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.

BACKGROUND: Epilepsy accounts for a significant portion of the global disease burden. However, little is known about the disease burden of epilepsy in China and its provinces. METHODS: We assessed the burden of epilepsy in China and its provinces, municipalities, and autonomous regions from 1990 to 2019. Burden was measured as incidence, prevalence, deaths, years lived with disability, years of life lost, and disability-adjusted life years (DALYs), by age, sex, year, and province. We used the Socio-Demographic Index (SDI) to determine the association between the provincial development level and age-standardized DALY rates of epilepsy from 1990 to 2019. RESULTS: In 2019, epilepsy caused 1367.51 thousand (95% uncertainty interval [UI]: 979.92-1837.61 thousand) DALYs, and the age-standardized DALY rate was 99.77 (95% UI: 71.33-133.52)/100,000. The age-standardized incidence and prevalence rates for epilepsy in China were 24.65/100,000 and 219.69/100,000, increased by 45.00% (95% UI: 8.03-98.74%) and 35.72% (95% UI: 0.47-86.19%) compared with that in 1990, respectively. From 1990 to 2019, the proportion of DALY caused by epilepsy in the age group under 25 years steadily decreased. The proportion of DALYs caused by epilepsy in people aged 50 years and over increased from 9.45% and 10.22% in 1990 to 29.01% and 32.72% for male and female individuals in 2019, respectively. The highest age-standardized mortality rates were seen in Tibet (4.26 [95% UI: 1.43-5.66]/100,000), Qinghai (1.80 [95% UI: 1.15-2.36]/100,000), and Yunnan (1.30 [95% UI: 0.88-1.62]/100,000), and the lowest mortality rates were in Guangdong (0.48 [95% UI: 0.39-0.64]/100,000), Zhejiang (0.56 [95% UI: 0.44-0.70]/100,000), and Shanghai (0.57 [95% UI: 0.41-0.73]/100,000). The age-standardized DALY rates across the country and in provinces, municipalities, and autonomous regions generally decreased as their SDI increased. CONCLUSIONS The disease burden of epilepsy is still heavy in China, especially in the western provinces. The incidence and prevalence of epilepsy increased between 1990 and 2019, and the burden of epilepsy in the elderly increases gradually. This study provides evidence on epilepsy prevention and care of different regions in China.
Aged ; Humans ; Male ; Female ; Middle Aged ; Adult ; Global Burden of Disease ; China/epidemiology* ; Quality-Adjusted Life Years ; Cost of Illness ; Epilepsy/epidemiology* ; Prevalence

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 evaluate the clinical and histological outcomes in a cohort of chronic hepatitis B (CHB) patients who had histologically confirmed severe liver fibrosis and received lamivudine (LAM) therapy for up to 10 years. Methods Thirty-nine CHB patients with severe liver fibrosis (Ishak fibrosis score≥4) were treated with LAM for up to 10 years. Disease progression liver histological improvement, virological and biochemical responses were evaluated during follow-up. Data were analyzed using paired t test, Fisher exact test and Willcoxon test. Results Twenty-eight patients completed the 10-year follow-up. There were 5 (17.9% ) patients with disease progression.At the end of follow up, 16 patients received a second liver biopsy, which showed significant improvement of histological activity index (1.1 ± 1.4 vs 7. 1 ± 3.2, t =- 0.82, P＜0.01 ) and Ishak fibrosis score (3.6±2.2 vs 5.3±0.7, t= -2.89, P＜0.05) compared to baseline. There were 3 cases with Ishak fibrosis score improved from F5 to F0. Among 27 patients, 3(11% ) cases achieved hepatitis B surface antigen (HBsAg) loss and 2 (7 % ) achieved HBsAg seroconversion. At the end of follow-up, 19 out of 23 (83% ) hepatitis B e antigen (HBeAg) positive patients obtained HBeAg loss and 9 (39 % ) obtained HBeAg seroconversion. During LAM treatment, 11 patients experienced virological breakthrough or detected documented LAM-related resistance mutation. The viral loads of all patients were below 1 ×103 copy/mL at the end of follow-up after rescued by add-on or switch to another nucleotide analog.Conclusions Long-term LAM therapy can delay the disease progression in CHB patients with severe liver fibrosis, increase HBsAg and HBeAg loss rates, sustain suppression of HBV replication at a low level and even totally reverse the liver fibrosis in some patients. The effect of LAM resistance mutation on disease outcomes would be reduced by rescue therapy.

