Medical studies have found that tumor mutation burden (TMB) is positively correlated with the efficacy of immunotherapy for non-small cell lung cancer (NSCLC), and TMB value can be used to predict the efficacy of targeted therapy and chemotherapy. However, the calculation of TMB value mainly depends on the whole exon sequencing (WES) technology, which usually costs too much time and expenses. To deal with above problem, this paper studies the correlation between TMB and slice images by taking advantage of digital pathological slices commonly used in clinic and then predicts the patient TMB level accordingly. This paper proposes a deep learning model (RCA-MSAG) based on residual coordinate attention (RCA) structure and combined with multi-scale attention guidance (MSAG) module. The model takes ResNet-50 as the basic model and integrates coordinate attention (CA) into bottleneck module to capture the direction-aware and position-sensitive information, which makes the model able to locate and identify the interesting positions more accurately. And then, MSAG module is embedded into the network, which makes the model able to extract the deep features of lung cancer pathological sections and the interactive information between channels. The cancer genome map (TCGA) open dataset is adopted in the experiment, which consists of 200 pathological sections of lung adenocarcinoma, including 80 data samples with high TMB value, 77 data samples with medium TMB value and 43 data samples with low TMB value. Experimental results demonstrate that the accuracy, precision, recall and F1 score of the proposed model are 96.2%, 96.4%, 96.2% and 96.3%, respectively, which are superior to the existing mainstream deep learning models. The model proposed in this paper can promote clinical auxiliary diagnosis and has certain theoretical guiding significance for TMB prediction.
Humans ; Lung Neoplasms/pathology* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Mutation ; Adenocarcinoma of Lung/genetics* ; Biomarkers, Tumor/genetics*

Objective To evaluate smooth muscle protein of 22 kDa (SM22) in the diagnosis of acute intestinal ischemia.Methods 96 healthy adult SD rats were evenly divided into experimental group and control group,with each group subdivided into 6 subgroups,subject respectively to superior mesenteric artery ligation or sham operation.The venous blood samples were extracted from each group rats' right heart atO.5,1,2,4,8,12 h after the operation,for SM22 testing and small intestines tissues for direct immunofluorescence staining of SM22.Results The serum SM22 concentration reached a peak at 4 h (265 ± 15) mg/L,then gradually decreased (P ＜ 0.05).The I-FABP was mainly expressed in the epithelium of intestinal mucosa.During the 4 hours of intestinal ischemia,The number of SM22 positive particles did not change.After 4 hours,the number of SM22 positive granules had gradually decreased compared with the control group (all P ＜ 0.05).Conclusion SM22 mainly exists in the smooth muscle of intestinal,during the ischemic necrosis of the intestinal muscle layer SM22 leaks into blood stream,resulting in high serum levels of SM22 facilitating early diagnosis of acute intestinal ischemia.

[Objective] To investigate the clinical characteristics and blood transfusion status of patients of liver cirrhosis and analyze its rationality.[Methods] We designed questionnaires to collect the data of patients admitted with liver cirrhosis including clinical features,blood transfusion,smoking,drinking and other living habits.We follow up the patients and analyze the blood transfusion rationality.[Results] Data on 198 patients was collected.34.8％ (69/198) of all patients were transfused at least one blood component.Total blood transfusion was 371 times,of which 52.2％ of the blood transfusion cases (36/69) were transfused with two or more blood during hospitalization.Among the 69 cases of blood transfusion,11 cases were treated with the first blood transfusion for the purpose of treatment and 58 cases for prevention.18 of those cases were infused with red blood cells of 90.5 units.54.55 ％ (60/110) and 60.91％ (67/110) of patients who had a pre-transfusion INR＞1.3 did not receive plasma.2.27％ (2/88) of patients who had a pre-transfusion INR≤1.3 received plasma.29.41％ (5/17)who had a pre-transfusion fib≤1.0 received cryoprecipitate.3.87％(7/181) who had a pre-transfusion fib＞1.0 received cryoprecipitate.[Conclusions] Blood transfusion is common in patients with liver cirrhosis.Empirical and preventive blood transfusion is common also.We should take a more scientific restrictive blood transfusion strategy.

