Objective To investigate the role of HK2 and VDAC1 in diacetylmorphine-induced cardiomyocyte apoptosis.Methods A dose-escalation method was used to establish a rat model of diacetylmorphine addiction.Forty SD rats were randomly divided into three groups,the normal group(n=10)was injected with an equal amount of saline subcutaneously,the model group(n=15)was injected with 5 mg/kg of diacetylmorphine for the first time,and then the dose was increased by 2.5 mg/(kg·d)day by day for 20 days,and the group of model +10 D(n=15)continued to increase the dose based on the model group up to the 10th day.Lactate dehydrogenase(LDH)and glutamic oxaloacetic transaminase(GOT)were detected by ELISA;HE staining was used to observe the pathological changes of myocardial tissues in each group;TUNEL staining was used to detect apoptosis in myocardial tissues in each group;and immunohistochemistry,RT-q-analysis,and immunochemistry were used to detect apoptosis in myocardial tissues in each group.Immunohistochemistry,RT-qPCR and Western bl-ot were used to detect the mRNA and protein expression of HK2,VDAC1 and apoptosis-related factors.Results HE staining revealed that myocardial tissues exhibited different degrees of damage with the prolongation of diacetylmorphine intervention.Compared with the normal group,serum LDH,GOT content and myocardial apoptosis rate increased in the model group,mRNA and protein levels of HK2 and anti-apoptotic factor Bcl-2 decreased,mRNA and protein levels of VDAC1 and pro-apoptotic factors Bax and Caspase-3 increased,and the protein level of Clevead Caspase-3 increased;in the model +10 D group the above indexes,there was a statistically significant difference(P<0.05).Conclusion Diacetylmorphine can cause cardiomyocyte apoptosis,and VDAC1 may be involved in the process of cardiomyocyte apoptosis caused by diacetylmorphine.

Objective: To summarize the clinical characteristics of patients with skip metastasis at esophageal resection margin during radical gastrectomy. Methods: This is a descriptive study of case series. Relevant data from 2006 to 2022 were collected from two major gastric cancer consultation and treatment centers: Nanjing Drum Tower Hospital and Jinling Hospital.Characteristics, surgical approach, number of dissected lymph nodes, immunohistochemical staining, and pathological staging were summarized and analyzed. The distribution of residual tumor cells at the esophageal margins was further analyzed at the cellular and tissue levels. Skip metastasis at the esophageal resection margin was defined as a negative esophageal margin with a positive margin in the cephalad donut. Results: Thirty (0.33%, 30/8972) eligible patients, 24 (80.0%) of whom were male, were identified in the two centers. The mean age was 63.9±11.0 years. Seventeen (56.7%) of these patients had papillary or tubular adenocarcinomas, including 13 (43.3%) poorly- and four (13.3%) moderately-differentiated tumors; four (13.3%) had signet-ring cell carcinomas; four (13.3%) mucinous adenocarcinomas; three (10.0%) mixed adenocarcinomas, including two with poorly-differentiated tubular adenocarcinomas mixed with signet-ring cell carcinoma and mucinous adenocarcinoma; and one had a poorly differentiated tubular adenocarcinoma mixed with signet-ring cell carcinoma. Two patients (6.7%) had other types of cancer, namely adenosquamous carcinoma in one patient and undifferentiated carcinoma in the other one. The predominant tumor sites were the lesser curvature (n=26, 86.7%) and the cardia (n=24, 80.0%). The mean tumor diameter was 6.6 cm, mean distance between tumor and esophageal resection margin was 1.5 cm, and proportions of tumor invasion into the dentate line, nerves, and vessels were 80.0% (24/30), 86.7%(26/30), and 93.3% (28/30), respectively. The mean number of lymph nodes resected was 20.4±8.9. The pathological stage was mainly T4 (n=18, 60.0%) and N3 (n=21, 70.0%), the median Ki67 was 52.7%, and the rates of positivity for HER2, EGFR, VEGFR, E-cadherin and PD-L1 were 40.0% (12/30), 46.7% (14/30), 80.0% (24/30), 86.7% (26/30) and 16.7% (5/30), respectively. At the cellular level, cancer cells were mainly distributed in small focal areas, as cell masses, or as tumor thrombi; large numbers of widely distributed atypic cells were seldom observed. At the tissue level, cancer cells were located in the mucosal layer in seven patients (23.3%), in the submucosal layer in 18 (60.0%), and in the muscular layer in five (16.7%); no cancer cells were identified in the outer membrane. Five of the seven tumors were located in the lamina propria, two in the muscularis mucosae, and none in the mucosal epithelium. Conclusion: Patients with skip metastasis at the esophageal resection margin at radical gastrectomy have unfavorable tumor biology and a high proliferation index, are at a late pathological stage, and the residual cancer is mostly located in the submucosa.
Humans ; Male ; Middle Aged ; Aged ; Female ; Margins of Excision ; Adenocarcinoma/pathology* ; Carcinoma, Signet Ring Cell/pathology* ; Lymph Nodes/pathology* ; Adenocarcinoma, Mucinous/pathology* ; Stomach Neoplasms/pathology* ; Gastrectomy ; Neoplasm Staging ; Retrospective Studies

