Pancreatic cancer is a rapidly progressive and highly malignancy of the digestive system. In recent years, the diagnosis and treatment of pancreatic cancer has been in a slow stage of development, and the 5-year survival rate of patients remains very low. The main objective of translational medicine is to remove the barriers between basic medical research and clinical medical applications, to achieve practical integration between laboratory and clinic, and to accelerate the translation of the results obtained from basic research into clinical diagnosis, evaluation and treatment of diseases, thus promoting the development of life sciences. With the rapid development of the concept and technology of translational medicine, its application in the early diagnosis of pancreatic cancer can bring new hope for effectively improving the overall prognosis of patients. The authors comprehensively analyzed the latest research progress of translational medicine in the early diagnosis of pancreatic cancer in order to improve the early diagnosis and long-term survival of pancreatic cancer patient.

Objective To discuss the value of intrapartum operation in management of birth defects and the prognosis. Methods From August 2008 to November 2009, 11 fetuses were identified with birth defects through 3D color Doppler ultrasound and confirmed by MRI and fetal karyotype in the Maternal Fetal Medicine Center, Affiliated Shengjing Hospital, China Medical University including three lymphangiomas,two congenital diaphragmatic hernias (CDH), one sacrococcygeal teratoma, three omphalocele and two gastroschisi. All the above identified birth defects were indications for surgery. All fetuses were born abdominally and received intrapartum operations, including three intrapartum fetal operations with placental infusion (two repairs of CDH, one sacrococcygeal teratoma resection), six ex-utero intrapartum treatment (EXIT; two repairs of omphalocele, two repairs of gastroschisi, two lymphangioma resection) and two surgeries in house (one omphalocele repair and one lymphangioma resection). Both the mothers and fetuses were regularly followed up. Results ( 1 ) Operations: the average operating time for the three intrapartum fetal operations was 89 minites, 5.5 minites for the six EXIT, during which EXIT was performed first,followed by blocking the umbilical circulation and neonatal surgery, and 37 minites for the two surgeries in house. All neonates survived except for one death from severe CDH at 3.5 hours after the operation. The average blood loss for cesarean section and fetal operation was 275 ml. All mothers recovered soon without fever or infection and were discharged three to five days after the operation. (2) Follow-ups: the ten survived neonates were followed up at 1 - 18 mouths at the pediatric clinics and all were growing and developing normally except for one baby with gastroschisi suffered from enteral torsion and feeding intolerance showed lower weight than babies at the same age, but catched up to normal at four months old after posture therapy. One baby with mild CDH developed pulmonary infection at two months after operation with 1/4 pneumothorax on chest X-ray, and were hospitalized for two weeks. At six months old, patent ductus arteriosus was diagnosed in the same baby and chest X-ray was normal. The baby with omphalocele was complicated with ventricular septal defect before operation and the cardiac function was normal during followups for one year. The baby with sacrococcygeal teratoma was reported to have no automatic micturition, but recovered to normal at one month of age. Conclusion Babies with certain birth defects can be managed through intrapartum operation with better outcomes.

Objective To investigate the expression variation of aquaporin in colon tissues in acute necrotizing pancreatitis (ANP).Methods ANP rat model was induced by the retrograde injection of sodium taurocholate into the biliopancreatic duct.The rats were killed at 4 h, 8 h, 12 h and 24 h after modeling with 6 rats for each time point.The pancreas and colon tissues were harvested for pathological examination.The levels of IL-6, TNF-α mRNA expression and AQR (aquaporin-3, aquaporin-4, aquaporin-8) mRNA expression in proximal and distant colon were detected by RT-PCR.The levels of aquaporin protein in colon were examined by immunohistochemistry.Results After the establishment of ANP SD rat model, the integrity of colonic mucosa was continuously damaged, the structure of epithelial cells was unclear and the colonic villus were broken and destroyed, and inflammatory cell infiltration in submucosa was observed.The pathological score increased with the time of modeling.In 4 h, except that the mRNA levels of AQP-4 in distal colon was not obviously changed, mRNA levels of IL-6 and TNF-α, mRNA and protein expression of AQP-3 and AQP-8 in the proximal and distal colon of ANP rats were significantly elevated compared with shame group (P<0.05).AQP-3 and AQP-8 mRNA in proximal colon of ANP rats reached its peak in 8 h after the establishment and AQP-4 mRNA peaked at 24 h.AQP-3 and AQP-4 mRNA in distant colon of ANP rats reached its peak in 8 h after the establishment and AQP-8 mRNA peaked at 24 h.Protein expression of AQP-3, AQP-4 and AQP-8 in proximal and distant colon was strongest in 12 h and 24 h after the establishment.Conclusions With the progression of the ANP, the expression levels of AQP-3, AQP-4 and AQP-8 in both proximal and distal colons were elevated in various degrees, indicating that the aquaporins may participate in water metabolism of colon during ANP.

