Effect of acacetin on inhibition of apoptosis in Helicobacter pyloriinfected gastric epithelial cell line

BACKGROUND Helicobacter pylori(H.pylori)infection can cause extensive apoptosis of gastric epithelial cells,serving as a critical catalyst in the progression from chronic gastritis,gastrointestinal metaplasia,and atypical gastric hyperplasia to gastric carcinoma.Prompt eradication of H.pylori is paramount for ameliorating the pathophysiological conditions associated with chronic inflammation of the gastric mucosa and the primary prevention of gastric cancer.Acacetin,which has multifaceted pharmacological activities such as anti-cancer,anti-inflammatory,and antioxidative properties,has been extensively investigated across various domains.Nevertheless,the impact and underlying mechanisms of action of acacetin on H.pylori-infected gastric mucosal epithelial cells remain unclear.AIM To explore the defensive effects of acacetin on apoptosis in H.pylori-infected GES-1 cells and to investigate the underlying mechanisms.METHODS GES-1 cells were treated with H.pylori and acacetin in vitro.Cell viability was assessed using the CCK-8 assay,cell mortality rate via lactate dehydrogenase assay,alterations in cell migration and healing capacities through the wound healing assay,rates of apoptosis via flow cytometry and TUNEL staining,and expression levels of apoptosis-associated proteins through western blot analysis.RESULTS H.pylori infection led to decreased GES-1 cell viability,increased cell mortality,suppressed cell migration,increased rate of apoptosis,increased expressions of Bax and cle-caspase3,and decreased Bcl-2 expression.Conversely,acacetin treatment enhanced cell viability,mitigated apoptosis induced by H.pylori infection,and modulated the expression of apoptosis-regulatory proteins by upregulating Bcl-2 and downregulating Bax and cleaved caspase-3.CONCLUSION Acacetin significantly improved GES-1 cell viability and inhibited apoptosis in H.pylori-infected GES-1 cells,thereby exerting a protective effect on gastric mucosal epithelial cells.

Chemotherapy and resection for gastric cancer with synchronous liver metastases

AIM: To investigate the effect of surgery and chemotherapy for gastric cancer with multiple synchronous liver metastases (GCLM). METHODS: A total of 114 patients were entered in this study, and 20 patients with multiple synchronous liver metastases were eligible. After screening with preoperative chemotherapy, 20 patients underwent curative gastrectomy and hepatectomy for GCLM; 14 underwent major hepatectomy, and the remaining six underwent minor hepatectomy. There were 94 patients without aggressive treatment, and they were in the non-operative group. Two regimens of perioperative chemotherapy were used: S-1 and cisplatin (SP) in 12 patients, and docetaxel, cisplatin and 5-fluorouracil (DCF) in eight patients. These GCLM patients were given preoperative chemotherapy consisting of two courses chemotherapy of SP or DCF regimens. After chemotherapy, gastrectomy and hepatectomy were preformed. Evaluation of patient survival was by follow-up contact using telephone and outpatient records. All patients were assessed every 3 mo during the first year and every 6 mo thereafter. RESULTS: Twenty patients underwent gastrectomy and hepatectomy and completed their perioperative chemotherapy and hepatic arterial infusion before and after surgery. Ninety-four patients had no aggressive treatment of liver metastases because of technical difficulties with resection and severe cardiopulmonary dysfunction. In the surgery group, there was no toxicity greater than grade 3 during the course of chemotherapy. The response rate was 100% according to the Response Evaluation Criteria in Solid Tumors Criteria. For all 114 patients, the overall survival rate was 8.0%, 4.0%, 4.0% and 4.0% at 1, 2, 3 and 4 years, respectively, with a median survival time (MST) of 8.5 mo (range: 0.5-48 mo). For the 20 patients in the surgery group, MST was 22.3 mo (range: 4-48 mo). In the 94 patients without aggressive treatment, MST was 5.5 mo (range: 0.5-21 mo). There was a significant difference between the surgery and unresectable patients (P = 0.000). Three patients in surgery group were still alive at the end of the cut-off date. CONCLUSION: Perioperative weekly DCF and SP achieved a good response, and combined with surgery, they could improve prognosis of GCLM.

