GCSF may improve the prognosis of severe liver disease by promoting liver regeneration and immune restoration. Our Aim was to investigate its controversial efficacy in decompensated cirrhosis, acute alcoholic hepatitis (AAH), or acute-on-chronic liver failure (ACLF) through meta-analysis.
Meta-analysis of proportions (random effect model) including 19 RCTs (1287 patients from 16 Asian and 3 European studies including 487 ACLF, 231 AAH and 569 cirrhotic patients) evaluating survival at day-28, day-90, 6 months, one year, and/or occurrence of sepsis as major outcomes.
In patients with decompensated cirrhosis, G-CSF administration was associated with a reduction in the weight-adjusted risk of mortality of 9% at day-90 (OR=0.33; 95%CI: 0.18-0.58; p = 0.0002), 16% at 6 months (OR=0.31; 95%CI: 0.15-0.62; p = 0.0009), 26% at one year (OR=0.21; 95%CI:0.12-0.38, p<0.0001) and a weight-adjusted 28% risk reduction for sepsis (OR=0.28; 95%CI: 0.16-0.49; p<0.0001). Only Asian studies were positive. In AAH, G-CSF was associated with an 18% reduction in weight-adjusted mortality risk at day-28 (OR=0.31; 95%CI:0.11-0.83, p = 0.021), 32% at day-90 (OR=0.20; 95%CI:0.09-0.46, p<0.0001) and a weight-adjusted 42% risk reduction for sepsis (OR=0.17; 95%CI: 0.08-0.38; p<0.0001). Only Asian studies, in which corticosteroids were not given systematically in case of severe AAH, were positive. In patients with ACLF, the results on mortality at day-28 were heterogeneous, and GCSF had no beneficial effect on sepsis or survival at day-90.
G-CSF may be effective in patients with decompensated cirrhosis or AAH by reducing the occurrence of sepsis and mortality. Further meta-analyses of individual data, or new, powerful and methodologically flawless therapeutic trials, are warranted to confirm these results, which harbor wide divergences between Asian and European RCTs.

OBJECTIVE: To investigate the mechanism of Xuanhusuo powder (XHSP) inhibiting the differentiation of spleen myeloid-derived suppressor cells (MDSCs) in breast cancer mice.
METHODS: Forty-eight BALB/c female mice aged 4-5 weeks were selected, 6 of them were in normal control group, while others were in tumor-bearing models established by orthotopic injection of 4T1 cells into the subcutaneous fat pad of the second pair of left mammary glands. The tumor-bearing mice were divided into granulocyte colony stimulating factor (G-CSF) control group, G-CSF knock-down group, model control group, XHSP small dose group, XHSP medium dose group, XHSP high dose group, and cyclophosphamide (CTX) group, with 6 mice in each group. G-CSF control group and G-CSF knock-down group were constructed by stably transfecting 4T1 cells established by shRNA lentivirus combined with puromycin selection. 48 h after the model was established, XHSP small, medium, high dose group were given 2, 4, 8 g·kg－1·d－1 intragastric administration once a day, respectively. CTX was given 30 mg/kg by intraperitoneal injection, once every other day. The other groups were given an equal volume of 0.5% hydroxymethylcellulose sodium. The drugs in each group were continuously administered for 25 d. Histological changes in spleen were observed by HE staining, the proportion of MDSCs subsets in the spleen were detected by flow cytometry, the co-expression of CD11b and Ly6G in the spleen was detected by immunofluorescence, and the concentration of G-CSF in peripheral blood was detected by ELISA. The spleen of tumor-bearing mice was co-cultured with 4T1 stably transfected cell lines in vitro, treated with XHSP (30 μg/mL) for 24 h, and the co-expression of CD11b and Ly6G in the spleen was detected by immunofluorescence. 4T1 cells were treated by XHSP (10, 30, 100 μg/mL) for 12 h. The mRNA level of G-CSF was detected by realtime RT-PCR.
