ObjectiveTo investigate the effect of blueberry-derived tectorigenin （TEC） on hepatocellular carcinoma cell lines HepG2 and Huh7 and its mechanism. MethodsTEC was extracted from blueberries and purified， and a bioinformatics analysis was performed to identify potential target genes and signaling pathways. HepG2 and Huh7 cell lines were used and divided into 0， 30， 60， and 90 μg/mL groups according to the concentration of TEC. CCK-8 assay was used to measure cell viability； wound healing assay and Transwell assay were used to assess the migration ability of cells； flow cytometry was used to measure cell apoptosis rate； Western Blot was used to measure the protein expression levels of CCNB1， p53， MDM2， Bax， Bcl-2， and active-Caspase 3. Cell models with low CCNB1 expression （NC group， si-NC group， si-NC+TEC group， si-CCNB1 group， and si-CCNB1+TEC group） and CCNB1 overexpression （OE-NC group， OE-NC+TEC group， OE-CCNB1 group， and OE-CCNB1+TEC group） were established to validate the targets. A one-way analysis of variance or two factors analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Wilcoxon signed rank sum test was used to compare the expression levels of genes between cancer tissue and paracancerous tissue. ResultsIn HepG2 and Huh7 cells under the same concentration of TEC， cell viability at 24 hours of TEC intervention was significantly lower than that at 12 and 48 hours （all P<0.05）， and at 24 hours of intervention， the TEC 90 μg/mL group had a significantly lower cell viability than the other groups （all P<0.05）. Therefore， TEC intervention for 24 hours at a concentration of 90 μg/mL was used for subsequent studies. Compared with the TEC 0 μg/mL group， the 30， 60， and 90 μg/mL groups had significant reductions in the number of migrated cells and wound healing rate （all P<0.05）， and compared with the NC group and si-NC group， the si-NC+TEC group and the si-CCNB1 group for HepG2 and Huh7 cells had significant reductions in the number of migrated cells and wound healing rate （all P<0.05）. Compared with the NC group and si-NC group， the si-NC+TEC group and the si-CCNB1 group for HepG2 and Huh7 cells had a significant increase in cell apoptosis rate （all P<0.05）. For HepG2 cells， compared with the 0 μg/mL group， the 30， 60， and 90 μg/mL groups had significant reductions in the protein expression levels of CCNB1 and Bcl-2 （all P<0.05）， and the 60 and 90 μg/mL groups had significant increases in the protein expression levels of p53， Bax， and active-Caspase 3 （all P<0.001） and a significant reduction in the protein expression level of MDM2 （both P<0.05）. For Huh7 cells， compared with the 0 μg/mL group， the 30， 60， and 90 μg/mL groups had a significant reduction in the protein expression level of CCNB1 （all P<0.01）； the 60 and 90 μg/mL groups had significant increases in the protein expression levels of p53 and Bax and a significant reduction in the protein expression level of MDM2 （all P<0.05）； the 90 μg/mL group had a significant reduction in the protein expression level of Bcl-2 and a significant increase in the protein expression level of active-Caspase 3 （both P<0.01）. Compared with the si-NC group， the si-NC+TEC group and the si-CCNB1 group for HepG2 and Huh7 cells had significant reductions in the protein expression levels of CCNB1， MDM2， and Bcl-2 and significant increases in the protein expression levels of p53 and Bax （all P<0.05）. Compared with the OE-NC group， the OE-NC+TEC group for HepG2 and Huh7 cells had significant reductions in the protein expression levels of CCNB1 and MDM2 and a significant increase in the protein expression level of p53 （all P<0.05）， while the OE-CCNB1 group had significant increases in the protein expression levels of CCNB1 and MDM2 and a significant reduction in the protein expression level of p53 （all P<0.05）， and there were no significant differences in the protein expression level of CCNB1， MDM2， and p53 between the OE-CCNB1 group and the OE-CCNB1+TEC group （all P>0.05）. ConclusionTEC can inhibit the proliferation and migration of HepG2 and Huh7 cells and promote their apoptosis in vitro， possibly by downregulating the expression of CCNB1 and activating the p53 signaling pathway.

