Objective To prepare SDF-1 α-loaded nanoliposome ( SNP )-SonoVue complex and investigate its tracing abilities, sustained-release property and effect on migration of bone marrow mesenchymal stem cells (BMSCs). Methods The SNP was prepared to detect its physical characteristics including particle size,zeta potential, morphology, encapsulation efficiency and drug loading.SNP-SonoVue was constructed to detect the sustained release situation of SNP and SNP-SonoVue after low frequency ultrasound ( LIFU ) irradiation, and the connection of SNP-SonoVue was observed by fluorescence microscope. Effects of SNP-SonoVue on migration of BMSCs were detected to evaluate its bioactivity. BMSCs were divided into 6 groups,including Group A: SDF-1α+ 1% serum medium;Group B: SNP- SonoVue+ 1% serum culture medium;Group C:SNP-SonoVue+ 1% serum culture medium + LIFU ( 1 MHz,0.5 W/cm2, expose 30 s stop 30 s, 4 min);Group D: BNP-SonoVue+1% serum medium;Group E:BNP-SonoVue+1% serum medium+LIFU ( 1 MHz, 0.5 W/cm2, expose 30 s stop 30 s, 4 min),Group F:PBS+1% serum culture medium (control group). Its tracing abilitie were investigated in vitro. Results The average particle size of SNP was(220.4±9.9)nm,and the particle dispersion index(PDI) was(0.172± 0.015), the average zeta potential was ( 35.6 ± 1.7) mv. It was showed spherical dispersion by transmission electron microscopy. The encapsulation efficiency was up to 96.7% and the drug entrapment content was 481.76 ng/mg. Flow cytometric showed the suitable conditions for SNP-SonoVue preparation was that the ratio of SNP quality(mg) to Sono Vue microbubbles number(a) was20:(2.8×109)to40:(2.8× 109). Fluorescence microscopy showed that shells of SonoVue microbubbles connected with large numbers of SNP labeled with red fluorescent DiI. Drug release experiment showed that the cumulative SDF-1α release amount of SNP and SNP-SonoVue exposed to LIFU respectively were ( 68.61 ± 3.97 )% and ( 63.21 ± 5.68)% in vitro within 7 days, and the difference was not statistically significant ( P ＞ 0.05 ). Cell migration experiments confirmed that the transfer function of BMSCs in Group A, Ggroup B and group C was significantly higher than that in control group ( P ＜ 0.05 ), but there was no significant difference among the Group A, Ggroup B and group C ( P ＞0.05). In vitro development experiment showed that the SNP-SonoVue complex had obviously enhanced development effect. Conclusions SNP-SonoVue complex is successfully prepared. It has obviously enhanced development effect and can lead to migration of BMSCs.

Objective To explore the mechanisms of ligament of Marshall (LOM) initiat and sustain atrial fibrillation (AF).Methods The electrophysiologic properties of canine LOM were investigated using multipolar catheter mapping(normal canines,n =4,group A;AF canines,n =5,group B).The programmed stimulation were performed in the LOM,PV-left atrium(LA)junction and LA,respectively.Activations maps of LOM were analyzed from episodes of spontaneous onset of AF and initiation of induced AF by a single extrastimulus.The effectives refractory period of each part was compared and statistically analyzed among three parts in each group and between the two groups.LOM were cutted with surgical incision technology.The inducing rate of AF and the mapping rate of double potential and fragmented electrocardiogram were compared and statistically analyzed pro and post isolation of LOM.Results The incidence of abnormal potential of LOM in the two groups was significantly different(P ＜0.01),re-entry cycle(group A 25％ vs.B group 80％),tachycardia(group A 25％ vs.B 100％),double potential(group A 25％ vs.group B 80％),fragmentation potential(group A 25％ vs.group 80％).There was a significant difference in the rate of LOM tachycardia induction before and after LOM intervention in group B (P ＜ 0.05,before 100％ vs.after 20％).Conclusion There are two possible mechanisms of LOM involved in the occurrence and maintenance of AF:one is that LOM induces AF through spontaneous excitation,the other is that LOM participates in the reentry of left atrium and pulmonary vein in the form of bypass to induce and maintain AF.

Objective To observe the effects of the Diaomo-Zhibeng liquid on the expression of Bcl-2/Bax mRNA and their protein in vitro endometrial glandular epithelial cells in patients of endometrial hyperplasia Methods The endometrial tissue in patients with the pathological diagnosis of endometrial hyperplasia were collected.After isolation,culture and identification,the endometrial cells were divided into four groups:low dosage group (12.5 μg/ml),middle dosage group (25 μg/ml),high dosage group (50μg/ml) and blank control group at randomaccording to the random number table.Three duplicate samples were set for each group.After 48h,the expression of Bcl-2 and Bax were detected by RT-PCR and Western-blot.Results Compared with the blank control group,the expression of Bcl-2 mRNA (1.51 ± 0.07,1.09 ± 0.06,0.93 ± 0.07 vs.1.92 ± 0.08) and protein (0.91 ± 0.02,0.72 ± 0.03,0.62 ± 0.03 vs.1.28 ± 0.02) significantly decreased,while the expression ofBax mRNA (5.73 ± 0.37,8.00 ± 0.23,10.72 ± 0.40 vs.3.27 ± 0.34) and protein (0.45 ± 0.02,0.63 ± 0.02,0.78 ± 0.03 vs.0.32 ± 0.02) sifnificantly promoted in low dosage group,medium dosage group and high dosage group of Diaomo-Zhibeng liquid (P＜0.05).Compared with low dosage group,the expression of Bcl-2 mRNA and protein significantly decreased in middle and high dose group (P＜0.05),but Bax mRNA and protein significantly increased (P＜0.05).Conclusions The Diaomo-Zhibeng liquid can increase the susceptibility of epithelial cells to apoptosis,regulate the balance of cell proliferation and apoptosis tends to apoptosis,have the effect of accelerating cells apoptosis.

