Dry eye(DE)is a multifactorial ocular surface disorder arising from numerous pathologies. The pathogenesis of DE includes immune inflammation, oxidative stress, changes in tear film composition, corneal nerve abnormalities, and meibomian gland dysfunction. Among them, the immune inflammatory response is the most crucial in the pathogenesis of DE, which is regulated by both innate and acquired immune responses on the ocular surface. Multiple environmental stresses trigger the ocular surface innate immune response leading to corneal epithelial cell damage and inflammation and activate acquired immunity to participate in the ocular surface immune inflammatory response. Currently, multiple immune cells and inflammatory factors have been shown to be involved in the occurrence and development of DE. This article reviewed the immune progress and focused on the initiation and maintenance of acquired immunity in DE. Through the analysis of the latest viewpoints and research hot spots, we systematically introduced the immunomodulating mechanism underlying the mechanisms of the pathogenesis of DE and provided references for the prevention and treatment of DE.

Berberine is a commonly used traditional Chinese medicine,which has the antimicrobial and anti-inflammatory properties.Ongoing investigations have identified berberine as an effective medicine for systemic diseases,such as cardiovascular diseases,diabe-tes mellitus and neurological disorders.At the same time,there exists a close relationship between oral microbiota and these systemic diseases.This review focuses on the relationship between berberine,oral microbiota and systemic diseases,offering new insights for the treatment of systemic diseases.

Harmine(HM)is a type of β-Carboline alkaloid abundant in nature and has many biological effects.In recent years.Studies have found that HM had a significant positive effect on Alzheimer's disease(AD)both in vivo and in vitro.Its mechanism may be related to the reduction of abnormal deposition of β-amyloid protein(Aβ),excessive phosphorylation of Tau protein,regulation of the cholinergic system,antioxidant stress,and antineuritis.This article reviews the research progress on the improvement effect and mechanism of HM in AD in order to provide an experimental basis for the clinical application of HM and the development of drugs in the area of AD the prevention and treatment.

AIM:To explore the impact of histidine triad nucleotide-binding protein 2(HINT2)on atheroscle-rosis(AS),and to elucidate its underlying mechanisms.METHODS:Peripheral blood mononuclear cells(PBMCs)were isolated from patients with chest pain and induced to differentiate into macrophages for assessing HINT2 expression.In vitro,RAW264.7 mouse macrophages were cultured to evaluate inflammatory cytokine levels and cell death in superna-tants.An apolipoprotein E gene knockout(apoE-/-)mouse model of AS was developed to analyze plaque formation,lipid metabolism and macrophage foaminess in the aortic root.Pyroptosis-related protein expression in cultured RAW264.7 cells and the aorta of apoE-/-mice was determined by RT-qPCR and Western blot.RESULTS:Significantly reduced HINT2 expression was observed in PBMCs from patients with acute coronary syndrome,which was negatively correlated with pro-inflammatory and positively correlated with anti-inflammatory serum factors,suggesting HINT2's potential role in mitigating AS-related inflammation.In vitro experiments demonstrated that HINT2 overexpression inhibited lipid accumu-lation and foam cell formation in macrophages induced by oxidized low-density lipoprotein(ox-LDL).It also reduced se-cretion of inflammatory cytokines,including interleukin-6(IL-6),IL-1β,IL-18 and tumor necrosis factor-α,and de-creased cell death and pyroptosis-related protein expression.In vivo experiments in apoE-/-mice confirmed that HINT2 overexpression lessened plaque burden in the aortic root,reduced macrophage foaminess,and inhibited the expression of pyroptosis-related proteins such as nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1,gasdermin D(GSDMD),IL-1β and IL-18.CONCLUSION:HINT2 potentially inhibits ox-LDL-induced macrophage pyroptosis,attenuates inflammatory responses in AS,and may slow the progression of this disease.