M1-type microglia can induce astrocytes to deposit chondroitin sulfate proteoglycan after spinal cord injury

After spinal cord injury(SCI),astrocytes gradually migrate to and surround the lesion,depositing chondroitin sulfate proteoglycan-rich extracellular matrix and forming astrocytic scar,which limits the spread of inflammation but hinders axon regeneration.Meanwhile,microglia gradually accumulate at the lesion border to form microglial scar and can polarize to generate a pro-inflammatory M1 phenotype or an anti-inflammatory M2 phenotype.However,the effect of microglia polarization on astrocytes is unclear.Here,we found that both microglia(CX3 CR1^(+))and astrocytes(GFAP^(+))gathered at the lesion border at 14 days post-injury(dpi).The microglia accumulated along the inner border of and in direct contact with the astrocytes.M1-type microglia(i NOS^(+)CX3 CR1^(+))were primarily observed at 3 and 7 dpi,while M2-type microglia(Arg1^(+)CX3 CR1^(+))were present at larger numbers at 7 and 14 dpi.Transforming growth factor-β1(TGFβ1)was highly expressed in M1 microglia in vitro,consistent with strong expression of TGFβ1 by microglia in vivo at 3 and 7 dpi,when they primarily exhibited an M1 phenotype.Furthermore,conditioned media from M1-type microglia induced astrocytes to secrete chondroitin sulfate proteoglycan in vitro.This effect was eliminated by knocking down sex-determining region Y-box 9(SOX9)in astrocytes and could not be reversed by treatment with TGFβ1.Taken together,our results suggest that microglia undergo M1 polarization and express high levels of TGFβ1 at 3 and 7 dpi,and that M1-type microglia induce astrocytes to deposit chondroitin sulfate proteoglycan via the TGFβ1/SOX9 pathway.The study was approved by the Institutional Animal Care and Use Committee of Anhui Medical University,China(approval No.LLSC20160052)on March 1,2016.

Feasibility of differentiating T3 from T4a gastric cancer in different Lauren classification by determining serosa invasion：Diagnostic performance of high enhanced serosa sign

Objective： To study the value of high enhanced serosa sign on contrast-enhanced computed tomography（CT）in differentiating T3 from T4a gastric cancer in different Lauren classification.Methods： This study included 276 consecutive patients with surgically confirmed p T3 or p T4a gastric cancers.The pre-operative CT images were reviewed by two radiologists blinded. The demonstration of the high enhanced serosa on CT between T3 and T4a was compared with chi-square test. The diagnostic performance of this sign on CT in the differentiation of T4a from T3 in different Lauren classification was calculated.Results： The accuracy, sensitivity, specificity, positive predictive value（PPV） and negative predictive value（NPV） for the judgement of serosa invasion using the high enhanced serosa sign on CT was 74.6%, 63.7%, 83.6%,76.0% and 73.8% by one radiologist and 76.4%, 66.1%, 84.9%, 78.1% and 75.4% by the other radiologist.Compared to the intestinal-type, the sensitivity of the judgement of serosa invasion using the high enhanced serosa sign on CT in diffuse-type was significant higher（80% in both readers）, while the specificity trended to be lower（65.9% and 80.5%, respectively）. There is no significant difference in the accuracy of diagnosis between intestinaltype and diffuse-type of gastric cancers（the P-values of two radiologists were 0.968, 0.591, respectively）. The combination of the high enhanced serosa sign with conventional CT signs is significant different in diagnosis of T3 and T4a（P〈0.001）. The diagnostic accuracy was increased in both radiologists after the combination. The two readers achieved substantial agreement, with Kappa coefficient of 0.63, P〈0.001.Conclusions： The high enhanced serosa sign on CT is associated with serosa involvement. The sensitivity of the judgement of serosa invasion using this sign on CT in diffuse-type was significant higher than that in intestinal-type.

