AIM:To investigate the effect of urantide on the liver function and histomorphology in the rats with atherosclerosis (AS).METHODS:The AS Wistar rat model was induced by intraperitoneal injection of vitamin D3 (VD3) and feeding with high-fat diet.The rats were randomly divided into normal control group, AS model group, positive medicine group and urantide group.The liver function indexes of the rats were measured by biochemical test, and the pathological changes of the aorta and liver of the rats were observed by hematoxylin-eosin (HE) staining.The mRNA expression of urotensinⅡ (UII) and GPR14 at mRNA and protein levels in rat livers was determined by RT-qPCR and Western blot.RESULTS:The levels of alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , γ-glutamyltransferase (γ-GT) , lactate dehydrogenase (LDH) , total bilirubin (TBIL) , indirect bilirubin (IBIL) and alkaline phosphatase (ALP) in AS model group were significantly increased compared with normal control group (P<0.05).The above indexes in urantide group were remarkably decreased compared with AS model group (P<0.05).No change of the levels of direct bilirubin (DBIL) , total protein (TP) , globulin (GLB) and albumin (ALB) in each group was observed.Urantide postponed hepatocyte fatty degeneration and repaired hepatocyte injury in the AS rats.Compared with normal control group, the mRNA and protein levels of UII and GPR14 in the liver were significantly increased in AS model group (P<0.05).With the prolongation of dosing time, the mRNA and protein levels of UII and GPR14 in the liver were significantly decreased in urantide group compared with AS model group (P<0.05).CONCLUSION:Urantide significantly attenuates the liver damage caused by liver fatty degeneration in AS rats.

Objective To investigate the effects and safety of short-term telbivudine intervention on blocking mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in pregnant women with hepatitis B e antigens (HBeAg) positive during mid-gestation. Methods Fifty-four chronic HBV infection pregnant women with HBeAg positive from November 2016 to November 2017 in Dalian Sixth People′s Hospital Affiliated to Dalian Medical University were selected, and the serum HBV DNA (logarithmic transformation) of pregnant women was ≥1010 U/L. The pregnant women began oral telbivudine 600 mg at the 24th week of pregnancy, 1 time/d, and stopped at the day of delivery. The neonates were injected 10 μg hepatitis B vaccine and 100 U HBV immunoglobin 12 h after parturition, and they were injected 10 μg hepatitis B vaccine at 1 and 6 months of birth. The HBV DNA, creatine kinase (CK), alanine aminotransferase (ALT) and total bilirubin (TBIL) at 12th, 24th, 28th, 32th week of pregnancy and 1, 7 months after parturition were detected. The hepatitis B surface antibody (HBsAb) and hepatitis B surface antigen (HBsAg) of infants during 28 to 32 weeks of birth were detected. Results There were no statistical differences in CK, ALT and TBIL of 54 pregnant women (P＞0.05). The HBV DNA at 28th, 32th week of pregnancy and 1 month after parturition was significantly lower than that at 12th week of pregnancy (5.7 ± 2.2, 5.1 ± 2.3 and 8.3 ± 1.7 vs. 9.5 ± 1.0), and there was statistical difference (P＜0.05); there was no statistical difference between 7 months and 12th week of pregnancy after parturition (P＞0.05). During 28 to 30 weeks of birth, all the neonates showed serum HBsAb>109 U/L and HBsAg < 30 U/L. Conclusions Short-term intervention with telbivudine in mid-gestation for pregnant women infected with HBV could significantly reduce the level of serum HBV-DNA to the safety level or below. The adverse effects are not found during the telbivudine intervention period. Of note, after drug withdrawal, the HBV DNA level will rebound variously. The virus related detection conducted on the neonates indicates that short-term telbivudine intervention can realize complete MTCT blocking.

