BACKGROUND: Dysfunction of the gap junction channel protein connexin 43 (Cx43) contributes to myocardial ischemia/reperfusion (I/R)-induced ventricular arrhythmias. Cx43 can be regulated by small ubiquitin-like modifier (SUMO) modification. Protein inhibitor of activated STAT Y (PIASy) is an E3 SUMO ligase for its target proteins. However, whether Cx43 is a target protein of PIASy and whether Cx43 SUMOylation plays a role in I/R-induced arrhythmias are largely unknown. METHODS: Male Sprague-Dawley rats were infected with PIASy short hairpin ribonucleic acid (shRNA) using recombinant adeno-associated virus subtype 9 (rAAV9). Two weeks later, the rats were subjected to 45 min of left coronary artery occlusion followed by 2 h reperfusion. Electrocardiogram was recorded to assess arrhythmias. Rat ventricular tissues were collected for molecular biological measurements. RESULTS: Following 45 min of ischemia, QRS duration and QTc intervals statistically significantly increased, but these values decreased after transfecting PIASy shRNA. PIASy downregulation ameliorated ventricular arrhythmias induced by myocardial I/R, as evidenced by the decreased incidence of ventricular tachycardia and ventricular fibrillation, and reduced arrythmia score. In addition, myocardial I/R statistically significantly induced PIASy expression and Cx43 SUMOylation, accompanied by reduced Cx43 phosphorylation and plakophilin 2 (PKP2) expression. Moreover, PIASy downregulation remarkably reduced Cx43 SUMOylation, accompanied by increased Cx43 phosphorylation and PKP2 expression after I/R. CONCLUSION PIASy downregulation inhibited Cx43 SUMOylation and increased PKP2 expression, thereby improving ventricular arrhythmias in ischemic/reperfused rats heart.
Rats ; Male ; Animals ; Myocardial Reperfusion Injury/metabolism* ; Connexin 43/genetics* ; Sumoylation ; Down-Regulation ; Rats, Sprague-Dawley ; Arrhythmias, Cardiac/drug therapy* ; Myocardial Ischemia/metabolism* ; RNA, Small Interfering/metabolism*

Objective:To investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT.Methods:Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ2 test were used for comparison between the two groups. Results:The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P=0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions:The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.

Objective:To explore the clinical characteristics, diagnosis and treatment of acute leukemia patients during pregnancy.Methods:The clinical data of 16 cases with acute leukemia during pregnancy from January 2009 to December 2018 in the First Affiliated Hospital of USTC were retrospectively analyzed. The diagnosis and treatment regimens, pregnancy outcome, the early fetus and survival status of patients were also analyzed.Results:All 16 leukemia cases were confirmedly diagnosed and classified by bone marrow puncture, including 13 cases of acute myeloid leukemia (5 cases of non-acute promyelocytic leukemia and 8 cases of acute promyelocytic leukemia) and 3 cases of acute lymphoblastic leukemia. At the time of confirmed diagnosis, 6 patients were in first trimester, 6 cases in second trimester and 4 cases in late trimester. As for pregnancy outcome, 1 patient had natural birthing, 5 patients underwent cesarean operation, 9 patients underwent artificial abortion and 1 patient had spontaneous abortion. Chemotherapy was performed in 15 patients during pregnancy, 11 patients received chemotherapy for treatment of primary disease after pregnancy, 3 patients died during the treatment. During the follow-up of 13 cases, 8 patients survived and 5 patients lost follow-up.Conclusions:Early diagnosis of acute leukemia during pregnancy is very important. Bone marrow puncture should be performed timely to make clear diagnosis when blood routine result is abnormal during antenatal care. Multidisciplinary consultation should be initiated in time, and the best treatment plan should be worked out to guard against serious complications during pregnancy.

