Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Objective To explore the effect of different pontic designs in resisting stress interruption effect and roller coaster phenomenon through three-dimensional finite element analysis,providing clinical guidance for the application of clear aligners in extraction cases.Methods Four three-dimensional finite element models of different pontic designs in the extraction area of clear aligners were established,including the pontic-free connection design,the conventional hollow pontic design,the partially solid-filled pontic design and the fully solid-filled pontic design.All four aligner models were individually assembled with the dental arch model.A 0.2 mm distal movement of the canine was simulated to observe the initial displacement and periodontal ligament stress distribution of canine and second premolar in each group of models.Results The initial displacement tendency diagram revealed that in all experimental conditions,both the canine and second premolar exhibited tipping movement patterns.However,significant variations in initial displacement magnitudes were observed across different pontic designs.The fully solid-filled pontic-connected clear aligner model exhibited the greatest initial displacement values(both crown and root)and the maximum initial displacement magnitude.Notably,this kind of design displayed movement characteristics closer to bodily movement,indicating superior control efficacy in tooth positioning.Periodontal ligament stress analysis revealed that the fully solid-filled pontic-connected clear aligner model generated the highest maximum principal stress in the periodontal ligament.Conclusion This three-dimensional finite element study reveals that the application of solid-filled pontic in clear aligner therapy could improve biomechanical control at extraction sites by minimizing aligner distortion,reducing stress interruption effect and preventing the roller coaster phenomenon.

Objective To explore the effect of different pontic designs in resisting stress interruption effect and roller coaster phenomenon through three-dimensional finite element analysis,providing clinical guidance for the application of clear aligners in extraction cases.Methods Four three-dimensional finite element models of different pontic designs in the extraction area of clear aligners were established,including the pontic-free connection design,the conventional hollow pontic design,the partially solid-filled pontic design and the fully solid-filled pontic design.All four aligner models were individually assembled with the dental arch model.A 0.2 mm distal movement of the canine was simulated to observe the initial displacement and periodontal ligament stress distribution of canine and second premolar in each group of models.Results The initial displacement tendency diagram revealed that in all experimental conditions,both the canine and second premolar exhibited tipping movement patterns.However,significant variations in initial displacement magnitudes were observed across different pontic designs.The fully solid-filled pontic-connected clear aligner model exhibited the greatest initial displacement values(both crown and root)and the maximum initial displacement magnitude.Notably,this kind of design displayed movement characteristics closer to bodily movement,indicating superior control efficacy in tooth positioning.Periodontal ligament stress analysis revealed that the fully solid-filled pontic-connected clear aligner model generated the highest maximum principal stress in the periodontal ligament.Conclusion This three-dimensional finite element study reveals that the application of solid-filled pontic in clear aligner therapy could improve biomechanical control at extraction sites by minimizing aligner distortion,reducing stress interruption effect and preventing the roller coaster phenomenon.

Objective:To compare the efficacy of oral sulfate solution (OSS) and polyethylene glycol (PEG) electrolyte powder for colonoscopy bowel preparation.Methods:A total of 283 randomized patients from 9 centers in China taking OSS ( n=143) or PEG ( n=140) using two-day split bowel preparation regimen received colonoscopy and assessment. The primary index was the bowel preparation success rate [global Boston bowel preparation scale (BBPS)≥ 6 by independent assessment center]. Secondary indices included BBPS global and segmental scores, investigator satisfaction (5-point Likert scale) with the quality of bowel preparation, patient satisfaction assessed by questionnaires, and patient tolerance assessed by Sharma scale. Compliance and safety were compared between the two groups. Results:The bowel preparation success rates were 100.0% for OSS and 99.3% for PEG [adjusted difference 0.7% (95% CI: -5.3% - 6.7%), P<0.001 for non-inferiority]. The BBPS global score in OSS group was significantly higher than that in PEG group (8.1 VS 7.7, P<0.001). The segment BBPS scores were also higher in OSS group than those in PEG group for all 3 segments (right colon: 2.4 VS 2.3, P=0.002; transverse colon: 2.8 VS 2.7, P=0.018; left colon: 2.8 VS 2.7, P=0.007). Investigator Likert score in the OSS group was significantly higher than that in the PEG group (2.6 VS 2.3, P<0.001). There was no significant difference in compliance between OSS and PEG, except for the second dose (90.9% VS 82.6%, P=0.039). There was no significant difference in patient satisfaction, Sharma score or proportion of patients with tolerance-related symptoms between the two groups. Safety was comparable between the two groups, and all adverse events were mild to moderate. Conclusion:OSS has comparable efficacy with PEG, with higher BBPS scores in all segments, better investigator satisfaction, better compliance in split dose, and comparable patient tolerance and safety.