Objective:To investigate the efficacy of Da Vinci robot-assisted surgery for mediastinal tumor, and summarize the value of Da Vinci system in mediastinal surgery.Methods:The clinical data of 339 cases of robot-assisted mediastinal mass in Shanghai Chest Hospital from April 2015 to September 2020 were retrospectively analyzed, to compare perioperative outcomes of robotic surgery and conventional video-assisted thoracoscopic surgery 2 949 cases.Results:All the operations were successfully completed as planned. No residual lesions, conversion or second operation was observed in the consecutive cohort. The operating time[(81.8±36.8)min vs.(95.6±58.3)min, P=0.015]and post-operation stay[(3.1±1.9)days vs.(3.8±2.3)days, P=0.002] were statistically shorter in robotic group than those inconventional thoracoscopic group. Intraoperative blood loss in two groups was similar[(43.2±22.6)ml vs.(44.0±33.4)ml, P>0.05]. Conclusion:The Da Vinci robot system in mediastinal surgery is safe and feasible with great perspective in the new age of minimally invasive thoracic surgery. Compared with thoracoscopic surgery, it can shorten the operation time and reduce the postoperative hospital stay. It has certain advantages in operator experience and patient recovery.

Objective To observe the effects of total enteral nutrition ( TEN) and early combined parenteral nutrition ( PEN+TEN) in patients with esophageal cancer after operation .Methods The prospective,random, controlled clinical trial was adopted.One hundred patients receiving esophageal cancer operation were randomly assigned to the TEN group (50 cases) and the PEN+TEN group(50 cases).The differences in nutritional status, inflammatory response, immune status and postop-erative complications were compared in the two groups before and after operation.Results The levels of total serum protein, albumin or retinol binding protein were higher in the PEN group than the TEN group at the 10th day after operation, respective-ly[(60.1 ±6.2)g/L vs(55.3 ±9.3)g/L,(36.4 ±4.2)g/L vs(34.6 ±1.6)g/L,(43.3 ±5.9)g/L vs(34.9 ±3.3)g/L, P<0.05] .The levels of ESR or CRP were higher in PEN +TEN group than the TEN group at the 10th day after operation, re-spectively [(54.9 ±25.8)mm/h vs(31.8 ±14.2)mm/h,(30.9 ±13.2)g/L vs(15.8 ±6.1)g/L, P<0.01] .The levels of CD3+, CD4 +, or CD8 +were higher at the 10 th day after operation than at the day before surgery in TEN group [(59.6 ±9.8)％vs(68.3 ±4.4)％,(41.7 ±7.8)％vs(46.5 ±5.5)％,(23.2 ±5.5)％vs(20.0 ±2.7)％, P<0.05], but not in PEN+TEN group.The levels of IgA or IgG were significant higher in the TEN group than the PEN +TEN group at the 10th day after operation[(1.9 ±0.5)g/L vs(1.6 ±0.3)g/L,(11.9 ±3.3)g/L vs(9.4 ±2.2)g/L, P<0.01].Con-clusion The inflammatory reaction and immune function in TEN group are better than those in PEN +TEN group.Although the nutritional status is worse in the TEN group than that in the PEN group , but the rate of postoperative complications has not increased.

In recent years, with the continuous studies on tumor metabonomics, more and more results have shown that changes of metabolism play important roles in the occurrence and development of malignant tumor. Carcinogenic factors can destroy the metabolic balance of human body, induce metabolic reprogramming, and then mediate a variety of biological behaviors to partici-pate in the proliferation and invasion of cancer cells. Lipids provide the body with the necessary energy and essential fatty acids, and a variety of lipid molecules and metabolites are involved in cell signal transduction. Lipid metabolism is an important link in the metabolic system of the body, and the relationship between the occurrence and development of pancreatic cancer and lipid metabo-lism is not clear. The purpose of this paper is to reveal the changes of lipid metabolism in pancreatic cancer, summarize some preclinical studies and clinical trials, and deeply explain the research status of abnormal lipid metabolism associated with pancreatic cancer, so as to provide new ideas for the study of pancreatic cancer pathogenesis and accurate treatment.

Objective:To investigate the clinical features, risk factors and prognosis of Clostridium difficile infection/colonization (CDI/CDC) in emergency intensive care unit (EICU) of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, then provides theoretical basis for clinical treatment. Methods:A retrospective case-control study was conducted. The data of EICU patients admitted to Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from June 2016 to June 2020 were collected. Taking the CDI/CDC patients as research objects [ Clostridium difficile (CD) positive group] and the CD negative patients with the same gender and age difference less than 5 years who were admitted to the hospital during the same period as the control (CD negative group). Demographic information, risk factors, prognosis and stool samples were collected. Single factor analysis and binary Logistic regression were used to analyze the CD positive infection rate, risk factors, and hospital death of patients with different clinical characteristics. Results:About 487 patients in EICU were included, 76 cases were taken into CD positive group, CD positive rate was 15.6%, including CDI 11 cases, CDC 65 cases. Among the CD positive group, all of the cases used proton pump inhibitor (PPI), and 75 cases used at least one antibiotic. Seventy-six CD negative patients with or without diarrhea (CD negative group) were included in this study. Among them, 75 patients used PPI and 74 patients used at least one antibiotic. Univariate analysis showed that acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), duration of hospitalization, and carbapenem use were the risk factors for CDI/CDC. There were significant differences in the above indicators between CD positive group and CD negative group [APACHEⅡ: 18.0 (12.2, 25.8) vs. 10.0 (7.0, 14.0), duration of hospitalization (days): 46.0 (30.5, 72.5) vs. 18.5 (9.2, 37.0), proportion of carbapenems: 81.6% (62/76) vs. 64.5% (49/76), all P < 0.05]. Binary Logistic analysis regression analysis showed that APACHEⅡ score [odds ratio ( OR) = 0.802, 95% confidence interval (95% CI) was 0.730-0.882, P < 0.01] and duration of hospitalization ( OR = 0.960, 95% CI was 0.942-0.978, P < 0.01) were independent risk factors for CDI/CDC. There was no difference in overall mortality between the CD positive group and CD negative group [27.6% (21/76) vs. 38.2% (29/76), P = 0.167]. Conclusions:Critically ill patients in EICU routinely use PPI and antibiotics, and the use of antibiotics does not affect the CD positive rate. The independent risk factors of CDI/CDC are the APACHEⅡ score and the duration of hospitalization, but fecal CD positive has no obvious influence on death.

