Acute leukemias caused by mixed lineage leukemia(MLL)gene rearrangements(MLL-r)are characterized by high invasiveness and a poor prognosis,with few specific treatment options available.MLL protein is essential in embryonic development and hematopoiesis.It exhibits histone methyltransferase activity and can interact with various proteins through its functional domains,thus regulating downstream target gene expression through epigenetic modifications.MLL-r leads to the formation of MLL fusion proteins(MLL-FPs),in which the C-terminal is replaced by fusion partner proteins;over 100 such partner proteins have been identified to date.In numerous studies of the molecular mechanism,Menin serves as an important cofacter in the leukemogenesis of MLL-FPs and participates in forming the key complex when interacting with the N terminal of MLL protein,resulting in the disregulation of certain targeted genes,which makes the development of Menin-MLL inhibitors theoretically possible.To date,several small molecules have been identified that inhibit Menin-MLL interaction,including thienopyrimidine derivatives,piperidine derivatives,pyrimidine derivatives,and macrocyclic mimic peptides.Based on these prototypes,at least seven drugs are currently undergoing clinical evaluation,with some promising preliminary data regarding safety,tolerability,and efficacy.This review summarizes the structure and function of MLL,the mechanism of the occurrence of MLL-r leukemia,and current Menin-MLL inhibitors tested in MLL-r leukemia.

Objective:To explore the value of monocyte subsets and CD64 expression in the diagnosis and prognosis of sepsis.Methods:A prospective case-control study was designed. 30 septic patients and 30 non-septic patients who were admitted to the intensive care unit (ICU) of the PLA Army Characteristic Medical Center from March 2021 to March 2022 were enrolled. After 1, 3, and 5 days of ICU admission, peripheral blood samples were taken from patients. Flow cytometry was used to detect the proportion of monocyte subsets and the expression level of CD64 on the surface, and the difference of expression between patients in two group was analyzed. The risk variables for sepsis were analyzed using single-factor and multi-factor Logistic regression. The diagnostic efficacy of each risk factor for sepsis was determined using the receiver operator characteristic curve (ROC curve).Results:One day after ICU admission, the proportions of monocytes and classic monocytes in white blood cells (WBC) of septic patients were significantly lower than those of non-septic patients [proportion of monocytes to WBC: (4.13±2.03)% vs. (6.53±3.90)%, proportion of classic monocytes to WBC: 1.97 (1.43, 2.83)% vs. 3.37 (1.71, 5.98)%, both P < 0.05]. The proportion of non-classical monocytes in monocytes was significantly higher in septic patients than that in non-septic patients [(11.42±9.19)% vs. (6.57±4.23)%, P < 0.05]. The levels of CD64 expression in monocytes, classic monocytes, intermediate monocytes and non-classic monocytes were significantly higher in sepsis patients than those in non-septic patients [mean fluorescence intensity (MFI): 13.10±6.01 vs. 9.84±2.83 for monocytes, 13.58±5.98 vs. 10.03±2.84 for classic monocytes, 13.48±6.35 vs. 10.22±2.99 for intermediate monocytes, 8.21±5.52 vs. 5.79±2.67 for non-classic monocytes, all P < 0.05]. Multivariate Logistic regression research showed that CD64 in typical monocytes [odds ratio ( OR) = 1.299, 95% confidence interval (95% CI) was 1.027-1.471, P = 0.025] and the proportion of non-typical monocytes in monocytes ( OR = 1.348, 95% CI was 1.034-1.758, P = 0.027) were the independent risk factors for sepsis. ROC curve showed that the area under the ROC curve (AUC) of CD64 expression of classical monocytes, the fraction of non-classical monocytes in monocytes, and procalcitonin (PCT) in the diagnosis of sepsis was 0.871. A correlation analysis revealed a negative relationship between the acute physiology and chronic health status evaluation Ⅱ (APACHE Ⅱ) on the first, third, and fifth days following ICU admission and the expression level of CD64 in patients' classic monocytes ( r values were -0.264, -0.428 and -0.368, respectively, all P < 0.05). Conclusions:Combining the proportion of non-classical monocytes in monocytes, the level of plasma PCT, and the CD64 expression of classic monocytes in peripheral blood has good efficacy in identifying sepsis and assessing its severity.

