Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H₂O₂-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H⁺ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H₂O₂-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.

ObjectiveTo explore the effect of virtual reality on upper limb function in stroke patients through diffusion tensor imaging (DTI). MethodsFrom September, 2021 to March, 2023, 80 stroke patients in the Fuzhou Second General Hospital were randomly divided into control group (n = 40) and experimental group (n = 40). Both groups received routine rehabilitation, while the experimental group received virtual reality training additionally, for four weeks. They were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and Action Research Arm Test (ARAT) before treatment, after treatment and after four-week follow-up; and they were scaned with DTI to measure the fractional anisotropy (FA) and relative anisotropy (RA) of cerebral peduncle and posterior limb of inner capsule of the affected side before and after treatment. ResultsTwo cases dropped in each group. The FMA-UE and ARAT scores increased in both groups after treatment and follow-up (F > 2.790, P < 0.001), and increased more in the experimental group than in the control group (t > 2.297, P < 0.05). FA and RA in the posterior limb of inner capsule increased in both groups after treatment (t > 21.013, P < 0.001), and increased more in the experimental group (t > 2.006, P < 0.05). The d-value of FA of the posterior limb of internal capsule before and after treatment (ΔFA) was positively correlated with the d-value of FMA-UE score (r > 0.362, P < 0.05) in both groups, the ΔFA of the posterior limb of internal capsule was positively correlated with the d-value of ARAT score (r = 0.459, P < 0.01). ConclusionVirtual reality training can promote the recovery of upper limb function in stroke patients, which may associate with the conductivity of posterior limb of inner capsule.

AIM: To investigate the differences in varying stages of non-proliferative diabetic retinopathy(NPDR)using optical coherence tomography angiography(OCTA).METHODS: Cross-sectional study. A total of 77 cases(77 eyes)of diabetic patients were included, and they were divided into non-diabetic retinopathy(NDR; 23 eyes)and non-proliferative diabetic retinopathy(NPDR; 54 eyes)groups, further subdivided into mild NPDR(20 eyes), moderate NPDR(20 eyes), and severe NPDR(14 eyes). Foveal avascular zone(FAZ)area, superficial and deep capillary plexus densities(SSP and DSP), and visual acuity(LogMAR)were compared between NDR and NPDR groups. Furthermore, the visual acuity, FAZ area and levels of SSP and DSP were compared in different degrees of NPDR. Correlation analysis were conducted to elucidate relationships between FAZ area, visual acuity, SSP, DSP, and severity of the disease.RESULTS: Compared with the NDR group, the visual acuity(LogMAR)and macular FAZ area increased, while SSP and DSP were decreased in the NPDR group(P<0.05); there were significant differences in visual acuity, FAZ area and SSP and DSP levels in different degrees of NPDR(P<0.05). Visual acuity(LogMAR)and FAZ area displayed a positive correlation with the severity of disease, while SSP and DSP showed a negative correlation.CONCLUSION: With the progression of NPDR, the visual acuity(LogMAR)and FAZ area increased, and the SSP and DSP decreased.

Objective:To investigate the effects of myeloid differentiation protein-2 (MD-2) on paclitaxel resistance cells in triple negative breast cancer (TNBC) through EGFR signaling pathway.Methods:Immunohistochemical method was used to detect the expression of MD-2 in cancer tissue and adjacent tissue of TNBC patients, and the relationship between MD-2 expression and clinicopathological parameters of patients was analyzed. The TNBC paclitaxel-resistant cell line was constructed and MD-2 expression in cells was interfered. Cell invasion was detected by Transwell, and cell apoptosis was detected by flow cytometry. The signaling pathways regulated by MD-2 were screened by transcriptome sequencing and verified by Western blot.Results:The expression of MD-2 was significantly enhanced in cancer tissues relative to adjacent tissues. High expression of MD-2 was closely related to clinical stage, tumor size, tumor recurrence and metastasis ( χ2=4.50, P=0.032; χ2=2.55, P=0.011; χ2=4.40, P=0.036). In cell experiments, compared with normal breast cells, the expression of MD-2 in TNBC cell lines was significantly enhanced. Compared with sh-NC group (100±11.52) (6.81±0.57), knockdown of MD-2 could inhibit the invasion (61.44±6.78) ( t=4.99, P=0.008) but promote apoptosis (15.19±1.06) ( t=12.06, P<0.001) of paclitaxel resistant TNBC cells. Transcriptome sequencing and Western blot results showed that MD-2 mainly affects the biological behavior of TNBC cells by regulating the EGFR signaling pathway. Conclusions:MD-2 promoted TNBC cell invasion and paclitaxel resistance, which may be achieved by affecting the EGFR signaling pathway. MD-2 is expected to become an effective target in TNBC treatment.