AIM:To investigate the effects of celecoxib on viability , apoptosis and autophagy in acute myeloid leukemia (AML) cell lines HL-60 and HL-60A.METHODS:The HL-60 cells and HL-60A cells were cultured with vari-ous concentrations (0, 20, 40, 60, 80 and 100μmol/L) of celecoxib.The inhibitory effect of celecoxib on the cell viabil-ity was evaluated by MTT assay .Apoptosis was analyzed by Annexin-V/PI staining.Apoptosis-related and autophagy-relat-ed proteins were determined by Western blot .RESULTS:IC50 of celecoxib were 49.4 μmol/L, 32.0 μmol/L and 25.1μmol/L for HL-60 cells treated with celecoxib for 24 h, 48 h and 72 h, respectively.For HL-60A cells, the corresponding IC50 were 69.1 μmol/L, 42.5 μmol/L and 29.6 μmol/L, respectively.The results of flow cytometry analysis showed the proportions of Annexin-Ⅴ+PI-, Annexin-Ⅴ+PI+and Annexin-Ⅴ-PI+cells were increased in the HL-60 cells, and those of Annexin-Ⅴ+PI-and Annexin-Ⅴ+PI+cells were increased in the HL-60A cells treated with celecoxib for 24 h. After treated with celecoxib , the induction of apoptosis was observed , the apoptosis-related proteins cleaved caspase-3 and cleaved PARP were upregulated , the autophagy-related proteins LC3 II and P62 were both increased , and mTOR, p-mTOR, 4-EBP and p-4-EBP were not changed , indicating that celecoxib inhibited autophagy in the AML cells without the mTOR pathway involvement .CONCLUSION:Celecoxib inhibits the viability of HL-60 cells and HL-60A cells in a time-and dose-dependent manner by its effects of inducing apoptosis and necrosis .Celecoxib inhibits mTOR-independent autoph-agy in AML cells, indicating a possible way of using celecoxib for enhancing the antitumor activity of therapeutic agents to induce cytoprotective autophagy in the AML cells .

Objective:To investigate the effects of early postoperative enteral nutrition on recovery of patients with gastric cancer.Methods:Sixty-five cases of patients with gastric cancer were randomized into early enteral nutrition (EEN) group and enteral nutrition (EN) group.Serum total protein (TB),albumin(ALB),Prealbumin,white blood cell count (WBC),C-reactive protein (CRP),immunoglobulin,peripheral T-lymphocyte subsets,gastrointestinal recovery time,hospital stay and cost were recorded.The nutritional and cellular immunity parameters of the EEN group on 7th day after operation were higher than those of the EN group.Inflammatory response of the EEN group on 3th day after operation was lower than EN group.EEN group showed better immunological response and clinical recovery than the EN group (P ＜ 0.05).Conclusion:Early enteral nutrition in postoperative gastric cancer patients can improve early postoperative nutritional status and immune function,alleviate inflammatory response,promote the recovery of intestinal function and shorten hospital stay.

Objective To explore regional anatomical features of fascia and spaces related to complete mesocolic excision (CME)dur-ing laparoscopic right hemicolectomy.Methods Observe and describe the regional anatomical features of related mesenterium,fascia and spaces through autopsy and somatoscopy.Results Superior mesenteric vein is the anatomic landmark in CME with medial access for laparo-scopic right hemicolectomy.Right mesocolon and ileal mesentery are the main mesenterium,and the fascia contains the prerenal fascia and the pancreatic fascia.The right retrocolic space and the colon transversum space are two important anatomical spaces,and their fusion fascia space served as a natural surgical plane.Conclusion There is a natural surgical plane which made of mesenterium,fascia and spaces be-tween mesocolon and prerenal fascia in CME during laparoscopic right hemicolectomy,and the surgery is feasible.

AIM:To investigate the expression of aplasia rashomolog member I ( ARHI) gene in acute myeloid leukemia cells (AML) and to study the effects of ARHI on the growth of AML cell line U937.METHODS:The mRNA ex-pression of ARHI in AML cells, 293FT cells, AML primary cells and healthy volunteer blood cells were detected by RT-PCR.After transfection with the MSCV-IRES-GFP-ARHI plasmid to the U937 cells, the growth curve was analyzed by MTT assay.U937 cells were re-suspended by fresh medium and cultured for 24 h, then the cell cycle distribution and ap-optotic rate were determined.RESULTS:The mRNA of ARHI was positively detectable in 293FT cells and healthy volun-teer blood cells instead of AML cell line and AML primary cells.The growth curve showed that cell viability in U937 cells with high expression of ARHI (U937-ARHI) was lower than that in the control cells (U937-GFP) on 6th~8th day.The ratio of G2/M phase and apoptotic rate in the U937-ARHI cells were increased compare with control group ( P<0.05 ) . CONCLUSION:The mRNA level of ARHI is low in AML cells.High expression of ARHI gene in U937 cells inhibits cell growth, arrests the cells at G2/M phase and induces apoptosis.

