Analysis on the Effects of PPARγ Gene-silenced Human Bone Marrow Stromal Cells on Hematopoietic Function in Mice with Bone Marrow Suppression / 华中科技大学学报(医学版)

Objective To investigate the effects of peroxisome proliferator activated receptor-gamma(PPARγ)gene silen-cing in human bone marrow stromal cells(HS-5)on hematopoietic function in bone marrow-suppressed mice,and to explore the potential mechanisms involved.Methods A bone marrow-suppressed mouse model was established by whole-body X-ray irradi-ation.Two hours after modeling,the mice were randomly divided into three groups:experimental group(intravenous injection of PPARγ RNAi-interfered HS-5 cells through the tail vein),control group(intravenous injection of PPARγ RNAi-uninterfered HS-5 cells through the tail vein),and blank group(intravenous injection of an equal amount of saline through the tail vein),with 5 mice in each group.Peripheral blood routine tests were performed before,24 hours after,1 week after,and 2 weeks after radio-therapy.In vitro osteogenic and adipogenic induction was performed in cells,and the cells were divided into experimental group(PPARγ RNAi-interfered HS-5 cells),control group(PPARγ-uninterfered HS-5 cells),and blank group(HS-5 cells without os-teogenic/adipogenic induction).Osteogenic/adipogenic staining was observed.The effects of PPARγ gene-silenced HS-5 cells on mouse bone marrow hematopoietic stem cells(HSCs)were detected by CCK-8 proliferation assay.The groups included experi-mental group(PPARγ RNAi-interfered HS-5 cells were co-cultured with mouse HSCs after 3 days of osteogenic induction dif-ferentiation),positive control group(HS-5 cells treated with 50 μmol/L PPARγ inhibitor were co-cultured with mouse HSCs af-ter 3 days of osteogenic induction differentiation),negative control group(PPARγ RNAi-uninterfered HS-5 cells were co-cul-tured with mouse HSCs after 3 days of osteogenic induction differentiation),and blank group(Mouse HSCs were cultured alone without co-culturing with HS-5 cells).Results After radiotherapy,the hematological parameters of mice in each group showed a decreasing trend initially,and then increased.One week after radiotherapy,there were significant differences in platelet and white blood cell levels among the three groups(experimental group＞control group＞blank group,all P＜0.05).Two weeks after radiotherapy,there were significant differences in the percentage of adipocyte vacuole area among the three groups(experi-mental group＜control group＜blank group,all P＜0.05).Pearson correlation analysis showed a negative correlation between hematological parameters and PPARγ expression levels(all P＜0.05),as well as a negative correlation between hematological parameters and the percentage of adipocyte vacuole area(all P＜0.05).After in vitro osteogenic/adipogenic induction differenti-ation,compared to the control group,the experimental group showed a significantly lower proportion of orange-red cells and a significantly higher proportion of red calcium nodules.After 3 days of osteogenic induction differentiation,the experimental group,positive control group,and negative control group of human bone marrow stromal cells were co-cultured with mouse HSCs,while HSCs were solely cultured in the blank group.The results showed that after 24 h,48 h and 72 h of co-culture,the A values of mouse HSC cells in the experimental group and positive control group were higher than those in the negative control group and blank group(all P＜0.05).Conclusion Silencing of the PPARγ gene in HS-5 cells implanted into bone marrow-sup-pressed mice contributes to enhanced hematopoietic function in mice.After interference and silencing of the PPARγ gene,the os-teogenic differentiation ability of HS-5 cells is enhanced,while the adipogenic differentiation ability is weakened.Furthermore,osteogenic-induced HS-5 cells can further enhance the proliferation capacity of mouse HSCs.

Regularity and mechanism of medicinal and edible herbs in the treatment of myelosuppression / 新乡医学院学报

Objective To explore the regularity and potential mechanisms of medicinal and edible herbs(MEHs)in the treatment of myelosuppression through the retrieval,summary,sorting and visual analysis of relevant literature.Methods Literature about MEHs treatment for myelosuppression was reviewed in document databases,such as Web of Science,CNKI,Wanfang Data Knowledge Service Platform,China Science and Technology Journal Database,and China Biology Medicine Disc.Multivariate statistical analysis was performed using the SPSS and CiteSpace software to explore the frequency,efficacy and correlation of MEHs,as well as the potential mechanisms of MEHs in treating myelosuppression.Results A total of 123 recipes involving 170 traditional Chinese medicines(including 38 MEHs)were screened out.Five pairs of MEHs core combinations in the treatment of myelosuppression were obtained by cluster analysis.Their main functions included benefiting qi and nourishing blood,invigo-rating spleen and dispelling dampness,replenishing qi and solidifying kidney.The potential mechanisms were associated with many related signal pathways,such as Janus kinase 2-signal transducer and activator of transcription 5 andβ-catenini.Conclusion MEHs such as radix astragali combined with angelica sinensis,poria cocos and codonopsis pilosula are mainly used clinically to treat myelosuppression induced by chemotherapy.They play their therapeutic effects by promoting proliferation and delaying senescence of hematopoietic stem cells.