Objective:To investigate whether transplantation of gingival mesenchymal stem cells (GMSCs) can inhibit radiation-induced senescence of alveolar epithelial cells type Ⅱ (AECⅡ) and its role in the prevention of radiation-induced pulmonary fibrosis (RIPF).Methods:Mouse type Ⅱ alveolar epithelial cells (MLE12) were irradiated with 6 Gy X-rays and then co-cultured with GMSCs. The extent of cellular senescence of MLE12 cells was assessed by cell morphology, β-Gal staining, and senescence secretion-associated phenotype (SASP) assay. RIPF model was constructed by unilaterally irradiating the right chest of C57BL/6 mice with 17 Gy X-rays. GMSCs were transplanted 1 d after irradiation. At 180 d after irradiation, the pulmonary organ ratio, HE staining, and Masson staining were used to assess intra-pulmonary structure and interstitial collagen deposition in the lung. β-Gal immunohistochemistry and immunofluorescence co-localization with AECⅡ were measured to assess the degree of cellular senescence in the lung. The SASP expression changes in lung tissue were detected by qRT-PCR. The protein expressions in P53-P21 and P16 pathways were detected by Western blot assay. P21 expression in AECⅡ was detected by immunofluorescence co-localization assay.Results:GMSCs effectively inhibited radiation-induced senescence of MLE12 cells, reduced the ratio of radiation-elevated β-Gal positive cells by 11.8% ( t=6.72, P<0.05), and decreased the expressions of SASP (IL-6, IL-8, IL-1β) ( t=28.43, 28.43, 4.82, P<0.05). GMSCs transplantation improved the survival rate of irradiated mice, prevented radiation-induced alveolar structural collapse thickening and collagen deposition, reduced the number of senescent cells in the irradiated lung tissues by 23.9% ( t=21.83, P<0.05), and inhibited the expressions of SASP ( t=8.86, 20.63, P<0.05). GMSCs also inhibited the expression of P53-P21, P16-related proteins in MLE12 cells and lung tissues of mice after irradiation. Conclusions:GMSCs inhibit senescence-related P53-P21 and P16 pathways, prevent radiation-induced AECⅡ senescence, as well as the development of RIPF.

Objective:To study the genotyping and regional distribution characteristics of Yersinia pestis by single nucleotide polymorphism (SNP) in Gansu Province. Methods:A total of 52 strains of Yersinia pestis isolated from Himalaya Marmot plague foci and Spermophilus alaschanicus plague foci in Gansu Province from 1962 to 2017 were selected for culture and extraction of DNA. The genomic DNA of Yersinia pestis was sequenced by the second generation of Illumina PE150 to identify the SNP sites. The species characteristics of Yersinia pestis in Gansu Province was determined by the Kimura-2-parameter model of neighbor joining of Mega 10.0 software based on the SNP sites. The molecular evolutionary tree of the groups was determined by Hasegawa-Kishino-Yano model of maximum likelihood method according to the SNP sites. Results:A total of 103 SNP sites were identified in 52 strains of Yersinia pestis in Gansu Province, including 28 intergenic loci, 43 non-synonymous mutations, 31 synonymous mutations and 1 nonsense mutation. The 52 strains of Yersinia pestis were divided into 2 biotypes and 3 groups, which were ancient type (1.IN2, 3.ANT) and medieval type (2.MED). Among them, 35 strains belonged to 1.IN2 group, 13 strains belonged to 3.ANT group, and 4 strains belonged to 2.MED group. The 1.IN2 group was further divided into 5 subgroups: the groups of Yuerhong Town and Dangchengwan Town in Subei County, the groups of Mati Town and Dahe Town in Sunan County, and the group of Xiahe County. The 3.ANT group was further divided into 2 subgroups: the groups of Hongliuwan Town in Aksay County and Machang in Dangchengwan Town of Subei County. Conclusion:The SNP method can be used to genotype Yersinia pestis from different plague foci in Gansu Province, which has certain regional characteristics.

In the last half-century, the multi-cooperation of conventional therapies including chemotherapy, radiotherapy and bone marrow hematopoietic stem cell transplantation has saved a lot of children with lymphocyte malignancies, but the outcomes of relapsed and/or refractory diseases remain dismal.Thus, it is in urgent need of novel approaches to improve clinical efficiency.After decades of rapid development, immunotherapy has achieved remarkable results from the treatment of pediatric lymphocyte malignancies, especially chimeric antigen receptors T(CAR-T), bi-specific T cell engager(BiTE), and immune checkpoint blockader(ICB). However, a part of patients is still resistant to immunotherapy.The review will focus on CAR-T, BiTE and ICB to elucidate the pre-clinical studies and clinical trials that have been intensively conducted in pediatric leukemia and lymphoma, as well as the brief introduction of their limitations and probably optimal strategies.