RESULTS: Compared with normal mice, the red pulp of the spleen in tumor-bearing mice was widened with megakaryocyte infiltration. The proportion of spleen polymorphonucleocyte-like MDSCs (PMN-MDSCs) was significantly increased (P<0.01) and the co-expression of CD11b and Ly6G was increased, and the concentration of G-CSF in peripheral blood was significantly increased (P<0.01). However, XHSP could significantly reduce the proportion of PMN-MDSCs (P<0.05) and the co-expression of CD11b and Ly6G in the spleen, down-regulate the mRNA level of G-CSF in 4T1 cells (P<0.01). The concentration of G-CSF in peripheral blood of tumor-bearing mice also decreased (P<0.05) and tumor volume was reduced and splenomegaly was improved (all P<0.05).
CONCLUSIONS: XHSP may play an anti-breast cancer role by down-regulating G-CSF, negatively regulating the differentiation of MDSCs, and reconstruct the spleen myeloid microenvironment.
目的: 探讨玄胡索散抑制乳腺癌小鼠脾脏髓源抑制细胞（MDSC）分化的作用机制。方法: 4~5周龄BALB/c雌性小鼠48只，其中6只为正常对照组，其他42只采用小鼠左侧第二对乳腺皮下脂肪垫接种4T1细胞构建乳腺癌荷瘤小鼠模型，分为粒细胞集落刺激因子（G-CSF）对照组、G-CSF敲减组、模型对照组、玄胡索散小剂量组、玄胡索散中剂量组、玄胡索散大剂量组和环磷酰胺组，每组6只。其中G-CSF对照组和G-CSF敲减组分别采用shRNA慢病毒转染联合嘌呤霉素构建相应4T1稳转细胞模型。各组造模48 h后，玄胡索散小剂量组、玄胡索散中剂量组、玄胡索散大剂量组分别按2、4、8 g·kg－1·d－1玄胡索散灌胃，每天一次；环磷酰胺组按30 mg/kg腹腔注射环磷酰胺，隔天一次；其他组给予等体积0.5%羟甲基纤维素纳。各组连续给药25 d。苏木精-伊红染色观察脾脏组织病理学改变，流式细胞术测定脾脏MDSC亚群比例，免疫荧光法检测脾脏CD11b、Ly6G共表达，酶联免疫吸附测定外周血G-CSF浓度。在体外，建立荷瘤小鼠脾脏与4T1稳转株共培养体系，玄胡索散（30 μg/mL）处理24 h，免疫荧光检测脾脏CD11b、Ly6G共表达；不同浓度的玄胡索散（10、30、100 μg/mL）处理4T1细胞12 h，实时逆转录PCR检测G-CSF mRNA水平。结果: 与正常对照组比较，模型鼠脾脏红髓增宽伴巨核细胞浸润，脾脏多形核细胞样MDSC（PMN-MDSC）比例增加（P<0.01），脾脏CD11b、Ly6G共表达增多，外周血G-CSF浓度上升（P<0.01）。玄胡索散干预后脾脏PMN-MDSC比例减小（P<0.05），脾脏CD11b、Ly6G共表达减少，4T1细胞G-CSF mRNA水平下调（P<0.01），模型鼠外周血G-CSF浓度减少（P<0.05），肿瘤体积缩小，脾脏增大情况改善（均P<0.05）。结论: 玄胡索散可能通过下调G-CSF，阻碍MDSC向PMN-MDSC分化，重建脾脏髓系微环境，从而发挥抗乳腺癌作用。.

