AIM: To investigate the effects of human umbilical cord-derived mesenchymal stem cells ( hUC-MSCs) on the proliferation and migration of osteosarcoma cells ( Saos-2 ) and the underlying molecular mechanism. METHODS:hUC-MSCs were isolated and cultured by tissue explants adherent method.The cell surface markers on hUC-MSCs were identified by flow cytometry.The effects of conditioned medium ( CM) from hUC-MSCs ( hUC-MSCs-CM) , re-combinant human interleukin-6 (rhIL-6) and IL-6 neutralizing antibody on the proliferation of Saos-2 cells were detected by CCK-8 assay and cell counting.IL-6 secretion of hUC-MSCs was assayed by ELISA.RT-PCR was used to assess the tran-scription level of proliferation-related genes proliferating cell nuclear antigen ( PCNA) , cyclin D1 and survivin.The migra-tion potential of hUC-MSCs and Saos-2 cells was measured by Transwell assay.RESULTS:hUC-MSCs migrated to Saos-2 cells.hUC-MSCs-CM contained a high concentration of IL-6, up to (1 835.5 ±134.1) ng/L.hUC-MSCs-CM and rhIL-6 promoted the proliferation and migration of Saos-2 cells.Addition of neutralizing antibody against IL-6 in the hUC-MSCs-CM impaired this proliferation and migration of Saos-2 cells.The mRNA expression of PCNA, cyclin D1 and survivin was up-regulated by hUC-MSCs-CM and rhIL-6, while this effect was dramatically attenuated by treatment with IL-6 neutralizing antibody.CONCLUSION:hUC-MSCs migrate to osteosarcoma cells and promote the proliferation and migration of osteo-sarcoma cells through secreting IL-6 in vitro.

Objective To evaluate the clinical effects of the Masquelet technique combined with antibiotic calcium sulfate pellets in treating infected bone defects.Methods From February 2014 to February 2016,9 patients with infected bone defects were treated in our department,including 7 males and 2 females,with an average age of 37.0 years (range,24-56 years).6 cases were infected because of open fractures,3 infected after internal fixation operation.All defects were located in the lower limb diaphysis and metaphysis (3 cases in femur,6 cases in tibia).The length of the bone defects were 4-12 cm after debridement,all defects filled with PMMA loaded with Vancomycin,and fixed with exterual fixators.After 6-10 weeks,the bone cement spacers were taken out and the antibiotic calcium sulfate pellets were implanted into the membrane.A certain amount of autogenous cancellous bone granules would be mixed into the calcium sulfate pellets if the defect was larger than 6-8 cm.5 cases remained fixed with external fixators,3 cases replaced for plates,1 case replaced for plaster external fixator.Regular X-ray follow-ups were taken and complications recorded as well.Evaluate the healing of bone defect and functional recovery of adjacent joints by Samantha X score system,visual analogue scale (VAS) and Paley method,respectively.Results The 9 cases were followed up for a mean duration of 9.3 months (range,6-15 months).All bone defects healed after a mean time of 14 weeks (range,10-24 weeks).The wound poor healing occurred in only 1 case in the first stage of surgery,and cured by dressing changes.No complications of the recurrence of infection and implant failure.At the last follow-up,the average Samantha X score was 4.9,the VAS score was 0 to 3 (average 1.5) for patients standing on crutches and all the bone defect healing graded excellent evaluated by Paley method,the functional recovery of the adjacent joints graded:excellent in 6 cases,good in 2 cases,and fair in 1 case (the excellent and good rate was 89％).Conclusion Masquelet technique combined with antibiotic calcium sulfate particles is effective in the treatment of infected bone defects.