BACKGROUND:Icariin can promote bone formation and inhibit bone resorption,but it is difficult to dissolve in water,and its bioavailability is very low in vivo.Therefore,a suitable carrier is essential to fully utilize the biological activity of icariin.OBJECTIVE:To prepare an icariin/β-tricalcium phosphate (β-TCP) composite scaffold and to characterize its biological characteristics.METHODS:Three-dimensional printing technology was utilized to prepare porous β-TCP scaffolds carrying nano zinc oxide,and the compressive strength of porous β-TCP scaffolds was detected before and after addition of nano zinc oxide.Water absorption and porosity of the porous β-TCP scaffolds were also measured.Ultrasonic emulsification solvent dialysis was performed to prepare icariin/poly(lactic-co-glycolic acid) (PLGA) microspheres,followed by the detection of water absorption and porosity.The porous β-TCP scaffolds and icariin/PLGA microsphere suspension were mixed to prepare icariin/β-TCP composite scaffolds.Microstructure observation of the composite scaffolds was done by scanning electron microscope,and meanwhile,water absorption and porosity were detected.The composite scaffold was then immersed into PBS,and icariin concentration in the supematant was measured at corresponding time points,based on which Icariin cumulative release curve was drawn.RESULTS AND CONCLUSION:(1) The porous microstructure of the porous β-TCP scaffold was regular,well distributed,and the connectivity was good.The pore spacing was about 600 μm.After addition of nano zinc oxide particles,the surface structure of the scaffold was more compact and the crystallinity was higher.(2) PLGA microspheres were spherical with a diameter of 1-4 μm,and the microspheres were uniform in size.(3) The maximum compressive strength of the porous beta tricalcium phosphate scaffold was (2.98±0.78) MPa,and increased to (8.95±0.29) MPa after addition of nano zinc oxide.(4) The water absorption rate and porosity were (25.09±0.96)％ and (66.93±2.84)％ for the porous β-TCP scaffold,(28.46±1.85)％ and (32.65±3.32)％ for the icariin/β-TCP composite scaffold,respectively.(5)The average encapsulation efficiency of the PLGA microspheres was (78.87±2.31)％,and the drug loading was (6.04±1)％.(6) The release amount of icariin could reach 52％ of the total amount at 16 days and 60％ of the total amount at 32 days.These findings indicate that the icariin/β-TCP composite scaffold has good mechanical properties and sustained-release performance.

Objective To investigate the variation of renal pelvic pressure during percutaneous nephrolithotomy (PCNL) via standard nephrostomy tract and explore its influence on renal function. Methods 156 patients with renal calculi were selected for PCNL in standard-tract. The patients were divided into normal, mild hydronephrosis, moderate hydronephrosis groups according to the image by color Doppler ultrasonograph. A transurethral 6F ureteral catheter was inserted into renal pelvis and connected to the pressure monitering system before PCNL. During the operations, all the nephrostomy tracts were dilated to F24 size after successful puncture. Energy used was pneumatic and ultrasound lithotripsy. Renal function of the patients was evaluated with glomerular filtration rate (GFR) determined by 99mTc-DTPA dynamic renal imaging before and one week after PCNL. Data were analyzed by SPSS 19.0 software. Results The stone clearance rate was 75.0％ in one-session procedure. Severe complications did not occur during the operation, such as hemorrhage needing nephrectomy and abdominal organ injury or pneumothorax. There were no statistically significant differences between normal and mild hydronephrosis groups for the variation of renal pelvic pressure during preoperative versus intraoperative PCNL (P > 0.05). The renal pelvic pressure was significantly higher during operation than those of preoperation in moderate hydronephrosis group (P < 0.05), and it was greater than those of normal and mild hydronephrosis groups during operation (P < 0.05). Renal pelvic pressure generally remained lower than a level to 30.00 mmHg. There were no significant differences of preoperative and postoperative glomerular filtration rate in all the groups (P > 0.05). Conclusions There were no significant differences on the renal pelvic pressure in normal group and mild hydronephrosis group during operation via standard nephrostomy tract. It should be careful to maintain the lower intrapelvic pressure in order to avoid reflux and infection in moderate hydronephrosis group. Percutaneous nephrolithotomy via standard- tract does not cause significant effects on glomerular filtration rate during the perioperative period of PCNL .

