Cancer vaccines represent a promising immunotherapeutic treatment modality. The promotion of cross-presentation of extracellular tumor-associated antigens on the major histocompatibility complex (MHC) class I molecules and dendritic cell maturation at the appropriate time and place is crucial for cancer vaccines to prime cytolytic T cell response with reduced side effects. Current vaccination strategies, however, are not able to achieve the spatiotemporal control of antigen cross-presentation. Here, we report a liposomal vaccine loading the second near-infrared window (NIR-II, 1000-1700 nm) fluorophore BPBBT with an efficient photothermal conversion effect that offers an NIR-light-triggered endolysosomal escape under the imaging guidance. The NIR-II image-guided vaccination strategy specifically controls the cytosolic delivery of antigens for cross-presentation in the draining lymph nodes (DLNs). Moreover, the photothermally induced endolysosomal rupture initiates autophagy. We also find that the adjuvant simvastatin acts as an autophagy activator through inhibiting the PI3K/AKT/mTOR pathway. The light-induced autophagy in the DLNs together with simvastatin treatment cooperatively increase MHC class II expression by activating autophagy machinery for dendritic cell maturation. This study presents a paradigm of NIR-II image-guided light-triggered vaccination. The approach for remote control of antigen cross-presentation and autophagy represents a new strategy for vaccine development.

Waterborne viruses that can be harmful to human health pose significant challenges globally,affecting health care systems and the economy.Identifying these waterborne pathogens is essential for preventing diseases and protecting public health.However,handling complex samples such as human and waste-water can be challenging due to their dynamic and complex composition and the ultralow concentration of target analytes.This review presents a comprehensive overview of the latest breakthroughs in waterborne virus biosensors.It begins by highlighting several promising strategies that enhance the sensing performance of optical and electrochemical biosensors in human samples.These strategies include optimizing bioreceptor selection,transduction elements,signal amplification,and integrated sensing systems.Furthermore,the insights gained from biosensing waterborne viruses in human sam-ples are applied to improve biosensing in wastewater,with a particular focus on sampling and sample pretreatment due to the dispersion characteristics of waterborne viruses in wastewater.This review suggests that implementing a comprehensive system that integrates the entire waterborne virus detection process with high-accuracy analysis could enhance virus monitoring.These findings provide valuable insights for improving the effectiveness of waterborne virus detection,which could have sig-nificant implications for public health and environmental management.

Objective:To investigate the value of synthetic MRI for evaluating lumbar intervertebral disc degeneration.Methods:A total of 414 lumbar intervertebral discs from 85 patients were included prospectively from September 2018 to February 2019 in First Affiliated Hospital of China Medical University. The T 1, T 2 and proton density (PD) mapping were generated from synthetic MRI. Two doctors measured the T 1, T 2 and PD values to evaluate intraobserver agreement by using ICC. For Pfirrmann grade comparisons, the variables with normal distribution were analyzed with the one-way analysis of variance, whereas those with skewed distribution were analyzed with the Kruskal-Wallis H test. Furthermore, the ROC curves were used on significant parameters to evaluate their diagnostic efficacy. The Z test was used to compare the differences of area under the ROC curves (AUC). Results:The color of the quantitative mapping changed along with the increase of the Pfirrmann grade of the intervertebral discs, which corresponded to the decrease of the T 2WI signal intensity. The ICC values of the quantitative values of nucleus pulposus indicated excellent agreement (ICC>0.900), followed by anterior annulus fibrosus (ICC>0.700) and then the posterior annulus fibrosus (ICC>0.600). The results of the adjacent Pfirrmann grade comparisons were as follows: between Pfirrmann grade Ⅰ and Ⅱ, the differences of T 2 and PD values of nucleus pulposus were statistically significant ( P=0.004 and P<0.001, respectively); between Pfirrmann grade Ⅱ and Ⅲ, the differences of T 1, T 2 and PD values of nucleus pulposus were statistically significant (all P<0.001); between Pfirrmann grade Ⅲ to Ⅳ, the T 1, T 2 and PD values of nucleus pulposus (all P<0.001) and the T 1 and PD values of posterior annulus fibrosus ( P=0.025, P<0.001, respectively) had statistically significant differences; between Pfirrmann grade Ⅳ to Ⅴ, the difference of T 2 values of nucleus pulposus were statistically significant ( P=0.031). The AUC of T 2 values of nucleus pulposus between Pfirrmann grade Ⅱ to Ⅲ and grade Ⅳ to V were higher than those of the PD values ( Z=2.443, 3.591 and P=0.015,<0.001). Conclusions:Synthetic MRI can quantitatively evaluate lumbar disc degeneration, in which the T 2 value of nucleus pulposus may be the most effective parameter with high repeatability.