Correlation Analysis of Myelosuppression after Chemotherapy for Triple-Negative Breast Cancer and Its Prognosis / 中山大学学报(医学科学版)

ObjectiveTo investigate whether severe myelosuppression after chemotherapy is associated with prognosis in patients with breast cancer. MethodsTriple negative breast cancer （TNBC） patients who received chemotherapy at the Second Affiliated Hospital of Nanchang University from May 2， 2013 to May 2， 2018 were divided into a control group （no/mild myelosuppression） and a case group （severe myelosuppression）. In this study， 251 patients with TNBC met the inclusion and exclusion criteria， including 125 patients in the control group （20 patients with grade 0 myelosuppression， 43 patients with grade I myelosuppression， 62 patients with grade Ⅱ myelosuppression）， 126 patients in the case group （114 patients with grade Ⅲ myelosuppression， 12 patients with grade Ⅳ myelosuppression）. The general clinicopathological data of the patients in the two groups， including age， pathological type of tumor， tumor T stage， tumor N stage， tumor Nottingham grade， intravascular cancer thrombus， were analyzed using the χ2 test. The disease-free survival （DFS） and overall survival （OS） of the two groups were analyzed using the Kaplan-Meier method. A Cox proportional hazards regression model with multiple factors was used to analyze the impact of post-chemotherapy severe myelosuppression on disease-free survival （DFS） and overall survival （OS） in patients with TNBC. ResultsThe differences in general clinicopathologic data between the two groups of patients were not statistically significant （all P＞0.05）. The 5-year disease-free survival （DFS） rate was significantly lower in the control group compared with the case group （75.2% vs. 85.7%， P=0.027）. However， there was no statistically significant difference in the 5-year overall survival （OS） rate between the two groups （88.8% vs. 95.2%， P=0.057）. The analysis of the multifactorial Cox proportional hazards regression model revealed that post-chemotherapy severe myelosuppression was an independent protective factor for disease-free survival （DFS） （HR=0.332， 95% CI： 0.173-0.638， P=0.001） and overall survival （OS） （HR=0.193， 95% CI： 0.062-0.602， P=0.005） in TNBC patients. ConclusionOur results show that TNBC patients with severe myelosuppression after chemotherapy have longer disease-free survival （DFS） than those with no/mild myelosuppression， and overall survival （OS） also tend to be prolonged compared with those with no/mild myelosuppression， and severe myelosuppression after chemotherapy can be used as an independent predictor of a good prognosis in breast cancer.

Chemotherapy-induced oral mucositis induced by low dose methotrexate: a case report and literature review / 口腔疾病防治

Objective@# To investigate the diagnosis and treatment for oral mucositis induced by low-dose methotrexate and to provide a reference for clinicians@*Methods @# A case of severe chemotherapy-induced oral mucositis caused by short-term use of low-dose methotrexate (the maximum cumulative dose within 1 week) was reported and reviewed in combination with the literature.@*Results@# The patient was treated with low-dose methotrexate (2.5 mg orally every other day at weeks 1, 2, and 4; the third week, 2.5 mg each time for 3 consecutive days for twice, with a maximum cumulativedose of 15 mg within a week). After irregular medication for approximately three weeks, the patient gradually developed severe erosion of the lips, pain, difficulty eating, and skin erosion on both legs. Methotrexate was stopped after admission, and local symptomatic treatments such as Kangfuxin solution were given. Recombinant human granulocyte colony-stimulating factor was used systemically when combined with neutropenia. After treatment, the chemotherapy-induced oral mucositis and skin lesions were improved. A literature review shows that chemotherapy-induced oral mucositis is a toxic reaction to high-dose methotrexate, while cases of severe chemotherapy-induced oral mucositis caused by low-dose methotrexate are rare. Studies have found that the more risk factors patients have, such as poor local oral conditions and systemic diseases such as liver and kidney dysfunction and diabetes, the higher the risk of chemotherapy-induced oral mucositis. Clinicians should cooperate with dentists to address oral diseases as much as possible before using chemotherapy drugs. In addition, when ordering patients to take methotrexate, we should pay attention to the patient's general condition and susceptibility factors, standardize the frequency and dose of administration, adopt personalized treatment plans, and give patients detailed medication education to prevent the occurrence of adverse consequences caused by medication errors. If methotrexate poisoning occurs, the drug should be stopped in time, detoxification and active symptomatic and supportive treatment should be given. Basic oral care, cryotherapy, laser therapy, nutritional support and analgesic drugs are common treatments for chemotherapy-induced oral mucositis. Systemic administration of granulocyte colony-stimulating factor may be considered when accompanied by neutropenia.@*Conclusion@# It is necessary to be alert to the occurrence of severe chemotherapy-induced oral mucositis caused by low-dose methotrexate in clinical practice.