Objective To investigate the changes of peripheral blood expression levels of soluble fibrinogen-like protein 2 (sFGL2) in patients with chronic hepatitis B (CHB) before and after antiviral treatment.Methods From July 2013 to December 2014,initial CHB patients with entecavir antiviral therapy and healthy controls were enrolled.Clinical data at baseline and during follow-up were collected.Plasma levels of sFGL2 of all the included objects were measured by enzyme-linked immunosorbent assay (ELISA).All the patients received liver biopsy at baseline,and part of patients received a second liver biopsy at week 78 after treatment.The expression of sFGL2 in liver tissues were examined by immunohistochemistry.T test,Wilcoxon test and correlation analysis were performed for statistical analysis.Results A total of 71 CHB patients and 20 healthy controls were enrolled.At baseline,the level of plasma sFGL2 of CHB patients was significantly higher than healthy controls (105.6 μg/L (78.3 μg/L to 151.6 μg/L) vs 25.2 μg/L (18.8 μg/L to 34.3 μg/L),Z=-5.887,P＜ 0.01).The plasma sFGL2 level of patients with liver cirrhosis was 146.0 μg/L (111.3 μg/L to 166.8 μg/L),which was higher than that of patients without liver cirrhosis (79.0 μg/L (65.4 μg/L to 107.4 μg/L)),and the difference was statistically significant (Z=-4.912,P＜0.01).Plasma levels of sFGL2 were positively correlated with liver stiffness,liver inflammation and fibrosis stages (r=0.426,0.240 and 0.655;all P＜0.05).At 26 weeks and 52 weeks after treatment,the plasma levels of sFGL2 were 89.1 μg/L (69.8 μg/L to 125.5 μg/L) and 75.8 μg/L (53.4 μg/L to 98.9 μg/L),respectively,which gradually decreased compared with that at baseline (26 weeks vs baseline Z=-4.499,P＜0.01;52 weeks vs 26 weeks Z=-4.762,P＜0.01).Furthermore,at baseline the number of sFGL2 positive cells in the liver tissue of liver cirrhosis group was 33.0 ± 10.4,which was higher than that of non-liver cirrhosis group (17.6 ±6.7),and the difference was statistically significant (t=7.541,P＜0.01).Compared with that at baseline (24.5±2.0),the number of sFGL2 positive cells in liver tissue at week 78 after treatment decreased (11.3± 1.6),and the difference was statistically significant (t=11.980,P＜0.01).Conclusion Plasma level of sFGL2 is closely correlated with the degree of liver inflammation and fibrosis in CHB,and the plasma level of sFGL2 significantly decreases after long-term antiviral therapy.

Objective To investigate the value of D-dimer in predicting the progression of lower extremity deep venous thrombosis (DVT) during perioperative period of gastrointestinal surgery.Methods Color Doppler ultrasound was used to dynamically monitor the formation and changes of perioperative deep venous thrombosis (DVT) in 239 patients receiving abdominal surgery in our department from Nov 2014 to Aug 2016.Changes of plasma D-dimer were measured,and clinical data of malignant tumor,infection,age,BMI were collected.The relationship between D-dimer elevation and DVT progression was analyzed.Results Lower extremity DVT after surgery developed in 97 patients,and thrombosis progression occurred in 16.6％ (16/97).Univariate logistic regression analysis showed that continuous increase of postoperative D-dimer was closely related to the progression of thrombosiss.Multivariate Logistic regression analysis showed that the continuous rise of D-dimer was an independent risk factor for thrombosis.ROC curve analysis showed significantly increased risk of thrombosis progression,when plasma D-dimer polymerization increased ＞0.87 mg/L on the 3rd day.Conclusion The continuous increase of D-dimer ＞ 0.87 mg/L predicts DVT progression of lower extremity DVT.