Objective:To evaluate the effect of age factor on the potency of cisatracurium-induced neuromuscular block in the obese patients.Methods:American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ obese patients, with a body mass index of 30-35 kg/m 2 and waist circumference (female ≥ 80 cm, male ≥ 90 cm), 40 elderly patients (age 65-75 yr) and 40 young and middle-aged patients (age 18-64 yr), scheduled for elective surgery with general anesthesia, were included in this study. Based on the random number table method, the patients were assigned into dosage groups of 40, 50, 60 and 70 μg/kg, served as OF1-4 groups and YF1-4 groups, with 10 patients in each group. The consumption of cisatracurium was calculated based on fat-free mass using a single-dose method. The neuromuscular block of cisatracurium was monitored by recording the response of the adductor pollicis muscle to TOF stimulation, the maximum suppression degree of T 1 and onset time were recorded using the Mindray BeneVision N17 monitor, and the dose-response relationship regression equation was developed to calculate the median effective dose. Results:There was no significant difference in the onset time among groups ( P>0.05). The median effective dose in elderly obese patients and young and middle-aged obese patients were 50.01 and 48.71 μg/kg, respectively, and there was no significant difference between the two groups ( P>0.05). Conclusions:There is no significant difference in the potency of cisatracurium-induced neuromuscular block between elderly obese patients and young and middle-aged obese patients, suggesting that age factor has no significant effect on it.

Objective:To evaluate the long-term outcome of Viabahn stent graft in the treatment of complex femoropopliteal occlusive lesions.Methods:From Sep 2013 to Mar 2020, clinical data of TASC C and D femoropopliteal lesions treated with Viabahn were retrospectively analyzed. Patency rates, the freedom rate from clinically-driven target lesion revascularization (F-TLR), limb salvage and survival after five years were calculated.Results:A total of 65 patients (67 lower limbs) were included. 20 limbs were TASC C lesions, 47 limbs were TASC D lesions. The mean lesion length was (29.1±9.4) cm, including 48 chronic total occlusion (CTO) lesions (71.6%) with mean lesion length of (26.1±10.4) cm. Technique success rate was 98.6%. Mean length of stent graft was (31.3±10.1) cm.Major amputation was performed in 4.2% cases within 5 years. All-cause mortality in 5 years was 23.1%. Primary patency rates at 1,3,and 5 years were 76.8%,59.4%,50.9%, Assisted primary patency rates were 88.4%, 83.4%, 83.4% and secondary patency rates were 88.4%, 85.8%, and 85.8% . F-TLR at 1, 3 and 5 year was 88.2%,76.9%,73.1% .Conclusion:Viabahn for complex and long femoropopliteal artery occlusions is an acceptable treatment with fair long-term outcome.

Objective:To investigate the effects of curcumin on proliferation, cell cycle, and apoptosis of human thyroid cancer TPC-1 cells.Methods:Logarithmic growth phase TPC-1 cells were treated with 0.0, 7.5, 15.0 and 22.5 μmol/L curcumin for 48 h. Cell proliferation levels were determined using the methylthiazolyl tetrazolium (MTT) assay. Cell cycle and apoptosis levels were measured using flow cytometry. Western blot method was used to determine the expression levels of B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax).Results:The inhibition rates of cell proliferation in 7.5, 15.0 and 22.5 μmol/L curcumin groups were higher than that of 0.0 μmol/L curcumin group ( P < 0.05); the proportion of G0/G1 phase was higher than that of 0.0 μmol/L curcumin group, but the proportions of G2/M and S phase were lower than those of 0.0 μmol/L curcumin group ( P < 0.05); the cell apoptosis rate was higher than that of 0.0 μmol/L curcumin group [(14.13 ± 0.57)%, (25.27 ± 0.62)%, (36.01 ± 0.84)% vs (8.48 ± 0.43)%, P < 0.05]; the protein expression of Bcl-2 was lower than that of 0.0 μmol/L curcumin group, and protein expression of Bax was higher than that of 0.0 μmol/L curcumin group ( P < 0.05). Conclusion:Curcumin can inhibit the proliferation of TPC-1 cells, block the cell cycle in G0/G1 phase, and promote cell apoptosis by downregulating Bcl-2 expression and upregulating Bax expression.