OBJECTIVE: To review the application and research progress of artificial intelligence (AI) technology in trauma treatment. METHODS: The recent research literature on the application of AI and related technologies in trauma treatment was reviewed and summarized in terms of prehospital assistance, in-hospital emergency care, and post-traumatic stress disorder risk regression prediction, meanwhile, the development trend of AI technology in trauma treatment were outlooked. RESULTS: The AI technology can rapidly analyze and manage large amount of clinical data to help doctors identify patients' situation of trauma and predict the risk of possible complications more accurately. The application of AI technology in surgical assistance and robotic operations can achieve precise surgical plan and treatment, reduce surgical risks, and shorten the operation time, so as to improve the efficiency and long-term effectiveness of the trauma treatment. CONCLUSION There is a promising future for the application of AI technology in the trauma treatment. However, it is still in the stage of exploration and development, and there are many difficulties of historical data bias, application condition limitations, as well as ethical and moral issues need to be solved.
Humans ; Artificial Intelligence ; Operative Time ; Robotic Surgical Procedures ; Technology

Background: The onset and progression of type 1 diabetes mellitus (T1DM) is closely related to autoimmunity. Effective monitoring of the immune system and developing targeted therapies are frontier fields in T1DM treatment. Currently, the most available tissue that reflects the immune system is peripheral blood mononuclear cells (PBMCs). Thus, the aim of this study was to identify key PBMC biomarkers of T1DM. Methods: Common differentially expressed genes (DEGs) were screened from the Gene Expression Omnibus (GEO) datasets GSE9006, GSE72377, and GSE55098, and PBMC mRNA expression in T1DM patients was compared with that in healthy participants by GEO2R. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network analyses of DEGs were performed using the Cytoscape, DAVID, and STRING databases. The vital hub genes were validated by reverse transcription-polymerase chain reaction using clinical samples. The disease-gene-drug interaction network was built using the Comparative Toxicogenomics Database (CTD) and Drug Gene Interaction Database (DGIdb). Results: We found that various biological functions or pathways related to the immune system and glucose metabolism changed in PBMCs from T1DM patients. In the PPI network, the DEGs of module 1 were significantly enriched in processes including inflammatory and immune responses and in pathways of proteoglycans in cancer. Moreover, we focused on four vital hub genes, namely, chitinase-3-like protein 1 (CHI3L1), C-X-C motif chemokine ligand 1 (CXCL1), matrix metallopeptidase 9 (MMP9), and granzyme B (GZMB), and confirmed them in clinical PBMC samples. Furthermore, the disease-gene-drug interaction network revealed the potential of key genes as reference markers in T1DM. Conclusion These results provide new insight into T1DM pathogenesis and novel biomarkers that could be widely representative reference indicators or potential therapeutic targets for clinical applications.