ZNF804A rs1344706 has been identified as one of the risk genes for schizophrenia. However, the neural mechanisms underlying this association are unknown. Given that ZNF804A upregulates the expression of COMT, we hypothesized that ZNF804A may influence brain activity by interacting with COMT. Here, we genotyped ZNF804A rs1344706 and COMT rs4680 in 218 healthy Chinese participants. Amplitudes of low-frequency fluctuations (ALFFs) were applied to analyze the main and interaction effects of ZNF804A rs1344706 and COMT rs4680. The ALFFs of the bilateral dorsolateral prefrontal cortex showed a significant ZNF804A rs1344706 × COMT rs4680 interaction, manifesting as a U-shaped modulation, presumably by dopamine signaling. Significant main effects were also found. These findings suggest that ZNF804A affects the resting-state functional activation by interacting with COMT, and may improve our understanding of the neurobiological effects of ZNF804A and its association with schizophrenia.

Objective To discuss the clinical effects of forward lateral malleolus perforator flap in the repair of skin and soft tissue defect of ankle or dorsal foot.Methods From November,2014 to June,2017,16 cases of skin and soft tissue defect in ankle or dorsal foot had been repaired,which were 11 males and 5 females,aged from 25to 58 years old(average,32.5 years).The rotation points were on proximal 5 cm of the lateral malleolus in 11 cases and on the level of tarsal sinus in 5 cases.The largest flap was 10.0 cm×18.0 cm and the smallest flap was 6.0 cm×4.0 cm.The color,thickness,texture,sensation,appearance,donor site shape and functional were followed-up after operation.Results All the 16 patients were followed-up from 1 to 24 months.The distal flap appeared dark in 1 case 2 days after operation,and blood supply was improved after stitches;One case was superficial necrosis and healed after dressing.All the flaps had good appearance and texture,no pigmentation,scar contracture,and so on.Conclusion The forward lateral malleolus perforator flaps have perforator constantly and the color,thickness are similar with the receiving areas,the rotation point could on proximal 5 cm of the lateral malleolus and on the level of tarsal sinus,which is a good method to repair skin and soft tissue defect of ankle or dorsal foot.

Objective: To evaluate theresult of Screwless Scarf osteotomy for the treatment of moderate to severe hallux valgus. Methods: From January 2016 to May 2017, 13 patients with 15 feet underwent Screwless (without internal fixation) Scarf osteotomy for the treatment of moderate to severe hallux valgus.The hallux valgus angle (HVA) and intermetatarsal angle(IMA) were compared before and after surgery.Clinical outcomes were assessed by American Orthopedic Foot and Ankle Society (AOFAS) scoring. Results: The mean follow-up was 6 months in all the patients(range, 2-12 months). HVA was decreased by 25.7°(form 38.8°preoperative to 13.1°postoperative). IMA was decreased by 9.6°(form 18.3°preoperative to 8.7°postoperative). AOFAS sore was increase by 39.7 points (45.7 points preoperative to 85.4 points). The incidence of excellence was 86.7%. Conclusions Satisfactory clinical outcomes can be achieved by screwless Scarf osteotomy for moderate or severe hallux valgus.However, strict indications and sufficient surgical skills are crucial.

Objective To investigate the efficacy of dexmedetomidine on sedation in post-cardiac surgery patients with NIV intolerance.The changes of respiratory function and hemodynamics of the patients as well as non-invasive ventilation (NIV) failure rate were also under evaluation.Methods Thirty-five post-cardiac surgery patients with NIV intolerance and hypoxemia were enrolled in this prospective study.All patients were sedated with dexmedetomidine.NIV was standardized according to the uniform protocol.The main outcome was NIV success (avoiding endotracheal intubation) or NIV failure (requiring endotracheal intubation or die).The cardiorespiratory parameters (BP,HtR and RR) and artery blood gas analysis were prospectively recorded before and after sedation.The respiratory function and hemodynamics changes in both groups (NIV success group and NIV failure group) were then evaluated.Factors independently associated with NIV failure were identified using a logistic regression model.Results Twenty out of 35 patients (57.14％) survived while 15 (42.86％) patients failed NIV.After 1 h and 4 h of NIV with dexmedetomidine sedation,respiratory rate in both groups were decreased compared with baseline,especially in NIV success group.The PaO2/FiO2 was also improved after 1h and 4h of NIV treatment compared with baseline.The improvement was more significantly in NIV success group.The heart rate was decreased compared with baseline with no differences between two groups.There were no significant changes on PaCO2 and mean arterial pressure (MAP) during the treatment.The respiratory and hemodynamics variables identified as predictors of NIV failure were included in a multivariate logistic regression.RR ＞ 23 time/min (OR =3.2,95％ CI:2.043 ～ 4.301,P ＜ 0.01) 1 h after NIV,RR ＞ 20 time/min (OR =2.1,95％ CI:1.659～3.231,P=0.025) 4 h after NIV,PaO2/FiO2 ＜178 mmHg (OR=2.4,95％CI:1.892 ～ 3.287,P ＜0.01) 1 h after NIV and PaO2/FiO2 ＜ 185 mmHg (OR =1.7,95％ CI:1.243 ～ 2.365,P =0.041) 4 h after NIV independendy predicted NIV failure.Conclusions Dexmedetomidine might be considered as an effective and safe sedative for post-cardiac surgery patients with NIV intolerance.Early identification of predictors of NIV failure may facilitate early intervention.