Bletilla striata polysaccharide improves toxic and side effects induced by 5-FU: an untargeted metabolomics study / 中国中药杂志

This study aimed to analyze the effect of Bletilla striata polysaccharide(BSP) on endogenous metabolites in serum of tumor-bearing mice treated with 5-fluorouracil(5-FU) by untargeted metabolomics techniques and explore the mechanism of BSP in alleviating the toxic and side effects induced by 5-FU. Male BALB/C mice were randomly divided into a normal group, a model group, a 5-FU group, and a 5-FU + BSP group, with eight mice in each group. Mouse colon cancer cells(CT26) were transplanted into the mice except for those in the normal group to construct the tumor-bearing mouse model by subcutaneous injection, and 5-FU chemotherapy and BSP treatment were carried out from the second day of modeling. The changes in body weight, diarrhea, and white blood cell count in the peripheral blood were recorded. The mice were sacrificed and sampled when the tumor weight of mice in the model group reached approximately 1 g. TUNEL staining was used to detect the cell apoptosis in the small intestine of each group. The proportions of hematopoietic stem cells and myeloid progenitor cells in bone marrow were measured by flow cytometry. Five serum samples were selected randomly from each group for untargeted metabolomics analysis. The results showed that BSP was not effective in inhibiting colon cancer in mice, but diarrhea, leukopenia, and weight loss caused by 5-FU chemotherapy were significantly improved after BSP intervention. In addition, apoptotic cells decreased in the small intestinal tissues and the percentages of hematopoietic stem cells and myeloid progenitor cells in bone marrow were significantly higher after BSP treatment. Metabolomics results showed that the toxic and side effects of 5-FU resulted in significant decrease in 29 metabolites and significant increase in 22 metabolites in mouse serum. Among them, 19 disordered metabolites showed a return to normal levels in the 5-FU+BSP group. The results of pathway enrichment indicated that metabolic pathways mainly involved pyrimidine metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis. Therefore, BSP may ameliorate the toxic and side effects of 5-FU in the intestinal tract and bone marrow presumably by regulating nucleotide synthesis, inflammatory damage, and hormone production.

Effect of Recombinant Human Thrombopoietin (rhTPO) on Long-term Hematopoietic Recovery in Mice with Acute Radiation Sickness and Relative Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect and relative mechanism of Recombinant Human Thrombopoietin (rhTPO) on long-term hematopoietic recovery in mice with acute radiation sickness.@*METHODS@#Mice were intramuscularly injected with rhTPO (100 μg/kg) 2 hours after total body irradiation with 60Co γ-rays (6.5 Gy). Moreover, six months after irradiation, peripheral blood, hematopoietic stem cells (HSC) ratio, competitive transplantation survival rate and chimerization rate, senescence rate of c-kit+ HSC, and p16 and p38 mRNA expression of c-kit+ HSC were detected.@*RESULTS@#Six months after 6.5 Gy γ-ray irradiation, there were no differences in peripheral blood white blood cells, red blood cells, platelets, neutrophils and bone marrow nucleated cells in normal group, irradiated group and rhTPO group (P>0.05). The proportion of hematopoietic stem cells and multipotent progenitor cells in mice of irradiated group was significantly decreased after irradiation (P<0.05), but there was no significant changes in rhTPO group (P>0.05). The counts of CFU-MK and BFU-E in irradiated group were significantly lower than that in normal group, and rhTPO group was higher than that of the irradiated group(P<0.05). The 70 day survival rate of recipient mice in normal group and rhTPO group was 100%, and all mice died in irradiation group. The senescence positive rates of c-kit+ HSC in normal group, irradiation group and rhTPO group were 6.11%, 9.54% and 6.01%, respectively (P<0.01). Compared with the normal group, the p16 and p38 mRNA expression of c-kit+ HSC in the irradiated mice were significantly increased (P<0.01), and it was markedly decreased after rhTPO administration (P<0.01).@*CONCLUSION@#The hematopoietic function of mice is still decreased 6 months after 6.5 Gy γ-ray irradiation, suggesting that there may be long-term damage. High-dose administration of rhTPO in the treatment of acute radiation sickness can reduce the senescence of HSC through p38-p16 pathway and improve the long-term damage of hematopoietic function in mice with acute radiation sickness.