【Objective】 To develop a new approach for the preparation of 0.7~0.8 hematocrit concentrated washed red blood cells(RBCs) for fetal anemia in utero transfusion and apply it in clinical. 【Methods】 The erythrocyte suspension and frozen stored erythrocytes within expiry date in Guangzhou Blood Center from March 2020 to February 2021 were taken to prepare concentrated washed RBCs. According to the derivation formula, corresponding weight of RBC preservation solution was added to obtain 0.7~0.8 hematocrit concentrated washed RBCs. Routine blood test data were statistically analyzed by single-sample t test, and P<0.05 was considered statistically significant. Qualified Rh-negative/ O-type 0.7~0.8 hematocrit concentrated RBCs within expiry date were used in clinical intrauterine blood transfusion. 【Results】 The hematocrit of concentrated washing RBCs prepared by the new approach could reach 0.7~0.8. The RBCs count (8.389 ±0.808)×1 0¹²/ L and hemoglobin content(233.730±15.498)g/L were higher while the erythrocyte count (0.732±0.469)×10⁹ /L and platelets count(26.000±26.276)×10⁹/L were lower than the normal values of adults. The mean erythrocyte volume(fL), hemoglobin content(pg) and concentration(g/L )were 88.123±6.359, 30.004±2.809 and 339.980±11.865, respectively, which were normal values of adults. Fetal anemia was significantly improved and the prognosis was good after intrauterine blood transfusion. 【Conclusion】 The 0.7~0.8 hematocrit concentrated washed RBCs prepared by the new approach is consistent with the special blood requirements during fetal anaemia transfusion, meets the clinical treatment standards, and can be applied in clinical.

Objective:To investigate the efficacy of microsurgical treatment in cavernous sinus tumors.Methods:The clinical data of 87 patients with cavernous sinus tumor treated by microsurgery from January, 2010 to August, 2019 were analysed retrospectively. The surgical approaches and microsurgical skills for common tumors in Cavernous Sinus region were discussed. The follow-up included outpatient and telephone follow-ups, and the follow-up results were evaluated by KPS score.Results:Among the 87 cases, 57 were totally resected (65.5%), 14 were subtotal resected (16.1%) and 16 were major resected (18.4%). Hospitalisation ranged from 14 to 98 days, with an average of 29 days. Postoperative complications occurred in 30 cases with cranial nerve injury, 2 brain stem injury, 4 postoperative bleeding, 5 cerebrospinal fluid leakage, 4 infection, 1 Pituitary damage and 1 death. Prognosis and follow-up analysis showed 68 cases with KPS>60 and 66 with KPS>80 at 1 month after surgery; 74 with KPS>70 and 72 with KPS>80 at 3 months after surgery; 78 with KPS>80 by 12 months after surgery. During the follow-up period of 6-120 months, 3 cases died. Recurrence: 6 of incomplete resection of meningioma, were in 1-6 years after the surgery, 4 of incomplete resection of schwannoma in 1-8 years, 2 of pituitary adenoma respectively in 13 and 16 months after the surgery. There was no recurrence after reoperation. Two cases of chondrosarcoma, 3 of chordoma and 3 of germinoma were treated with radiotherapy, and during the follow-up, there was no progress of the focus. No tumor progression or recurrence was found in other cases during follow-up.Conclusion:Surgery of cavernous sinus tumor is difficult due to frequent postoperative complications. Reasonable preoperative plan, surgical approach and precise microsurgical techniques are the keys in reduction of postoperative complications and in the improvement of prognosis.