Intestinal failure (IF) is defined as the critical reduction of functional intestines below the minimum needed to absorb nutrients and fluids, so that intravenous supplementation with parenteral nutrition (PN) is required to maintain health and/or growth. Although the benefits are evident, patients receiving PN can suffer from serious cholestasis due to lack of enteral feeding and small intestinal bacterial overgrowth (SIBO). One such complication that may arise is intestinal failure-associated liver disease (IFALD). Evidences from recent studies suggest that alterations in the intestinal microbiota, as well as intraluminal bile acid driven signaling, may play a critical role in both hepatic and intestinal injury. Since Marshall first proposed the concept of the gut-liver axis in 1998, the role of gut-liver axis disorders in the development of IFALD has received considerable attention. The conversation between gut and liver is the key to maintain liver metabolism and intestinal homeostasis, which influences each other and is reciprocal causation. However, as a "forgotten organ" , intestinal microbiota on the pathogenesis of IFALD has not been well reflected. As such, we propose, for the first time, the concept of gut-microbiota-liver axis to emphasize the importance of intestinal microbiota in the interaction of gut-liver axis. Analysis and research on gut-microbiota-liver axis will be of great significance for understanding the pathogenesis of IFALD and improving the prevention and treatment measures.
Bacterial Infections/physiopathology* ; Bile Acids and Salts/physiology* ; Cholestasis/physiopathology* ; Enteral Nutrition ; Gastrointestinal Microbiome/physiology* ; Humans ; Intestinal Diseases/physiopathology* ; Intestines/physiopathology* ; Liver/physiopathology* ; Liver Diseases/physiopathology* ; Parenteral Nutrition/adverse effects* ; Short Bowel Syndrome/physiopathology* ; Signal Transduction

Objective:To evaluate the ability of Sysmex urine automatic analyzer UF-5000 to detect renal tubular epithelial cells, and to explore the value of detection of renal tubular epithelial cells in renal tubular injury of diabetes mellitus.Methods:Case control study. 452 urine samples were collected from the third Xiangya Third Hospital of Central South University from October 2018 to April 2019 (252 in the control group, 113 in diabetes without renal injury group and 87 in diabetes with renal injury group). All samples were detected by both UF-5000 and microscopic examination, established reference range for normal population, then contrasted the coincidence rate and uniformity of the two methods, to evaluate the ability of urine automatic analyzer UF-5000 to detect renal tubular epithelial cells, and the diagnostic value of tubular epithelial cells for renal tubular injury in diabetic patients. All statistical analyses were performed using SPSS17.0, Kappa consistency analysis, ROC curve analysis, Kruskal-Wallis test and Chi-square test were used.Results:The reference range of renal tubular epithelial cells by Sysmex urine automatic analyzer UF-5000 is 0-1.7/μl. The results of the two methods were analyzed by Kappa consistency analysis. The Kappa value was 0.699, P>0.05, which meant highly consistent. ROC curve analysis showed when cut-off value was 1.7/μl. The sensitivity, specificity and area under ROC curve were 0.791, 0.817 and 0.861 respectively. The median of renal tubular epithelial cells was 0.4/μl, 2.0/μl and 2.3/μl in the healthy control group, the diabetes without renal injury group and the diabetes with renal injury group, respectively; the positive rate of renal tubular epithelial cells in the three groups were 2.78%, 56.64% and 75.86% respectively. Compared with the control group, the median and positive rate of renal tubular epithelial cells in the diabetes without renal injury group and the diabetes with renal injury group were significant different; there was also significant difference in the positive rate of renal tubular epithelial cells between the two groups. Conclusion:Compared with the control group, the positive rate of urine renal tubular epithelial cells indiabetes without renal injury group is significantly higher, which is helpful to detect renal tubular injury, to carry out early intervention and to prolong the time of progression to chronic kidney disease.

