 2017. The incidence, risk factors, treatment and survival of patients with PTLD were statistically analyzed.</p><p><b>RESULTS</b>Among the 244 cases the PTLD occurred in 22 cases, the incidence rate was 9.02%, 5 of them were diagnosed by pathology, and 17 were diagnosed clinically. All of them had EB virus infection. They were all ATG user, either underwent related haploidentical hematopoietic stem cell transplantation or unrelated hematopoietic stem cell transplantation, 20 cases were treated with rituximab or rituximab combined with γ-globulin, glucocorticoid, ERV+CTL, chemotherapy and 17 showed the effective response, with a total effective rate of 85%. The median follow-up time was 122 days, the median survival time was 5 months (1-22 months) and the total survival rate was 50%.</p><p><b>CONCLUSION</b>The incidence of PTLD after allogeneic peripheral blood hematopoietic stem cell transplantation closely relates with EB virus infection. The application of ATG in the preconditioning scheme is a high risk factor for the onset of PTLD. In the case of no pathological diagnosis, clinical and laboratory examinations should be actively combined so as to define clinical diagnosis. The riturimab should be used more and more for patients with PTLD.</p>

Research Advances on BK Virus Associated Hemorrhagic Cystitis after HSCT-Review / 中国实验血液学杂志

BK virus（BKV）associated hemorrhagic cystitis is one of the most common complications after hematopoietic stem cell transplantation（HSCT）, which can increase the suffering, become time consuming and even life threatening. However, BKV infection has not attracted enough attention in clinical practice. Accurate BKV monitoring and effective clinical treatments are still in urgent need. In recent years, BKV-DNA monitoring has shown a significant clinical value in BKV-associated hemorrhagic cystitis after HSCT. As for clinical treatments, traditional antivirus agent cidofovir is still to show promising effects, in the meantime, the virus-specific lymphocytes and other new therapies are continuously appearing. Here, the most recent advances on pathogenesis, treatment, virus monstoring and so on for BKV associated hemorrhagic cystitis after HSCT are reviwed.

Application of Chimeric Antigen Receptor-Modified NK Cells in Multiple Myeloma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To explore the killing effect of CAR (CD138-CD28-CD3ζ)-NK cells on myeloma cells through construction of CAR(CD138-CD28-CD3)-NK cells.</p><p><b>METHODS</b>The antiCD138scFv-CD28-CD3 zeta plasmid pcDNA3.1 was constructed, which then together with 3 plasmid lentiviral packaging system were transfected into 293T cells, the virus was collected. Furthermore, in order to get the stably transfected cell line, the NK92MI cell line was infected by the virus, then the positive cells were screened by puromycin. The expression of the CARNK cells were verified by RT-PCR and Western blot. At last the ability of secreting cytokine CD107a was detected by flow cytometry, and the statistical analysis was carried out to verify the anti-myeloma effect of CAR-NK cells.</p><p><b>RESULTS</b>Gene fragment of the CAR(antiCD138scFv-CD28-CD3ζ) was constructed successfully by gene engineering technique in vitro, and the gene sequence was verified to be correct by sequencing. By virus packaging technology, the virus expressing the protein of the CAR was obtained. PCR and Western blot verified the expression of CAR fusion protein on the sufurce of NK cells. The cell killing experiment confirmed that the CAR-NK cells possessed the ability to secrete cytokine CD107a superior to control cells and showed the obvious killing effect on multiple myeloma cells.</p><p><b>CONCLUSION</b>The CAR can be constructed in vitro, and express on NK92 cells. The CAR-NK cells can kill the multiple myeloma cells expressing CD138 antigen, thereby plays an antimyeloma effect.</p>

Clinical outcomes of peripheral blood stem cell transplantation for aggressive peripheral T-cell lymphoma / 中华血液学杂志

Objective: To evaluate clinical outcomes of autologous and allogeneic peripheral blood stem cell transplantation (PBSCT) for aggressive peripheral T-cell lymphoma (PTCL). Methods: From June 2007 to June 2017, clinical data of PTCL patients who underwent PBSCT were assessed retrospectively. Results: Among 41 patients, 30 was male, 11 female, and median age was 38(13-57) years old. Seventeen patients with autologous PBSCT (auto-PBSCT) and 24 patients with allogeneic PBSCT (allo-PBSCT) were enrolled in this study. Eight patients (8/17, 47.1%) in auto-PBSCT group were ALK positive anaplastic large cell lymphoma (ALCL), 7 patients (7/24, 29.2%) with NK/T cell lymphoma and 9 patients (9/24, 37.5%) with PTCL-unspecified (PTCL-U) in allo-PBSCT group (P=0.035). There were 58.8% patients (10/17) in complete response (CR) status and 11.8% (2/17) in progression disease (PD) status before transplantation in auto-PBSCT group, and 8.3% (2/24) in CR status and 45.8% (11/24) in PD status before transplantation in allo-PBSCT group (P=0.026). The 2-years cumulative overall survival (OS) were (64.0±10.8)% and (53.5±9.7)% for auto-PBSCT and allo-PBSCT respectively (P=0.543). The 2-years cumulative disease-free survival (DFS) were (57.1±12.4)% and (53.5±10.6)% for auto-PBSCT and allo-PBSCT respectively (P=0.701). In patients with dead outcomes after PBSCT, 83.3% (5/6) of death cause was relapse in auto-PBSCT and 41.7% (5/12) of death cause was relapse in allo-PBSCT. Conclusion: Both auto-PBSCT and allo-PBSCT were effective for PTCL. Allo-PBSCT maybe was better than auto-PBSCT for high-risk PTCL with poor prognosis.

