Endothelial NLRP3 inflammasome regulation in atherosclerosis.

AIM: The activation of Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in endothelial cells (ECs) contributes to vascular inflammation in atherosclerosis. Considering the high glycolytic rate of ECs, we delineated whether and how glycolysis determines endothelial NLRP3 inflammasome activation in atherosclerosis. METHODS AND RESULTS: Our results demonstrated a significant upregulation of 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3 (PFKFB3), a key regulator of glycolysis, in human and mouse atherosclerotic endothelium, which positively correlated with NLRP3 levels. Atherosclerotic stimuli upregulated endothelial PFKFB3 expression via sterol regulatory element binding protein 2 (SREBP2) transactivation. EC-selective haplodeficiency of Pfkfb3 in Apoe-/- mice resulted in reduced endothelial NLRP3 inflammasome activation and attenuation of atherogenesis. Mechanistic investigations revealed that PFKFB3-driven glycolysis increased the NADH content and induced oligomerization of C-terminal binding protein 1 (CtBP1), an NADH-sensitive transcriptional co-repressor. The monomer form, but not the oligomer form, of CtBP1 was found to associate with the transcriptional repressor Forkhead box P1 (FOXP1) and acted as a transrepressor of inflammasome components, including NLRP3, caspase-1, and interleukin-1ß (IL-1ß). Interfering with NADH-induced CtBP1 oligomerization restored its binding to FOXP1 and inhibited the glycolysis-dependent upregulation of NLRP3, Caspase-1, and IL-1ß. Additionally, EC-specific overexpression of NADH-insensitive CtBP1 alleviates atherosclerosis. CONCLUSIONS: Our findings highlight the existence of a glycolysis-dependent NADH/CtBP/FOXP1-transrepression pathway that regulates endothelial NLRP3 inflammasome activation in atherogenesis. This pathway represents a potential target for selective PFKFB3 inhibitors or strategies aimed at disrupting CtBP1 oligomerization to modulate atherosclerosis.

Glycolysis Promotes Angiotensin II-Induced Aortic Remodeling Through Regulating Endothelial-to-Mesenchymal Transition via the Corepressor C-Terminal Binding Protein 1.

BACKGROUND: Endothelial dysfunction plays a crucial role in aortic remodeling. Aerobic glycolysis and endothelial-to-mesenchymal transition (EndoMT) have, respectively, been suggested to contribute to endothelial dysfunction in many cardiovascular diseases. Here, we tested the hypothesis that glycolytic reprogramming is critical for EndoMT induction in aortic remodeling through an epigenetic mechanism mediated by a transcriptional corepressor CtBP1 (C-terminal binding protein 1), a sensor of glycolysis-derived NADH. METHODS: EndoMT program, aortic remodeling, and endothelial expression of the glycolytic activator PFKFB3 (6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3) were evaluated in Ang (angiotensin) II-infused mice. Mice with endothelial-specific Pfkfb3 deficiency or CtBP1 inactivation, immunoprecipitation, chromatin immunoprecipitation, and luciferase reporter assay were employed to elucidate whether and how PFKFB3/CtBP1 epigenetically controls EndoMT. RESULTS: The EndoMT program and increased endothelial PFKFB3 expression were induced in remodeled thoracic aortas. In TGF-ß (transforming growth factor-ß)-treated human endothelial cells, activated SMAD2/3 (SMAD Family Member 2/3) transcriptionally upregulated PFKFB3 expression. In turn, the TGF-ß/SMAD signaling and EndoMT were compromised by silencing or inhibition of PFKFB3. Mechanistic studies revealed that PFKFB3-mediated glycolysis increased NADH content and activated the NADH-sensitive CtBP1. Through interaction with the transcription repressor E2F4 (E2F Transcription Factor 4), CtBP1 enhanced E2F4-mediated transcriptional repression of SMURF2 (SMAD ubiquitin regulatory factor 2), a negative regulator of TGF-ß/SMAD2 signaling. Additionally, EC-specific Pfkfb3 deficiency or CtBP1 inactivation in mice led to attenuated Ang II-induced aortic remodeling. CONCLUSIONS: Our results demonstrate a glycolysis-mediated positive feedback loop of the TGF-ß signaling to induce EndoMT and indicate that therapeutically targeting endothelial PFKFB3 or CtBP1 activity could provide a basis for treating EndoMT-linked aortic remodeling.