Objective To investigate the anti-inflammatory/immune modulatory effects of high-expressing membrane bound M-CSF-hematopoietic malignant cells on macrophages. Methods After coculturing RAW264.7 and murine macrophage cell line with Namalwa-M, a cell line stably expressing mM-CSF, and companing with Nainalwa-V, a cell line stably transfected with the empty vector as the control, flow cytometry was used to detect the expression of the marker of alternatively activated macrophages, CD206, and intracellular expression of IL-10, IL-12, IL-6 and TNF-α to study the immunophenotype of RAW264.7; phagocytic assays to investigate their functional activity in vitro. Results RAW264.7 cocultured with Namalwa-M consistently showed high-level expression of CD206, which indicated activities of these macrophage cells were increased. Furthermore, these RAW264.7 expressing high levels of IL-10, TNF-a and low levels of IL-12, IL-6, as determined by intracellular staining were suggested that the phagocytic activity was increased. Functionally, RAW264.7 cocultured with Namalwa-M showed a higher level of phagocytic activity. Conclusion Macrophage generated in vitro after cocultured with mM-CSF-expressing hematopoietic malignant cell line could be transformed into abnormal macrophage with an immunophenotype defined as IL-10-high, IL-12-low, IL-6-low and TNF-α-high.

Purpose:Analysing the imaging performance of solitary plasmacytoma of spine,to raise the awareness and the diagnosis accuracy.Materials and Methods: Five cases of spinal solitary plasmacytoma confirmed by clinical pathology were retrospectively analysed,to sum up the imaging performance characteristics.Results: All lesions were single vertebra involved,3 cases in thoracic and 2 cases in lumbar,3 cases occurred vertebral compression fracture.X-ray and CT showed osteolytic destruction,expansive growth and soft tissue mass,MRI showed diversity of signals,and remarkable enhancement after contrast injection.Conclusions: X-ray presents lower diagnostic sensitivity,but contributes to exclude multiple myeloma.CT and MRI can depict the morphological features and extent of tumor regions definitely,CT shows better than MRI on the thickening trabecula and residual bone in the tumor,MRI can provide a lot of information for plasmacytoma,including the diagnosis,identification and staging,which is considered as the best imaging diagnostic methods of plasmacytoma.

Objective To report the MRI findings of brain damage obsenrved in neonatal patients who suffered from isolated hypoglycemia and to explore the value of diffusion-weighted imaging(DWI) inearly detection of neonatal hypoglycemic brain iniun,. Methods Twelve neonates with isolated hypoglycemia(10 of the 12 were diagnosed to suffer from hypoglycemic encephalopathy)were enrolled in this study.They were first scanned at age from 3 days to 10 days with Tl WI,T,WI and DWI(b is 0 s/mm2,1000 s/mm2),and 4 of them were then scanned from 7 days to 10 days following the initial scan.All acquired MR images were retrospectively analysed.Results First series of DWl images showed distinct hyperintense signal in 11 cases in several areas including bi lateral occipital cortex(2 cases),right occipital cortex(1 case),left occipital cortex and subcortical white matter(1 case),biIateral occipital cortex and flubcortical white matter(2 cases),bilateral parieto-occipital cortex(2 cases),bilateral parieto-occipital cortex and subcortical white matter(2 cases),the splenium of corpus catlosum(4 cases),bilateral corona radiata(2 cases),left eaudate nucleus and globus pallidus(1 case),bilateral thalamus(1 case),bilaterally posterior limb of internal capsule(1 ease).In the initial T1 WI and T2,WI images,there were subtle hypointensity in the damaged cortical areas(3 cases),hyperintensity in the bilaterally affected occipital cortex(1 case)on T1 weighted images,and hyperintensity in the affected cortex and subcortieal white matter with poor differentiation on T2 weighted images.The followed-up MRI of 4 cases showed regional encephalomalaeia in the affected occipital lobes(4 cases),slightly hyperintensity on T2 weighted images in the damaged occipital cortex(2 cases),extensive demyelination(1 case).disappearance of hyperintensity of the splenium of corpus callosum(1 case),and persistent hyperintensity in the splenium of corpus callosum (1 case)on T2 weighted images.Conclusion The findings suggest that posterior parieto-occipital regions are most frequently injured in neonatal period due to severe hypoglycemia.DWI is a useful technique in the early detection and evaluation of hypoglycemic brain injury of neonates.