Objective:To investigate the association between occupational hazard exposures and small airway function among middle-aged and elderly people.Methods:From July to December in 2015, a multistage cluster random sampling method was used to select 3 600 residents aged 40 years old and above from 6 chronic obstructive pulmonary disease surveillance points in Jiangsu province. A cross-sectional survey was conducted to collect relevant information. Multivariable linear regression model was performed to determine the relationship between occupational hazard exposures and small airway function.Results:A total of 3 347 participants were included in the final analysis, and 44.6% of participants had been exposed to occupational hazard exposures. Compared with participants without the exposure history of occupational hazards, the significantly lower post-bronchodilator FEF 50%, FEF 75% and MMEF levels were observed in those with the exposure history of occupational hazards (β=-82.74, -55.43 and -91.57, respectively). Post-bronchodilator FEF 75% and MMEF (β=-51.78 and -79.47, respectively) in the participants with the exposure history of occupational dust and post-bronchodilator FEF 50%, FEF 75% and MMEF (β=-96.84, -32.87 and -75.72, respectively) in the participants with the exposure history of occupational harmful gas all showed a lower level. Post-bronchodilator FEF 75% was negatively associated with occupational hazard exposures in males (β male=-91.65 vs. β female=-27.21, P for interaction=0.022). Conclusions:The small airway function is worse in the middle-aged and elderly population with the exposure history of occupational hazards, and it is more significant in the male population.

Objective:To investigate the association between occupational hazard exposures and small airway function among middle-aged and elderly people.Methods:From July to December in 2015, a multistage cluster random sampling method was used to select 3 600 residents aged 40 years old and above from 6 chronic obstructive pulmonary disease surveillance points in Jiangsu province. A cross-sectional survey was conducted to collect relevant information. Multivariable linear regression model was performed to determine the relationship between occupational hazard exposures and small airway function.Results:A total of 3 347 participants were included in the final analysis, and 44.6% of participants had been exposed to occupational hazard exposures. Compared with participants without the exposure history of occupational hazards, the significantly lower post-bronchodilator FEF 50%, FEF 75% and MMEF levels were observed in those with the exposure history of occupational hazards (β=-82.74, -55.43 and -91.57, respectively). Post-bronchodilator FEF 75% and MMEF (β=-51.78 and -79.47, respectively) in the participants with the exposure history of occupational dust and post-bronchodilator FEF 50%, FEF 75% and MMEF (β=-96.84, -32.87 and -75.72, respectively) in the participants with the exposure history of occupational harmful gas all showed a lower level. Post-bronchodilator FEF 75% was negatively associated with occupational hazard exposures in males (β male=-91.65 vs. β female=-27.21, P for interaction=0.022). Conclusions:The small airway function is worse in the middle-aged and elderly population with the exposure history of occupational hazards, and it is more significant in the male population.

OBJECTIVE： To investigate the protective effect and its mechanism of thymoquinone （TQ） on myocardial fibrosis （MF） induced by lipopolysaccharide in rats. METHODS： Totally 40 male Wistar rats were randomly divided into control group， model group， TQ low-dose and high-dose groups [5， 10 mg/（kg?d）]， with 10 rats in each group. Except that control group was given constant volume of normal saline intraperitoneally， other groups were given LPS intraperitoneally to induce MF model， once a day， for consecutive 3 weeks. Since the first day of modeling， administration group was given relevant medicine intraperitoneally， once a day， for consecutive 3 weeks. After last medication， ELISA method was used to detect the contents of serum inflammation factors （IL-1β， IL-6， TNF-α） in rats. Cardiac mass parameters （HW/BM， LVW/BW） were weighed and calculated. HE staining was used to observe the histopathological changes of myocardial tissue. The contents or activities of oxidative stress indicators （MDA， SOD） and myocardial collagen indexes （HYP， Col-Ⅰ， Col-Ⅲ） were detected by chemical analysis， xanthine oxidase method or ELISA. mRNA expression of regulation genes （Col-Ⅰ， Col-Ⅲ， MMP-3， MMP-9， TGF-β1 and Smad3） related to myocardial fibrosis were determined by real-time fluorescence quantitative PCR. RESULTS： Compared with control group， there were swollen myocardial cells， disordered nuclei of different sizes and visible fiber hyperplasia in model group； the levels of serum inflammatory factors and LVW/BW， cardiac contents of MDA， HYP， Col-Ⅰand Col-Ⅲ， mRNA expression of Col-Ⅲ， TGF-β1 and Smad3 in model group were increased significantly （P＜0.05）， while SOD activity was decreased significantly （P＜0.05）. Compared with model group， the degree of myocardial fibrosis was improved in TQ groups to different extents； serum content of IL-1β and the contents of MDA， HYP and Col-Ⅰ in cardiac tissue in TQ low-dose group， serum contents of IL-1β， IL-6 and TNF-α， LVW/BW and the contents of MDA， HYP， Col-Ⅰ and Col-Ⅲ in cardiac tissue of TQ high-dose group as well as mRNA expression of Col-Ⅰ， Col -Ⅲ， TGF-β1 in TQ groups were decreased significantly （P＜0.05）. The activities of SOD in cardiac tissue were increased significantly in TQ groups （P＜0.05）. There was no statistical significance in other indexes among groups （P＞0.05）. CONCLUSIONS： TQ can protect against MF model rats to certain extent， the mechanism of which may be associated with the inhibition of inflammation reaction and oxidant stress reaction， and down-regulation of mRNA expression of Col-Ⅰ， Col-Ⅲ and TGF-β1.