Objective: To investigate the clinical manifestations, imaging features, clinicopathologic features, and differential diagnosis of solitary fibrous tumors/anginoblastomas (SFT/HPCs) originating in the central nervous system. Methods: Sixty cases of SFT/HPCs originating in the central nervous system were collected at Nanjing Jinling Hospital, from January 1, 2008 to December 31, 2016. The clinical data, imaging data, histomorphologic changes and immunohistochemical finding were analyzed in the sixty cases. Results: The 60 cases included 26 males and 34 females, aged 14 to 85 (median 49) years. The main clinical manifestations were headache, dizziness with nausea and vomiting. Radiologically, the tumors were large, enhancing, solid and cystic masses attached to the dura. Histopathologically, the neoplasms were composed of spindle cells with oval nuclei, inconspicuous nucleoli and moderate amount of eosinophilic cytoplasm arranged in fascicles with areas of hyalinized stroma, myxoid changes and a staghorn vascular pattern. Immunohistochemically, tumor cells of all cases were positive for vimentin (100.0%, 60/60), STAT6 (98.3%, 59/60), CD34 (61.7%, 37/60), and the tumor cells were typically positive for CD99, bcl-2, EMA and SSTR2 as well.Negative for S-100 protein, SOX10, E-cadherin, GFAP. Ki-67 index ranged from 1% to 50%. Forty cases were followed up for 6 to 82 months with average of 40 months, 30 patients were alive and 10 patients died. Conclusions Central nervous system SFT/HPCs can be aggressive and relapses may occur several years after diagnosis. STAT6 is highly sensitive and specific for the diagnosis. Complete tumor resection is optional treatment followed by radiotherapy and chemotherapy. There is a correlation between the prognosis and the location of the disease, the histological grade, Ki-67 index, and fusion gene variants.

Objective To investigate the changes of coagulatory function in septic rats induced by cecal ligation and puncture(CLP). Methods Cecal ligation and puncture(CLP)were performed to induce sepsis in SD rats. Coagulation indexes were detected at 8,16 and 48 h after operation, and histopathological changes of the lung, kidney, liver and spleen were examined using HE staining. Results The 12-day survival rate of the CLP-induced septic rats was 30%,with an acute onset and high mortality. In the acute phase of disease development of the CLP rats, the activated partial thromboplastin time(APTT)was prolonged(P<0.05)at 8 h,the prothrombin time(PT)was prolonged at 16 h (P<0.05), the factor XII activity in the endogenous coagulation pathway and the factor VII activity in the extrinsic coagulation pathway showed a transient inhibition, the thrombin time(TT)was prolonged at 48 h(P<0.01), and the content of fibrinogen(FIB)was increased gradually from 16 h(P<0.001). Among the other important coagulation and anticoagulation indexes,the number of platelets(PLT)was decreased gradually from 8 h(P<0.01),while the number of vWF:Ag increased gradually from 8 h(P<0.001). The D-dimer amount gradually increased from 16 h(P<0.05),and the amount of PS:Ag significantly decreased until 48 h(P<0.001). However, there was no significant change in the antithrombin-III(AT-Ⅲ)content. The histopathological examination showed that there are different degrees of damages in the lung,kidney,liver and spleen tissues,but no obvious venous thrombosis and bleeding were found. Conclusions In the acute phase,there is coagulatory dysfunction in the septic rats,however,no histopathological changes such as venous thrombosis and bleeding were observed in the lung,kidney,liver and spleen tissues due to coagulatory dysfunction.

OBJECTIVETo investigate the effects of microRNA(miRNA)-29b on the proliferation and migration of breast cancer cells and its molecular mechanism.

METHODSThe recombinant lentiviral expression vector (lenti-miRNA-29b) was constructed and transfected into 293T cells to obtain lentivirus particles that were used to infect breast cancer MCF-7 cells. Transfection efficiency of lenti-miRNA-29b in MCF-7 cells was identified by the expression of green fluorescent protein (GFP). The expression of miRNA-29b was detected by real-time PCR. The cell proliferation and migration were detected by CCK8 assay and Transwell assay, respectively. The bioinformatics softwares were used to predict and screen the downstream target genes regulated by miRNA-29b, which were verified by double luciferase reporter gene assay, RT-PCR and Western blot. The effects of screened target gene RTKN on the growth and migration of MCF-7 cells were verified by RTKN siRNA.

RESULTSRecombinant lentiviral expression vector of miRNA-29b were successfully constructed. About 90% and 60% of the breast cancer cells showed green fluorescence in lenti-miRNA-29b and lenti-miRNA-NC groups, respectively. The expression of miRNA-29b in lenti-miRNA-29b group increased significantly compared with the lenti-miRNA-NC group and blank control group (all<0.05); the proliferation and migration ability of MCF-7 cells significantly reduced compared with the control group (all<0.05). The screening with bioinformatics softwares found that the 3'UTR coding region RTKN had the binding site to miRNA-29b; the dual luciferase reporter gene assay showed that the luciferase activity decreased significantly after the MCF-7 cells were co-transfected with wild type RTKN-WT-3'UTR and miRNA-29b mimics report gene vector (<0.05). The RTKN proteins in MCF-7 cells were significantly decreased after transfection with siRNA-RTKN, and the proliferation and migration ability of MCF-7 cells were significantly reduced (all<0.05).