Objective To summarize the clinical experience of successful liver transplantation from infant donation after cardiac death (DCD) for infant with biliary astresia (BA).Methods The donor was a 16-months-old girl with a body weight of 10 kg,who died of irreversible anoxic cerebral damage after sudden asphyxiation.The recipient was a 24-months-old girl with a body weight of 12 kg,who suffered from icteric concurrent late biliary cirrhosis after the Porta-jejunum anastomosis because of congenital BA.The DCD liver was classically orthotopically transplanted into the infants recipient.The warm ischemia time was 7 min,the cold ischemia time was 360 min,and the graft volume to the standard liver volume (GV/SLV) was 1.02.After operation,the vital signs and transplanted liver function of the recipient were monitored,and the recipient was given treatments of anti-infection,anticoagulation,and improving the microcirculation.The recipient was treated with the triple immunosuppression protocol of tacrolimus,mycophenolate and prednisone to prevent rejection.Results The operating time of the recipient was 480 min,the non-liver stage was 65 min,and the blood loss was 230 mL.The endotracheal intubation was removed from the recipient at 12 h,and the recipient started to eat at 48 h aftcr operation.The recipient had a hepatic artery thrombus on the 3rd and 15th day after operation,and the hepatic artery had re-blood-supply after the hepatic artery catheterization and continuous perfusion with urokinase.The recipient was discharged on the 42nd day,and the recipient was in satisfactory condition to present.Conclusion The infant DCD liver is a better graft for infant liver transplantation for BA.The surgical complications can be reduced with matched volume of donor-recipient liver; and it can guarantee a successful operation with perfect operative technique and careful perioperative management.

Objective To investigate the Influence of beta-thalassemia minor on four different HbA1c detection systems.Methods All 65 blood samples from March 2014 to August 2014 were collected from Zhongshan Hospital of Sun Yat-sen University , and divided to normal control group ( 40 cases ) , no diabetic group(20 cases) and diabetic group (5 cases) combining with beta-thalassemia minor.The fresh mixed whole-blood samples were used for transferring value-assignment in order to improve the comparability of Bio-Rad variant ⅡTurbo, Primus Ultra2 ,Roche Modular PPI to Bio-Rad Variant Ⅱwhich was NGSP Ⅰlaboratory certificated.The whole-blood concentration of HbA 1c were measured by four detection systems . Differences between normal control group and no diabetic group were compared using the Independent Samples T Test.Then Taking the Primus Ultra 2 as comparable system and others as experimental system ,the HbA1c results from no diabetic group and diabetic group were compared by the standardization NGSP Ⅰlaboratory and statistical techniques of consistency test .Results Compared with Variant Ⅱ detection system, after transferring value-assignment, deviations of Variant Ⅱ, Modular PPI and Variant Ⅱ Turbo were -6%to +6%.The HbA1c testing results from normal control group and no diabetic group had no statistical significance (P>0.05).Linear regression analysis demonstrated that the correlation coefficient of Primus Ultra2 with Variant Ⅱ, Modular PPI, VariantⅡTurbo were 0.995, 0.999 and 0.995, respectively (P<0.01).The percentage deviation of the reference system and experimental system was -6.0% to+6.0%.Conclusion There was no obviously significant influence of beta-thalassemia minor on Bio-Rad Variant Ⅱ,Bio-Rad variant ⅡTurbo,Primus Ultra2,Roche Modular PPI detection systems.

Accurate identification of compound-protein interactions (CPIs) in silico may deepen our understanding of the underlying mechanisms of drug action and thus remarkably facilitate drug discovery and development. Conventional similarity-or docking-based computational methods for predicting CPIs rarely exploit latent features from currently available large-scale unlabeled com-pound and protein data and often limit their usage to relatively small-scale datasets. In the present study, we propose DeepCPI, a novel general and scalable computational framework that combines effective feature embedding (a technique of representation learning) with powerful deep learning methods to accurately predict CPIs at a large scale. DeepCPI automatically learns the implicit yet expressive low-dimensional features of compounds and proteins from a massive amount of unla-beled data. Evaluations of the measured CPIs in large-scale databases, such as ChEMBL and Bind-ingDB, as well as of the known drug-target interactions from DrugBank, demonstrated the superior predictive performance of DeepCPI. Furthermore, several interactions among small-molecule compounds and three G protein-coupled receptor targets (glucagon-like peptide-1 recep-tor, glucagon receptor, and vasoactive intestinal peptide receptor) predicted using DeepCPI were experimentally validated. The present study suggests that DeepCPI is a useful and powerful tool for drug discovery and repositioning. The source code of DeepCPI can be downloaded from https://github.com/FangpingWan/DeepCPI.