High-performance sorbents from ionic liquid activated walnut shell carbon: an investigation of adsorption and regeneration.

In this paper, walnut shells were selected to make activated charcoal using ionic activators. Based on the physical/chemical activation process and the properties of activated carbon products, the Fourier Transform Infrared reflection and Brunauer-Emmett-Teller analysis methods were adopted to comparatively analyse activation principles and pore-structure parameters. Also ciprofloxacin adsorption was compared among various activated carbon. Then, an absence of microporous structure in both walnut shells and their carbonized derivatives was found. Moreover, the specific surface area of activated carbon, prepared via KOH wet activation within physical/chemical procedures, attains a noteworthy 1787.06 m2 g-1, underlining its commendable adsorption performance. The specific surface areas of five distinct activated carbons, processed via ionic activation, extend from 1302.01 to 2214.06 m2 g-1. Concurrently, the micropore volumes span from 0.47 to 0.93 cm3 g-1. Obviously, the adsorption proficiency of ion-activated carbon markedly exceeds that of carbons activated physically or chemically. Of all materials investigated in this paper, ion-activated carbon D consistently exhibits superior performance, maintaining a ciprofloxacin removal rate nearing 100% at 40 °C. Remarkably, the maximum regeneration frequency of ion-activated carbons can reach up to 10 cycles. In conclusion, these five ion-activated carbons, demonstrating superior pore-structure parameters and adsorptive capacities, outperform those prepared through physical/chemical methods. They emerge as promising contenders for new, high-performing adsorbents.

Glycolysis and de novo fatty acid synthesis cooperatively regulate pathological vascular smooth muscle cell phenotypic switching and neointimal hyperplasia.

Switching of vascular smooth muscle cells (VSMCs) from a contractile phenotype to a dedifferentiated (proliferative) phenotype contributes to neointima formation, which has been demonstrated to possess a tumor-like nature. Dysregulated glucose and lipid metabolism is recognized as a hallmark of tumors but has not thoroughly been elucidated in neointima formation. Here, we investigated the cooperative role of glycolysis and fatty acid synthesis in vascular injury-induced VSMC dedifferentiation and neointima formation. We found that the expression of hypoxia-inducible factor-1α (HIF-1α) and its target 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3), a critical glycolytic enzyme, were induced in the neointimal VSMCs of human stenotic carotid arteries and wire-injured mouse carotid arteries. HIF-1α overexpression led to elevated glycolysis and resulted in a decreased contractile phenotype while promoting VSMC proliferation and activation of the mechanistic target of rapamycin complex 1 (mTORC1). Conversely, silencing Pfkfb3 had the opposite effects. Mechanistic studies demonstrated that glycolysis generates acetyl coenzyme A to fuel de novo fatty acid synthesis and mTORC1 activation. Whole-transcriptome sequencing analysis confirmed the increased expression of PFKFB3 and fatty acid synthetase (FASN) in dedifferentiated VSMCs. More importantly, FASN upregulation was observed in neointimal VSMCs of human stenotic carotid arteries. Finally, interfering with PFKFB3 or FASN suppressed vascular injury-induced mTORC1 activation, VSMC dedifferentiation, and neointima formation. Together, this study demonstrated that PFKFB3-mediated glycolytic reprogramming and FASN-mediated lipid metabolic reprogramming are distinctive features of VSMC phenotypic switching and could be potential therapeutic targets for treating vascular diseases with neointima formation. © 2023 The Pathological Society of Great Britain and Ireland.

Preliminary analysis of qualitative changes in suspended red blood cells under different low-pressure and hypoxic conditions / 中国输血杂志

【Objective】 To evaluate the quality of suspended red blood cells (SRBC) under low-pressure and hypoxic conditions, in order to lay a theoretical foundation for airline delivery, air drop and storage of SRBC on plateau. 【Methods】 The low-pressure and hypoxic conditions (0.026 MPa and 0.047 MPa) were simulated by a pressure control device. SRBC were divided into 3 groups (5 bags/group, 1.5 U/bag). Each group was stored in 0.026 MPa environment at 2℃-6℃ for 24 hours (named 0.026 MPa), in 0.047MPa environment at 2℃-6℃ for 7 days (named 0.047 MPa), and in a blood storage refrigerator at 4℃ (named the control), respectively. The storage cell characteristics were examined on day 2, 9, 14, 28 and 35. 【Results】 We found that HCT, MCV, K+, Na+, FHb, hemolytic ratio, 2, 3-DPG and rheological properties in group 0.026 MPa and 0.047 MPa were not significant different compared with that in control (P>0.05). The consumptions of Glu in group 0.026 MPa and 0.047 MPa were significantly higher (P<0.05), and a transient increase in LAC concentration of group 0.026 MPa and 0.047MPa were observed, compared to the control. 【Conclusion】 The conditions of low-pressure and hypoxia have no significant effect on the quality of suspended red blood cells.