Objective:To investigate the effectiveness of an enhanced CT automatic recognition system based on Faster R-CNN for pancreatic cancer and its clinical value.Methods:In this study, 4 024 enhanced CT imaging sequences of 315 patients with pancreatic cancer from January 2013 to May 2016 at the Affiliated Hospital of Qingdao University were collected retrospectively, and 2 614 imaging sequences were input into the faster R-CNN system as training dataset to create an automatic image recognition model, which was then validated by reading 1 410 enhanced CT images of 135 cases of pancreatic cancer.In order to identify its effectiveness, 3 750 CT images of 150 patients with pancreatic lesions were read and a followed-up was carried out.The accuracy and recall rate in detecting nodules were recorded and regression curves were generated.In addition, the accuracy, sensitivity and specificity of Faster R-CNN diagnosis were analyzed, the ROC curves were generated and the area under the curves were calculated.Results:Based on the enhanced CT images of 135 cases, the area under the ROC curve was 0.927 calculated by Faster R-CNN. The accuracy, specificity and sensitivity were 0.902, 0.913 and 0.801 respectively.After the data of 150 patients with pancreatic cancer were verified, 893 CT images showed positive and 2 857 negative.Ninety-eight patients with pancreatic cancer were diagnosed by Faster R-CNN.After the follow-up, it was found that 53 cases were post-operatively proved to be pancreatic ductal carcinoma, 21 cases of pancreatic cystadenocarcinoma, 12 cases of pancreatic cystadenoma, 5 cases of pancreatic cyst, and 7 cases were untreated.During 5 to 17 months after operation, 6 patients died of abdominal tumor infiltration, liver and lung metastasis.Of the 52 patients who were diagnosed negative by Faster R-CNN, 9 were post-operatively proved to be pancreatic ductal carcinoma.Conclusion:Faster R-CNN system has clinical value in helping imaging physicians to diagnose pancreatic cancer.

Objective:To investigate the effectiveness of an enhanced CT automatic recognition system based on Faster R-CNN for pancreatic cancer and its clinical value.Methods:In this study, 4 024 enhanced CT imaging sequences of 315 patients with pancreatic cancer from January 2013 to May 2016 at the Affiliated Hospital of Qingdao University were collected retrospectively, and 2 614 imaging sequences were input into the faster R-CNN system as training dataset to create an automatic image recognition model, which was then validated by reading 1 410 enhanced CT images of 135 cases of pancreatic cancer.In order to identify its effectiveness, 3 750 CT images of 150 patients with pancreatic lesions were read and a followed-up was carried out.The accuracy and recall rate in detecting nodules were recorded and regression curves were generated.In addition, the accuracy, sensitivity and specificity of Faster R-CNN diagnosis were analyzed, the ROC curves were generated and the area under the curves were calculated.Results:Based on the enhanced CT images of 135 cases, the area under the ROC curve was 0.927 calculated by Faster R-CNN. The accuracy, specificity and sensitivity were 0.902, 0.913 and 0.801 respectively.After the data of 150 patients with pancreatic cancer were verified, 893 CT images showed positive and 2 857 negative.Ninety-eight patients with pancreatic cancer were diagnosed by Faster R-CNN.After the follow-up, it was found that 53 cases were post-operatively proved to be pancreatic ductal carcinoma, 21 cases of pancreatic cystadenocarcinoma, 12 cases of pancreatic cystadenoma, 5 cases of pancreatic cyst, and 7 cases were untreated.During 5 to 17 months after operation, 6 patients died of abdominal tumor infiltration, liver and lung metastasis.Of the 52 patients who were diagnosed negative by Faster R-CNN, 9 were post-operatively proved to be pancreatic ductal carcinoma.Conclusion:Faster R-CNN system has clinical value in helping imaging physicians to diagnose pancreatic cancer.

Objective: To examine the value and clinical application of convolutional neural network in pathological diagnosis of metastatic lymph nodes of gastric cancer. Methods: Totally 124 patients with advanced gastric cancer who underwent radical gastrectomy plus D2 lymphadenectomy at Affiliated Hospital of Qingdao University from July 2016 to December 2018 were selected in the study. According to the chronological order, the first 80 cases were served as learning group. The remaining 44 cases were served as verification group. There were 45 males and 35 females in the study group, with average age of 57.6 years. There were 29 males and 15 females in the validation group, with average age of 9.2 years. The pre-training convolutional neural network architecture Resnet50 was trained and fine-tuned by 21 352 patches with cancer areas and 14 997 patches without cancer areas in the training group. A total of 78 whole-slide image served as a test dataset including positive (n=38) and negative (n=40) lymph nodes. The convolutional neural network computer-aided detection (CNN-CAD) system was used to analyze the ability of convolutional neural network system to screen metastatic lymph nodes at the level of slice by setting threshold, and evaluate the system′s classification accuracy by calculating its sensitivity, specificity, positive predictive value, negative predictive value and area under the receiver operating characteristic curve (AUC). Results: The classification accuracy of CNN-CAD system at slice level was 100%.The AUC for the CNN-CAD system was 0.89. The sensitivity was 0.778, specificity was 0.995, overall accuracy was 0.989. Positive and negative predictive values were 0.822 and 0.994, respectively. The CNN-CAD system achieved the same classification results as pathologists. Conclusions The CNN-CAD system has been constructed to distinguished benign and malignant lymph node slides with high accuracy and specificity. It could achieve the similar classification results as pathologists.