The maxilla is the most important bony support of the mid-face skeleton and is critical for both esthetics and function.Maxillary defects,resulting from tumor resection,can cause severe functional and cosmetic deformities.Furthermore,maxillary reconstruction presents a great challenge for oral and maxillofacial surgeons.Nowadays,vascularized composite bone flap transfer has been widely used for functional maxillary reconstruction.In the last decade,we have performed a comprehensive research on functional maxillary reconstruction with free fibula flap and reported excellent functional and acceptable esthetic results.However,this experience based clinical procedure still remainssome problems in accuracy and efficiency.In recent years,computer assisted techniques are now widely used in oral and maxillofacial surgery.We have performed a series of study on maxillary reconstruction with computer assisted techniques.The computer assisted techniques used for maxillary reconstruction mainly include:(1) Three dimensional (3 D) reconstruction and tumor mapping:providing a 3 D view of maxillary tumor and adjacent structures and helping to make the diagnosis of maxillary tumor accurate and objective;(2) Virtual planning:simulating tumor resection and maxillectomy as well as fibula reconstruction on the computer,so that to make an ideal surgical plan;(3) 3D printing:producing a 3D stereo model for prebending individualized titanium mesh and also providing template or cutting guide for the surgery;(4) Surgical navigation:the bridge between virtual plan and real surgery,confirming the virtual plan during the surgery and guarantee the accuracy;(5) Computer assisted analyzing and evaluating:making a quantitative and objective of the final result and evaluating the outcome.We also performed a series of studies to evaluate the application of computer assisted techniques used for maxillary reconstruction,including:(1)3D tumor mapping technique for accurate diagnosis and treatment of maxillary tumor;(2) Maxillary reconstruction with free fibula flap used computer assisted techniques;(3) Computer assisted orbital floor reconstruction after maxillectomy.The results suggested that computer assisted techniques could significantly improve the clinical outcome of maxillary reconstruction.

Senescence-associated secretory phenotype (SASP) is often a concomitant result of cell senescence, embodied by the enhanced function of secretion. The SASP factors secreted by senescent cells include cytokines, proteases and chemokines, etc, which can exert great influence on local as well as systemic environment and participate in the process of cell senescence, immunoregulation, angiogenesis, cell proliferation and tumor invasion, etc. Relative to the abundance of SASP models in human cells, the in vitro SASP model derived from mouse cells is scarce at present. Therefore, the study aimed to establish a mouse SASP model to facilitate the research in the field. With this objective, we treated the INK4a-deficient mouse NIH-3T3 cells and the wildtype mouse embryonic fibroblasts (MEF) respectively with mitomycin C (MMC), an anticarcinoma drug which could induce DNA damage. The occurring of cell senescence was evaluated by cell morphology, β-gal staining, integration ratio of EdU and Western blot. Quantitative RT-PCR and ELISA were used to detect the expression and secretion of SASP factors, respectively. The results showed that, 8 days after the treatment of NIH-3T3 cells with MMC (1 μg/mL) for 12 h or 24 h, the cells became enlarged and the ratios of β-gal-positive (blue-stained) cells significantly increased, up to 77.4% and 90.4%, respectively. Meanwhile, the expression of P21 protein increased and the integration ratios of EdU significantly decreased (P < 0.01). Quantitative RT-PCR detection showed that the mRNA levels of several SASP genes, including IL-6, TNF-α, IL-1α and IL-1β increased evidently. ELISA detection further observed an enhanced secretion of IL-6 (P < 0.01). On the contrary, although wildtype MEF could also be induced into senescence by MMC treatment for 12 h or 24 h, embodied by the enlarged cell volume, increased ratios of β-gal-positive cells (up to 71.7% and 80.2%, respectively) and enhanced expression of P21 protein, the secretion of IL-6 displayed no significant change. Our study indicated that, although MMC could induce senescence in both mouse NIH-3T3 cells and wildtype MEF, only senescent NIH-3T3 cells displayed the canonical SASP phenomena. Current study suggested that senescent NIH-3T3 cells might be an appropriate in vitro SASP model of mouse cells.
Animals ; Cell Proliferation ; Cellular Senescence ; drug effects ; Cyclin-Dependent Kinase Inhibitor p21 ; genetics ; metabolism ; Cytokines ; genetics ; metabolism ; DNA Damage ; Fibroblasts ; drug effects ; Interleukin-6 ; secretion ; Mice ; Mitomycin ; pharmacology ; NIH 3T3 Cells ; Phenotype

