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 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 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 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 quantitatively assess the early alterations of retinal and choroidal microcirculation and microstructure in systemic lupus erythematosus(SLE)patients without coexisting retinopathy via ultra-widefield swept-source optical coherence tomography angiography(UWF SS-OCTA).METHODS:Cross-sectional study. Totally 64 cases(64 eyes)that diagnosed as SLE without associated retinopathy at the Affiliated Hospital of Xuzhou Medical University from May to October 2024 were enrolled as the study group(Randomly assign one eye to the study group). Simultaneously, age-and gender-matched healthy individuals were recruited as the control group. All participants underwent UWF SS-OCTA. The deep capillary plexus(DCP), superficial capillary plexus(SCP), total retina, choriocapillaris(CC), as well as the choroidal medium and large vessel density(VD)in both the central and peripheral retinal areas of both groups of patients were compared. Additionally, parameters such as choroidal vascularity volume(CVV), choroidal vascularity index(CVI), thickness of the inner retina, outer retina, entire retina, and choroid in both central and peripheral area. SLE patients were categorized into three subgroups based on the SLE disease activity index(SLEDAI-2K), including 20 cases(20 eyes)in mild-and no-activity group(SLEDAI-2K≤6), 20 cases(20 eyes)in moderate-activity group(7

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.

AIM: To assess the stability of the tear film and the characteristics of corneal nerves in patients with Parkinson's disease(PD).METHODS: This cross-sectional observational study included 72 PD patients and 50 healthy controls. Disease severity was determined using the Hoehn-Yahr(H-Y)scale, dividing patients into mild and moderate PD groups. Dry eye symptoms were evaluated via the ocular surface disease index(OSDI)questionnaire, while tear secretion was quantified using the Schirmer I test. Ocular surface damage was assessed through staining scores, and comprehensive ocular examinations were performed utilizing the LipiView ocular surface interferometer and an ocular surface analyzer. Corneal nerve parameters were examined using corneal confocal microscopy in conjunction with automated analysis software ACCMetrics, with correlations drawn between these parameters, PD course, and severity.RESULTS: PD patients exhibited significantly elevated OSDI scores, indicative of more pronounced dry eye symptoms compared to the control group(F=70.290, P<0.01). Tear film stability was markedly compromised, with significantly shorter tear film breakup time and increased corneal fluorescein staining, both showing statistically significant differences relative to controls(all P<0.01). Tear secretion indices, including Schirmer I test results and tear meniscus height, were significantly reduced in PD patients(all P<0.01), whereas lipid secretion indices, such as lipid layer thickness and meibomian gland dropout score, did not show significant variation. Corneal nerve analysis revealed significant reductions in corneal nerve fiber density, nerve branch density, fiber length, and total branch density in PD patients compared to controls(all P<0.01). Furthermore, blink frequency was markedly prolonged(F=62.353, P<0.01). Correlation analysis demonstrated a significant relationship between alterations in tear film stability and both disease duration and H-Y scores.CONCLUSION: PD patients have obvious dry eye manifestations in the early stage of the disease, including the reduction of tear film stability and corneal nerve fiber density, and gradually aggravate with the progress of the disease. Neurodegenerative disease-related dry eye needs to be diagnosed early and actively treated.

AIM:To evaluate the clinical efficacy of 0.05% cyclosporine eye drops(Ⅱ)combined with sodium hyaluronate eye drops in treating patients with type 2 diabetes mellitus(T2DM)and moderate-to-severe dry eye.METHODS:A total of 120 T2DM patients(120 eyes)with moderate-to-severe dry eye, treated at the endocrinology and ophthalmology departments at the Affiliated Hospital of Xuzhou Medical University from January 2024 to September 2024, were enrolled in the study. The patients were randomly divided into two groups: combination group [0.05% cyclosporine eye drops(Ⅱ)+ sodium hyaluronate eye drops] and control group(sodium hyaluronate eye drops alone), with 60 cases(60 eyes)in each group. Assessments were conducted at baseline and at 1, 2, and 3 mo post-treatment, including the ocular surface disease index(OSDI), non-contact tear meniscus height(NITMH), first non-invasive tear breakup time(NIBUTf), meibomian gland loss score, lipid layer thickness grade, conjunctival hyperemia grade, and corneal fluorescein staining(FL)score. At 3 mo after treatment, changes in tear inflammatory factors were observed, and corneal subbasal nerve plexus(SBN)morphology/density were analyzed using in vivo confocal microscopy(IVCM).RESULTS:At 1, 2, and 3 mo post-treatment, both groups showed statistically significant increases in NITMH and NIBUTf compared to baseline(all P<0.05), with greater improvement observed in the combination group(both P<0.05). OSDI and FL scores significantly decreased from baseline(all P<0.05), with more pronounced reductions in the combination group(both P<0.05). Meibomian gland loss scores showed no significant improvement in either group(all P>0.05). At 3 mo after treatment, tear levels of interleukin 6(IL-6)and matrix metalloproteinase-9(MMP-9)significantly decreased in both groups(all P<0.001), with a greater reduction noted in the combination group(both P<0.001). The combination group displayed increased corneal nerve branch density and nerve fiber density, along with decreased nerve tortuosity and dendritic cell(DC)density compared to baseline(all P<0.001), while the control group did not show significant changes(all P>0.05).CONCLUSION: The combination of 0.05% cyclosporine eye drops(Ⅱ)and sodium hyaluronate eye drops significantly improves clinical outcomes in T2DM patients with moderate-to-severe dry eye. This treatment effectively alleviates ocular surface inflammation, restores corneal nerve morphology and density, and demonstrates a favorable safety profile.

AIM: To explore the risk factors associated with diabetic retinopathy(DR)based on ultra-widefield swept-source optical coherence tomography angiography(UWF-SS-OCTA), and to establish a clinical prediction model.METHODS:A total of 235 patients(235 eyes)with type 2 diabetes mellitus who were treated in the Affiliated Hospital of Xuzhou Medical University from July to November 2024 were selected as the research objects. According to the presence or absence of DR, they were divided into 120 cases(120 eyes)in non-DR group(NDR group)and 115 cases(115 eyes)in non-proliferative DR group(NPDR group). Data on general characteristics, laboratory tests, and OCTA results were collected for both groups. Univariate analysis was employed to identify DR-related risk factors. Logistic regression analysis was conducted to analyze these risk factors and to establish a DR prediction model. The efficacy of the model was evaluated using the receiver operating characteristic(ROC)curve, calibration curve, and decision curve analysis(DCA).RESULTS: The duration of diabetes, fasting blood glucose, blood urea nitrogen(BUN), history of hypertension, and the choroidal vascular index(CVI)were found to be statistically significant in the model(all P<0.05). Specifically, the duration of diabetes, fasting blood glucose, BUN, and history of hypertension were identified as risk factors for DR among diabetic patients, while CVI was recognized as a protective factor. The area under the curve for the model predicting the probability of DR was 0.898(0.859-0.938), with a diagnostic threshold of 0.438. The corresponding sensitivity and specificity were 87.8% and 78.3%, respectively, indicating that the model possesses high predictive value for the occurrence of DR.CONCLUSION: The duration of diabetes, fasting blood glucose, BUN, history of hypertension, and CVI are significantly correlated with DR. The established prediction model demonstrates a substantial screening capability for DR.

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.