OBJECTIVE: To compare the effects of robotic and laparoscopic-assisted radical total gastrectomy on lymph node dissection and short-term outcomes in patients with Siewert type II adenocarcinoma of esophagogastric junction (AEG). METHODS: Inclusion criteria: the tumor center was located between 2 cm above and below the esophagogastric junction and was confirmed as adenocarcinoma by endoscopic biopsy. EXCLUSION CRITERIA: tumor with local invasion of the liver,spleen, pancreas or other organs; intraoperative finding of tumor dissemination or distant metastasis; patients undergoing palliative surgical treatment or preoperative neoadjuvant chemotherapy; patients with serious heart diseases, lung diseases, liver diseases, kidney diseases and other comorbidities; patients with multiple primary cancers;patients receiving emergency surgery. According to the above criteria, 82 patients with Siewert type II AEG who underwent gastrointestinal surgery at the Affiliated Hospital of Qingdao University from October 2014 to October 2018 were enrolled in the study. They were randomly divided into robotic surgery groups (41 cases) and laparoscopic group (41 cases) according to a computer-generated randomized allocation table. Both groups underwent radical total gastrectomy plus D2 lymph node dissection through the transabdominal esophageal hiatus approach. The intraoperative conditions and postoperative short-term outcomes were compared between two groups, including surgery time, intraoperative blood loss, length of esophagectomy, postoperative complications, postoperative gastrointestinal recovery time, length of hospital stay, postoperative unplanned reoperation rate and rehospitalization rate. Mean±SD is used for the measurement data that conforms to the normal distribution, and two independent sample t-tests are used to compare the two groups; the comparison of the count data is performed by the χ² test. RESULTS: There were 35 males (85.4%) with age of (62.3±10.0) years and body mass index of (24.4±3.2) kg/m² in the robotic surgery group. There were 37 males (90.2%) with age of (62.5±10.0) years and body mass index of (23.8±2.6) kg/m² in the laparoscopic group. No significant differences in the baseline data between two groups were found (all P>0.05). All the patients of both groups completed R0 resection successfully without conversion to laparotomy or perioperative death. Compared with the laparoscopic group, the robotic group had less intraoperative blood loss [(70.7±39.9) ml vs. (110.2±70.6) ml, t=3.118, P=0.003], longer resected esophagus [(3.0±0.7) cm vs. (1.9±0.5) cm, t=8.759, P<0.001], but longer setup time [(56.5±7.4) minutes vs. (36.0±6.6) minutes, t=4.241, P<0.001], and higher hospitalization costs [(122 317.31±57 789.33) yuan vs. (99 401.56±39 349.53) yuan, t=2.099, P=0.039], whose differences were statistically significant (all P<0.05). The total number of harvested lymph node in the robotic surgery group was 39.2±15.3,which was significantly higher than that in the laparoscopic group (33.0±12.1) (t=0.733, P=0.047). In the robotic group and the laparoscopic group, the mediastinal lymph node No.110 and No.111 were 3.6±1.2 vs. 1.5±1.0 and 3.7±2.0 vs. 1.8±1.1, respectively, with significant difference (t=10.138, P<0.001, t=8.227, P<0.001); axillary lymph node No.19 and No.20 were 2.3±1.2 vs. 1.1±0.9 and 2.0±1.0 vs. 1.0±0.1, respectively, with significant difference (t=7.082, P<0.001,t=8.672,P<0.001). There were no significant differences in the total number of abdominal lymph node and the number of lymph node in abdominal stations between two group (all P>0.05). The highest lymph node metastasis rate was approximately 20% and observed in No.1, No.2, No.3, and No.7, followed by No.8a, No.9, No.11p, and No.110 with around 5%. The lymph node metastasis rate in other stations (No.4sa, No.4sb, No.4d, No.5, No.6, No.11d, No.12a, No.19, No.20 and No.111) was less than 5%.There were no significant differences in postoperative complication rate, postoperative fever time, postoperative exhaust and defecation time, fluid diet time, and postoperative hospital stay (all P>0.05). There were 2 patients(4.9%) with unplanned reoperation and 1 patient (2.4%) with unplanned re-admission in the laparoscopic group,while 3 patients (7.3%)with unplanned reoperation and 2 patients (4.9%)with unplanned re-admission in the robotic surgery group, whose differences were also not statistically significant (χ²=0.240,P=0.675;χ²=0.346,P=1.000). CONCLUSION Robot-assisted radical total gastrectomy for Siewert II AEG is safe and feasible, which is characterized by more sophisticated operation, less blood loss and higher quality of lymph node dissection, especially for subphrenic and inferior mediastinal lymph nodes.
Adenocarcinoma ; classification ; pathology ; surgery ; Aged ; Esophageal Neoplasms ; classification ; pathology ; surgery ; Esophagectomy ; Esophagogastric Junction ; pathology ; surgery ; Female ; Gastrectomy ; Humans ; Laparoscopy ; Lymph Node Excision ; methods ; Male ; Middle Aged ; Retrospective Studies ; Robotic Surgical Procedures ; Stomach Neoplasms ; classification ; pathology ; surgery ; Treatment Outcome