Objective:To investigate the preliminary clinical and radiographic outcomes of percutaneous endoscopic lumbar discectomy (PELD) combined with oblique lateral interbody fusion (OLIF) for the degenerative lumbar spondylolisthesis, lumbar spine instability or lumbar spinal stenosis with ruptured disc herniation.Methods:Data of 11 patients with degenerative lumbar spondylolisthesis, lumbar spine instability or lumbar spinal stenosis with ruptured disc herniation who had undergone PELD combined with OLIF between March 2017 to July 2018 in our spine surgery center were retrospectively analyzed. There were 5 males and 6 females with an average age of 61.2±6.8 years old. All the patients were diagnosed with degenerative lumbar diseases including lumbar spondylolisthesis (7 cases), lumbar spinal stenosis (3 cases) and segmental instability (1 case). The patients were treated with PELD combined with OLIF. The visual analogue scale (VAS) scores of low back pain and lower limb pain and the Oswestry disability index (ODI) of lumbar function, spinal canal anteroposterior diameter, intervertebral disc height, vertical diameter of intervertebral foramen, segmental angle and the whole lumbar lordotic angle were collected.Results:All patients received PELD with local anesthesia before OLIF with general anesthesia. The mean operation time was 52.3±13.2 min and the mean blood loss was 10.9±4.7 ml for PELD. The mean operation time was 56.8±18.0 min and the mean blood loss was 65.5±24.6 ml for OLIF. All patients were followed up for an average of 11.2 months. At the latest follow-up, the mean VAS score for back pain was 1.3±0.8, the mean VAS score for leg pain 1.1±0.5, the mean ODI 14.6%±5.3%, thus all of those were improved significantly compared to those of pre-operation ( t=10.37, 16.49, 8.73; P< 0.05). The radiographic results showed the mean pre-operative intervertebral disc height, vertical diameter of intervertebral foramen, spinal canal anteroposterior diameter, segmental angle, and lumbar lordosis angle was 7.1±1.2 mm, 15.3±2.2 mm, 6.2±1.3 mm, 10.2°±3.5°, 16.2°±6.2°, and thus all of those were increased significantly to the latest follow-up 11.5±1.8 mm, 19.2±2.6 mm, 10.4±2.5 mm, 19.3°±7.8°, 27.4°±8.3°, respectively ( t=5.83, 4.21, 6.59, 10.32, 7.65; P< 0.05). One of the patients had weakness of flexor hip strength and one had a transient paresthesia immediately post-operation. All symptoms were relieved within 1 month. Another one case had cage subsidence and encountered serious back pain after 1 month, and alleviated after percutaneous pedicle screw fixation. Conclusion:PELD combined with OLIF can overcome the limitations of OLIF with indirect decompression effects, resulting in successful direct neural decompression without posterior decompressive procedures and providing a satisfactory outcome for the patients with degenerative lumbar diseases with ruptured disc herniation.

Objective:To evaluate the value of intraoperative magnetic resonance imaging (iMRI) combined with neuronavigation for the resection of insular gliomas.Methods:From August 2014 to October 2017 in the First Hospital Affiliated to Sun Yat-sen University,clinical data of 41 patients with insular glioma,who underwent the surgery assisted with 3.0T iMRI and neuronavigation,were analyzed retrospectively,and the resection extent,complications and prognosis were evaluated.Results:Subtotal tumor resection was achieved in 21 patients and partial resection was done in 20 after iMRI scanning.After further resection,total tumor resection was achieved in 16 patients,subtotal resection in 18 and partial resection in 7.There was a statistical significant difference in tumor resection between pre-iMRI and post-iMRI according to the Fisher test (P＜0.05).In the follow-up from 3 months to 3 years,the symptoms of the 41 patients had improved.Conclusion:iMRI corrected the shift of brain.Neuronavigation can accurately and timely assess the degree of resecting tumor.The combination of neuronavigation with surgery can maximally and safely resect insular glioma.

Objective To evaluate the relationship between the degree of brain injury during the perioperative period of liver transplantation and postoperative cognitive dysfunction (POCD).Methods Thirtythree patients,undergoing elective liver transplantation,were enrolled in this study.Before induction of anesthesia (T0),at 5 min before blocking the portal vein (T1),5 min after opening the portal vein (T2),5 min after opening the hepatic artery (T3),and at 24 h after surgery (T4),blood samples were collected from the central vein for determination of the serum concentrations of S1O0β protein and neuron-specific enolase (NSE) by enzyme-linked immunosorbent assay.Patients were divided into POCD group and control group (group C) according to whether POCD happened within 7 days after surgery.Results Compared with the baseline value at T0,the serum concentrations of S100β protein were significantly increased at T2 and T3,and the serum concentrations of NSE was increased at T3 (P＜0.05).There was no significant difference in serum concentrations of S100β and NSE at each time point between group POCD and group C (P＞0.05).Conclusion The degree of brain injury during the perioperative period of liver transplantation is not the dominant factor for the development of POCD in the patients.