Prognosis of patients with gastric cancer and solitary lymph node metastasis

AIM:To investigate the relationship of solitary lymph node metastasis(SLNM)and age with patient survival in gastric cancer(GC).METHODS:The medical records databases of China’s Beijing Cancer Hospital at the Peking University School of Oncology and Shanghai Tenth People’s Hospital affiliated to Tongji University were searched retrospectively to identify patients with histologically proven GC and SLNM who underwent surgical resection between October 2003 and December 2012.Patients with distant metastasis or gastric stump carcinoma following resection for benign disease were excluded from the analysis.In total,936 patients with GC+SLNM were selected for analysis and the recorded parameters of clinicopathological disease and follow-up(range:13-2925 d)were collected.The Kaplan-Meier method was used to stratify patients by age(≤50 years-old,n=198;50-64 years-old,n=321;≥65 years-old,n=446)and by metastatic lymph node ratio[MLR<0.04(1/25),n=180;0.04-0.06(1/25-1/15),n=687;≥0.06(1/15),n=98]for 5-year survival analysis.The significance of intergroup differences between the survival curves was assessed by a log-rank test. RESULTS:The 5-year survival rate of the entire GC+SLNM patient population was 49.9%.Stratification analysis showed significant differences in survival time(post-operative days)according to age:≤50 yearsold:950.7±79.0 vs 50-64 years-old:1697.8±65.9 vs≥65 years-old:1996.2±57.6,all P<0.05.In addition,younger age(≤50 years-old)correlated significantly with mean survival time(r=0.367,P<0.001).Stratification analysis also indicated an inverse relationship between increasing MLR and shorter survival time:<0.04:52.8%and 0.04-0.06:51.1%vs≥0.06:40.5%,P<0.05.The patients with the shortest survival times and rates were younger and had a high MLR(≥0.06):≤50 years-old:496.4±133.0 and 0.0%vs 50-65 years-old:1180.9±201.8 and 21.4%vs≥65 years-old:1538.4±72.4 and 37.3%,all P<0.05.The same significant trend in shorter survival times and rates for younger patients was seen with the mid-range MLR group(0.04-0.06),but the difference between the two older groups was not significant.No significant differences were found between the age groups of patients with MLR<0.04.Assessment of clinicopathological parameters identified age group,Borrmann type,histological type and tumor depth as the most important predictors of the survival rates and times observed for this study population.CONCLUSION:GC patients below 51 years of age with MLR of SLNM above 0.06 have shorter life expectancy than their older counterparts.

Imatinib mesylate in clinically suspected gastric stromal tumors

Gastrointestinal stromal tumors （GISTs） occur most frequently in the stomach.Diagnosis of gastric GIST is not always clear before surgery.Flexible endoscopy may suggest the nature of the lesion （a bulky tumor with preserved mucosa）; however,biopsy is rarely diagnostic.Therefore,diagnostic medication with safe drugs may provide a feasible way under such conditions after an informed consent is obtained.Based on the excellent efficacy of imatinib mesylate （IM） in the treatment of GIST,we successfully applied it in the diagnostic medication of two patients with clinically suspected gastric stromal tumors.In conclusion,the diagnostic medication with IM can be an alternative option for patients with suspected GIST that can not be confirmed pathologically.

Neoadjuvant chemoradiotherapy followed by laparoscopic distal gastrectomy in advanced gastric cancer: A case report and review of literature

BACKGROUND The laparoscopic technique has been widely applied for early gastric cancer,with the advantages of minimal invasion and quick recovery.However,there is no report about the safety and oncological outcome of laparoscopic gastrectomy with D2 lymph node dissection for patients after neoadjuvant chemoradiotherapy.CASE SUMMARY A 60-year-old man was diagnosed with advanced distal gastric cancer,cT4aN1M0 stage III.The neoadjuvant chemoradiotherapy was performed based on the regimen of gross tumor volume 50G y/25 f and clinical target volume 45 Gy/25 f,as well as concurrent S-160 mg Bid.Then laparoscopic distal gastrectomy with D2 lymph node dissection was undertaken successfully for him after achieving partial response evaluated by radiological examination.The patient recovered smoothly without moderate or severe postoperative complications.The postoperative pathological stage was ypT3N0M0 with American Joint Committee on Cancer tumor regression grade 1.He was still in good condition after 5 years of follow-up.CONCLUSION Neoadjuvant chemoradiotherapy followed by laparoscopic technique could be applicable and may achieve satisfactory oncological outcomes.Our finding requires further validation by cohort studies.

深度神经网络结合迁移学习和基因遗传算法加速金属团簇结构全局优化

在团簇科学中,搜索金属团簇的全局最小能量结构具有重要的意义.最近,深度神经网络结合迁移学习的全局优化方法被开发出来,以提高金属团簇结构的优化效率,该方法可以大幅减少训练深度神经网络所需的样本数量.为了进一步提高势能面的采样效率和深度神经网络结合迁移学习的全局优化方法的全局搜索能力,本文提出了一种将基因遗传算法嵌入到深度神经网络结合迁移学习中的全局优化方法.在Pt_(n)(n=9-15)团簇的全局优化中,该方法只需要深度神经网络结合迁移学习的全局优化方法一半的样本数量就能优化得到全局最优结构,同时节省了约70%~80%的计算成本,这表明全局搜索能力的显著提升。在Pt_(14)团簇势能面上的采样结果显示,该方法搜索到低能量的样本(占比25%)比深度神经网络结合迁移学习方法的样本(占比<1%)更多.在Pt_(16)和Pt_(17)团簇的全局最优结构搜索中,本文报道了文献中尚未报道的新结构,证明本论文建立的方法的可行性和先进性.