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Objective To study the antitumor activities of RRx-001 derivatives with novel covalent fragments. Methods Four targeted compounds were designed and synthesized. The structures were confirmed by ¹H NMR and HRMS. A549 and HCT116 cancer cell lines were selected for antiproliferative activity assays. Results All the compounds revealed antitumor activities and compound ZM528 showed the best antitumor activity against these two cell lines with IC₅₀ values of （5.1±4.8） μmol/L and （6.0±2.7） μmol/L, respectively. Conclusion The result indicated that bromoacetyl group of RRx-001 could be substituted with other covalent fragments.

As cardiac magnetic resonance imaging technology advances,T1 mapping has emerged as a non-invasive method offering visual and quantitative insights into myocardial fibrosis,edema,and infiltration associated with cardiac dis-eases.The application of T1 mapping in myocardial diseases allows for evaluating both focal and diffuse myocardial fibro-sis,playing a crucial clinical role in the differentiation,treatment,and prognostic risk assessment of diseases.This arti-cle aims to provide a thorough overview of the clinical applications of T1 mapping in patients with cardiomyopathy,summa-rizing the commonly employed scanning techniques and imaging principles.

As cardiac magnetic resonance imaging technology advances,T1 mapping has emerged as a non-invasive method offering visual and quantitative insights into myocardial fibrosis,edema,and infiltration associated with cardiac dis-eases.The application of T1 mapping in myocardial diseases allows for evaluating both focal and diffuse myocardial fibro-sis,playing a crucial clinical role in the differentiation,treatment,and prognostic risk assessment of diseases.This arti-cle aims to provide a thorough overview of the clinical applications of T1 mapping in patients with cardiomyopathy,summa-rizing the commonly employed scanning techniques and imaging principles.

Objective: This study aimed to determine the predictive performance of non-contrast CT (NCCT) signs for hemorrhagic growth after intracerebral hemorrhage (ICH) when stratified by onset-to-imaging time (OIT). Materials and Methods: 1488 supratentorial ICH within 6 h of onset were consecutively recruited from six centers between January 2018 and August 2022. NCCT signs were classified according to density (hypodensities, swirl sign, black hole sign, blend sign, fluid level, and heterogeneous density) and shape (island sign, satellite sign, and irregular shape) features. Multivariable logistic regression was used to evaluate the association between NCCT signs and three types of hemorrhagic growth: hematoma expansion (HE), intraventricular hemorrhage growth (IVHG), and revised HE (RHE). The performance of the NCCT signs was evaluated using the positive predictive value (PPV) stratified by OIT. Results: Multivariable analysis showed that hypodensities were an independent predictor of HE (adjusted odds ratio [95% confidence interval] of 7.99 [4.87–13.40]), IVHG (3.64 [2.15–6.24]), and RHE (7.90 [4.93–12.90]). Similarly, OIT (for a 1-h increase) was an independent inverse predictor of HE (0.59 [0.52–0.66]), IVHG (0.72 [0.64–0.81]), and RHE (0.61 [0.54– 0.67]). Blend and island signs were independently associated with HE and RHE (10.60 [7.36–15.30] and 10.10 [7.10–14.60], respectively, for the blend sign and 2.75 [1.64–4.67] and 2.62 [1.60–4.30], respectively, for the island sign). Hypodensities demonstrated low PPVs of 0.41 (110/269) or lower for IVHG when stratified by OIT. When OIT was ≤ 2 h, the PPVs of hypodensities, blend sign, and island sign for RHE were 0.80 (215/269), 0.90 (142/157), and 0.83 (103/124), respectively. Conclusion Hypodensities, blend sign, and island sign were the best NCCT predictors of RHE when OIT was ≤ 2 h. NCCT signs may assist in earlier recognition of the risk of hemorrhagic growth and guide early intervention to prevent neurological deterioration resulting from hemorrhagic growth.