Objective To conclude the experience of restoration of fat compartments volume intreatment of facial volume lost aging.Methods From May 2015 to May 2018,126 patients with facialvolume lost aging,aged from 34 to 52 years (mean age 42.6 years),were corrected by restoring fatcompartments volume using different sized autologous fat granule grafting technique.Patients' satis-faction was rated using Visual Analogue Scale (VAS) ranging from 1 (most unsatisfactory) to 10(most satisfactory).Results 126 patients with volume lost aging face were followed up from 3months to 2.5 years,the sculpted appearance became more fullness,the laxity,wrinkles and textureof skin were improved obviously,the patients' VAS score was (8.2±1.4).Conclusions Restorationof fat compartments by using different sized autologous fat granule grafting can augment the facicalfullness,reshape the facial contour and improve the aging skin.Therefore it proves to be a safe,multi-effecive and satisfying technique in the treatment of facial volume lost aging.

Objective: To elucidate the clinicopathological characters and prognostic factors of invasive micropapillary carcinoma of the breast (IMPC) by compared with invasive ductal carcinoma, not otherwise specified of the breast (IDC). Methods: The retrospective study was performed with female patients who had undergone curative resection for breast cancer without neoadjuvant chemotherapy from June 2008 to April 2016 in Breast Center of Beijing Hospital. Forty-seven mixed or pure IMPC patients and 93 pure IDC patients(admitted in the same center from October 2008 to January 2016 ) were matched for tumor stage, nodal status and age. Follow-up was done every 3 to 6 months postoperatively. The deadline was July 31, 2016. The curves of disease free survival and overall survival were drawn by the Kaplan-Meier method, and survival rates were compared by means of the Log-rank test. Potential prognostic variables that were identified on univariate analysis were analyzed with Cox′s proportional hazards regression model for multivariate analysis. The χ² test or Fisher′s exact test was used to compare distributions across 2 groups and the Mann-Whitney U test or t test was used to analyze the medians or means of 2 groups. Results: With exact matches, the rates of lymphovascular invasion (LVI) (29.8% vs. 12.9%, χ²=5.885, P=0.015)and histological grade 3 (40.4% vs. 21.5%, χ²=-2.690, P=0.007) were both significantly higher in patients with IMPC than that in IDC group, but the survival between the two pathological types were not significantly different (all P>0.05). The percent of IMPC component didn′t influence the clinicopathologic characters (all P >0.05), but a significantly longer median disease free survival (χ²=11.731, P=0.001) when the patients had more than 50% of IMPC component was found. Conclusions Higher rates of LVI and histological grade 3 were found in IMPC than that in IDC, but the survival was comparable between the two groups. A longer DFS occurred in patients with IMPC component more than 50%.

Objective:To investigate the effect of compound 48/80(C48/80) activated mast cell on dendritic cell homing to draining lymph nodes(DLN) in order to explore the potential mechanism of C48/80 promoting adaptive immune response.Methods: C57BL/6 mice bone marrow derived dendritic cells(BM-DC) and MC/9 mast cell line were propagated in vitro.Chemotaxis of BM-DC supplemented with supernatant of C48/80 treated MC/9 to CCL21 was measured by transwell chemotaxis assay.C48/80 was injected into murine scapular site,local skin mast cell degranulation was detected by toluidine blue staining method.The number of CD11c+ DC in draining lymph nodes(DLN) was detected by Flow cytometry.Exogenous green microbeads labeled BM-DC homing to DLN was detected by fluromicroscope.The mice pretreated with or without C48/80 were vaccinated by ovalbumin pulsed DC(OVA-DC),DLN lymphocyte proliferation was detected by WST-8 reagent.Results: A large amount of typical BM-DC were harvested from media supplemented with murine recombinant IL-4 and GM-CSF.Product of activated MC/9 enhanced chemotaxis of BM-DC to CCL21(P<0.01).Intradermal injection of C48/80 induced local mast cell obvious degranulation and local inflammation.Mice pretreated with C48/80 demonstrated high number of total cells and DC cells in DLN.The number of fluorescent positive BM-DC in DLN also increased in C48/80 pretreated mice.Antigen specific lymphocyte proliferation enhanced in OVA-DC inoculated C48/80 pretreated mice.Conclusion: Mast cell activation induced by C48/80 can enhance DC homing to DLN and increase specific lymphocyte proliferation,which may be one of a mechanism of C48/80 in promoting adaptive immune response.