Effect of Lulong Zaisheng Decoction II on chemotherapy-induced bone marrow suppression and its mechanism / 中国药理学通报

Aim To investigate the effect of Lulong Zaisheng Decoction II on chemotherapy-induced bone marrow suppression in nude mice bearing colorectal cancer. Methods Male BALB/C nude mice were inoculated with human colon cancer cell HT-29 under the armpit. The tumor bearing nude mice were randomly divided into five groups: control group, chemotherapy group, positive drug group, Lulong Zaisheng Decoction II groups with high and low doses. The mice were given drugs by gavage once a day for 10 consecutive days. From the fourth day of the experiment, except for the control group, the nude mice were intraperitoneally injected with 5-FU at dose of 25 mg • kg

Whole Course Management and Therapeutic Strategy of Traditional Chinese Medicine for Thrombocytopenia Induced by Tumor Treatment / 中医杂志

Based on the traditional Chinese medicine （TCM） theories of holism， syndrome differentiation and treatment， and preventive treatment of disease， the concept of whole course management of tumors throughout the treatment process is advocated. The strategy includes preventive treatment before tumor therapy， focusing on protecting the body's vital qi and strengthening the spleen and Qi. TCM formulas such as Sijunzi Decoction （四君子汤）， Shenling Baizhu San （参苓白术散） and Xiangsha Liujunzi Decoction（香砂六君子汤） are used to enhance platelet reserves. The main therapeutic methods during tumor conventional therapy include preventing disease transformation and strengthening vital qi to eliminate pathogenic factor， by invigorating spleen and soothing liver， nourishing liver and kidney， purging fire for removing toxin， and removing blood stasis for promoting tissue regeneration. TCM formulas such as Xiangsha Liujunzi Decoction （香砂六君子汤）， Shenling Baizhu Powder （参苓白术散）， Fuzi Lizhong Decoction （附子理中汤）， Zhibai Dihuang Decoction （知柏地黄汤）， and Qiangen Powder （茜根散）are used to reduce platelet destruction and depletion during tumor therapy and reverse the worsening trend. After tumor conventional therapy， the focus is on preventing relapse， adjusting the balance of Yin and Yang， by nourishing the kidneys， spleen， and lungs. TCM formulas such as Dingkun Pill （定坤丹）and Zuogui Pill （左归丸） are used with modifications to prevent thrombocytopenia. The staged prevention and treatment of tumor treatment-induced thrombocytopenia using TCM can maximize the benefits for patients.

Risk Factors and Predictive Model for Severe Myelosuppression due to Chemotherapy in Triple-negative Breast Cancer / 中山大学学报(医学科学版)

ObjectiveTo investigate the risk factors and construct a predictive model for severe myelosuppression due to chemotherapy in triple negative breast cancer （TNBC）. MethodsPatients with TNBC who received anthracycline combined with cyclophosphamide sequential paclitaxel chemotherapy regimen at the Second Affiliated Hospital of Nanchang University from September 2， 2016 to September 2， 2021 were selected and assigned to severe myelosuppression group and no/mild myelosuppression group. The χ2 test and binary logistic regression were used to analyze the risk factors for severe myelosuppression due to chemotherapy and to develop a prediction model. Hosmer-Lemeshow test and receiver operating characteristic （ROC） curve were used to evaluate the predictive efficiency of the regression model. Kappa consistency test was used to verify the regression model externally. ResultsA total of 207 patients who met the inclusion were enrolled and 106 patients （51%） had severe myelosuppression. Binary logistic regression multivariate analysis showed that age 40 to 60 years （OR = 3.463， 95% CI： 1.144 to 10.486， P = 0.028）， age >60 years （OR = 3.474， 95% CI： 1.004 to 12.020， P = 0.049）， body mass index （BMI） 18.5 to 24.0 （OR = 1.445， 95% CI： 0.686 to 3.087， P = 0.328）， BMI <18.5 （OR = 3.582， 95% CI： 1.260 to 10.182， P = 0.017）， tumor TNM stage Ⅱ （OR = 1.698， 95% CI： 0.831 to 3.468， P = 0.146）， tumor TNM stage Ⅲ （OR = 2.943， 95% CI： 1.199 to 7.227， P = 0.019）， previous diabetes （OR = 2.441， 95% CI： 1.076 to 5.539， P = 0.033）， low pre-treatment albumin level （OR = 2.759， 95% CI： 1.141 to 6.669， P = 0.024） and low pre-treatment lymphocytes （OR = 3.428， 95% CI： 1.689 to 6.958， P = 0.001） were independent risk factors for severe myelosuppression due to chemotherapy. The χ2 value for the logistic regression model Hosmer-Lemeshow test was 11.507， P= 0.175， the area under the ROC curve was 0.763， standard error 0.033， 95% CI： 0.698-0.828， P=0.000. External validation showed that the prediction model had a specificity of 88% and a sensitivity of 80%； the kappa value was 0.679， standard error 0.081， P=0.000. conclusionThis logistic regression model had high predictive efficacy and is useful for clinicians to predict whether patients with TNBC develop severe myelosuppression.

Research progress on the mechanism of bone marrow suppression after chemotherapy / 国际肿瘤学杂志

As an effective treatment for cancer, chemotherapy not only removes tumor cells, but also produces obvious killing effects on proliferating cells, especially hematopoietic cells, resulting in bone marrow suppression after chemotherapy, and affecting the effects of chemotherapy drug treatment and treatment cycle. Therefore, starting from the aspects of hematopoietic microenvironment damage and hematopoietic stem cell aging, to explore the mechanism of myelosuppression after chemotherapy, which provides new ideas and theoretical support for the intervention and management of bone marrow suppression after cancer chemotherapy.