Objective: To evaluate the advantages and safety of Plerixafor in combination with granulocyte colony-stimulating factor (G-CSF) in autologous hematopoietic stem cell mobilization of lymphoma. Methods: Lymphoma patients who received autologous hematopoietic stem cell mobilization with Plerixafor in combination with G-CSF or G-CSF alone were obtained. The clinical data, the success rate of stem cell collection, hematopoietic reconstitution, and treatment-related adverse reactions between the two groups were evaluated retrospectively. Results: A total of 184 lymphoma patients were included in this analysis, including 115 cases of diffuse large B-cell lymphoma (62.5%) , 16 cases of classical Hodgkin\'s lymphoma (8.7%) , 11 cases of follicular non-Hodgkin\'s lymphoma (6.0%) , 10 cases of angioimmunoblastic T-cell lymphoma (5.4%) , 6 cases of mantle cell lymphoma (3.3%) , and 6 cases of anaplastic large cell lymphoma (3.3%) , 6 cases of NK/T-cell lymphoma (3.3%) , 4 cases of Burkitt\'s lymphoma (2.2%) , 8 cases of other types of B-cell lymphoma (4.3%) , and 2 cases of other types of T-cell lymphoma (1.1%) ; 31 patients had received radiotherapy (16.8%) . The patients in the two groups were recruited with Plerixafor in combination with G-CSF or G-CSF alone. The baseline clinical characteristics of the two groups were basically similar. The patients in the Plerixafor in combination with the G-CSF mobilization group were older, and the number of recurrences and third-line chemotherapy was higher. 100 patients were mobilized with G-CSF alone. The success rate of the collection was 74.0% for one day and 89.0% for two days. 84 patients in the group of Plerixafor combined with G-CSF were recruited successfully with 85.7% for one day and 97.6% for two days. The success rate of mobilization in the group of Plerixafor combined with G-CSF was substantially higher than that in the group of G-CSF alone (P=0.023) . The median number of CD34(+) cells obtained in the mobilization group of Plerixafor combined with G-CSF was 3.9×10(6)/kg. The median number of CD34(+) cells obtained in the G-CSF Mobilization group alone was 3.2×10(6)/kg. The number of CD34(+) cells collected by Plerixafor combined with G-CSF was considerably higher than that in G-CSF alone (P=0.001) . The prevalent adverse reactions in the group of Plerixafor combined with G-CSF were grade 1-2 gastrointestinal reactions (31.2%) and local skin redness (2.4%) . Conclusion: The success rate of autologous hematopoietic stem cell mobilization in lymphoma patients treated with Plerixafor combined with G-CSF is significantly high. The success rate of collection and the absolute count of CD34(+) stem cells were substantially higher than those in the group treated with G-CSF alone. Even in older patients, second-line collection, recurrence, or multiple chemotherapies, the combined mobilization method also has a high success rate of mobilization.
目的： 分析普乐沙福（Plerixafor）联合粒细胞集落刺激因子（G-CSF）在淋巴瘤患者中进行自体造血干细胞动员的效果及安全性。 方法： 收集2019年4月至2021年12月在上海交通大学医学院附属瑞金医院采用普乐沙福联合G-CSF（普乐沙福+G-CSF组）或单用G-CSF（G-CSF组）进行自体造血干细胞动员的淋巴瘤患者，回顾性分析两组之间临床资料、干细胞动员/采集成功率、移植后造血重建和治疗不良反应。 结果： 全部184例淋巴瘤患者包括弥漫大B细胞淋巴瘤115例（62.5%）、经典型霍奇金淋巴瘤16例（8.7%）、滤泡性非霍奇金淋巴瘤11例（6.0%）、血管免疫母细胞T细胞淋巴瘤10例（5.4%）、套细胞淋巴瘤6例（3.3%）、间变大细胞淋巴瘤6例（3.3%）、NK/T细胞淋巴瘤6例（3.3%）、伯基特淋巴瘤4例（2.2%）、其他类型B细胞淋巴瘤8例（4.3%）、其他类型T细胞淋巴瘤2例（1.1%）。31例（16.8%）患者曾接受放疗。普乐沙福+G-CSF组84例，G-CSF组100例。普乐沙福+G-CSF组患者年龄较大、复发及三线化疗患者占比较高，其他临床特征基本一致。G-CSF组动员后1 d采集成功率为74.0%，2 d采集成功率为89.0%；普乐沙福+ G-CSF组1 d采集成功率为85.7%，2 d采集成功率为97.6%。普乐沙福+G-CSF组的动员成功率明显高于单用G-CSF组（P=0.023）。普乐沙福+G-CSF组、G-CSF组采集CD34(+)细胞中位数分别为3.9（0.7~21.2）×10(6)/kg、3.2（0.6~19.4）×10(6)/kg（P=0.001）。普乐沙福+G-CSF组常见的不良反应为1~2级胃肠道反应（31.2%）、局部皮肤发红（2.4%）。 结论： 普乐沙福联合G-CSF用于淋巴瘤患者自体造血干细胞动员/采集成功率、CD34(+)细胞采集量均明显高于单用G-CSF，不良反应少，即使在年龄较大、二线动员、复发或者多次化疗的患者中也具有较高的动员成功率。.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) plus plerixafor has been shown to improve the efficacy of peripheral blood stem cell (PBSC) mobilization, however, due to its high price, the use of plerixafor is limited in China. The purpose of this study was to assess the efficacy of residual plerixafor for second-day stem cell mobilization in multiple myeloma (MM) patients.