The protective efficacy of DNA plasmids encoding avian infectious bronchitis virus (IBV) S1, N, or M protein was investigated in chickens. Chickens were inoculated monovalently (with plasmid pVAX1-16S1, pVAX1-16M, or pVAX1-16N alone) or multivalently (combination of the three different plasmids, pVAX1-16S1/M/N). A prime-boost immunization protocol against IBV was developed. Chickens were immunized with the multivalent DNA vaccine twice and then boosted with an inactivated vaccine once. Antibody titers of the chickens immunized with pVAX1-16S1/M/N were much higher than those of the monovalent groups (p < 0.01). A protective rate up to 90% was observed in the pVAX1-16S1/M/N group. The serum antibody titers in the prime-boost birds were significantly higher than those of the multivalent DNA vaccine group (p < 0.01) but not significantly different compared to the inactivated vaccine group at 49 days of age. Additionally, the prime-boost group also showed the highest level of IBV-specific cellular proliferation compared to the monovalent groups (p < 0.01) but no significant difference was found compared to the multivalent DNA vaccine group, and the prime-boost group completely protected from followed viral challenge.
Aging ; Animals ; Antibodies, Viral/blood ; Cell Proliferation ; Chickens ; Coronavirus Infections/prevention & control/*veterinary/virology ; Immunization, Secondary/veterinary ; Infectious bronchitis virus/*immunology ; Poultry Diseases/*prevention & control/virology ; T-Lymphocyte Subsets/cytology/physiology ; Vaccines, DNA/immunology ; Vaccines, Inactivated/immunology ; Viral Vaccines/*immunology

Objective To construct an objective analysis system of corneal nerve tortuosity and detect the changes of corneal subbasal nerve tortuosity in patients with dry eye and diabetes. Methods GradeⅠtoⅣnerve tortuosity were evaluated and 80 photos of each grade were randomly chosen from the in vivo confocal microscopy library. Nerve fibers were extracted,segmented and then analyzed by 6 tortuosity related parameters including L C, Seg L C mean,Cur mean,Specific p,ICM and SCC mean. After verifying the validaty of parameters above,a cross-sectional study was conducted. Subjects were collected from June,2018 to February,2019 in Peking University Third Hospital,and were divided into healthy control group (28 persons 56 eyes),dry eye without diabetes group (28 patients 56 eyes),diabetes without dry eye group(24 patients 48 eyes),diabetes with dry eye group (23 patients 46 eyes) . Basic and dry eye information includes sex,age,ocular surface disease index ( OSDI) ,tear film break-up time (TBUT),Schirmer Ⅰ test (SⅠt) and corneal fluorescence staining (CFS) score. Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) were detected in diabetic patients. Cochet-Bonnet examination (C-BE) was detected to evaluate corneal sensation and 2 corneal subbasal nerve photos of each eye were selected for effective tortuosity and density related parameters analysis. Data was analyzed by SPSS and diagnostic test were perfomed by MedCalc. This study followed the Declaration of Helsinki. This study protocol was approved by Ethic Committee of Peking University Third Hospital ( No. IRB00006761-M2017354 ) . Written informed consent was obtained from each subject prior to entering study cohort. Results L C,Seg L C mean,Cur mean,Specific p,ICM and SCC mean increased as the nerve tortuosity increased from Grade Ⅰ to Grade Ⅳ,with an overall significance among 4 groups (F=39. 100, 36. 367,57. 743,4. 043,6. 818,33. 493;all at P<0. 01). Among the above 6 parameters,Cur mean and L C of any two groups were of significant difference (all at P<0. 01). Twenty three to twenty eight persons were enrolled in each group of the cross-sectional study. Sex and age were comparable among 4 groups. Diagnostic criteria were met in dry eye and diabetes. Corneal sensation parameter C-BE decreased in diabetes without dry eye group and diabetes with dry eye group compared with healthy control group ( all at Adj P<0. 05 ) , other than in dry eye without diabetes group (AdjP≥0. 05). Nerve density of diabetes without dry eye group and diabetes with dry eye group was lower compared with healthy control group(all at P<0. 001),while no significant difference between dry eye without diabetes group and healthy control group(P≥0. 05). Among the effective parameters of tortuosity,L C,Cur mean,Seg L C mean and SCC mean of dry eye without diabetes group,diabetes without dry eye group,diabetes with dry eye group were higher compared with healthy control group ( all at P<0. 05 ) . Diagnostic tests of tortuosity related parameters all showed an area under curve (AUC) from 0. 5 to 0. 7. Conclusions L C and Cur mean can be used to analyze corneal nerve curvature more reliably. Compared with normal volunteers,patients of dry eye or diabetes show higher corneal subbasal nerve tortuosity.

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.