激光改性YAG/YSZ双陶瓷热障涂层的高温氧化与TGO生长行为

以Inconel738合金为基体、NiCoCrAlY为黏接层,采用大气等离子喷涂(APS)技术制备YAG/YSZ双陶瓷热障涂层(TBC),并对YAG层表面进行激光改性,以提高TBC的抗高温氧化性能。通过恒温氧化实验研究喷涂态(AS)与激光改性(LM)TBC的高温氧化及热生长氧化物(TGO)的生长行为。结果表明,AS-TBC与LM-TBC的TGO厚度与结构呈现相似变化趋势,即厚度随氧化时间增加而增加,结构则均由单一Al_(2)O_(3)层演变为混合氧化物层在上、Al_(2)O_(3)层在下的双层形貌。基于激光改性对氧气渗透的强烈抑制作用,LM-TBC中混合氧化物出现的时间推迟,在氧化中后期LM-TBC的总体TGO厚度也有所减少。经过相同的氧化时间,LM-TBC中Al_(2)O_(3)厚度在总体TGO厚度中占比始终大于或等于AS-TBC,并且LM-TBC的抛物线氧化速率相比AS-TBC下降了18.42%。因此,YAG/YSZ LM-TBC呈现更优异的高温抗氧化性能与更低的TGO生长速率。

Intestinal stem cell marker LGR5 expression during gastric carcinogenesis

AIM:To investigate the differential expression of leu-cine-rich repeat-containing G protein-coupled receptor5(LGR5)in gastric cancer tissues and its significance related to tumor growth and spread.METHODS:Formalin-fixed biopsy specimens of intestinal metaplasia(n=90),dysplasia(n=53),gastric adenocarcinoma(n=180),metastases in lymph nodes and the liver(n=15),and lesion-adjacent normal gastric mucosa(controls;n=145)were obtained for analysis from the Peking University Cancer Hospital’s Department of Pathology and Gastrointestinal Surgery tissue archives(January 2003 to December 2011).The biopsied patients’demographic and clinicopathologic data were retrieved from the hospital’s medical records database.Each specimen was subjected to histopathological typing to classify the tumor node metastasis(TNM)stage and to immunohistochemistry staining to detect the expression of the cancer stem cell marker LGR5.The intergroup differences in LGR5 expression were assessed by Spearman’s rank correlation analysis,and the relationship between LGR5 expression level and the patients’clinicopathological characteristics was evaluated by theχ2test or Fisher’s exact test.RESULTS:Significantly more gastric cancer tissues showed LGR5+staining than normal control tissues(all P<0.01),with immunoreactivity detected in 72.2%(65/90)and 50.9%(27/53)of intestinal metaplasia and dysplasia specimens,respectively,52.8%(95/180)of gastric adenocarcinoma specimens,and 73.3%%(11/15)of metastasis specimens,but 26.9%(39/145)of lesion-adjacent normal gastric mucosa specimens.Comparison of the intensity of LGR5+staining showed an increasing trend that generally followed increasing dedifferentiation and tumor spread(normal tissue<dysplasia,<gastric adenocarcinoma<metastasis;all P<0.001),with the exception of expression level detected in intestinal metaplasia which was higher than that in normal gastric tissues(P<0.001).Moreover,gastric cancer-associated enhanced expression of LGR5 was found to be signifcantly associated with age,tumor differentiation,Lauren type and TNM stage(Ⅰ+ⅡvsⅢ+Ⅳ)(all P<0.05),but not with sex,tumor site,location,size,histology,lymphovascular invasion,depth of invasion,lymph node metastasis or distant metastasis.Patients with LGR5+gastric cancer specimens and without signs of metastasis from the original biopsy experienced more frequent rates of recurrence or metastasis during follow-up than patients with LGR5-specimens(P<0.05).CONCLUSION:Enhanced LGR5 is related to progressive dedifferentiation and metastasis of gastric cancer,indicating the potential of this receptor as an early diagnostic and prognostic biomarker.