Objective:To understand the characteristics and associated factors of newly reported HIV/AIDS cases with non-marital or non-commercial heterosexual transmission, in Guangxi Zhuang Autonomous Region (Guangxi), 2015-2018.Methods:Information of newly reported HIV/AIDS cases aged ≥18 years in Guangxi between 2015 and 2018 was collected from the National Comprehensive HIV/AIDS Information System. Unconditional logistic regression model was used to access those factors that were associated with HIV infections through non-marital or non-commercial heterosexual contact.Results:Between 2015 and 2018, a total number of 35 497 HIV/AIDS cases, aged ≥18 years were newly reported in Guangxi. Among them, 32 648 (92.0 %) were infected heterosexually while 10 500 were infected through non-marital or non-commercial heterosexual behavior. Non-marital or non-commercial heterosexual transmission accounted for 29.6 % (10 500/35 497) of the newly reported HIV/AIDS cases, and 32.2 % (10 500/32 648) of those with heterosexual transmission. Males counted for 53.5 % (5 617/10 500) of non-marital or non-commercial heterosexual transmission and males to females ratio was 1.2∶1 (5 617∶4 883). Those married or had regular sexual partners counted for 55.9 % (5 873/10 500). Commercial heterosexual transmission appeared the main mode of HIV transmission for males (64.4 %,16 516/25 633) while main mode for females was non-marital or non-commercial heterosexual transmission and counted for 49.5 % (4 883/9 864). Results from the multivariate logistic regression analysis showed that adjusted OR of female HIV/AIDS infected HIV via non-marital or non-commercial heterosexual transmission, was 3.98 times (95 %CI: 3.78-4.20) hight than that of males. Among the group aged<50 years and the aged 50-59 years, the adjusted ORs were 1.35 times (95 %CI: 1.27-1.44) and 1.13 times (95 %CI: 1.05-1.21) hight than that of aged ≥60 years. Those who were single/divorced/widowed, the adjusted OR was 1.53 times (95 %CI: 1.45-1.61) hight than that of those married/regular partners. Those with junior high school education, high school education and above the adjusted ORs were 1.22 times (95 %CI: 1.16-1.29) and 1.18 times (95 %CI: 1.10-1.27), compared to those only with education levels of primary school or below. Conclusions:The number of HIV/AIDS cases via non-marital or non-commercial heterosexual transmission accounted for nearly 30.0 % of all the routes of HIV transmission in Guangxi, 2015-2018. Female, aged<60 years old, single/divorced/widowed and having had junior and above high school education etc., appeared as risk factors on non-marital or non-commercial heterosexual transmission, among newly reported HIV/AIDS in Guangxi.

Objective: To understand the characteristics of HIV/AIDS epidemic in Guangxi Zhuang Autonomous Region (Guangxi) with a purpose to accurately provide scientific basis for prevention and control measures, 2010-2017. Methods: Data were retrieved from case reporting cards of Guangxi during 2010 to 2017 through National HIV/AIDS Comprehensive Response Information Management System. Data was analyzed using epidemiological methods such number of cases, proportion and rate. χ² test was used for statistical analysis. Results: The HIV positive rate was 12.53 per ten thousand (85 182/67 959 000) in Guangxi during 2010 to 2017. The number of newly diagnosed HIV/AIDS cases and the number of death yearly respectively increased by 22.34%(2 602/11 648) and 32.83% (952/2 900) in 2011 compared with 2010, and both showed a six-year continuous downward trend (the number of newly diagnosed cases respectively 12 229 cases, 10 877 cases, 9 460 cases, 9 190 cases, 8 848 cases, 8 680 cases, and the number of death respectively 3 888 cases, 3 316 cases, 2 914 cases, 2 717 cases, 2 595 cases, 2 600 cases) from 2012 to 2017. But proportion of late discovery remained above 50.00% (50.53%-57.06%) for eight-years continuously. The ratio of male and female was 2.47 ∶ 1 (60 639/24 543). The ratio of males and females aged 50 and over was 2.71∶1 (28 654/10 557). Proportion of the cases in 25-49 years old group and 50 years old group accounting for 47.40%(40 377/85 182) and 46.03% (39 211/85 182) respectively. The occupation was farmers accounting for 68.40% (58 262/85 182), housekeeping, housework and unemployment accounting for 11.21% (9 546/85 182), student accounting for 0.86% (729/85 182). Heterosexual transmission accounted for 90.60% (77 171/85 182, homosexual transmission accounted for 3.13% (2 669/85 182), injection drug use transmission accounted for 4.60%(3 924/85 182) and mother-to-child transmission accounted for 0.73% (619/85 182). Conclusions The number of newly diagnosed cases and the number of death yearly showed a continuous downtrend for six-years from 2012 to 2017. However, proportion of late discovery remained above 50.00% for eight-years. The major route of infection was heterosexual transmission. With the change of HIV/AIDS newly epidemic mode in Guangxi, there are many new challenges for HIV/AIDS prevention and control work. Strategy of targeted intervention modes should be innovated for a new breakthrough.