Establishment of A20 Murine B Lymphoma Transplantation Model Labeled with Luciferase / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To establish the animal model of luciferase-transfected A20 murine B cell lymphoma, so as to provide experimental tools to explore the effect of graft versus tumor.</p><p><b>METHODS</b>Luciferase- labeled A20 cells were cloned with puromycin selection. Transfected A20 cells and CBL/6 bone marrow were inoculated into the irradiated BALB/c mice by injection in tailvein to establish the transplantation model. The bioluminescent imaging technique was used to monitor the tumor growth, and then the survival, body weight, tumor formation and pathological characteristics of target organs were observed.</p><p><b>RESULTS</b>A20 cell line stably expressing luciferase gene was successfully obtained. The the bioluminicent imaging found that the tumor luminescence could be observed on day 8 of A20 cell inoculation, and the mean fluorescent intensity was increased along with the tumor growth. Compared with the BMT group, the survival rate and body weight of BMT+A20-Lucmice were decreased significantly. General anatomy showed the tumor mainly formed in the liver and spleen.</p><p><b>CONCLUSION</b>A mouse transplantation model with luciferase- transfected A20 cells has been successfully established, thus laying a foundation for investigation of graft-versus-tumor.</p>

Effect of G-CSF in vitro Stimulation on Distribution of Peripheral Lymphocyte Subsets in the Healthy Persons / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of granulocyte-colony stimulating factor (G-CSF) in vitro stimulation on the distribution of lymphocyte subset in healthy human.</p><p><b>METHODS</b>Peripheral blood mononuclear cells (PBMNCs) were collected from 8 healthy volunteers by density gradient centrifugation on Ficoll-Paque. In vitro 200 ng/ml G-CSF or 200 ng/ml G-CSF plus 10 µg/ml ConA directly act on PBMNCs, then the colleted cells were cultivated for 3 days. Lymphocyte subsets were stained with the corresponding fluoresce labeled antibodies and detected by flow cytometry.</p><p><b>RESULTS</b>The levels of T cells in G-CSF group and G-CSF+ConA group were both higher than that in the control group (P<0.001, P<0.05). However, there were not significantly different in B cells and NK cells levels among the 3 groups. Furthermore, analysis of the effect of G-CSF on T cell subsets indicated that the levels of CD4T cells and CD8T cells in G-CSF group were both significantly higher than those in control group (P<0.01, P<0.05), Treg cells was not different between G-CSF and control group. Compared with the control group, the level of CD4T cells, CD8T cells and Treg cells in G-CSF+ConA group significantly increased (P<0.05, P<0.01, P<0.01). Analysis of G-CSF receptor (G-CSFR) expression showed that G-CSFR expression on T cells in G-CSF+ConA group dramatically increased, as compared with control group (P<0.01).</p><p><b>CONCLUSION</b>The levels of CD4T cells and CD8T cells in healthy human peripheral blood can be increased by G-CSF stimulation. ConA can enhance the level of T cells and induce G-CSFR expression on T cells.</p>

Role of Intestinal Microbiota in Hematopoietic Stem Cell Transplantation - Review / 中国实验血液学杂志

Graft-versus-host disease (GVHD) and infection are the frequently encountered complications after hematopoietic stem cell transplantation (HSCT), which influence the outcome and limit the widespread application of HSCT. Intestinal microbiota plays an important role in maintaining intestinal immune balance. The diverse levels of intestinal microbiota associated with the incidences of GVHD, infection and the prognosis of HSCT, thus remodeling intestinal microbiota can alleviate GVHD and infection after HSCT. Herein, the recent research progress about the role and the involved mechanisms of intestinal microbiota in HSCT, and the novel manipulation strategies of intestinal microbiota are systematically reviewed.

Abnormal Notch-Hes Signaling Pathways and Acute Leukemia -Review / 中国实验血液学杂志

The abnormal activation of Notch signaling is closely related to the development of acute leukemia (AL). The core elements of the Notch signaling system include Notch receptors, Notch ligands, CSL DNA-binding proteins, and effectors like target genes. Any factors, which affect ligands, receptors, signal transducers and effectors, can influence the signal transduction of Notch signaling greatly. Based on the role of Notch signaling in AL, several targeted drugs against Notch upstream signaling have been developed. However, due to the complexity and pleiotropic effects of Notch upstream signaling, these targeted drugs display strong side effects. Thus, Hes (Hairy Enhancer of Split) factors as a primary Notch effector, also play an important role in the pathogenesis of AL. This review summarizes recent progresses on Notch-Hes signaling in AL, hopping to provide references for further excavation of the Notch-Hes signaling, and lay foundations for developing the next generation of targeted drugs.

Advances of Diagnostic Biomarkers on Acute Graft Versus Host Disease -Review / 中国实验血液学杂志

Acute graft-versus-host disease (aGVHD) is one of the main complications after allogeneic hematopoietic stem cell transplantation (HCT), resulting in considerable morbidity and mortality. Diagnosis of aGVHD is typically based on clinical presentation and confirmed by biopsy. In recent years, aGVHD researches have been focused on diagnostic biomarkers, and several microRNAs, cytokines and immunoregulated cells have been dicovered currently. This review summarizes the advances on aGVHD biomarkers.

Treatment of Chronic Graft versus Host Disease -Review / 中国实验血液学杂志

Chronic graft versus host disease (cGVHD) is the major reason of late non-relapse related death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The therapeutic regimen based on glucocorticoids remains as the standard initial treatment of cGVHD. But due to the significant side effects and unsatisfactory outcomes, particularly for patients with steroid-refractory disease, the more effective and less toxic therapies should be needed. Abnormal regulation for the stable state of T lymphocytes and B lymphocytes for allo-HSCT patients is the current focus of studying cGVHD pathogenesis. This article summarizes the treatment of cGVHD targeted to pathogenic factors and signaling pathways in pathogenetic process.