Objective:To evaluate the efficacy and safety of drug-coated balloon (DCB) with paclitaxel in the treatment of femoropopliteal arteriosclerosis obliterans (ASO).Methods:From Dec 2016 to Dec 2018, clinical data of femoropopliteal artery disease patients treated with paclitaxel DCB in Renji Hospital, School of Medicine, Shanghai Jiaotong University were retrospectively analyzed.Results:A total of 83 patients (95 lower limbs) underwent DCB therapy. Including 50 chronic total occlusion (CTO) lesions (52.6%) with mean lesion length of (18.35±10.61) cm. Twenty-four lesions (25.3%) were moderately or severely calcified. Bail-out stent implantation was performed in 29.5% cases. The mean follow-up time was 17.5 months. Twelve months after intervention, the all-cause mortality rate was 6.0%, the major amputation rate was 4.3%, the primary patency rate was 60.6%, the primary assisted patency rate was 72.4%, the secondary patency rate was 83.4%, and the freedom rate from clinically-driven target lesion revascularization(F-TLR) was 77.0%. Moderate to severe calcification was an independent risk factor for the primary patency of DCB therapy.Conclusion:DCB is a safe and effective endovascular therapy for femoropopliteal artery disease.

Purpose To develop the folate-targeted theranostic nanoprobe, investigate the active targeting behavior of nanoprobes to hepatocellular carcinoma(HCC)in vitro,and discuss the effect of enhanced US/MRI dual-mode imaging in vitro and the synergistic effect of high intensity focused ultrasound on HCC killing. Materials and Methods The folate-targeted nanoprobe loaded with iron oxide nanoparticles (Fe3O4) and phase-shift material perfluorohexane (PFH) was prepared by double emulsion method and carbodiimide method. The average particle size, morphological structure and the ability of liquid-gas phase transition were detected. The active targeting ability of the nanoprobe to HCC BEL-7402 was observed in vitro.The ultrasonic imaging effect of nanoprobe was observed by HIFU irradiation in vitro.MRI was performed on the Fe3O4nanoprobe with different content of magnetic particles.The synergistic killing ability of the nanoprobe combined with HIFU on liver cancer cells was detected with in vitro apoptosis experiment. Results The folate-targeted nanoprobe loading iron oxide nanoparticles (Fe3O4) and phase-shift material PFH was prepared, with the average size of (402.50±66.43) nm. It was in the shape of regular sphere with the magnetic particle Fe3O4scattered inside. The HIFU irradiation caused liquid and gas phase transition.In vitro targeting experiments showed that BEL-7402 cells were surrounded by a large number of nanoscale probes.In vitro dual mode imaging showed that the ultrasonic echo intensity was obviously enhanced after HIFU irradiates nanoscale probes. The MR negative imaging ability of the nanoprobe was also enhanced with the enhancement of Fe3O4concentration in nanoparticles. In vitro apoptosis experiments showed that the nanoscale probe had the ability to significantly enhance the effect of HIFU on the killing of HCC. Conclusion The prepared folate-targeted theranostic nanoprobes exhibit the excellent capability for in vitro targeting.They can be used for ultrasound and MRI as multimodal imaging agents and coordinates with HIFU to enhance the effect on killing HCC, which realizes the early diagnosis of tumor and targeted precision therapy.

Sleep deficiency is a common public health problem associated with many diseases, such as obesity and cardiovascular disease. In this study, we established a sleep deprivation (SD) mouse model using a ‘stick over water’ method and observed the effect of sleep deficiency on ocular surface health. We found that SD decreased aqueous tear secretion; increased corneal epithelial cell defects, corneal sensitivity, and apoptosis; and induced squamous metaplasia of the corneal epithelium. These pathological changes mimic the typical features of dry eye. However, there was no obvious corneal inflammation and conjunctival goblet cell change after SD for 10 days. Meanwhile, lacrimal gland hypertrophy along with abnormal lipid metabolites, secretory proteins and free amino-acid profiles became apparent as the SD duration increased. Furthermore, the ocular surface changes induced by SD for 10 days were largely reversed after 14 days of rest. We conclude that SD compromises lacrimal system function and induces dry eye. These findings will benefit the clinical diagnosis and treatment of sleep-disorder-related ocular surface diseases.