Objective To explore the reproductive toxicity of 2,4-D butylate to the testis in male mice.Methods Forty-eight ICR male mice were randomly divided into four groups : the control group, and three 2,4-D butylate experimental groups (10, 20, 40 mg/kg), 12 mice in each group.2,4-D butylate was intragastrically administered once a day and six days per week for five weeks .At the end of the exposure, the activities of total antioxidant capacity (T-AOC), Na+ K+-ATPase, Ca+ + Mg+ +-ATPase, lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) in testis homogenate were measured by spectrophotometry .Results The activity of T-AOC was gradually decreased with the increase of doses, with a significant difference between the high dose group and other groups .The activities of LDH in the moderate and high dose groups were significantly lower than those of the low dose group and control group , and there was a significant difference between the high dose group and moderate dose group .The activities of SDH in the testis was gradually decreased with the increase of the 2,4-D butylate dose, showing significant differences between the high dose group and the moderate dose and control groups , and between the high and moderate dose groups and the low dose group . The activities of Na +K +-ATPase in the moderate and high dose groups were significantly lower than that of the control and low dose group.The activities of Ca++Mg++-ATPase was significantly lower in the experimental groups than that in the control group.Conclusion Exposure to 2,4-D butylate has certain toxic effect on the testicular tissue in male mice .

Objective To establish mouse poisoning model by inhaling benzene, and to investigate the induction effect of benzene on the apoptosis of mouse bone marrow cells and its mechanism, and to provide an experimental basis for study on bone marrow toxicity mechanism.Methods 24 male mice were randomly divided into four groups (n=6).The mice in one group were exposed to ambient air (control group)and the mice in the other three groups were exposed to different doses (400,800,1 600 mg·m-3 )of benzene (low,middle and high doses of benzene groups)for 1 5 d in the respective inhalation chambers. At the end of the experiment, the mice were killed. The bone marrow of the mice was obtained. The pathological changes of the bone marrow cells of the mice in various groups were observed under light microscope with HE staining.The apoptotic rates and mitochondrial membrane potential (MMP ) of the mice in various groups were detected by flow cytometry, and the expressions of mitochondrial-deperdent apoptosis related gene proteins were determined with immunohistochemistry method. Results The number of distal and central cells in different doses of benzene groups were significantly reduced,and accompanied by blood sinus expansion in high dose of benzene group.The apoptotic rates of the cells in middle and high doses of benzene groups were obviously higher than that in control group (Ρ<0.01),and there were also significant differences between high dose group and low,middle doses of benzene groups (Ρ<0.05).The MMP was significantly decreased with the increasing of benzene doses, and there were significant differences between middle,high doses of benzene groups and control group (Ρ<0.05).The number of Bax,CytC positive cells in different doses of benzene groups and the number of Caspase-9,Caspase-3 positive cells in middle and high doses of benzene groups were significantly increased compared with control group(Ρ<0.05);the number of Bcl-2 positive cells in different doses of benzene groups was decreased(Ρ<0.05),and number of Bcl-2 positive cells in middle and high doses of benzene groups was decreased compared with low dose of benzene group (P<0.05). Conclusion Benzene with certain dose can induce the apoptosis of mouse bone marrow cells, and promote the expressions of mitochondrial apoptosis related gene proteins. Benzene-induced apoptosis through mitochondrial-dependent apoptosis pathway may be an important mechanism of bone marrow toxicity induced by benzene.

BACKGROUND:Because of their immunological properties, bone marrow mesenchymal stem cells transfusion is developed as a new treatment for refractory graft-versus-host disease. OBJECTIVE:To analyze the safety and curative effect of bone marrow mesenchymal stem cells transfusion on treating different organ damages in graft-versus-host disease after al ogeneic hematopoietic stem celltransplantation. METHODS:Eight patients with malignant hematologic disease were included in this study. The patients developed severe steroid-resistant graft-versus-host disease after al ogeneic hematopoietic stem celltransplantation and received transfusion of mesenchymal stme cell(1×106 of immunosuppressive agent. RESULTS AND CONCLUSION:For the total y eight patients, six got response (two cases of complete remission, and four cases of partial remission) and two showed no remission. Four of five cutaneous damages were ameliorated and one showed no effect. For three cases of oral graft-versus-host disease, two acquired complete remission and one showed partial remission. Two cases of liver graft-versus-host disease and two cases of astro-intestinal graft-versus-host disease obtained complete remission. No response was displayed to three cases of ocular graft-versus-host disease, one case of bronchiolitis obliterans, and one case of urinary graft-versus-host disease. In the median fol ow-up of 28 months (7-62 months), three patients developed posttransplant lymphoproliferative disorders within 3 months after mesenchymal stem cells transfusion. Administration of mesenchymal stem cells is safe for treatment of severe graft-versus-host disease after al ogeneic hematopoietic stem celltransplantation. Mesenchymal stem cells transfusion may be a promising/kg) together with the primary therapy therapy for refractory cutaneous , astro-intestinal, liver and oral graft-versus-host disease but not for pulmonary, ocular and urinary graft-versus-host disease. Whether mesenchymal stem cells transfusion is associated with posttransplant lymphoproliferative disorders needs more case data.