METHODS: In this single-center retrospective study, 69 MM patients received G-CSF + plerixafor to mobilize PBSCs, which were collected from 28 patients only for one day and 41 patients for two days. Some of the patients received residual plerixafor, and PBSCs were collected on the second day. The data on the characteristics, different doses of plerixafor and efficacy of PBSC mobilization were collected and analyzed.
RESULTS: After 1 or 2 apheresis procedures, 85.5% of patients collected more than 2 × 106 cells/kg PBSCs. There was no statistically significant difference in the success rate of CD34 + PBSC mobilization with the different doses of plerixafor on the first day, but the higher residual plerixafor dose resulted in better success rates on the second day (P＜0.001). Among the patients who collected PBSCs for two days, the level of the CD34 + cell yield of 24 patients (58.5%) changed better, which was significantly correlated with the dose of residual plerixafor on the second day (P = 0.001).
CONCLUSIONS: These results suggested that the administration of residual plerixafor to mobilize stem cells on the second day is an economical, efficient and clinically feasible method.

Acute-on-chronic liver failure (ACLF) has a high mortality rate. The role of granulocyte colony-stimulating factor (G-CSF) in ACLF remains controversial. Monocytes/macrophages are core immune cells, which are involved in the initiation and progression of liver failure; however, the effect of G-CSF on monocytes/macrophages is unclear. The study aimed to verify the clinical efficacy of G-CSF and explore the effect of it on monocytes in hepatitis B virus (HBV)-related ACLF (HBV-ACLF) paitents.
We performed a large randomized controlled clinical trial for the treatment of HBV-ACLF using G-CSF. A total of 111 patients with HBV-ACLF were prospectively randomized into the G-CSF group (5 μg/kg G-CSF every day for 6 days, then every other day until day 18) or the control group (standard therapy). All participants were followed up for at least 180 days. The relationship between monocyte count and mortality risk was analyzed. The effect of G-CSF on the phenotype and function of monocytes from patients with HBV-ACLF was evaluated using flow cytometry in vivo and in vitro experiments.
The survival probability of the G-CSF group at 180 days was higher than that of the control group (72.2% vs. 53.8%, P = 0.0142). In the G-CSF-treated group, the monocyte counts on days 0 and 7 were independently associated with an evaluated mortality risk in the fully adjusted model (Model 3) [at day 0: hazard ratio (HR) 95% confidence interval (CI): 15.48 (3.60, 66.66), P = 0.0002; at day 7: HR (95% CI): 1.10 (0.50, 2.43), P=0.8080]. Further analysis showed that after treatment with G-CSF in HBV-ACLF patients, the expression of M1-like markers (HLA-DR and CD86) in monocytes decreased (HLA-DR: P = 0.0148; CD86: P = 0.0764). The expression of MerTK (M2-like marker) increased (P = 0.0002). The secretion of TNF-α, IL-6, and IL-10 from monocytes decreased without lipopolysaccharide (LPS) stimulation (TNF-α: P < 0.0001; IL-6: P= 0.0025; IL-10: P = 0.0004) or with LPS stimulation (TNF-α: P = 0.0439; P = 0.0611; IL-10: P = 0.0099). Similar effects were observed in vitro experiments.
G-CSF therapy confers a survival benefit to patients with HBV-ACLF. G-CSF can promote the anti-inflammatory/pro-restorative phenotype (M2-like) transition of monocytes, which may contribute to the recovery of ACLF.Clinical Trial Registration Number: ClinicalTrials.gov, identifier (NCT02331745).