Prognostic predictors in patients with sepsis after gastrointestinal tumor surgery:A retrospective study

BACKGROUND There have been different reports on mortality of sepsis;however,few focus on the prognosis of patients with sepsis after surgery.AIM To study the clinical features and prognostic predictors in patients with sepsis after gastrointestinal tumor surgery in intensive care unit(ICU).METHODS We retrospectively screened patients who underwent gastrointestinal tumor surgery at Peking University Cancer Hospital from January 2015 to December 2019.Among them,181 patients who were diagnosed with sepsis in ICU were included in our study.Survival was analysed by the Kaplan-Meier method.Univariate and multivariate adjusted analyses were performed to identify predictors of prognosis.RESULTS The 90-d all-cause mortality rate was 11.1%in our study.Univariate analysis showed that body mass index(BMI),shock within 48 h after ICU admission,leukocyte count,lymphocyte to neutrophil ratio,international normalized ratio,creatinine,procalcitonin,lactic acid,oxygenation index,and sequential organ failure assessment(SOFA)score within 24 h after ICU admission might be all significantly associated with the prognosis of sepsis after gastrointestinal tumor surgery.In multiple analysis,we found that BMI≤20 kg/m^(2),lactic acid after ICU admission,and SOFA score within 24 h after ICU admission might be independent risk predictors of the prognosis of sepsis after gastrointestinal tumor surgery.Compared with SOFA score,SOFA score combined with BMI and lactic acid might have higher predictive ability(area under the receiver operating characteristic curve,0.859;95%confidence interval,0.789-0.929).CONCLUSION Lactic acid and SOFA score within 24 h after ICU admission are independent risk predictors of the prognosis of sepsis after gastrointestinal tumor surgery.SOFA score combined with BMI and lactic acid might have good predictive value.

Comparison of tumor regression grading systems for locally advanced gastric adenocarcinoma after neoadjuvant chemotherapy

BACKGROUND Current tumor regression grade(TRG)evaluations are based on various systems which brings confusion for oncologists and pathologists when interpreting results.The recent six-tier system(JGCA2017-TRG)recommended by the Japanese Gastric Cancer Association(JGCA)is worth investigating,as four-tier TRG systems are favored in various parts of the world.AIM To compare the predictive accuracies of five published TRG systems.METHODS Data were retrospectively collected from patients with locally advanced gastric cancer(LAGC)who underwent neoadjuvant chemotherapy followed by D2 Lymphadenectomy between January 2005 and January 2014 at our institution.Outcomes were overall survival(OS)and disease-free survival(DFS),which were evaluated separately using the following TRG systems:JGCA2017,JGCA,Becker,AJCC/CAP,and Mandard.RESULTS All five published TRG systems were independent predictors for OS and DFS.Concordance indices of the JGCA2017,JGCA,Becker,AJCC/CAP-TRG,and Mandard systems were 0.651/0.6480.652/0.649,0.693/0.695,0.688/0.685,and 0.674/0.675 for OS and DFS,respectively.The four-tier Becker system showed the highest c-index,which was significantly greater than that of the six-tier JGCA2017 and five-tier JGCA systems(P<0.05 in OS and DFS).When residual tumor percentages were reset as:“no residual tumor”,<10%,<100%,and“no response”,the rearranged cutoff values achieved a maximum c-index with 0.728 for OS and 0.737 for DFS,which was superior to the other five systems.CONCLUSION The newly introduced six-tier JGCA-TRG system cannot increase prognostic stratification.The four-tier Becker system is more suitable for LAGC patients.A population-based study is warranted to define the optimal criterion for TRG in LAGC patients.

Activation of Dinitrogen by Gas-Phase Species

Reactions of gas-phase species with small molecules are being actively studied to understand the elementary steps and mechanistic details of related condensed-phase processes.Activation of the very inert N≡N triple bond of dinitrogen molecule by isolated gas-phase species has attracted considerable interest in the past few decades.Apart from molecular adsorption and dissociative adsorption,interesting processes such as C-N coupling and degenerate ligand exchange were discovered.The present review focuses on the recent progress on adsorption,activation,and functionalization of N2 by gas-phase species(particularly metal cluster ions)using mass spectrometry,infrared photo-dissociation spectroscopy,anion photoelectron spectroscopy,and quantum chemical calculations including density functional theory and high-level ab initio calculations.Recent advances including characterization of adsorption products,dependence of clusters’reactivity on their sizes and structures,and mechanisms of N≡N weakening and splitting have been emphasized and prospects have been discussed.