Objective To explore the effect of Protectin DX(PDX) on acute liver injury(ALI) induced by sepsis in mice and the underlying mechanism. Methods Mice received cecum ligation and puncture(CLP) to induce sepsis-associated acute liver injury. Male C57BL/6 mice were randomly (random number) divided into 3 groups (n=10 each group): (1) sham group (S group), (2) CLP group and (3) CLP +PDX group (PDX group ). Mice in the PDX group were received PDX 1 μg (intraperitoneal injection). One hour after CLP operation, mice in the S and CLP groups were received equal amounts of saline. The serum and liver tissues were collected at 24 h after CLP. The histological changes of the liver were observed by HE staining. The ALT and AST levels in the serum were assessed by using the automatic biochemical analyzer. The levels of cytokines (TNF-α, IL-6, IFN-γ and IL-10) in the serum were quantified by ELISA. MPO activity in the liver tissues were assessed. Western blot was used to detect the expression of pNF-kB p65 and NF-kB p65 in liver tissues. Results Compared with the S group, HE staining in the CLP group showed disordered hepatic cords, hepatocyte swelling and necrosis, infiltrations of inflammatory cells, congestion and bleeding, and the score of liver injury was increased significantly (P<0.05). Levels of ALT, AST, TNF-α, IL-6, IFN-γ, and IL-10 were increased in the CLP group (P<0.05). The activities of NF-κB and MPO in the liver tissues were obviously enhanced (P<0.05). The levels of liver injury, cytokines (TNF-α, IL-6, IFN-γ), MPO and activities of NF-κB in the CLP+PDX group were significantly decreased when compared with those in the CLP group (P<0.05),while the concentration of IL-10 was significantly increased (P<0.05). Conclusions PDX can alleviate sepsis-induced acute liver injury through inhibiting NF-KB activity in the liver tissues.

Objective To assess the effects of two different methods on differential cell count and the detection on inflammatory mediators in the process of induced sputum. Methods Induced sputum samples from outpatients with respiratory diseases were collected. Each sample was equally divided into two parts. One portion was processed at a regular way by incubation at 37 ℃ for 15 min in 0.1% dithiothreitol (DTT). Another was processed at 0 ℃ for 60 min in 0.1% DTT. The cell pellet was used for the cytology analysis by HE staining. The levels of IL-4,IL-5 and IL-8 were measured by Elisa Kit. Results Induced sputum was successfully collected from 20 subjects with chronic airway diseases ,including 7 males and 13 females . Total cell counts was lower in 0 ℃-incubated group than in 37 ℃-incubated group(P < 0.05). However,there was no difference in differential cell counts between two groups ,as well as the levels of IL-4 ,IL-5 and IL-8 in sputum supernatants(all P >0.05). Conclusions Except a difference in the total cell number ,there was no difference between two methods on the differential cell count and levels of certain inflammatory mediators.

Objective:To study the relationship among lipoprotein‐associated phospholipase A2 (Lp‐PLA2 ) gene A379V and T403V locus polymorphisms and genetic susceptibility of coronary heart disease (CHD) .Methods:Lp‐PLA2 gene A379V and T403V locus polymorphisms of 160 coronary angiography confirmed CHD patients (CHD group ) and 117 healthy subjects (healthy control group ) were measured using gene sequencing technique .ELISA was used to measure blood lipids and plasma Lp‐PLA2 level in two groups ,and they were compared between two groups . Results:Compared with healthy control group ,there were significant rise in age ,male proportion ,plasma levels of hs‐cTnI ,hsCRP ,TC ,LDL‐C , Lp (a) ,WBC ,mononuclear cells (MNCs) and Lp‐PLA2 [ (119.98 ± 49.41) ng/ml vs .(248.59 ± 76.51) ng/ml] ,and significant reduction in HDL‐C level in CHD group ( P<0.01 all) .The CC , CT , TT genotype and C , T allele were de‐tected all in A379V and T403C locus of two groups .Compared with healthy control group ,there were significant rise in frequencies of CC genotype (1.7% vs .9.3% ) and C allele (13.7% vs .20.3% ) of Lp‐PLA2 gene T403C locus in CHD group , P< 0.05 both . All genotypes and alleles of A379V locus possessed no significant difference between CHD and healthy control group . Conclusion:Plasma Lp‐PLA2 level may be related to CHD risk .Lp‐PLA2 gene T403C locus poly‐morphism possesses certain relationship with genetic susceptibility of CHD .