Objective To investigate the capillarization of liver sinusoidal endothelial cells (LSECs) and its association with hepatic fibrosis during the development of alveolar echinococcosis, so as to provide the basis for unraveling the mechanisms underlying the role of LSEC in the development and prognosis of hepatic injuries and hepatic fibrosis caused by alveolar echinococcosis. Methods Forty C57BL/6 mice at ages of 6 to 8 weeks were randomly divided into a control group and 1-, 2- and 4-week infection groups, of 10 mice in each group. Each mouse in the infection groups was intraperitoneally injected with 2 000 Echinococcus multilocularis protoscoleces, while each mouse in the control group was given an equal volume of phosphate-buffered saline using the same method. All mice were sacrificed 1, 2 and 4 weeks post-infection and mouse livers were collected. The pathological changes of livers were observed using hematoxylin-eosin (HE) staining, and hepatic fibrosis was evaluated through semi-quantitative analysis of Masson’s trichrome staining-positive areas. The activation of hepatic stellate cells (HSCs) and extracellular matrix (ECM) deposition were examined using immunohistochemical staining of α-smooth muscle actin (α-SMA) and collagen type I alpha 1 (COL1A1), and the fenestrations on the surface of LSECs were observed using scanning electron microscopy. Primary LSECs were isolated from mouse livers, and the mRNA expression of LSEC marker genes Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf was quantified using real-time fluorescence quantitative PCR (qPCR) assay. Results Destruction of local liver lobular structure was observed in mice 2 weeks post-infection with E. multilocularis protoscoleces, and hydatid cysts, which were surrounded by granulomatous tissues, were found in mouse livers 4 weeks post-infection. Semi-quantitative analysis of Masson’s trichrome staining showed a significant difference in the proportion of collagen fiber contents in mouse livers among the four groups (F = 26.060, P < 0.001), and a higher proportion of collagen fiber contents was detected in mouse livers in the 4-week infection group [(11.29 ± 2.58)%] than in the control group (P < 0.001). Immunohistochemical staining revealed activation of a few HSCs and ECM deposition in mouse livers 1 and 2 weeks post-infection, and abundant brown-yellow stained α-SMA and COL1A1 were deposited in the lesion areas in mouse livers 4 weeks post-infection, which spread to surrounding tissues. Semi-quantitative analysis revealed significant differences in α-SMA (F = 7.667, P < 0.05) and COL1A1 expression (F = 6.530, P < 0.05) in mouse levers among the four groups, with higher α-SMA [(7.13 ± 3.68)%] and COL1A1 expression [(13.18 ± 7.20)%] quantified in mouse livers in the 4-week infection group than in the control group (both P values < 0.05). Scanning electron microscopy revealed significant differences in the fenestration frequency (F = 37.730, P < 0.001) and porosity (F = 16.010, P < 0.001) on the surface of mouse LSECs among the four groups, and reduced fenestration frequency and porosity were observed in the 1-[(1.22 ± 0.48)/μm² and [(3.05 ± 0.91)%] and 2-week infection groups [(3.47 ± 0.10)/μm² and (7.57 ± 0.23)%] groups than in the control group (all P values < 0.001). There was a significant difference in the average fenestration diameter on the surface of mouse LSECs among the four groups (F = 15.330, P < 0.001), and larger average fenestration diameters were measured in the 1-[(180.80 ± 16.42) nm] and 2-week infection groups [(161.70 ± 3.85) nm] than in the control group (both P values < 0.05). In addition, there were significant differences among the four groups in terms of Stabilin-1 (F = 153.100, P < 0.001), Stabilin-2 (F = 57.010, P < 0.001), Ehd3 (F = 31.700, P < 0.001), CD209b (F = 177.400, P < 0.001), GATA4 (F = 17.740, P < 0.001), and Maf mRNA expression (F = 72.710, P < 0.001), and reduced mRNA expression of Stabilin-1, Stabilin-2, Ehd3, CD209b, GATA4 and Maf genes was quantified in three infection groups than in the control group (all P values < 0.001). Conclusions E. multilocularis infections may induce capillarization of LSECs in mice, and result in a reduction in the expression of functional and phenotypic marker genes of LSECs, and capillarization of LSECs occurs earlier than activation of HSC and development of hepatic fibrosis.