Thymic epithelial tumors are the most common tumors in anterior mediastinum. They are used to be considered rare in incidence, with an indolent nature of biological behaviors, which led to the lack of high level evidence obtained from prospective randomized controlled trials to guide the clinical treatment. At present, the experience of diagnosis and treatment of thymic tumors varies greatly in different regions. And there are still many problems remain to be solved. This paper aims to establish a standardized surgical treatment based on the latest researches in surgical indications, resection extent, surgical approach, lymph node dissection and postoperative management of thymic tumors.

ObjectiveTo investigate the mechanism of action and main active components of Xiaoyaosan in the treatment of diabetic mellitus-induced erectile dysfunction （DMED）. MethodStreptozotocin （STZ） was used to induce a diabetic rat model. The therapeutic efficacy of Xiaoyaosan was evaluated by measuring intracavernous pressure/mean arterial pressure （ICP/MAP） and using Masson's trichrome staining. The main active components， key targets， and potential signaling pathways of Xiaoyaosan for the treatment of DMED were predicted by network pharmacology and molecular docking. The predicted results were then validated by in vitro and in vivo experiments. ResultThe ICP/MAP measurements and Masson's staining results showed that compared with the results in the control group， the erectile function of rats in the model group was significantly reduced （P<0.01）， and the ratio of smooth muscle/collagen fibers was significantly reduced （P<0.01）. After treatment with Xiaoyaosan， compared with the results in the model group， the ICP/MAP value of the diabetic rats was significantly elevated （P<0.01）， and the ratio of smooth muscle/collagen fibers was significantly higher （P<0.01）. The results of network pharmacology showed that Xiaoyaosan acted on key targets such as albumin （ALB）， protein kinase B1 （Akt1）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF） through its main active components， including quercetin， kaempferol， β-sitosterol， and stigmasterol. These components were involved in the regulation of the advanced glycation end-products/receptor for advanced glycation end-products （AGE/RAGE） signaling pathway and the phosphoinositide 3-kinases（PI3K）/Akt signaling pathway in diabetic complications. The results of molecular docking showed that the key components of Xiaoyaosan had good binding capabilities with core targets， with β-sitosterol showing the strongest binding affinity with ALB. In vivo experiments demonstrated that Xiaoyaosan could significantly increase the protein and mRNA expression of ALB and Akt1 in serum， and inhibit the expression of IL-6 and TNF-α. It also significantly upregulated the expression of protein and mRNA of phosphorylation（p）-PI3K and p-Akt， and inhibited the RAGE expression. The results of cellular thermal shift assay （CETSA） showed that β-sitosterol could significantly inhibit the degradation of ALB protein. ConclusionXiaoyaosan may restore erectile function in diabetic rats by modulating targets such as ALB， Akt1， IL-6， and TNF， and through the RAGE/PI3K/Akt signaling pathway， and its main active component is likely β-sitosterol.

Genome-scale metabolic network models have been successfully applied to guide metabolic engineering. However, the conventional flux balance analysis only considers stoichiometry and reaction direction constraints, and the simulation results cannot accurately describe certain phenomena such as overflow metabolism and diauxie growth on two substrates. Recently, researchers proposed new constraint-based methods to simulate the cellular behavior under different conditions more precisely by introducing new constraints such as limited enzyme content and thermodynamics feasibility. Here we review several enzyme-constrained models, giving a comprehensive introduction on the biological basis and mathematical representation for the enzyme constraint, the optimization function, the impact on the calculated flux distribution and their application in identification of metabolic engineering targets. The main problems in these existing methods and the perspectives on this emerging research field are also discussed. By introducing new constraints, metabolic network models can simulate and predict cellular behavior under various environmental and genetic perturbations more accurately, and thus can provide more reliable guidance to strain engineering.
Enzymes ; metabolism ; Genome ; genetics ; Metabolic Engineering ; Metabolic Networks and Pathways ; genetics ; Models, Biological ; Thermodynamics