Objective:To evaluate high-risk human papillomavirus (hrHPV) genotyping and viral load in predicting CIN (cervical intraepi-thelial neoplasia (CIN) grade 2 or worse in a Chinese rural area population with limited health resources. Methods:We performed a population-based prospective study and enrolled 2,257 women aged 35 to 64 years from three rural screening sites of Jiangxi prov-ince. We conducted a hybrid capture (HC-2) assay to predict viral load. A HC-2 relative light unit (RLU) threshold of 10 was set to differ-entiate samples between low (<10) and high (≥10) viral loads. We also carried out a HybriMax test to detect different hrHPV geno-types in the samples. Women exhibiting positive HC-2 or HybriMax results underwent colposcopy and colposcopically directed biopsy. Women with negative or positive hrHPV test results but with normal biopsy or CIN1 were followed-up for 24 months without interven-tion (n=2,211). We used histopathological findings as outcome. Results:Of the 2,211 women, 1,636 provided complete follow-up data. Of the 132 women with a high viral load, 4 (3.03%) developed CIN2+in the same period. The relative risk (RR) of CIN2+for HC-2 posi-tivity at baseline was 42.24 (95%CI=4.76-375.2). Of the 159 women who were positive for HPV16 or HPV18 upon screening, 4 (2.52%) progressed to CIN2+(RR=33.06, 95%CI=3.72-293.9). The 2-year cumulative incidence rates of CIN2+did not significantly differ be-tween the high viral load group and the HPV16/18 group. Conclusion:The risks of CIN2+progression were higher among women with a high viral load or HPV16/18 positivity than among women with negative hrHPV. Increasing the HC-2 cut-off value to 10 RLU or using HPV16/18 positivity may be similarly used to triage hrHPV-positive women for immediate colposcopy and comprehensive follow-up.Both approaches were equally predictive of the CIN2+risk in rural area. Increasing the HC-2 cut-off value to 10 RLU may also help allo-cate health resources effectively.

Objective The purpose of this study was to establish and evaluate a mouse model of sepsis for studying the mechanism of sepsis and development of anti-inflammatory drugs.Methods The sepsis in mice was induced by cecal ligation and puncture ( CLP) .The survival rates, microbial load, liver and kidney damages, cytokines and pathological changes were detected to evaluate the mouse models.Results The death of mice was closely related with the ligated sites. The mice with 50%cecal ligation displayed about 40% of 12-day survival rate, however, all the mice with 75% cecum ligation died within 4 days (P<0.01).Compared with the sham surgery group, the mice with 50% cecal ligation had a high microbial load in the blood and abdominal cavity.Leukopenia was also emerged (P<0.001).CLP mice demonstra-ted elevated levels of serum ALT, AST and BUN (P<0.01).The levels of IL1α, IL6, IL10, MIP1α, MIP1β, and TNFαwere increased a lot.The liver and lung showed obvious pathological injury at 48 h post CLP.Conclusions The established mouse model of CLP shows typical characteristics of sepsis and is an ideal tool for further study of anti-inflam-matory drugs.

This paper introduced the concept of humanistic therapy and its connotation and application in the field of surgery, the spiritual essence and the docking and bioethics.The authors also analyzed the perioperative patients need humanistic therapy, including technology, ethics, psychology, the needs of the practice; discusses the humanistic therapy in clinical practice,includes:practice conditions, personnel, measures and problems.

Objective To evaluate incisor root resorption of adults with skeletal classⅢmalocclusion through three-dimensional reconstruction of cone beam computed tomography (CBCT) image using interacting medical imaging control sys?tem (Mimics) and then offer guidance for labially tilted angle control in orthodontic treatment and distance of bone moving in surgery. Methods Adults of skeletal class Ⅲ malocclusion (n=30) who underwent orthodontic-orthognathic combination treatment were included in this study. CBCT images were then reconstructed three-dimensionally using Mimics 10.01. Each incisor were separated at cementum-enamel junction as crown and root. Labially tilted angle and root volumes of each inci?sor were measured before and after operations. At last, the correlativity between root resorption and labially tilted angle was calculated through statistic analysis. Results The decrement of upper, lower and front incisors’root volumes upon treat?ment is statistically significant. However, there is no statistically significant difference of incisor ’s root volumes among eight incisors nor between different gender. There is linear correlation between root volumes and labially tilted angle when the lat?ter changes 7° or more when they followed the fomular =-21.416+5.618X. Conclusion For adults with skeletal classⅢmalocclusion, orthodontic treatment before orthognathic surgery decrease incisor root volumes when labially tilted angle changes 7° or more.