Aim To investigate the role of FKBP38 in inhibiting apoptosis in a rotenone-induced Parkinson's disease(PD)cell model. Methods In vivo experiments:MPTP-induced PD in vivo models were constructed,and the expressions of α-synuclein,TH and FKBP38 in brains of PD mice were detected. In vitro experiments:Dopaminergic neuron MN9D cells were stimulated with rotenone to construct an in vitro model of PD; Western blot was used to detect the expression levels of α-synuclein,TH,Tom20 and FKBP38 in PD in vitro model; FKBP38 lentivirus was transferred into MN9D cells to construct stable overexpression and FKBP38 knockdown cell lines; CCK-8 assay was used to detect the cell viability of FKBP38 overexpression and knockdown cells stimulated by rotenone; Western blot was used to detect anti-apoptotic protein Bcl-2 and apoptosis protein in PD cell model expression levels of Bax. Results The expression level of FKBP38 was significantly down-regulated in both in vitro and in vivo models of PD(P<0.01). Knockdown of FKBP38 aggravated the decline of dopaminergic neuron cell viability caused by rotenone(P<0.05),while overexpression of FKBP38 significantly ameliorated the decline of dopaminergic neuron cell viability caused by rotenone(P<0.05). Western blot results showed that overexpression of FKBP38 could significantly up-regulate the expression level of anti-apoptotic protein Bcl-2 and increase the ratio of Bcl-2/Bax in PD dopaminergic neurons(P<0.05). Conclusion In the PD cell model regulation of FKBP38 can improve the apoptosis of dopaminergic neurons.

Objective:To analyze the research hotspots of the application of mobile health in cardiac function monitoring of patients with heart disease and to conduct a visual analysis.Method:Subject field retrieval was carried out based on Web of Science Core Collection. The retrieval time range was set from 2000 to 2022, and the type of paper was limited to treatise. The retrieved literatures were imported into Endnote 7 for screening, and the repetitive and unrelated literatures were excluded. A total of 291 literatures were included in this study. Open refine 2.8 was used for data cleaning of synonyms and then VOSviewer 1.6.18 was used for visualization analysis of country/region, author and keywords.Results:Research reports on the application of mobile medical in the field of cardiac function monitoring in patients with heart disease have been growing steadily since 2005, and the number of articles published in the field increased rapidly from 2020 to 2021. The top five countries with the highest number of publications were the United States (71) , Australia (20) , China (18) , the United Kingdom (14) and Sweden (13) . The cooperation and exchange among global researchers were relatively close, but they were still dominated by regional cooperation and had not formed a large core group of authors. A total of 71 high-frequency keywords were included, and the top five were mhealth (30 times) , heart failure (27 times) , smartphone (26 times) , telemedicine (15 times) and mobile phone (17 times) . Each cluster keyword was related to each other, which represented the current research hotspot content respectively.Conclusions:At present, number of publications in China ranks first in the world, but there is still a big gap compared with the United States. The development and optimization of monitoring equipment and mobile medical APP have become the focus and hot topics.

Objective:To explore the effect of high intensity interval training (HIIT) on cardiac rehabilitation in patients after heart transplantation.Methods:According to the search terms, the search was conducted on China National Knowledge Infrastructure, VIP, WanFang Data, China Biology Medicine disc, Web of Science, PubMed, Cochrane Library, Embase, and EBSCO. The search time limit was from the establishment of the database to January 31, 2022. After 2 researchers screened the article, extracted information, and evaluated the quality, a Meta-analysis was conducted using RevMan 5.4 software.Results:According to the inclusion and exclusion criteria, 10 English articles were selected, including 191 patients in the intervention group and 212 patients in the control group, with a total of 403 patients. Meta-analysis showed that during cardiac rehabilitation exercise in patients after heart transplantation, HIIT could improve peak oxygen uptake in cardiopulmonary function exercise testing [ MD=1.98, 95% confidence interval ( CI) (0.55, 3.41), P=0.007], peak heart rate in chronotropic responses [ MD=6.93, 95% CI (2.62, 11.24), P=0.002], and muscle exercise ability [ MD=337.18, 95% CI (12.02, 62.35), P=0.04]. There was no statistically significant difference in systolic blood pressure, diastolic blood pressure, peak systolic blood pressure, peak diastolic blood pressure, resting heart rate and respiratory exchange rate between the two groups ( P>0.05). A subgroup analysis of peak oxygen uptake was conducted based on the intervention period and the start time of rehabilitation exercise after heart transplantation. The results showed that there were statistically significant differences in peak oxygen uptake between the intervention group and the control group when the intervention period was ≤ 12 weeks or the start time was > 6 weeks ( P<0.01) . Conclusions:HIIT effectively improves the peak oxygen uptake, peak heart rate, and muscle exercise activity of patients after heart transplantation. HIIT has a significant impact on peak oxygen uptake when the rehabilitation exercise start time after heart transplantation is > 6 weeks or the intervention period is ≤ 12 weeks.