^(15)N/^(14)N Isotopic Exchange in the Dissociative Adsorption of N_(2) on Tantalum Nitride Cluster Anions Ta_(3)N_(3)

Adsorption and activation of dinitrogen(N_(2)) is an indispensable process in nitrogen fixation.Metal nitride species continue to attract attention as a promsing catalyst for ammonia synthesis.However,the detailed mechanisms at a molecular level between reactive nitride species and N_(2) remain unclear at elevated temperature,which is important to understand the temperature effect and narrow the gap between the gas phase system and condensed phase system.Herein,the ^(15)N/^(14)N isotopic exchange in the reaction between tantalum nitride cluster anions Ta_(3)^(14)N_(3)^(-) and ^(15)N_(2) leading to the regeneration of ^(14)N_(2)/^(14)N^(15)N was observed at elevated temperature(393-593 K)using mass spectrometry.With the aid of theoretical calculations,the exchange mechanism and the effect of temperature to promote the dissociation of N_(2) on Ta_(3)N_(3)^(-) were elucidated.A comparison experiment for Ta_(3)^(14)N_(4)^(-)/^(15)N_(2) couple indicated that only desorption of ^(15)N_(2) from Ta_(3)^(14)N_(4)^(15)N_(2)^(-) took place at elevated temperature.The different exchange behavior can be well understood by the fact that nitrogen vacancy is a requisite for the dinitrogen activation over metal nitride species.This study may shed light on understanding the role of nitrogen vacancy in nitride species for ammonia synthesis and provide clues in designing effective catalysts for nitrogen fixation.

H2 Dissociation by Au1-Doped Closed-Shell Titanium Oxide Cluster Anions

Dissociation of molecular hydrogen （H2） is extensively studied to understand the mechanism of hydrogenation reactions. In this study, H2 dissociation by Aul-doped closed-shell titanium oxide cluster anions AuTi3O7 and AuTi3O8 has been identified by mass spectrometry and quantum chemistry calculations. The clusters were generated by laser ablation and mass- selected to react with H2 in art ion trap reactor. In the reaction of AuTi3O8 with H2, the ion pair Au＋-O22 rather than Au＋-O2 is the active site to promote H2 dissociation. This finding is in contrast with the previous result that the lattice oxygen is usually the reactive oxygen species in H2 dissociation. The higher reactivity of the peroxide species is further supported by frontier molecular orbital analysis. This study provides new insights into gold catalysis involving H2 activation and dissociation.

Complex proximal femoral fracture in a young patient followed up for 3 years: A case report

BACKGROUND Ipsilateral femoral neck and intertrochanteric fractures in young patients are extremely rare,and there is no reference for fracture classification and treatment options.CASE SUMMARY We report a 27-year-old male patient who sustained ipsilateral femoral neck and intertrochanteric fractures and was treated with a proximal femoral locking compression plate(PFLCP).The literature on these fractures was also reviewed.At the last follow-up three years after surgery,the patient had no obvious pain in the hip,and the range of motion in the hip joint was slightly limited,but met the normal life and work needs.There were no complications such as necrosis of the femoral head.CONCLUSION The PFLCP can be used to treat these complex proximal femoral fractures,and selection should be based on the patient's specific fractures.

Nomogram for predicting the prognosis of tumor patients with sepsis after gastrointestinal surgery

BACKGROUND There were few studies on the prognosis of tumor patients with sepsis after gastrointestinal surgery and there was no relevant nomogram for predicting the prognosis of these patients.AIM To establish a nomogram for predicting the prognosis of tumor patients with sepsis after gastrointestinal surgery in the intensive care unit(ICU).METHODS A total of 303 septic patients after gastrointestinal tumor surgery admitted to the ICU at Peking University Cancer Hospital from January 1, 2013 to December 31, 2020 were analysed retrospectively. The model for predicting the prognosis of septic patients was established by the R software package.RESULTS The most common infection site of sepsis after gastrointestinal surgery in the ICU was abdominal infection. The 90-d all-cause mortality rate was 10.2% in our study group. In multiple analyses, we found that there were statistically significant differences in tumor type, septic shock, the number of lymphocytes after ICU admission, serum creatinine and total operation times among tumor patients with sepsis after gastrointestinal surgery(P < 0.05). These five variables could be used to establish a nomogram for predicting the prognosis of these septic patients. The nomogram was verified, and the initial C-index was 0.861. After 1000 internal validations of the model, the C-index was 0.876, and the discrimination was good. The correction curve indicated that the actual value was in good agreement with the predicted value.CONCLUSION The nomogram based on these five factors(tumor type, septic shock, number of lymphocytes, serum creatinine, and total operation times) could accurately predict the prognosis of tumor patients with sepsis after gastrointestinal surgery.