Prognostic Value of Pre-treatment Albumin/Fibrinogen Ratio in Patients with Diffuse Large B-cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the value of pre-treatment albumin/fibrinogen ratio (AFR) on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL).@*METHODS@#The data of DLBCL patients in the Affiliated Hospital of North Sichuan Medical College from April 2014 to March 2021 were retrieved, and 111 newly diagnosed patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with complete data were included in the study. The clinical, laboratory examination and follow-up data of the patients were collected, and the receiver operating characteristic curve (ROC) was drawn according to patients' AFR before treatment and the survival status at the end of the follow-up, which could be used to preliminarily evaluate the predictive value of AFR for disease progression and patients' survival outcome. Furthermore, the correlation of AFR with the clinical and laboratory characteristics, progression-free survival (PFS) and overall survival (OS) was analyzed, and finally, univariate and multivariate Cox proportional hazard regression models were used to analyze factors affecting PFS and OS of DLBCL patients.@*RESULTS@#The ROC curve indicated that AFR level had a moderate predictive value for PFS and OS in DLBCL patients, with the area under the curve (AUC) of 0.616 (P =0.039) and 0.666 (P =0.004), respectively, and the optimal cut-off values were both 9.06 for PFS and OS. Compared with high-AFR (≥9.06) group, the low-AFR (<9.06) group had a higher proportion of patients with Lugano III-IV stage ( P <0.001), elevated lactate dehydrogenase (P =0.007) and B symptoms (P =0.038). The interim analysis of response showed that the overall response rate (ORR) in the high-AFR group was 89.7%, which was significantly higher than 62.8% in the low-AFR group (P =0.001). With a median follow-up of 18.5 (3-77) months, the median PFS of the high-AFR group was not reached, which was significantly superior to 17 months of the low-AFR group (P =0.009). Similarly, the median OS of high-AFR group was not reached, either, which was significantly superior to 48 months of the low-AFR group (P < 0.001). In multivariate Cox regression analysis, AFR <9.06 was an independent risk factor both for PFS and OS (HR PFS=2.047, P =0.039; HR OS=4.854, P =0.001).@*CONCLUSION@#Pre-treatment AFR has a significant value for the prognosis evaluation in newly diagnosed DLBCL patients.

Gene-dosage effect of Pfkfb3 on monocyte/macrophage biology in atherosclerosis.

BACKGROUND AND PURPOSE: Macrophage-rich atherosclerotic arteries are highly active in glycolysis. PFKFB3, a key glycolytic enzyme, has emerged as a potential therapeutic target in atherosclerosis. Small-molecule inhibitors of PFKFB3, such as 3PO and PFK158, have demonstrated efficacy in hampering atherogenesis in preclinical models. However, genetic studies elucidating the role of Pfkfb3 in atherogenesis need to be conducted to validate pharmacological findings and to unveil potential pharmacological side effects. EXPERIMENTAL APPROACH: Apoe-/- mice with global heterozygous or myeloid cell-specific Pfkfb3 deficiency were fed a Western diet (WD), after which atherosclerosis development was determined. Monocyte subsets in atherosclerotic mice and patients were examined by flow cytometry. Monocyte infiltration was assayed by a Ly6Chi monocyte-specific latex labelling procedure. In situ efferocytosis was assessed on mouse aortic root sections. Additionally, metabolic status, macrophage motility, efferocytosis, and involved mechanisms were analysed in peritoneal macrophages. KEY RESULTS: Global heterozygous or myeloid cell-specific Pfkfb3 deficiency reduced atherogenesis in Apoe-/- mice. Mechanistic studies showed that PFKFB3 controlled the proliferation and infiltration of proinflammatory monocytes. Moreover, PFKFB3 expression was associated with inflammatory monocyte expansion in patients with atherosclerotic coronary artery disease. Surprisingly, homozygous loss of Pfkfb3 impaired macrophage efferocytosis and exacerbated atherosclerosis in Apoe-/- mice. Mechanistically, PFKFB3-driven glycolysis was shown to be essential for actin polymerization, thus aiding the efferocytotic function of macrophages. CONCLUSION AND IMPLICATIONS: Collectively, these findings suggest the existence of a double-edged sword effect of myeloid PFKFB3 on the pathogenesis of atherosclerosis and highlight the need for caution in developing anti-atherosclerotic strategies that target PFKFB3.