Discussion on Mechanism of Danggui Buxue Decoction in treatment of chemotherapy-induced myelosuppression based on network pharmaccology and molecular docking / 国际中医中药杂志

Objective:To screen the main active components of Danggui Buxue Decoction in improving chemotherapy-induced myelosuppression; To predict the key targets and signaling pathways; To establish a multi-level network structure and comprehensively reveal the synergistic mechanism of Danggui Buxue Decoction in improving chemotherapy-induced myelosuppression.Methods:Main components of Danggui Buxue Decoction were searched in TCMSP detabase, combined with literature reports to supplement and improve information. The protein targets of compounds were standardized in the UniProt protein database. Myelosuppression targets were obtained by querying TTD database, GeneCards database, DrugBank detabase and OMIM database. The effective components and common targets of Danggui Buxue Decoction were screened, and the protein-protein interaction (PPI) network of intersection targets was analyzed by String platform to construct the PPI network of effective components and disease targets. Gene ontology (GO) analysis and enrichment pathway analysis of Kyoto gene and genome encyclopedia (KEGG) of key target proteins were conducted through Metascape data platform. Both the results of GO and KEGG analysis were presented. AutoDock software was used for molecular docking to explore the interaction between core targets and active components, and the results were imported into PyMOL software for visual analysis.Results:Danggui Buxue Decoction has a total of 22 active components of Chinese materia medica for improving chemotherapy-induced myelosuppression, 294 potential targets, 3 301 disease targets, and 210 common targets of Chinese materia medica and diseases. Core targets were obtained through network topology analysis and molecular docking. The first five were ESR1, MAPK1, RELA, AKT1, PIK3R1; GO enrichment results obtained 2 430 biological processes, 125 cellular components and 217 molecular functions, including responses to inorganic substances, membrane rafts, micro-organisms membrane region, transcription factor binding, etc.; KEGG enriched 385 pathways, of which cancer pathway, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, etc. were the main signaling pathways; molecular docking results showed that β-sitosterol has the best binding performance with HSP90AA1, formononetin and RELA in astragalus when it was in Angelicae Sinensis Radix.Conclusion:Danggui Buxue Decoction regulates ESR1, MAPK1, RELA, AKT1 and other core targets through various active components such as quercetin, formononetin, and β-sitosterol. PI3K-AKT and other related signaling pathways can improve chemotherapy-induced myelosuppression and provide a basis for its clinical application.

Myelosuppression complicated with infection after chemotherapy in children with acute myeloid leukemia / 国际儿科学杂志

The overall survival rate of children with acute myeloid leukemia(AML) is significantly lower than that of acute lymphoblastic leukemia.The main causes of death include primary disease-related death and treatment-related death.Most of the treatment-related deaths are caused by infection, bleeding and organ failure.Infection is the most common complication of pediatric AML during the myelosuppression period after chemotherapy, and it is also the main cause of early death in AML.Based on the analysis of pathogens, laboratory tests and risk factors, this paper reviews the clinical characteristics and research progress of infection in myelosuppression following chemotherapy for AML, so as to provide a basis for early identification, clinical management and condition judgment, and further improve the survival rate of children with AML.

Study of mechanism of bone marrow perivascular niche injured by 5-fluorouracil / 中国药理学通报

Aim To investigate the injury of 5-fluorouracil(5-FU)to perivascular hematopoietic niche via isolating mouse bone marrow perivascular mesenchymal progenitor cells in vitro and its related mechanism. Methods The perivascular mesenchymal progenitor cells were isolated from femurs and tibias of C57BL/6J mice with type Ⅱ collagenase and cultured in vitro. Agarose gel electrophoresis was used to detect specific niche genes expression. The viable cells were counted by Trypan blue; the cellular proliferation was detected by CCK-8; the apoptosis was detected by Annexin V/PI double staining, and the cell senescence was detected by β-galactosidase staining. The levels of malondialdehyde(MDA)and superoxide dismutase(SOD)were detected by enzymatic assay. Osteogenic and adipogenic differentiation potential of cells were detected by osteogenic and adipogenic differentiation experiment and osteogenic related genes qRT-PCR assay. The mRNA expression of hematopoietic growth factors was detected by qRT-PCR. Hematopoietic cells were co-cultured with perivascular mesenchymal progenitor cells, and the adhesion molecules and signal molecules between stromal cells and hematopoietic cells were detected, also hematopoietic cell activity, redox indicators and β-galactosidase specific cell senescence were detected. Results 5-FU caused simultaneous apoptosis and senescence of perivascular mesenchymal progenitor cells, inhibited cell proliferation, induced oxidative stress, led to osteogenic/adipogenic differentiation imbalance, and down-regulated the transcription of hematopoietic factors SCF, CXCL12, and G-CSF. For the interaction between stromal cells and hematopoietic cells, the binding effects of VLA-4/VCAM-1, ICAM-1/LFA1 were weakened and TPO/MPL and ANG-1/Tie-2 signals were impaired, leading to oxidative stress of hematopoietic cells and cell senescence. Conclusions 5-FU induces oxidative damage of perivascular mesenchymal progenitor cells and indirectly induces premature senescence of hematopoietic cells.