Granulocyte colony-stimulating factor (G-CSF) has been reported to exert a protective effect against secondary brain damage, but the underlying mechanisms remain unknown. We explored the ability of G-CSF to protect the brain from injury in a rat autologous blood-induced model of intracerebral hemorrhage (ICH), with a special focus on the anti-inflammation effect. An ICH was induced in 8-week-old male rats by an infusion of autologous blood, and the rats were then randomly assigned to five treatment groups: sham, ICH, and ICH+ low-dose (25 µg/kg), middle-dose (50 µg/kg), and high-dose (75 µg/kg) G-CSF. We then evaluated the levels of brain inflammation-related genes and proteins. The levels of tumor-necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) mRNA increased between days 1 and 14 post-ICH, with the highest expression on day 3. These changes were rectified by G-CSF in a dose-dependent manner. At day 3 post-injury, an elevation of the nuclear factor-kappa B (NF-κB) p65 protein level and a reduction of the inhibitor of NF-κB alpha (IκBα) protein level were observed; G-CSF treatment exerted a beneficial effect on both protein expressions. The expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins were increased; these changes were rectified by the highest dose of G-CSF. The brain-protecting effects of G-CSF are likely to be attributable, at least in part, to attenuation of the TNF-α, IL-6, iNOS, and COX-2 expressions induced by NF-κB activation in the brain tissues of this autologous blood-induced ICH rat model.

Evidence accumulated in recent years has revealed that neutrophils are involved in the initial establishment of endometriosis, which is well-known as a chronic inflammatory disease. So far, why and how neutrophils promote the formation of early endometriosis are still unclear. In this study, using a mouse model of endometriosis, we demonstrated that endometriosis mice (EMs mice) had a significantly increased number of neutrophils in peritoneal fluids and lesions, and increased levels of granulocyte colony-stimulating factor (G-CSF) and IL-6 in serum and peritoneal fluids compared to the control group. In the neutrophils and uterine fragments co-injection experiment, neutrophils regulated by G-CSF and IL-6 had a similar effect to neutrophils from EMs mice, increasing the number, area, weight and microvessel density (MVD) of endometriotic lesions. Blocking the effect of G-CSF and IL-6 in EMs mice resulted in a decrease in the number, area and weight of endometriotic lesions. Following the depletion of neutrophils in vivo using a anti-Ly6G antibody, the MVD in the lesions of mice treated with neutrophils from EMs mice and neutrophils from pG/pI6 mice were significantly reduced. Neutrophils from EMs mice and neutrophils from pG/pI6 mice altered the expression levels of Mmp9, Bv8 and Trail genes compared to the neutrophils from PBS-treated mice. IL-6 together with G-CSF induced a higher expression of phospho-STAT3 and STAT3 in neutrophils. These findings suggest that neutrophils modulated by G-CSF and IL-6 through the STAT3 pathway alter the expression levels of the angiogenesis-related genes Mmp9, Bv8 and Trail, and may promote the establishment of early endometriosis.

BACKGROUND: Interstitial pneumonitis (IP), a fatal complication of DLBCL treatment, can bring great challenges to clinicians. We retrospectively investigated clinical characteristics and risk factors of previous IP patients, and analyzed their survival data.
METHODS: 556 DLBCL patients receiving CHOP-like regimens were enrolled between 2013 and 2018 in Sichuan Cancer Hospital.
RESULTS: The IP incidences were 4.9 % (27/556), 1.1 % (2/186), 5.2 % (10/191) and 8.4 % (15/179) in CHOP, R-CHOP and R-CDOP groups respectively (P = 0.005). When IP was diagnosed, monocyte and IL-6 were significantly higher while CD4 and CD4/CD8 significantly lower compared to baseline. 81.5 % (22/27) of IP patients were pathogen-negative with good response to glucocorticoid monotherapy. Only one patient died while the others recovered from IP and subsequently underwent previous chemotherapy. 19.2 % (5/26) of IP patients experienced IP recurrence, likely due to the reason of lower initial dose or faster withdrawal speed of glucocorticoid. Multivariate analysis identified male, in addition to G-CSF, rituximab and pegylated liposomal doxorubicin as risk factors. The 3-year PFS and OS were 74.1 % and 46.9 % respectively for patients with IP.