Glycolysis inhibition ameliorates brain injury after ischemic stroke by promoting the function of myeloid-derived suppressor cells.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells which are immunosuppressive and glycolytically inactive in inflammatory diseases. However, it is unknown whether MDSCs contribute to ischemic stroke and how glycolysis regulates MDSC function in such a context. Here, we showed that MDSCs arise in the blood of patients at early phase of stroke. Similar results were observed in temporary middle cerebral artery occlusion-induced cerebral ischemic mice. Pharmaceutical exhaustion of MDSCs aggravated, while adoptive transfer of MDSCs rescued the ischemic brain injury. However, the differentiation of MDSCs into immunopotent myeloid cells which coincides with increased glycolysis was observed in the context of ischemic stroke. Mechanistically, the glycolytic product lactate autonomously induces MDSC differentiation through activation of mTORC1, and paracrinely activates Th1 and Th17 cells. Moreover, gene knockout or inhibition of the glycolytic enzyme PFKFB3 increased endogenous MDSCs by blocking their differentiation, and improved ischemic brain injury. Collectively, these results revealed that glycolytic switch decreases the immunosuppressive and neuroprotective role of MDSCs in ischemic stroke and pharmacological targeting MDSCs via glycolysis inhibition constitutes a promising therapeutic strategy for ischemic stroke.

Progress on standardized nutrition therapy for head and neck cancer during the peri-radiotherapeutic period / 中华放射肿瘤学杂志

Malnutrition is a common complication of cancer patients, and solving nutrition problems is still one of the challenging tasks in clinical practice. The incidence of malnutrition in head and neck cancer patients during the peri-radiotherapeutic period is high, which is not only related to disease-mediated metabolic disorders, complications and psychological factors, but also associated with the toxic and side effects induced by radiotherapy. Malnutrition will reduce the tolerance, accuracy, and therapeutic effects of radiotherapy, which in turn lowers the quality of life and even adversely affects the prognosis of disease. Medical nutrition therapy can improve the nutritional status of the body, ensure smooth progress of radiotherapy, and improve the efficacy of comprehensive cancer treatment. It is necessary and urgent to deliver standardized nutrition therapy and management of head and neck cancer patients during the peri-radiotherapeutic period. Nutritional risk screening, nutritional assessment, and acute radiation injury assessment are required to develop an individualized nutrition treatment plan and make dynamic adjustment. In this article, relevant literature of nutrition therapy for head and neck radiotherapy at home and abroad was summarized, and the standardized nutrition therapy for head and neck cancer patients during the peri-radiotherapeutic period was reviewed.

Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development / 中华儿科杂志

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

Sleep initiation patterns and their influence on sleep quality in infants and young children / 中国当代儿科杂志

OBJECTIVES@#To investigate the current status of sleep initiation patterns, influencing factors for sleep initiation patterns, and the influence of sleep initiation patterns on sleep quality in infants and young children.@*METHODS@#A total of 521 infants and young children, aged 0-35 months, who underwent physical examination at the outpatient service of the Department of Growth and Development in Shenzhen Bao'an Women's and Children's Hospital Affiliated to Jinan University were enrolled as subjects. A self-designed questionnaire and Brief Infant Sleep Questionnaire were used to collect the information on family background, parenting behaviors, and sleep quality in the past one week. A multivariate logistic regression analysis was used to evaluate the influencing factors for sleep initiation patterns. A multiple linear regression analysis was used to evaluate the influence of sleep initiation patterns on the number of nighttime awakenings.@*RESULTS@#Among the 521 infants and young children, 258 (49.5%) were breastfed/bottle fed to initiate sleep, 62 (11.9%) were rocked/held to initiate sleep, 39 (7.5%) slept independently, and 162 (31.1%) initiated sleep accompanied by parents. The multivariate logistic regression analysis showed that the children with breastfeeding and a younger age were more likely to be breastfed/bottle fed to initiate sleep (P<0.05) and that the children with a younger age were also more likely to be rocked/held to initiate sleep (P<0.05). The multiple linear regression analysis showed that sleep initiation with breastfeeding/bottle feeding significantly increased the number of nighttime awakenings (P<0.05).@*CONCLUSIONS@#Most infants and young children initiate sleep by being breastfed/bottle fed, rocked/held, or accompanied. The sleep initiation pattern is associated with the age of children and whether they are still breastfeeding. Sleep initiation with breastfeeding/bottle feeding can increase the number of nighttime awakenings. io.