Clinical Evaluation and Mechanism of Xuesusheng Granule for Patients with Cancer Related Fatigue / 中国实验方剂学杂志

Objective:To discuss the clinical efficacy of Xuesusheng granule for cancer related fatigue （CRF） deficiency of both Qi and blood in clinical practice， and to investigate its effect on immune function and quality of life. Method:According to random number table method， 118 patients were divided into observation group （59 cases） and control group （59 cases）. Patients in control group got Ejiao Huangqi oral liquid， 10-20 mL/time， 2 times/day. Patients in observation group got Xuesusheng granule， 10 g/time， 3 times/day. The treatment was continued for 8 weeks in both groups. Before and after treatment， scores of cancer fatigue scale （CFS）， functional assessment of cancer therapy （FACT） and Qi and blood deficiency syndrome were graded， and degree of fatigue was discussed with brief fatigue inventory scale-Chinese （BFI-C）. Levels of white blood cell count （WBC）， neutrophil count （NEU）， platelet count （PLT）， red blood cell count （RBC）， and hemoglobin （Hb） were compared before and after treatment.T lymphocyte subsets of （CD3⁺， CD4⁺， CD8⁺） levels， natural killer （NK） cells， interleukin-1（IL-1）， IL-6， IL-8 and tumor necrosis factor -<italic>α</italic> （TNF -<italic>α</italic>） were also detected， and the safety was evaluated. Result:After treatment the scores of each factor in CFS scale and the total score of CFS in the observation group were lower than those in the control group （<italic>P</italic><0.01）， and the degree of fatigue was lower than that in control group （<italic>Z</italic>=2.101， <italic>P</italic><0.05）. The total score of FACT and the scores of four dimensions of physiology， society/family， emotion and function in the observation group were lower than those in the control group （<italic>P</italic><0.01）. Levels of WBC， NEU， RBC and Hb in the observation group were higher than those in the control group （<italic>P</italic><0.01）. Scores of BFI-C， deficiency of Qi and blood<italic> </italic>were lower than those in control group （<italic>P</italic><0.01）. Levels of NK， CD3⁺， CD4⁺ and CD4⁺/CD8⁺ in the observation group were all higher than those in the control group （<italic>P</italic><0.01）， while the IL-1， CD8⁺， IL-6， IL-8 and TNF-<italic>α</italic> levels in observation group were lower than those in the control group （<italic>P</italic><0.01）. Not observed， there was no adverse reaction related to Xususheng granule. Conclusion:Xuesusheng granule can improve the symptoms of fatigue， reduce the degree of fatigue， improve the quality of life， reduce the degree of bone marrow suppression， improve immune function， and regulate immune inflammatory factors with high clinical efficacy in the use for patients with CRF and deficiency of Qi and blood.

Effect of modified Sijunzi Decoction on myelosuppression in moderate- and advanced-stage lung cancer patients with Qi and Yin deficiency and investigation of the underlying mechanism / 中国基层医药

Objective:To investigate the effects of modified Sijunzi Decoction on myelosuppression in moderate- and advanced-stage lung cancer patients with Qi and Yin deficiency and analyze the underlying mechanism. Methods:A total of 100 moderate- and advanced-stage lung cancer patients with Qi and Yin deficiency who received treatment in Lishui Hospital of Traditional Chinese Medicine, China were included in this study. They were randomly assigned to receive chemotherapy with paclitaxel combined with cisplatin (control group, n = 50) or treatment with modified Sijunzi Decoction based on chemotherapy with paclitaxel combined with cisplatin (observation group, n = 50). Myelosuppression, traditional Chinese medicine symptom score, cellular immune function, serum levels of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor, and the dosage of recombinant human granulocyte-colony stimulating factor. Results:After treatment, the incidence of leucopenia, thrombocytopenia, hemoglobinopenia and neutropenia in the observation group were 60% (30/50), 18% (9/50), 18% (9/50) and 62% (31/50), respectively, which were significantly lower than those in the control group [90% (45/50), 30% (15/50), 32% (16/50) and 92% (46/50), χ2 = 6.979, 7.025, 6.534, 6.134, all P < 0.001]. The complete remission rate in the observation group was significantly higher than that in the control group [30% (15/50) vs. 8% (4/50), χ2 = 9.018, P < 0.001]. The traditional Chinese medicine symptom score in the observation group was significantly lower than that in the control group ( t = 6.982, P < 0.05). CD 8+, CD 4+ and CD 3+ levels in the observation group were (25.16 ± 2.87)%, (38.76 ± 4.16)%, (48.83 ± 5.61)%, respectively, and they were (28. 89 ± 4.02)%, (34.10 ± 4.59)%, (41.12 ± 77)%, respectively in the control group. There were significant differences in CD 8+, CD 4+ and CD 3+ levels between the observation and control groups ( t = 6.392, 6.235, 5.983, all P < 0.05). The dosage of recombinant human granulocyte-colony stimulating factor in the observation group was significantly lower than that in the control group [(2 567.34 ± 308.25) μg vs. (3 917.82 ± 411.67) μg, t = 11.258, P < 0.05]. Serum levels of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor were (25.53 ± 7.86) ng/L and (278.34 ± 28.74) ng/L, which were significantly higher than those in the control group [(21.30 ± 3.12) ng/L, (204.17 ± 11.98) ng/L, t = 9.136, 8.856, both P < 0.05]. Conclusion:Modified Sijunzi Decoction for the treatment of moderate- and advanced-stage lung cancer patients with Qi and Yin deficiency can decrease the incidence of myelosuppression possibly through increasing serum levels of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor and improving the immune function.