Objective To evaluate the use of unilateral pedicle lymphography (PLG) in preoperative localization and treatment of chyluria.Methods From October 2010 to March 2017,25 cases with severe chyluria and undergoing cystoscopy and unilateral PLG before renal pedicle lymphatic disconnection were reviewed.There were 11 males and 14 females,aged 44-71 years,with an average of 58.5 years.The course of the disease was 6 months to 30 years,with an average of 8.3 years.Of them,18 cases had undergone unilateral PLG and spiral CT angiography preoperatively.Surgical treatment was performed according to PLG imaging.Results Unilateral ureteral chyluria was discovered in 16 out of the 19 cases through cystoscopy,with the sensitivity of 84.2％ (16/19).In contrast,unilateral chyluria was only detected in 4 of the other 6 patients with bilateral chyluria.Albiduria were found in the remaining 5 cases in bladder,without ureteral excreted chyle.The sensitivity for chyluria positioning by cystoscopy was 64.5％ (20/31).The location of lesion in 19 patients with unilateral chyuria and 6 patients with bilateral chyluria could be correctly displayed by PLG and the sensitivity was 100％ (31/31).There was no significant difference in location between cystoscopy and PLG in 19 patients with unilateral chyluria (P =0.2482).But in total lesion location,the sensitivity of PLG was higher than cystoscopy(P =0.0026).Eighteen patients who had undergone PLG combined with spiral CT angiography,could not only locate the chylous fistula,but also determine the number of renal vessels as well as their relationship with diseased lymphatic vessels.Chyluria had disappeared immediately after unilateral renal pedicle lymphatic exfoliation in 23 patients.However,it still presented in the other 2 patients who were confirmed contralateral pyeloymphatic fistulas by PLG 3 months after surgery and cured by reoperation.Chyluria recurred in 6 cases during follow-up of 6 to 58 months,and 4 were confirmed bilateral pyelolymphatic fistulas by PLG.Two of these 4 cases were cured by laparoscopic surgery or open surgery,respectively.The other 2 patients were cured by conservative treatment.Moreover,2 patients with unilateral chyluria recurred in situ after the first laparoscopic surgery,which was confirmed by PLG.Notably,all these patients were cured by ESWL finally.Conclusions This study suggested that PLG displays remarkable advantage in terms of localization sensitivity.PLG combined with spiral CT angiography preoperatively can not only locate the chylous fistula,but also determine the number of renal vessels as well as their relationship with diseased lymphatic vessels.Depending on PLG and spiral CT angiography,renal pedicle lymphatic disconnection can effectively protect renal vessel.In addition,it can avoid the omission of ligation for perivascular lymphatic vessels.Furthermore,PLG plays a key role in temporarily obstructing the leakage of pyelolymphatic fistulas to some extent.

Objective This study aimed to investigate the role of pyrroloquinoline quinone (PQQ) in repairing oxidative nerve cells,and to study the antioxidant capacity of PQQ on the oxidative damage of rats caused by apolexis,as well as the effects on learning and memory abilities of apolexis rats.Methods Oxidative damage of PC12 was induced by H2O2,and the repairing rate of PQQ on oxidative PC12 cells was tested by methylthiazolyldiphenyl-tetrazolium bromide assay kit.The 18-month-old male SD rats were administered PQQ (0,10,20,40 mg/kg).After 4 weeks,Morris water maze test was used to test the learning and memory ability.After 6 weeks,serum and brain tissue related indicators and antioxidant capacity were recorded.Results The survival rate of PC12 cells increased from 59.1％ to 90.5％ with 200 nmol/L PQQ.Compared with the apolexis model group,the latency of the PQQ group (20,40 mg/kg) was shortened in the Morris water maze experiment,the swimming distance was reduced,pass-through counts were increased,and the first secure platform pass-through was reduced.Meanwhile,the levels of malondialdehyde and lipofuscin in serum and brain tissue of PQQ group decreased,the levels of superoxide dismutase,glutathione peroxidase vitality,antioxidant capacity of PQQ group (20,40 mg/kg) were enhanced.Conclusion PQQ could repair the oxidative damage of nerve cells,and it was confirmed that PQQ could play the same antioxidant effect in body and brain,and increase the learning and memory ability of apolexis rats.