Training the skills of obstetric forceps delivery for resident doctors by using simulation teaching method / 中华医学教育探索杂志

In this study, 15 second-year resident doctors who had standardized training of OBGYN were taken as research subjects to discuss the effect of training resident doctors with obstetrics forceps by using simulation teaching method. The simulation teaching process includes theoretical study, theoretical examination, simulation teaching of forceps skills and Assessment of forceps skills. In theoretical study section: before learning to use forceps, the students acquired the theoretical knowledge by flipped teaching micro-video mode. In theoretical examination section: the mastery of basic clinical knowledge of using forceps was evaluated through online assessment. In simulation teaching of forceps skills: students who scored 8/10 points were admitted to enter the simulation teaching process, and they had practical training of scenario simulation skills in Clinical Skills Center. In assessment of forceps skills: the mastery of forceps skills was evaluated by standardized forceps delivery procedure items. The results showed that the students in the simulation teaching group had excellent teaching assessment results, and the resident doctors had more confidence in operating forceps independently, and the teaching effect was ideal, which could further promote the simulation teaching of obstetric clinical skills.

Predictive Value of Pre-treatment Serum Uric Acid Level for Prognosis in Newly Diagnosed Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To evaluate the predictive value of pre-treatment serum uric acid (sUA) level for the prognosis of newly diagnosed multiple myeloma (NDMM) patients.@*METHODS@#The NDMM patients admitted to our center from January 2014 to December 2018 were analyzed retrospectively, and 94 patients among them who were initially treated with bortezomib-based chemotherapy for at least 4 cycles were included in this study. Clinical characteristics, laboratory data and follow-up information were collected, and the predictive value of sUA on the overall survival (OS) of NDMM was evaluated by using receiver operating characteristic (ROC) curve based on the patient's pre-treatment sUA level and the survival status at the end of follow-up, and the correlation of the sUA level with patient's clinical, laboratory characteristics and overall survival (OS) was further analyzed. The univariate and multivariate Cox proportional-hazards model were used to identify the potential factors affecting OS.@*RESULTS@#ROC analysis showed that the area under the curve for predicting OS in NDMM patients with sUA level was 0.702 (P<0.001), and the optimal cut-off value was 455.4 μmol/L. Compared to patients with low sUA (<455.4 μmol/L), patients with higher sUA (≥455.4 μmol/L) were more likely to have international staging system (ISS) stage III disease, beta2-microglobulin (β@*CONCLUSION@#Pre-treatment sUA level is a potential biomarker for the prognosis evaluation in NDMM patients, which deserves a further exploration and verification.

Second-generation Sequencing Analysis of Ph / 中国实验血液学杂志

OBJECTIVE@#To screen the core genes of Philadelphia chromosome positive/Ph like T-cell acute lymphoblastic leukemia (Ph@*METHODS@#The WES/RNA-seq examination results of Ph@*RESULTS@#For Ph@*CONCLUSION@#There are obviously abnormal DNA damage repair pathways in children with Ph

Short-Term Efficacy and Safety Profile of Generic Bortezomib in the Treatment of Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the short-term efficacy and safety of generic bortezomib in the treatment of Chinese patients with multiple myeloma (MM).@*METHODS@#Clinical data of 62 MM patients (median age of 62 years) who had accepted at least 2 cycles of chemotherapy based on generic bortezomib in our center from December 2017 to July 2019 were retrospectively analyzed, including 47 newly diagnosed patients and 15 with disease recurrence or progression.@*RESULTS@#Anemia, renal dysfunction, hypoproteinemia and high level of β @*CONCLUSION@#The disease severity can be rapidly alleviated after generic bortezomib-based chemotherapy, and a favorable short-term efficacy and survival have been observed with a generally acceptable toxicity profile. However, the long-term outcomes will be examined through further follow-up.