Objective To investigate the characteristics of amygdala neural circuitry in comorbidity of late-life depression (LLD) and cognitive impairment. Methods Twenty-four LLD,eighteen amnestic mild cognitive impairments (aMCI),thirteen aMCI with depression (dMCI) and thirty cognitive normal (CN) subjects completed resting-state functional magnetic resonance imaging scan. Main effects of depression and MCI and their interactions on the intrinsic amygdala functional connectivity network ( AFCN) connectivity were examined. Behavioral significance of AFCN that voxel-wised amygdala connectivity correlating with de-pression severity and memory scores were also tested after controlling the effects of covariates,including age, gender,education, gray matter atrophy, and group. Results The immediate memory and delayed memory function in the aMCI group (-0. 75 ± 0. 77 and -1. 13 ± 0. 56) and the dMCI group (-1. 07 ± 0. 79 and-1. 00±0. 52) were significantly lower than those of the CN group (0. 46±0. 73 and 0. 60±0. 61),and the difference was statistically significant (P<0. 01). Depression and anxiety in the LLD group (1. 00±0. 53 and 0. 93±0. 98) and the dMCI group (0. 86±0. 80 and 0. 78±0. 82) were significantly higher than those of the CN group (-0. 92±0. 25 and -0. 74±0. 22),and the difference was statistically significant (P<0. 01). Brain network analysis showed that separated neural circuits were implicated in the depression and cognitive im-pairment. Importantly,interactive effects of depression and MCI on the AFCN were also identified,especially in the bilateral somatomotor area,inferior parietal cortex/precuneus,posterior cingulate cortex,right medial prefrontal cortex/dorsolateral prefrontal cortex and hippocampus. Behavioral significance of AFCN also re-vealed the distinctive neural circuits involved in the depression severity and memory deficits,respectively. Conjunction analysis further identified the overlapped neural circuits associated with depression and memory deficits were primarily in the left DLPFC,insula,hippocampus,right inferior prefrontal cortex and dorsomedi-al prefrontal cortex. Conclusions Depression and cognitive impairment synergistically facilitate functional decoupling of AFCN and thus compromise the integrity of amygdala networks. Distinct depression-related or MCI-related neural constructs represent the characteristics of clinical phenotype of depression or MCI alone, while overlapped circuits probably reveal the neural basis of comorbidity of LLD and MCI.

AIM: To evaluate the efficacy of 0.01% hypochlorous acid as a conjunctival sac disinfectant before cataract phacoemulsification and its impact on the ocular surface.METHODS: Randomized controlled clinical trial. A total of 285 patients who were scheduled for cataract phacoemulsification surgery were randomly divided into the hypochlorous acid group and the povidone iodine group. Before and after disinfection, conjunctival sac swabs were taken, and bacterial culture and colony-forming units(CFUs)testing were performed using blood agar and chocolate agar media, respectively. All patients were evaluated for ocular symptom scores and pain severity scores 2 h, 1 d, and 1 wk after disinfection, and underwent corneal fluorescein staining, eye redness index, tear meniscus height, and noninvasive breakup time(NIBUT)examination. The incidence of endophthalmitis after surgery was recorded.RESULTS: Conjunctival sac disinfection with 0.01% hypochlorous acid significantly reduced the rate of positive bacterial cultures and colony-forming ability of the conjunctival sac, with statistically significant differences compared with the pre-disinfection period(both P<0.01), and the disinfecting ability of hypochlorous acid was comparable to that of povidone-iodine(χ2=0.811, P=0.368). The scores of ocular symptoms and pain severity in the hypochlorous acid group were significantly lower than those in the povidone-iodine group(both P<0.01). The corneal fluorescein staining and eye redness index in the hypochlorous acid group were significantly lower than those in the povidone-iodine group(all P<0.01). No endophthalmitis occurred in either group of patients. CONCLUSION: As a conjunctival sac disinfectant, 0.01% hypochlorous acid is safe and effective, with minimal discomfort and damage to the ocular surface in patients.

As one of the hallmarks of cancer, metabolic reprogramming leads to cancer progression, and targeting glycolytic enzymes could be useful strategies for cancer therapy. By screening a small molecule library consisting of 1320 FDA-approved drugs, we found that penfluridol, an antipsychotic drug used to treat schizophrenia, could inhibit glycolysis and induce apoptosis in esophageal squamous cell carcinoma (ESCC). Gene profiling and Ingenuity Pathway Analysis suggested the important role of AMPK in action mechanism of penfluridol. By using drug affinity responsive target stability (DARTS) technology and proteomics, we identified phosphofructokinase, liver type (PFKL), a key enzyme in glycolysis, as a direct target of penfluridol. Penfluridol could not exhibit its anticancer property in PFKL-deficient cancer cells, illustrating that PFKL is essential for the bioactivity of penfluridol. High PFKL expression is correlated with advanced stages and poor survival of ESCC patients, and silencing of PFKL significantly suppressed tumor growth. Mechanistically, direct binding of penfluridol and PFKL inhibits glucose consumption, lactate and ATP production, leads to nuclear translocation of FOXO3a and subsequent transcriptional activation of BIM in an AMPK-dependent manner. Taken together, PFKL is a potential prognostic biomarker and therapeutic target in ESCC, and penfluridol may be a new therapeutic option for management of this lethal disease.

Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca²⁺ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca²⁺-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.