AIM: To synthesis and characterize a multi-functional siRNA delivery agent with effective thera-peutic effects and MR-tracing ability for programmed death ligand-1 ( PD-L1 ) positive gastric cancer SGC-7901 cell line . METHODS:The characterization , binding ability , cytotoxicity , transfection efficiency and cellular internalization of the polyplex were determined .The PD-L1 knockdown effect was analyzed , and cytokines secreted by cocultured T cells were measured.RESULTS:We developed folic acid (FA)-PEG-SS-PEI-SPION as siRNA delivery agent for PD-L1 knockdown. At N/P ratio of 10, the FA-PEG-SS-PEI-SPION bound PD-L1 siRNA to form polyplex in a diameter of (116.7 ±2.5) nm with zeta potential of (9.14 ±0.80) mV.Transfection efficiency of the targeted polyplex was (95.06 ±0.44)%, com-pared with ( 93.87 ±1.05 )% of the untargeted polyplex .Mean fluorescence intensity of the targeted polyplex was 1892.67 ±81.51, significantly higher than 1324.33 ±186.58 of the untargeted.The cellular magnetic resonance (MR) imaging showed the polyplex also acted as T 2 weighted contrast agent for cancer MR imaging .The relative mRNA level of PD-L1 in polymer/siRNA-2 treatment group was (9.07 ±0.79)%.Decreased protein expression of PD-L1 was showed by Western blot .The secretion levels of IFN-γand TNF-αin cocultured T cells increased , while that of IL-10 decreased . CONCLUSION:Our findings highlighted the potential of the multifunctional theranostic nanoparticles for effective targe -ting PD-L1 knockdown therapy and MR imaging diagnosis in gastric cancers .

Objective:To investigate the cervical lymphatic metastasis rates of clinically negative neck lymph node (cN0) maxillary malignant tumors,to compare the cervical lymphatic metastasis rates of the various pathological types,and to provide the reference for the treatment of the neck of the patients with cN0 maxillary malignant tumor.Methods:The clinical data of 277 cases with cN0 maxillary malignant tumor,treated in the department of oral and maxillofacial surgery of Peking University School and Hospital of Stomatology from 1990 to 2010,were reviewed.The cervical lymph node metastasis and the related clinical information were recorded.The clinical information including histopathology type of the tumors,tumor grade,primary site and TNM staging,as well as other demographic and clinical data,were retrieved from the electronic medical record system (EMRS) of the hospital.The pathogenesis of cervical lymph node metastasis in maxillary malignant tumors of different histopathological types,and the factors related to lymph node metastasis of upper cervical malignancy were analyzed by SPSS 19.0 statistical software.Results:The overall cervical lymph node metastasis rate of the 277 patients with cN0 maxillary malignant tumor was 15.5％ (43/277).Maxillary squamous cell carcinoma (SCC) had a strong cervical lymph node metastasis tendency and the rate was 33.0％.The overall metastatic rate of adenocarcinoma was 7.6％ lower than that of SCC,and the occurrence of cervical lymph node metastasis time was relatively late,but the metastasis rate of highly malignant grade salivary gland carcinoma was significantly higher than that of intermediate and low grade carcinoma (P =0.037).The metastatic rates of some highly malignant cN0 salivary gland carcinomas including adenocarcinoma,not other specified,high-grade mucoepidermoid carcinoma (MEC),and salivary duct carcinoma were exceeded 15％,while the metastasis rates of adenoid cystic carcinoma and myoepithelial carcinoma were lower.The metastasis rate of the sarcomas was very low with the rate of 4.9％.Conclusion:Selective neck dissection (SND) is recommended for cN0 maxillary SCC and feasible for some highly malignant cN0 salivary gland carcinomas including adenocarcinoma,not other specified,high-grade MEC,salivary duct carcinoma.The neck can be closely observed for the patients with maxillary sarcoma.