CONCLUSIONS: We suggest that IL-6, monocyte and CD4 should be monitored closely, especially in R-CHOP/R-CDOP group. Sufficient initial dose and slow decrease of glucocorticoid based on radiographic remissions were critical strategies to reduce IP recurrence. We speculate that drug-induced immune imbalance could be trigger of developing IP, causing a lower intensity cytokine storm, resulting in a potential immunotherapy. This complication might bring benefit in patients\' survival through a mechanism similar to PD-1.

The aim of the present study was to investigate the effect of the mobilization of EPCs by AMD3100 combined with G-CSF on wound healing in diabetic mice.
The full-thickness excisional wounds model of diabetic mice (db/db) was examined by hematoxylin and eosin staining, immunohistochemical staining, and western blotting to compare the wound healing and neovascularization among the combination, AMD3100 alone, G-CSF alone, and control groups.
The wounds reached the complete closure in the combination, AMD3100 alone, G-CSF alone, and control groups on days 17, 20, 21, 21 after surgery, respectively. In addition, the combination group promoted the inflammatory cell recruitment and glandular formation. On day 10 from injury, the protein expression of CD31 in the combination group was significantly higher compared with the other three groups (p < 0.001). The level of SDF-1 protein remained high in the combined group until on day 10 after surgery (p < 0.001).
The mobilization of endogenous EPCs by AMD3100 combine with G-CSF is able to enhance the complete healing of full-thickness wounds and neovascularization in db/db mice may by SDF-1/CXCR4 axis. These findings provided a novel method and indication of duration of mobilization on diabetic wound healing and tissue regeneration.

BACKGROUND: Repeated implantation failure (RIF) is a stressful situation for subfertile women undergoing in vitro fertilisation (IVF) treatment and caregivers. Granulocyte-colony stimulating factor (G-CSF) seems to play an important role in assisted reproductive techniques. However, it is currently unknown whether G-CSF is effective in improving results for patients with RIF.
OBJECTIVE: To describe and summarize current evidence of the effect of the granulocyte colony stimulating factor (G-CSF) in treating RIF.
METHODS: Relevant scientific literature was thoroughly searched by computer in domestic and foreign database from the inceptions to November 2019. And relevant randomized controlled trials (RCTs) assessing the efficacy of G-CSF in unexplained RIF were included. The meta-analysis was conducted by Stata 12. 0 software, and we estimated relative risks (RRs) and associated 95 % confidence intervals (CIs) of G-CSF on implantation rate (IR), the clinical pregnancy rate (CPR), the abortion rate (AR) in patients with unexplained RIF using fixed-effect model. Besides, Subgroup analysis was performed according to the different administration methods.
RESULTS: A total of eleven articles were included for the final meta-analysis with sample sizes ranging from 13 to 107 patients. The G-CSF was associated with an increased IR [RR = 2.346, 95 %CI (1.615-3.409), I2 = 0. 0%] and CPR [RR = 1.910, 95 %CI (1.562-2.337), I2 = 0.0 %] in patients with unexplained RIF. When further stratified by the method of administration, the subgroup analysis revealed that both intrauterine injection and subcutaneous injection are capable of improving IR[subcutaneous injection:RR = 2.400, 95 %CI (1. 268-4. 542), I2 = 0.0 %; intrauterine injection:RR = 2.317, 95 %CI (1.462-3.673), I2 = 0.0 %] and CPR[subcutaneous injection: RR = 2. 022, 95 %CI (1.443-2.832), I2 = 0. 0%; intrauterine injeciton: RR = 1.848, 95 %CI (1.438-2.376), I2 = 0. 0%]. G-CSF was not associated with AR in patients with unexplained RIF [RR = 2.092, 95 %CI (0.815-5.369), I2 = 0.0 %].
CONCLUSIONS: The current evidence support G-CSF\'s positive effect on the implantation rate and clinical pregnancy rate of patients with unexplained RIF, especially when administrated by subcutaneous injection. There is no conclusive evidence for the association between G-CSF and the abortion rate. Moreover, few of the included articles reported side effects of G-CSF, so its safety remains to be investigated.Thus, future research should evaluate.