Effect and Mechanism of Traditional Chinese Medicine on Prevention and Treatment of Pathological Scar / 中国实验方剂学杂志

Pathological scar is a kind of skin fibrotic disease caused by abnormal wound healing, including hypertrophic scar and keloid. Pathological scar may lead to aesthetic flaws, limb dysfunction and local discomfort in patients. Due to the complexity of the wound healing process, the formation of scar is affected by many factors. In addition to traditional surgical, laser, cryostatic and hormone injection methods for the treatment of pathological scar, there are new therapies, such as mesenchymal stem cell therapy, fat transplantation, interferon, and botulinum toxin. They are widely used in clinical practice, but with such problems as high prices and many side effect. Traditional Chinese medicine (TCM) has a long history in treating pathological scar. In recent years, in vivo and in vitro studies have shown that TCM has effect IN reducing inflammation, inhibiting fibroblast proliferation, regulating fibroblast activation and migration, inducing fibroblast apoptosis and autophagy, promoting the degradation of extracellular matrix (ECM) and reducing angiogenesis in general. Besides, TCM has also a certain regulatory role in the signaling pathways, such as transforming growth factor-β1 (TGF-β1)/Smads, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) and sonic hedgehog (Shh). There are still some contradictions in relevant studies, and specific mechanisms remain to be further improved. This paper summarizes the study content, findings and relevant mechanisms of different TCM based on in vivo and in vitro experiments, analyzes the advantages and disadvantages of TCM in the prevention and treatment of pathological scar, and its prospects in clinical application, so as to provide basis and ideas for future scar studies.

Effect of High Dose Vitamin C on Proliferation and Apoptosis of Acute Myeloid Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of high dose vitamin C on proliferation and apoptosis of acute myeloid leukemia (AML) cell lines including HL-60, U937 and primary CD34 leukemia cells in AML.@*METHODS@#CD34 cells were sorted by using immunomagnetic cell sorting system, then the primary CD34 leukemia cells, including HL-60 and U937 cell lines were cultured in vitro. Cells in each group were treated with different concentrations of vitamin C, the survival rate of cells was determined by MTT assay, the apoptosis rate of cells was evaluated by Annexin V/PI double staining, the expression of apoptotic proteins-including cleaved caspase 3, cleaved caspase-9 and cleaved PARP were detected by Western blot.@*RESULTS@#The proliferation of HL-60 and U937 cells could be inhibited by high dose vitamin C, which showed a concentration-dependent manner (r=-0.9664; r=-0.9796). HL-60 and U937 cells were treated with different concentrations of vitamin C (8 and 20 mmol/L) for 24 hours, respectively, it was found that with the increasing of vitamin C concentration, cell apoptosis rate was significantly increased (r=0.9905; r=0.9971), and the expression of apoptosis related proteins including cleaved caspase 3, cleaved caspase-9 and cleaved PARP was aslo significantly increased with the increasing of concentration. In addition, it was found that with or without the mutation of TET2, high dose vitamin C could inhibit the proliferation (r=-0.9719; r=-0.9699) and promote the apoptosis (r=0.9998; r=0.9901) of primary CD34 leukemia cells in AML, which showed a dose-dependent manner, but it showed no effect on the proliferation (r=-0.2032) and apoptosis (r=0.1912) of normal CD34 cells.@*CONCLUSION@#High dose vitamin C can inhibit the proliferation and promote the apoptosis of acute myeloid leukemia cells, and selectively kill primary CD34 leukemia cells in AML.

Survey of related factors of maternal venous thromboembolism in nine hospitals of China / 中华妇产科杂志

Objective:To investigate and analyze disease status and risk factors of venous thromboembolism (VTE) during pregnancy and puerperium in our country.Methods:Clinical datas were collected from 575 patients diagnosed with VTE during pregnancy and puerperium and hospitalized in nine medical institutions in our country from January 1, 2015 to November 30, 2019, and retrospectively analyzed it′s disease status and risk factors.Results:(1) The proportion of VTE in pregnancy and puerperium was 50.6% (291/575) and 49.4% (284/575), respectively. Four patients died, the mortality rate was 0.7% (4/575). The cause of death was pulmonary embolism. (2) The location of VTE during pregnancy and puerperium was mainly in the lower limb vascular (76.2%, 438/575), followed by pulmonary vessels (7.1%, 41/575). (3) In the risk factors of VTE, cesarean section accounted for 32.3% (186/575), maternal advance age accounted for 27.7% (159/575), braking or hospitalization during pregnancy accounted for 13.6% (78/575), other risk factors accounted for more than 5% were previous VTE, obesity, preterm birth, assistant reproductive technology conception and so on, pre-eclampsia and multiple pregnancy accounted for 4.9% (28/575) respectively. In addition, some patients with VTE did not have any of the above risk factors, and the incidence rate was as high as 23.1% (133/575).Conclusions:The occurrence of VTE during pregnancy and puerperium is related to multiple risk factors, and could lead to matemal death, It is very necessary to screen VTE risk factors for all pregnant women, to make corresponding prevention and control measures.