OBJECTIVEThe aim of this study was to evaluate the effect of postoperative adjuvant therapy on the survival in patients with N1 lymph node metastasis of esophageal squamous cell carcinoma (ESCC).

METHODS110 patients with positive N1 lymph node metastasis of esophageal squamous carcinoma were included in this study. The surgery group included 46 cases and the postoperative adjuvant therapy group included 64 cases (24 cases in the adjuvant chemotherapy subgroup and 40 cases in the adjuvant concurrent chemoradiotherapy). The disease-free survival (DFS) and overall survival (OS) of the two groups were compared and the prognostic factors were analyzed by multivariate Cox model.

RESULTSIn the postoperative adjuvant therapy group, the DFS (16.8 months) and OS (21.3 months) were significantly prolonged compared with those in the surgery group (10.6 months, P=0.007) and (13.7 months, P=0.001), respectively. Postoperative adjuvant chemotherapy significantly extended the OS (31.1 months) of N1-positive patients compared with 13.7 months (P=0.002) in the surgery group. But there were no significant differences between the DFS in the two subgroups (16.3 and 16.8 months, P=0.346) and between the OS (23.4 and 21.3 months, P=0.491). Postoperative adjuvant therapy was an independent prognostic factor in the ESCC patients with N1 lymph node metastasis.

CONCLUSIONPostoperative adjuvant therapy can improve the prognosis and prolong the survival time in ESCC patients with positive N1 lymph node metastasis.

Carcinoma, Squamous Cell ; mortality ; secondary ; therapy ; Chemoradiotherapy ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Esophageal Neoplasms ; mortality ; pathology ; therapy ; Humans ; Lymph Nodes ; Lymphatic Metastasis ; Postoperative Care ; Prognosis ; Retrospective Studies

Objective:To investigate the role and mechanism of miR-143 in the proliferation and migration of gastric cancer (GC) cells. Methods:Western blot was performed to detect the expression level of avian erythroblastosis oncogene B-3 (ERBB3) in GC tissues, paired non-cancerous tissues, and SGC7901 GC cells. RT-qPCR was conducted to determine the mRNA and miR-143 of ERBB3 quantita-tively. Bioinformatics tools were used to predict the target gene of miR-143. Luciferase reporter assay was carried out to confirm the predicted target gene. Transwell and EdU assays were applied to observe the migration and proliferation of SGC7901 GC cells transfect-ed with miR-143 mimics/inhibitor/NC mimics/inhibitor. Results:Compared with the expression levels of ERBB3 and miR-143 in the paired non-cancerous tissues, the expression level of ERBB3 was upregulated and the expression level of miR-143 was downregulated in GC tissues. In the prediction of the potential target gene, miR-143 could bind to a specific sequence of the 3′-untranslated regions (UTR) of the mRNA of ERBB3. This finding was supported by luciferase reporter assay results. In vitro, ERBB3 protein expression and cell migration and proliferation were suppressed significantly in the SGC7901 cells transfected with miR-143 mimics. By contrast, these processes were remarkably enhanced when the cells were transfected with miR-143 inhibitor. Conclusion:miR-143 can suppress the migration and proliferation of GC cells by downregulating the expression of ERBB3.

Objective To analyze the CT characteristics of chronic schistosomiasis liver disease,in order to improve the accuracy of CT diagnosis for the disease.Methods We analyzed the CT features of 125 cases of clinical pathology diagnosis of chronic schistosomiasis liver and of 50 normal control group,and measured the hepatic lobe lines and spleen index.Results (1) Schistosoma calcification:In 125 cases,there were 120 patients with varying degrees of liver calcification,in which 76 cases of intrahepatic or subcapsularlinear calcification,44 cases of reticular or map-like calcification,33 cases of calcification portal system,15 cases of spleen calcification,85 cases of intestinal wall calcification;(2) Morphological changes of the liver and spleen:The transverse diameter of the left hepatic lobe,caudate lobe,and caudate lobe-right lobe ratio were larger in patients with chronic schistosomiasis than controls,the transverse diameter of the right hepatic lobe were smaller and there were statistically difference (P＜0.001).There were 82 cases of expanded gallbladder fossa in chronic schistosomiasis.Splenic index in patients with chronic schistosomiasis and had no obvious difference in the control group (P＞0.05);(3) Schistosomiasis liver's complications:there were 43 cases of cholecystitis and cholelithiasis,11 cases of liver cancer,5 cases of colon cancer,3 cases of bladder cancer.Conclusion Intrahepatic calcification and the left hepatic lobe and caudate lobe enlargement are CT signs of chronic schistosomiasis,which is often merged with many complications.