Effect of Jianpi Bushen Sequential Formula on Adjuvant Chemotherapy of Colon Cancer: Study Protocol for a Randomized Controlled Trial / 中国结合医学杂志

BACKGROUND@#The side effects of chemotherapy-induced nausea and vomiting (CINV) and myelosuppression reduce the cancer patients' adherence to chemotherapy. Many Chinese patients choose Chinese medicine (CM) during chemotherapy to reduce side effects; however, the evidence is lacking. The efficacy of a CM herbal treatment protocol, Jianpi Bushen Sequential Formula (, JBSF) will be evaluated on chemotherapy completion rate among patients with colon cancer.@*METHODS@#A multi-center double-blind randomized controlled trial (RCT) will be conducted on 400 patients with colon cancer who will receive 8 cycles of adjuvant chemotherapy with oxaliplatin and capecitabine (CAPEOX). Patients will be randomized 1:1 to receive the JBSF or placebo formula. The primary outcome is the overall chemotherapy completion rate. The secondary outcomes include individual chemotherapy completion rate, 4-cycle completion rate of chemotherapy, time to treatment failure, relative dose intensity and treatment toxicity. Follow-up visits will be scheduled before every and after last chemotherapy.@*DISCUSSION@#This study will provide evidence on whether JBSF can improve the chemotherapy completion rate and reduce side effects among patients with colon cancer. (Trial registration: ClinicalTrials.gov, No. NCT03716518).

Reduction of FXIII during myelosuppression in acute leukemia after chemotherapy and adverse relation with bleeding events / 中华血液学杂志

Objective@#To explore the relationship between plasma coagulation factor XIII (FXIII) and bleeding events.@*Methods@#A total of 55 cases of acute leukemia (AL) at the myelosuppression phase after chemotherapy hospitalized in our hospital from August 2017 to March 2018 were enrolled, with 35 normal controls. The concentration of plasma coagulation factor XIII (FXIII) was detected by ELISA to determine the relationship between the plasma FXIII levels in AL patients at the myelosuppression phase after chemotherapy with bleeding events.@*Results@#The level of FXIII in AL patients at the myelosuppression phase after chemotherapy was significantly lower than that in controls (P<0.001) . The level of FXIII was inversely related with the bleeding severity (the Spearman correlation coefficient -0.761) . Given the diagnosis cut-off point of FXIII concentration as 103.9 μg/L, the sensitivity of diagnosing bleeding in AL patients at the myelosuppression phase after chemotherapy was 0.939, and the specificity 0.909.@*Conclusion@#AL patients at the myelosuppression phase after chemotherapy had low level of plasma FXIII, and patients with lower plasma FXIII associated with higher incidence and severity of bleeding. FXIII level was an independent influencing factor of bleeding in AL patients at the myelosuppression phase after chemotherapy.

Study on the ineffective platelet transfusion in patients with hematologic malignancies during myelosuppression / 白血病·淋巴瘤

