Objective To study the changes of cytokines in aqueous humor of patients with proliferative diabetic retinopathy (PDR)after intravitreal bevacizumab (IVB) and the correlation of these cytokines.Methods Fifty-six patients(63 eyes) with severe PDR underwent pars piana vitrectomy (PPV) with IVB pretreatment in our hospital from April,2014 to February,2015 were collected.All the patients received IVB therapy from 3 days to 7 days before PPV.Aqueous humor samples were collected at the time of IVB and PPV treatment.The concentrations of vascular endothelial growth factor (VEGF),interleukin-6 (IL-6),interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) were measured by cytoinetric bead array (CBA).The changes of these cyto-kines after IVB were analyzed by using Wilcoxon rank sum test for paired data.The correlation between these cytokines was analyzed by using Spearman rank test.Results From 3 days to 7 days after IVB,the concentration of VEGF in aqueous humor was (6.57 ± 12.29)pg · mL-1,lower than the pre-operation of (278.71 ±340.20)pg · mL-1,the difference was statistically significant (P ＜ 0.05).The concentration of IL-8 was (385.60 ± 1099.47) pg · mL-1,higher than pre-operation of(298.87 ± 1005.79) pg ·mL-1,the difference was statistically significant (P ＜ 0.05).IL-6 and MCP-1 were increased after IVB,but the difference was not statistically significant (all P ＞ 0.05).VEGF,IL-6,IL-8 and MCP-1 had an obviously relationship between each two factors(all P ＜ 0.05).Conclusion Angiogenesis in patients with PDR are regulated by a variety of cytokines,and targeted reduction of VEGF may compensatory increase the concentration of other inflammatory cytokines.

Objective To assess the therapeutic effect of plum-blossom needle tapping combined with topical imiquimod immunotherapy on cutaneous squamous cell carcinoma (SCC) in SKH-1 mice,and to explore the immunological mechanism.Methods A total of 40 SKH-1 mice with ultraviolet light-induced cutaneous SCC were randomly and equally divided into 4 groups:control group receiving no treatment,plum-blossom needle group receiving plum-blossom needle tapping on all the tumors once a day,imiquimod group topically treated with imiquimod 5％ cream at a dose of 1.2 g/kg once a day,combination group firstly treated with plum-blossom needle tapping on all the tumors,and after the stop of bleeding topically treated with imiquimod 5％ cream at the same dose as the imiquimod group once a day.All the mice were treated for 30 days.Morphological changes of tumors in all groups were photographed and recorded every day.The tumor size was measured once every three days,and changes of total tumor volume and survival rate of the mice were compared among the 4 groups.At the end of treatment,tunor tissues were resected,and histopathological changes were compared among the 4 groups.Real-time fluorescence-based quantitative PCR (qRT-PCR) was performed to measure the mRNA expression of interferon-α (IFN-α),IFN-β,interleukin-1β (IL-1β),tumor necrosis factor-α (TNF-o) and IL-12 in tumor tissues.Results In the combination group,tumors on the back of mice grew slowly,and some even regressed.However,tumors grew fast in the control group,plum-blossom needle group and imiquimod group,and grew more slowly in the plum-blossom needle group and imiquimod group than in the control group.Before the treatment,there was no significant difference in the total tumor volume among the 4 groups (F =0.90,P ＞ 0.05).After 24-day treatment,the total tumor volume significantly differed among the 4 groups (F =5.16,P ＜ 0.05).The LSD-t test showed that the total tumor volume significantly decreased in the combination group compared with the control group (P ＜ 0.01),but no significant difference was observed among the other groups (P ＞ 0.05).Log-rank test revealed that survival curves significantly differed among the 4 groups (x2 =8.32,P ＜ 0.05).The survival rate was significantly higher in the combination group than in the control group (x2 =4.62,P =0.03),but did not differ between the plum-blossom needle group or imiquimod group and the control group or combination group (all P ＞ 0.05).Histopathological examination showed atypical cells arranged closely,a large number of tumor cells and some keratin pearls in the control group and plumblossom needle group,few dead tumor cells in the imiquimod group,and plenty of dead tumor cells,mild nuclear atypia and increased keratinization in the combination group.qRT-PCR revealed that the relative mRNA expression levels of IFN-α,IFN-β,IL-12,IL-1β and TNF-α were significantly higher in the combination group than those in the control group,plum-blossom needle group and imiquimod group (P ＜ 0.05).The imiquimod group showed significantly higher mRNA expression of IL-1β than the control group (P ＜ 0.01),but no significant differences were observed among the other groups (P ＞ 0.05).Conclusion Plum-blossom needle tapping can effectively enhance the anti-SCC activity and immunological effects of imiquimod in SKH-1 mice.