Multileaf collimator shielding technique to reduce cardiac dose in hybrid intensity modulated radiotherapy after breast conserving surgery for left-sided breast cancer / 中华放射医学与防护杂志

Objective To reduce the risk of radiation-induced cardiac injury in patients with left breast cancer after breast-conserving surgery by multileaf collimator (MLC) shielding technique.Methods A total of 18 patients with left breast cancer after breast conserving surgery were selected to obtain 3DCT and 4DCT images at free breathing state.The target area was identified on the 3DCT image by registration with 4DCT images and to develop a hybrid intensity-modulated treatment plan (H_IMRT) and a heart sparing hybrid intensity-modulated treatment plan (HSH_IMRT) to introduce MLC shielding technology to reduce the cardiac exposure dose,and to perform dosimetry verification of the treatment plan by using the Compass verification system.The prescription dose was 50 Gy in 25 fractions.The dosimetry parameters of the target area and the organs at risk were compared between the two treatment plans and the dose verification result.Results The result of the treatment plan showed that compared with H_IMRT,the dose uniformity of the target area of HSH_IMRT was better,and the difference of conformability was not statistically significant (P＞0.05).The mean dose of the whole heart decreased by 23.67％ (t =13.693,P＜0.05) compared with the former.Dmax and D of other substructures of the heart were lower than the former.The result of dose verification showed that there was no statistically significant difference in uniformity and conformity between the two planned target doses (P＞ 0.05).The mean dose of the whole heart of HSH_IMRT was 24.88％ (t =13.782,P＜0.05) lower than that of H_IMRT,and except for the left ventricle and right ventricle,the Dmax of other heart substructures and D of all heart substructures decreased.Both the planned and the dose verification result showed that the V20 and the D of the affected lung were lower in HSH_IMRT.Conclusions Reasonable introduction of MLC shielding technology in H_IMRT can reduce the exposure dose of cardiac and further reduce the risk of radiation damage in heart.

A meta-analysis of comparing hypofractionated radiotherapy versus conventionally fractionated radiotherapy in post-mastectomy breast cancer / 中华放射肿瘤学杂志

Objective To compare the efficacy between hypofractionated radiotherapy versus conventionally fractionated radiotherapy in post-mastectomy breast cancer by a meta-analysis.Methods The controlled clinical trials of comparing hypofractionated radiotherapy versus conventionally fractionated radiotherapy in post-mastectomy breast cancer were searched from PubMed,EMbase,Cochrane Library,Wanfang database,VIP,CNKI,and CBM databases.The obtained data were analyzed using RevMan 5.3 and Stata 14.0 software.The differences between two groups were estimated by calculating the odds ratio (OR) with 95％ confidence interval (CI).Results A total of 19 controlled clinical trials involving 2652 post-mastectomy breast cancer patients were selected in this meta-analysis according to the inclusion and exclusion criteria.The meta-analysis results demonstrated that no statistical significance was observed in the tumor-free survival (OR =1.10,95 ％ CI:0.78-1.56,P =0.59),overall survival (OR =1.18,95 ％ CI:0.92-1.53,P =0.19),locoregional recurrence (OR=1.01,95％CI:0.68-1.51,P=0.96),distant metastasis (OR=1.14,95％CI:0.82-1.59,P=0.43),skin toxicity (OR=1.01,95％CI=0.80-2.16,P=0.96),cardiac toxicity (OR=1.17,95％CI:0.71-1.93,P=0.53) and pulmonary toxicity (OR=0.78,95％CI:0.44-1.37,P=0.38) between two groups.Conclusions Hypofractionated radiotherapy and conventionally fractionated radiotherapy post-mastectomy yield similar clinical efficacy,both of which are safe and efficacious radiotherapy patterns.However,the findings remain to be validated by large-scale randomized clinical trials with long-term follow-up of the advanced stage complications.