Advanced atherosclerosis is the major global cause of death, as featured by the aggregation of apoptotic cells (ACs) in necrotic cores. The defective efferocytosis and dysfunctional cholesterol efflux of macrophages are the main reasons for forming necrotic cores in advanced atherosclerosis. In this study, we constructed self-assembled procyanidins (PC) NPs for loading pitavastatin (Pita). The designed HA@PC@Pita NPs with hyaluronic acid (HA) modification combined the advantages of efferocytosis restoration of Pita and cholesterol efflux enhancement of PC. In vitro assay indicated that HA@PC@Pita NPs could induce M1/M2 repolarization and upregulate ERK5/Mertk expression to restore efferocytosis of macrophages. Simultaneously, HA@PC@Pita NPs notably promoted cholesterol efflux by promoting macrophage lipophagy, a selective autophagy of lipid droplets. In vivo study showed that HA@PC@Pita NPs cleared necrotic core and enhanced plaque stability in the ApoE ^-/- mice model with advanced atherosclerosis. Taken together, this study demonstrated the potential of HA@PC@Pita NPs for the treatment of advanced atherosclerosis.

Objective:To explore the relationship between serum C-X-C motif chemokine ligand 16 (CXCL16) and thioredoxin 80 (Trx80) in patients with Alzheimer′s disease (AD) and cognitive function and prognosis.Methods:A total of 189 AD patients admitted to the Zhangjiakou First Hospital from January 2020 to August 2021 were selected as the AD group, and 110 healthy volunteers who underwent physical examinations in our hospital during the same period were selected as the control group. The serum levels of CXCL16 and Trx80 were detected using enzyme-linked immunosorbent assay (ELISA), and cognitive function was evaluated using the Mini Mental State Examination (MMSE) score. The Spearman correlation method was used to analyze the correlation between serum CXCL16, Trx80 levels and MMSE scores in AD patients. 189 AD patients were divided into poor prognosis group and good prognosis group based on their prognosis. Univariate and multivariate logistic regression methods were used to analyze the influencing factors of poor prognosis in AD patients. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of serum CXCL16 and Trx80 levels for poor prognosis in AD patients.Results:Compared with the control group, the AD group had higher serum levels of CXCL16 and Trx80, and lower MMSE scores (all P<0.05). Spearman correlation analysis showed that the serum levels of CXCL16 and Trx80 in AD patients were negatively correlated with MMSE scores (all P<0.05). After a one-year follow-up, the poor prognosis rate of 189 AD patients was 32.80%(62/189). Univariate analysis showed that age, disease duration, β-amyloid protein (Aβ) 1-40, Aβ 1-42, MMSE score, CXCL16, and Trx80 are associated with poor prognosis in AD patients (all P<0.05). Multivariate logistic regression analysis showed that age, prolonged disease course, and elevated levels of CXCL16 and Trx80 were risk factors for poor prognosis in AD patients (all P<0.05), while an increase in MMSE score was a protective factor ( P<0.05). ROC curve analysis showed that the area under the curve (AUC) of MMSE score, CXCL16, Trx80, CXCL16+ Trx80 combination, and MMSE score+ CXCL16+ Trx80 combination predicting poor prognosis in AD patients were 0.750, 0.763, 0.771, 0.851, and 0.896, respectively. The AUC of the three combination predicting poor prognosis in AD patients was the highest. Conclusions:Elevated serum levels of CXCL16 and Trx80 in AD patients are associated with decreased cognitive function and poor prognosis, and may become auxiliary predictive indicators for poor prognosis in AD patients.

Cognitive dysfunction refers to dysfunction of individual perception,memory,understanding,learning,creation and other dysfunctions caused by abnormal brain function and structure.Based on the fact that the spleen can't regulate transportation and transformation,govern blood and send up essential substance,combined with the microbiota-gut-brain axis,this article discussed the etiology and pathogenesis of intestinal flora imbalance affecting cognitive dysfunction in TCM.It was proposed that the spleen in TCM and intestinal flora are connected in physiology and pathology:the spleen regulates spirit and governs cognition,when the spleen fails to function normally that it can't dominate transportation and transformation,govern blood and send up essential substance will cause that the brain spirit can not be nourished;intestinal flora is closely related to the spleen in TCM,and affects brain function through the nervous system,endocrine,immune and metabolic mechanisms.This article can provide explore new ideas for the clinical research and treatment of cognitive dysfunction of traditional Chinese and Western medicine.