The Arabidopsis Transcription Factor AtTCP15 Regulates Endoreduplication by Modulating Expression of Key Cell-cycle Genes

Plant cells frequently undergo endoreduplication, a modified cell cycle in which genome is repeatedly rep- licated without cytokinesis. As the key step to achieve final size and function for cells, endoreduplication is prevalent during plant development. However, mechanisms to control the balance between endoreduplication and mitotic cell di- vision are still poorly understood. Here, we show that the Arabidopsis TCP （CINCINNATA-like TEOSINTE BRANCHED1~ CYCLOIDEA-_PCF）-family transcription factor gene AtTCP15 is expressed in trichomes, as well as in rapidly dividing and vascular tissues. Expression of AtTCP15SRDX, AtTCP15 fused with a SRDX repressor domain, induces extra endoredupli- cation in trichomes and cotyledon cells in transgenic Arabidopsis. On the contrary, overexpression of AtTCP15 suppresses endoreduplication in trichomes and other examined cells. Misregulation of AtTCP15 affects the expression of several im- portant genes involved in cell-cycle regulation. AtTCP15 protein binds directly to the promoter regions of CYCA2;3 and RETINOBLASTOMA-RELATED （RBR） genes, which play key roles in endoreduplication. Taken together, AtTCP15 plays an important role in regulating endoreduplication during Arabidopsis development.

MicroRNAs of bone marrow mesenchymal stem cell-derived exosomes regulate acute myeloid leukemia cell proliferation and apoptosis

Background:Acute myeloid leukemia(AML)is a malignant hematological disease,originating from hematopoiesis stem cell differentiation obstruction and clonal proliferation.New reagents or biologicals for the treatment of AML are urgently needed,and exosomes have been identified as candidate biomarkers for disease diagnosis and prognosis.This study aimed to investigate the effects of exosomes from bone marrow mesenchymal stem cells(BMSCs)on AML cells as well as the underlying microRNA(miRNA)-mediated mechanisms.Methods:Exosomes were isolated using a precipitation method,followed by validation using marker protein expression and nanoparticle tracking analysis.Differentially expressed miRNAs were identified by deep RNA sequencing and confirmed by quantitative real-time polymerase chain reaction(qPCR).Cell proliferation was assessed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt method,and cell cycle progression and apoptosis were detected by flow cytometry.Functional gene expression was analyzed by qPCR and Western blotting(WB).Significant differences were determined using Student’s t test or analysis of variance.Results:BMSCs-derived exosomes effectively suppressed cell proliferation(both P<0.0001 at 10 and 20μg/mL)and cell cycle progression(P<0.01 at G0-G1 stage),and also significantly enhanced cell apoptosis(P<0.001)in KG-1a cells.There were 1167 differentially expressed miRNAs obtained from BMSCs-derived exosomes compared with KG-1a cell-derived exosomes(P<0.05).Knockdown of hsa-miR-124-5p in BMSCs abrogated the effects of BMSCs-derived exosomes in regulating KG-1a such as the change in cell proliferation(both P<0.0001 vs.normal KG-1a cell[NC]at 48 and 72 h).KG-1a cells treated with BMSCs-derived exosomes suppressed expression of structural maintenance of chromosomes 4(P<0.001 vs.NC by qPCR and P<0.0001 vs.NC by WB),which is associated with the progression of various cancers.This BMSCs-derived exosomes effect was significantly reversed with knockdown of hsa-miR-124-5p(P<0.0001 vs.NC by WB).Conclusions:BMSCs-derived exosomes suppress cell proliferation and cycle progression and promote cell apoptosis in KG-1a cells,likely acting through hsa-miR-124-5p.Our study establishes a basis for a BMSCs-derived exosomes-based AML treatment.