Objective@#To investigate the causes of ineffective platelet transfusion in patients with hematologic malignancies during myelosuppression and the therapeutic effect of rituximab.@*Methods@#A total of 180 patients with different hematologic malignancies in the First People's Hospital of Changzhou from January 2017 to December 2018 were selected. And the incidence of ineffective platelet transfusion during myelosuppression was observed. The changes of T and B lymphocyte subgroups and platelet counts before and after rituximab therapy in acute leukemia patients with platelet antibody-positive were compared, and the incidence of ineffective platelet transfusion with different platelet suspensions was analyzed.@*Results@#The ineffective platelet transfusion was observed in 45 of 180 patients (25.0%) during myelosuppression, including 30 (27.8%) of 108 patients with acute leukemia, 10 (23.3%) of 43 patients with myelodysplastic syndrome, 2 (13.3%) of 15 patients with malignant lymphoma, and 3 (21.4%) of 14 patients with multiple myeloma. The incidence of ineffective platelet transfusion in patients transfused with irradiated leukocyte depleted apheresis platelets (17.0%, 16/94) was lower than that in those with apheresis platelets (33.7%, 29/86), and the difference was statistically significant (χ2 = 6.68, P = 0.01). In 8 acute leukemia patients with platelet antibody-positive and the ineffective platelet transfusion after rituximab therapy, the increase of platelet count was observed in 5 patients. The differences of levels of CD19, CD20, CD4 and platelet count before and after treatment with rituximab were statistically significant (all P < 0.05).@*Conclusions@#The incidence of ineffective platelet transfusion is the highest in acute leukemia patients. Transfusion of human leukocyte antigen-matched platelets can improve the effect of platelet transfusion. Rituximab is effective in the ineffective platelets transfusion caused by immune factors. The incidence of ineffective platelet transfusion in irradiated leukocyte depleted apheresis platelets is lower compared with that in apheresis platelets.

Prevention effect of transcutaneous electrical acupoint stimulation for chemotherapy-related myelosuppression in non-small cell lung cancer / 中国针灸

OBJECTIVE@#To observe the prevention effect of transcutaneous electrical acupoint stimulation (TEAS) for chemotherapy-related myelosuppression in non-small cell lung cancer.@*METHODS@#A total of 102 patients with non-small cell lung cancer who received initial chemotherapy were randomly divided into a conventional group, a medication group and a TEAS group, 34 cases in each one. The conventional group was treated with chemotherapy of gemcitabine combined with cisplatin and given routine care. On the basis of conventional group's treatment, the medication group was given tablets before chemotherapy, 2-3 tablets each time, 3 times a day. In the TEAS group, on the basis of conventional group's treatment, TEAS was applied at Dazhui (GV 14), Geshu (BL 17), Hegu (LI 4), Zusanli (ST 36) and Sanyinjiao (SP 6) on day 1, 2, 3, 5, 8, 14, 21 and 28 of chemotherapy. The treatment was given 30 min each time and once a day. In the three groups, the treatment for 28 days was as one course and one course of treatment was required. The changes of leukocytes, platelets, erythrocyte, hemoglobin indexes in patients of the three groups were observed one day before chemotherapy and on day 5, 8, 11, 14, 21 and 28 of chemotherapy. The comfort situation of patients was observed one day before chemotherapy and on the 5th, 11th and 21st day of chemotherapy.@*RESULTS@#Compared with before chemotherapy, the leukocyte counts of three groups were decreased at various time points after chemotherapy (<0.05). Compared with the conventional group, the leukocyte counts were higher on day 8 and 14 in the TEAS group and on day 14 in the medication group (<0.05). Compared with before chemotherapy, the platelet count decreased on the day 5, 8, 11 and 14 of chemotherapy in the conventional group (<0.05), and the platelet counts all decreased at each time point after chemotherapy in the medication group (<0.05). The platelet counts of the TEAS group on day 5, 8, 11 and 14 of chemotherapy were higher than those of the conventional group (<0.05), and the platelet counts of the TEAS group on day 5, 8, 11 and 21 of chemotherapy were higher than those of the medication group (<0.05). Compared with the conventional group, the comfort situation scores of the TEAS group were higher on the 5th and 11th days of chemotherapy (<0.05).@*CONCLUSION@#Transcutaneous electrical acupoint stimulation can prevent chemotherapy-induced myelosuppression (leukocyte, platelets) in patients with non-small cell lung cancer and improve patient comfort situation.

Reduction of FXIII during myelosuppression in acute leukemia after chemotherapy and adverse relation with bleeding events / 中华血液学杂志

Objective: To explore the relationship between plasma coagulation factor XIII (FXIII) and bleeding events. Methods: A total of 55 cases of acute leukemia (AL) at the myelosuppression phase after chemotherapy hospitalized in our hospital from August 2017 to March 2018 were enrolled, with 35 normal controls. The concentration of plasma coagulation factor XIII (FXIII) was detected by ELISA to determine the relationship between the plasma FXIII levels in AL patients at the myelosuppression phase after chemotherapy with bleeding events. Results: The level of FXIII in AL patients at the myelosuppression phase after chemotherapy was significantly lower than that in controls (P<0.001) . The level of FXIII was inversely related with the bleeding severity (the Spearman correlation coefficient -0.761) . Given the diagnosis cut-off point of FXIII concentration as 103.9 μg/L, the sensitivity of diagnosing bleeding in AL patients at the myelosuppression phase after chemotherapy was 0.939, and the specificity 0.909. Conclusion: AL patients at the myelosuppression phase after chemotherapy had low level of plasma FXIII, and patients with lower plasma FXIII associated with higher incidence and severity of bleeding. FXIII level was an independent influencing factor of bleeding in AL patients at the myelosuppression phase after chemotherapy.