Acute lung injury (ALI), as a common clinical emergency, is pulmonary edema and diffuse lung infiltration caused by inflammation. The lack of non-invasive alert strategy, resulting in failure to carry out preventive treatment, means high mortality and poor prognosis. Stimulator of interferon genes (STING) is a key molecular biomarker of innate immunity in response to inflammation, but there is still a lack of STING-targeted strategy. In this study, a novel STING-targeted PET tracer, [¹⁸F]FBTA, was labeled with high radiochemical yield (79.7 ± 4.3%) and molar activity (32.5 ± 2.9 GBq/μmol). We confirmed that [¹⁸F]FBTA has a strong STING binding affinity (K_d = 26.86 ± 6.79 nmol/L) and can be used for PET imaging in ALI mice to alert early lung inflammation and to assess the efficacy of drug therapy. Our STING-targeted strategy also reveals that [¹⁸F]FBTA can trace ALI before reaching the computed tomography (CT) diagnostic criteria, and demonstrates its better specificity and distribution than [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG).

Both Wnt/β-catenin signaling pathway and NF-κB signaling pathway are highly conservative pathways that regulate a variety of biological processes, and their cross-regulation have attracted attention in many biological and medical research fields. In this review, we summarize the cross-regulation between Wnt/β-catenin signaling pathway and NF-κB signaling pathway and discuss their involvement in the multi-directional differentiation of mesenchymal stem cells.

Fear memories are temporarily suppressed after repeated retrieval, a phenomenon known as memory extinction.How to reduce or even eliminate fear memory is the key to the treatment of fear related diseases such as post-traumatic stress disorder(PTSD). A single extinction training based on Pavlov's fear regulation task could only inhibit the expression of conditioned fear memory traces, but it could not eliminate the acquired conditioned fear memory. However, according to the reconsolidation theory based on memory, the retrieval-extinction paradigm has a more lasting effect on the erasure and rewriting of fear memory, and can effectively prevent the return of fear memory. Studies have shown that extraction-regression is closely related to a variety of neurotransmitter receptors such as glutamate receptor(GluR), dopamine receptor(DAR), L-type voltage-gated calcium channels(LVGCs) and cannabinoid. Moreover, its effect is closely related with factors such as retrieval-extinction memory stage. At present, most of the researches on extracted boundary conditions only stay at the level of behavior, with little understanding and exploration on the level of molecular mechanism. From the perspective of molecular neurobiology, with different stages of memory and different types of receptors and molecular mechanisms, this research reviewed the mechanisms of retrieval-extinction in recent years.It provided valuable signaling pathways, molecular targets and research directions for the treatment of fear-related diseases such as PTSD.

Although mesenchymal stem cell-derived exosomes (MSC-exos) have been shown to have therapeutic effects in experimental periodontitis, their drawbacks, such as low yield and limited efficacy, have hampered their clinical application. These drawbacks can be largely reduced by replacing the traditional 2D culture system with a 3D system. However, the potential function of MSC-exos produced by 3D culture (3D-exos) in periodontitis remains elusive. This study showed that compared with MSC-exos generated via 2D culture (2D-exos), 3D-exos showed enhanced anti-inflammatory effects in a ligature-induced model of periodontitis by restoring the reactive T helper 17 (Th17) cell/Treg balance in inflamed periodontal tissues. Mechanistically, 3D-exos exhibited greater enrichment of miR-1246, which can suppress the expression of Nfat5, a key factor that mediates Th17 cell polarization in a sequence-dependent manner. Furthermore, we found that recovery of the Th17 cell/Treg balance in the inflamed periodontium by the local injection of 3D-exos attenuated experimental colitis. Our study not only showed that by restoring the Th17 cell/Treg balance through the miR-1246/Nfat5 axis, the 3D culture system improved the function of MSC-exos in the treatment of periodontitis, but also it provided a basis for treating inflammatory bowel disease (IBD) by restoring immune responses in the inflamed periodontium.
Colitis ; Exosomes ; Humans ; Periodontitis/therapy* ; Periodontium ; T-Lymphocytes, Regulatory ; Th17 Cells

Objective To establish an accurate simulation model for proton scanning beam using Monte Carlo (MC) code.Methods The MC model of proton scanning beam treatment nozzle was established by using MC code FLUKA combined with the geometric structure of the treatment nozzle in Shanghai Proton and Heavy Ion Center (SPHIC).The MC beam model was established through the simulation of the integrated depth dose distribution (IDD) in water and the lateral profile in air at the isocenter points.The model was used to simulate the depth and lateral dose profile of Spread Out Bragg Peak (SOBP) of proton beam.The calucated result were compared with TPS calculation values.Results For the distal R90,the deviations of simulation and measurement at all energies were less than 0.5 mm.For distal fall off (R80-20),the deviations between simulation and measurement at each energy were within 0.1 mm.The biggest difference between measurement and simulation of the proton beam spot size was within 0.45 mm.The result of simulation and TPS calculation of proton SOBP matched well,with the γ index pass rate being higher than 90％ (Criteria:2 mm,2％).Conclusions The MC code FLUKA can be used to model the nozzle of scanning proton beam,which can meet the clinical requirements and accurately simulate the proton beam transport in material.After construction and verification on the basis of measurement,this model can be used as a dose verification tool to evaluate clinical proton treatment plans,in order to reduce the beam time for dose verification and thus increase the number of patient treatment in proton therapy.