Objective:Three-dimensional reconstruction of the enhanced CT is increasingly becoming a valuable tool in head and neck neoplasms.The aim of this study is to reconstruct three-dimensional imaging of tumor and its surrounding important anatomical structure using iPlan CMF software,and to investigate the application of three-dimensional tumor mapping technique for the diagnosis and treatment of the head and neck neoplasms.Methods:In the study,13 cases with head and neck tumors in Department of Oral and Maxilloficial Surgery,Peking University School and Hospital of Stomatology from June 2014 to June 2015 were studied using spiral CT scanning technology based on the same scanning condition.iPlan CMF software was used to read the original CT data,and surface shaded technology was applied to reconstruct the spatial relationship of the tumor,vessel and skull.The distance between the tumor and its surrounding important anatomical structure could be measured.iPlan CMF software was also used to accomplish the virtual osteotomy to expose the tumor,vessel and skull.The preoperative preparation,operative situation and postoperative complication were reviewed.Results:In this study 6 patients were male and 7 female.The age range was from 23 to 65 years,and the median patient age was 50 years.The threedimensional reconstruction image clearly demonstrated the extent of the tumor size,location,and the relation to its surrounding important anatomical structure.According to the three-dimensional image,the surgical risk of the patients was evaluated.The preoperative preparation and surgeries were successfully performed for 10 patients.Blood transfusion for 3 patients was considered before the surgery and actually accomplished during the operation.The operations for 2 patients were performed with the help of doctors from other departments.Only one patient had hoarseness because the tumor resulted from the pneumogastric nerves.For 10 patients,the average operation time was (202 ± 135) min,and the average operation bleeding was (235 ± 252) mL.The other 3 patients were not suitable cases for surgery.Conclusion:The three-dimensional reconstruction of enhanced CT image with iPlan CMF software is very helpful to make the treatment plan to avoid damaging important anatomical structures and postoperative complications.

Objective To accurately measure the motion angels of hand-related joints during manipulations of acupuncture needle thrusting-pulling and twirling, so as to provide quantitative references for acupuncture manipulation. Methods Six acupuncturists with over 3-year acupuncture experience and one volunteer were enrolled in this study. The angles of the forearm, wrist, metacarpophalangeal & interphalangeal joints of the thumb and index finger in each acupuncturist when performing thrusting-pulling and twirling manipulation were measured by the video motion capture (VMC) system, and the different ranges of above-mentioned angles among the 6 acupuncturists when performing 10 trails of thrusting-pulling and twirling manipulations on the volunteer’s thigh were compared. Results There was no significant difference in the ranges of relevant hand-related angles in the acupuncturist (P>0.05). The manipulation of thrusting-pulling was mainly managed by the wrist joint, with the range of (7.23±1.87)°, while the manipulation of twirling was mainly managed by the interphalangeal joints of the index finger, and the range of the first and second interphalangeal joints of the index finger was (28.33±2.18)°and (10.43±1.69)°, respectively. Conclusions The VMC can be a reliable method to quantify the parameters of acupuncture manipulation. Different acupuncture manipulation shows particular variation of the joint angles, which can be used as a reference to quantify the acupuncture manipulation.