Objective To investigate the clinical epidemiologic characteristics of patients with hepatitis C virus(HCV)infection post blood transfusion.Methods The polymerase chain reaction (PCR)and enzyme linked immunosorbent assay(ELlSA)were used to detect HCV RNA and antiHCV,respectively.Analysis was performed for patients' age distribution,cause of primary diseases,exposure years,ingredient and amount of transfusion,incubation period and liver function damage.The statistical processing were performed with chi-square test,t-test and correlation analysis.Results HCV RNA levels were higher than 3.0 log10 copy/mL in 85.3%infected patients with a median of 5.99log10 copy/mL,among which 19.7%patients showed viral load 3.0 to 4.0 log10 copy/mL and 69.9%showed 5.0 to 6.0 log10 copy/mL.Eighty-one point six percent(40/49)of infected persons were confirmed as HCV RNA positive by HCV RNA qualitative analysis,while 99.7%(383/384)patientswere detected as anti-HCV positive by serological test.The sensitivity of serological test was higher than both HCV RNA quantitative and qualitative assays(F=57.138,P=0.000;F=63.149,P=0.000,respectively).HCV infection post blood transfusion was more common in people of 30 to 60years old.Most cases(84.4%)got the first time exposure during 1990 to 1994.More than 10%cases had primary disease as obstetrics, orthopedics or gastrointestinal tract hemorrhage. Eighty percent received whole blood product transfusion.The mean interval between transfusion and clinical diagnosis was (86.0±54.6 ) months. Eighty nine percent of infected patients had liver function damage, while most of them showed elevated alanine aminotransferase (ALT) with no more than 5 upper limits of normal (ULN). Conclusions Post transfusion HCV infection mainly happened in adulthood. Infected patients usually have liver function damage with elevated ALT with no more than 5 ULN and medium HCV RNA levels.

Objective To assess the efficacy and safety of dl-3-butylphthalide on the treatment of acute ischemic stroke. Methods A total of 197 patients who were in the period of 72 hours of first attack of ischemic stroke of internal carotid artery with NIHSS from 5 to 25 scores were enrolled in this multi-center, randomized, double-blind and aspirin-control study. Compound " Dan Shen" was used as a baseline therapy. Results Basical recovery plus significant improvement was seen in 74.7% of the patients in dl-3-butylphthalide group and 60.9% in aspirin group (CMH value 4.0,P=0.047);There was a significant improvement for dl-3-butylphthalide group regarding NIHSS total score, total score difference value and Barthel index on the day 11th and 21st after treatment compared with control group. The main adverse reaction of dl-3-butylphthalide was increased aminotransferase and mainly the slight increase of aspartate aminotransferase, by 4.34% and 0 respectively. Conclusion dl-3-butyiphthalide should be regarded as an effective and safe treatment for ischemic stroke and a treatment without severe side effects.