CONCLUSIONSMiRNA-29b can inhibit the proliferation, invasion and metastasis of breast cancer cells by inhibiting the expression of RTKN.

OBJECTIVETo investigate the factors which may influence the imatinib plasma concentration in Chinese patients with gastrointestinal stromal tumor(GIST), and to illuminate the significance of monitoring imatinib plasma concentration in adjuvant therapy for patients with GIST.

METHODSA cross-sectional study with 60 GIST patients who accepted the imatinib therapy after surgery was conducted. They were respectively administrated in 10 domestic hospitals from December 2014 to April 2016, including The First Affiliated Hospital of Nanjing Medical University(n=28), The Affiliated Hospital of Nantong University(n=9), The Affiliated Hospital of Xuzhou Medical College(n=6), Nanjing Drum Tower Hospital(n=5), The Second Affiliated Hospital of Nanjing Medical University (n=2), Jingling Hospital (n=2), The Second People's Hospital of Lianyungang(n=2), Shandong Provincial Hospital(n=2), Jiangsu Province Tumor Hospital(n=2), and The First Affiliated Hospital of Zhejiang University(n=2). Some specific time points for collecting blood sample before and after taking imatinib were determined, then liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used for monitoring imatinib plasma concentration in patients with GIST. Linear regression analysis was used for the correlation analysis of imatinib plasma concentration with dosage, clinicopathologic feature and side effect.

RESULTSPatients who could not tolerate 400 mg imatinib per day(n=3) received 300 mg per day. There was no significant difference in imatinib plasma concentration between patients with 300 mg and those with 400 mg imatinib(n=53)(P=0.527). However, the imatinib plasma concentration in patients with 600 mg imatinib per day (n=4) was significantly higher as compared to those with 400 mg(P=0.000). Linear regression analysis indicated a negative correlation between the imatinib plasma concentration in patients with 400mg imatinib per day for 90 days continuously and body surface area(R=0.074, P=0.035), but no significant correlations of with age, creatinine clearance and serum albumin concentration were observed (all P>0.05). The differences in imatinib plasma concentration were not statistically significant between patients of different gender and those taking proton-pump inhibitor (PPI) or not (both P>0.05). Difference in imatinib plasma concentration between patients with different surgery was significant (P=0.026). Compared to patients who underwent wedge resection, enterectomy and other surgeries, the imatinib plasma concentration of patients with subtotal gastrectomy or total gastrectomy decreased significantly (all P<0.05). After 90 days of taking imatinib continuously, linear regression analysis revealed a negative correlation between imatinib plasma concentration in patients with 400 mg imatinib per day and white blood cell count (R=0.103, P=0.013), and a positive correlation with serum alanine aminotransferase (ALT) concentration (R=0.076, P=0.033).

CONCLUSIONSThe imatinib plasma concentration in patients with larger body surface area, subtotal gastrectomy or total gastrectomy may be lower. For these patients, dosage of imatinib should be considered to increase in order to achieve effective plasma concentration. Excessive imatinib plasma concentration can result in some side effects, such as decrease of white blood cells and liver damage. Therefore, it is significant for receiving optimal clinical therapeutic efficacy to monitor imatinib plasma concentration, adjust imatinib dosage timely and keep imatinib plasma concentration in effective and safe range.

Adult ; Antineoplastic Agents ; administration & dosage ; pharmacokinetics ; Benzamides ; Combined Modality Therapy ; Cross-Sectional Studies ; Female ; Gastrectomy ; Gastrointestinal Stromal Tumors ; drug therapy ; surgery ; Humans ; Imatinib Mesylate ; administration & dosage ; pharmacokinetics ; Male ; Middle Aged ; Piperazines ; Pyrimidines ; Tandem Mass Spectrometry