Objective: To explore the acute effect of fine particulate matters (PM_2.5), O₃, NO₂ on daily non-accidental mortality, cardiovascular disease mortality and respiratory mortality data in thirteen cities of Jiangsu province. Methods: Daily average concentrations of non-accidental mortality, cardiovascular disease mortality, respiratory mortality data and environmental data were collected from January 1, 2015 to December 31, 2017 in thirteen cities of Jiangsu Province. Daily air quality, mortality and meteorology data were collected from the Information System of Air Pollution and Health Impact Monitoring of Chinese Center for Disease Control and Prevention. We used generalized additive model to evaluate the association between daily concentrations of air pollutants and mortality at single-city level and multi-city level, after adjusting the long-term and seasonal trend, as well as meteorological factors and the effect of "days and weeks" . A multivariate Meta-analysis with random effects was applied to estimate dose-response relationship between air pollutants and mortality. Results: At multi-city level, per interquartile range increase of PM_2.5, O₃, NO₂ was associated with an increase of 1.10% (95%CI: 0.66%, 1.54%), 0.59% (95%CI: 0.18%, 1.00%), 2.00% (95%CI: 1.29%, 2.72%) of daily non-accidental mortality respectively; 1.01% (95%CI: 0.63%, 1.38%), 0.66% (95%CI: 0.02%, 1.30%), 1.62% (95%CI: 1.00%, 2.23%) of daily cardiovascular mortality respectively; 1.09% (95%CI: 0.35%, 1.82%), 0.44% (95%CI: -0.29%, 1.16%), 2.75% (95%CI: 1.42%, 4.08%) of daily respiratory mortality respectively. The air pollutants effect varied across different cities. The strongest effect of PM_2.5 was current day (excess risk (ER)=1.10%, 95%CI: 0.66%, 1.54%)), the strongest effect of O₃ was 2-day lag (ER=1.82%, 95%CI: 0.69%, 2.97%) and the strongest effect of NO₂ was 1-day lag (ER=2.09%, 95%CI: 1.34%, 2.83%) of daily non-accidental mortality respectively. Conclusion The increases of PM_2.5 and NO₂ concentration could result in the increases of daily non-accidental mortality, cardiovascular disease mortality and respiratory mortality. O₃ could result in the increases of daily non-accidental mortality and cardiovascular disease mortality. The acute effects for non-accidental mortality from high to low were NO₂, PM_2.5 and O_3, and the strongest effect of PM_2.5 was current day. O₃ and NO₂ had lagged effects.

Objective To investigate the dosimetric advantages of proton and heavy ion radiotherapy ( particle radiotherapy) for liver cancer adjacent to gastrointestinal tract. Methods Ten patients with liver cancer adjacent to gastrointestinal tract receiving radiotherapy were recruited in this study. The prescription was first given with 50 Gy ( RBE )/25 fractions to planning target volume 1 ( PTV-1 ) using proton irradiation,and then administered with 15 Gy ( RBE)/5 fractions to PTV-2 using carbon-ion irradiation. A simultaneous integrated boost regime was established using the same variables and prescription. The organ at risk ( OAR) constraints were referred to RTOG 1201. All plans were performed for dose evaluation after qualifying the OAR constraints. Results The dose coverage of 95％ of the prescribed dose ( V95) for PTV-1 from the photon plan (97.15％±4. 27％),slightly better than (96.25±6. 69％) from the particle plan (P=0. 049).The V95 of PTV-2 from the particle plan was (94.6％±6. 22％),comparable to (95.12％±3. 49％) from the photon plan (P=0. 277).The integral dose of Body-PTV-1 delivered by the particle plan was merely 39. 9％ of that delivered by the photon plan. The mean liver-GTV dose from the particle plan was only 81. 8％ of that from the photon plan. The low-dose irradiation to the stomach and duodenum from the particle plan was significantly lower than that from the photon plan. Conclusions The dose to the liver-gross tumor volume ( GTV) is the main factor limiting the increase of total dose to the tumors. When the absolute GTV in the liver is relatively large,particle radiotherapy can maintain comparable dose coverage to the tumors as the photon radiotherapy whereas significantly reduce the dose to the liver-GTV.