Objective To explore the predictive value of contrast-enhanced echocardiography com-bined with serum levels of CD137 and insulin-like growth factor binding protein 6(IGFBP-6)for cardiovascular adverse events(MACE)in elderly patients with stable coronary heart disease(CHD)after percutaneous coronary intervention(PCI).Methods A total of 108 elderly patients with stable CHD(CHD group)who visited Department of Cardiology of Changsha First Hospital from March 2020 to March 2022 were recruited in this study.They were grouped into a non-MACE group(81 cases)and a MACE group(27 cases)according to whether MACE occurred after PCI.Another 100 healthy individuals who taking physical examination during the same period served as control group.Their serum CD137 and IGFBP-6 levels were detected,and the contrast agent filling speed(β value)and maximum number of microbubbles(A value)were calculated based on the results of contrast-enhanced echocardiography.Their general clinical data were col-lected.ROC curve analysis and multivariate logistic regression analysis were used to analyze the data.Results The serum levels of CD137 and IGFBP-6 were significantly higher,while the β value and A value were obviously lower in the CHD group than the control group(P＜0.01).And the serum levels were notably higher,and the β value and A value were remarkably lower in the MACE group than the non-MACE group(P＜0.01).The AUC of cardiac ultrasound parameters βvalue and A value combined with serum CD137 and IGFBP-6 to predict MACE after PCI in CHD patients was 0.930,which was significantly higher than the AUC value of every single indicator(P＜0.01).β value,A value,CD137 and IGFBP-6 levels were all risk factors for the occurrence of MACE in CHD patients after PCI(P＜0.01).Conclusion Contrast-enhanced echocardiography,serum CD137 and IGFBP-6 levels have certain predictive value for MACE in elderly CHD patients after PCI,and combined detection has higher predictive value.

Objective:To investigate clinical manifestations and dermoscopic characteristics of lichen planus-like keratosis (LPLK) .Methods:Clinical data were collected from 21 patients with LPLK who visited Shanghai Skin Disease Hospital and underwent both dermoscopic and histopathological examinations from January 2017 to September 2019, and clinical and dermoscopic features were retrospectively analyzed.Results:These patients were aged 64.69 ± 13.29 years, and the ratio of males to females was 1∶2. Skin lesions were located on the face of 18 cases and legs of 3 cases, and were red/violaceous in color in 7 cases, reddish-brown in 5, brown/gray in 8, and brown/reddish in 1. There were 3 types of skin lesions, including plaque-like type in 10 cases, flat pigmented patch type in 6, and flat erythema-like type in 5. As dermoscopy showed, 12 cases were non-pigmented LPLK, and 9 were pigmented LPLK. Pigment granules were found in 13 lesions, and there was no significant difference in the prevalence of pigment granules between pigmented and non-pigmented LPLK ( P=0.07) ; pigment granules were often diffusely distributed (9/13) , and the diffuse distribution pattern was common paticularly in pigmented LPLK (8/9) ; locally distributed pigment granules were found in 4 cases of non-pigmented LPLK. Coarse pigment granules were seen in 10 cases (10/13) , including 8 of pigmented LPLK and 2 of non-pigmented LPLK, and the prevalence rate of coarse pigment granules significantly differed between the pigmented LPLK and non-pigmented LPLK groups ( P=0.002) . Moreover, special distribution patterns of pigment granules included the annular granular pattern (8/13) and peppered pattern (7/13) , and no significant difference was observed in the prevalence of the 2 special distribution patterns between the pigmented LPLK and non-pigmented LPLK groups (both P > 0.05) . Scales were seen in 13 cases (13/21) , and vascular structures in 7 (7/21) , and there was no significant difference in the prevalence of the 2 structures between the pigmented and non-pigmented LPLK groups ( P=0.67, 0.16, respectively) . Conclusions:LPLK mostly occurs on the face, and manifests as solitary red, reddish-brown or brownish-gray plaques or patches, whose surfaces may be covered with scales. The characteristic dermoscopic feature of LPLK is the presence of pigment granules, which are coarse, often diffusely distributed, and commonly observed in pigmented LPLK.

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).