Objective:To investigate the clinical characteristics of de novo malignancies (DNMs) after liver transplantation (LT) and to study the clinical management strategies.Methods:Adult LT recipients who were regularly followed-up in the Organ Transplantation Center, the Affiliated Hospital of Qingdao University from January 2005 to April 2021 were enrolled in this study. The clinical characteristics of DNMs were retrospectively analyzed. Of 601 LT recipients, there were 105 females and 496 males, aged (51.4±9.6) years old. They were divided into the DNMs group ( n=26) and the non-DNMs group ( n=575) according to whether there were DNMs on followed-up. Clinical data including age, sex, basic diseases before LT and operation time were collected. These patients were follow-up in outpatient clinics. Results:Twenty-six patients were diagnosed to develop DNMs after LT, but there were 28 DNMs (of which 2 patients were diagnosed to have DNMs twice). The incidence of DNMs after LT was 4.3% (26/601), the median time from LT to DNMs was 42 (20, 70) months, and the cumulative incidence rates of DNMs were 0.5%, 2.0%, 6.3%, 21.0% and 34.5% at 1, 3, 5, 10 and 15 years after LT, respectively. Among the 28 DNMs, digestive system tumors were most common, with 17 lesions (60.7%), followed by 3 lesions (11.1%) of lung cancer, 2 lesions (7.4%) of lymphoproliferative diseases, and 1 lesion (3.7%) of cervical cancer, thyroid cancer, soft palate cancer, eyelid cancer, laryngeal cancer, and prostate cancer. The follow-up time of 55.9 (36.6, 102.5) months in the DNMs group after LT was longer than the 33.4 (18.5, 58.9) months in the non-DNMs group ( P<0.001). The 1, 5, and 10 year survival rates of patients with DNMs after LT were 96.3%, 83.5%, and 49.8%, respectively. The 1, 5, and 10 year survival rates of patients with non-DNMs after LT were 94.5%, 77.7%, and 75.4%, respectively. There was no significant difference in the cumulative survival rates between the two groups (log rank=0.402, P=0.526). Conclusion:The incidence of DNMs in LT recipients was 4.3%. The majority of them were digestive system tumors. Early diagnosis and treatment of DNMs significantly improved the prognosis and quality of life of these patients.

BACKGROUND: Vascular intimal hyperplasia (IH) is one of the key challenges in the clinical application of smalldiameter vascular grafts. Current tissue engineering strategies focus on vascularization and antithrombotics, yet few approaches have been developed to treat IH. Here, we designed a tissue-engineered vascular scaffold with portulaca flavonoid (PTF) composition and biomimetic architecture.METHOD: By electrospinning, PTF is integrated with biodegradable poly(e-caprolactone) (PCL) into a bionic vascular scaffold. The structure and functions of the scaffolds were evaluated based on material characterization and cellular biocompatibility. Human vascular smooth muscle cells (HVSMCs) were cultured on scaffolds for up to 14 days. RESULTS: The incorporation of PTF and preparation parameters during fabrication influences the morphology of the scaffold, including fibre diameter, structure, and orientation. Compared to the PCL scaffold, the scaffolds integrated with bioactive PTF show better hydrophilicity and degradability. HVSMCs seeded on the scaffold alongside the fibres exhibit fusiform-like shapes, indicating that the scaffold can provide contact guidance for cell morphology alterations. This study demonstrates that the PCL/PTF (9.1%) scaffold inhibits the excessive proliferation of HVSMCs without causing cytotoxicity. CONCLUSION The study provides insights into the problem of restenosis caused by IH. This engineered vascular scaffold with complex function and preparation is expected to be applied as a substitute for small-diameter vascular grafts.

With prominent medicinal value, Gelsemium elegans has been overexploited, resulting in the reduction of the wild resource. As a result, artificial cultivation turns out to be a solution. However, this medicinal species is intolerant to low temperature, and thus genes responding to the low temperature are important for the cultivation of this species. Based on the transcriptome database of G. elegans at 4 ℃, 29 differentially expressed GeERF genes were identified. Bioinformatics analysis of 21 GeERF gene sequences with intact open reading frames showed that 12 and 9 of the GeERF proteins respectively clustered in DREB subgroup and ERF subgroup. GeDREB1 A-1-GeERF6 B-1, with molecular weight of 23.78-50.96 kDa and length of 212-459 aa, were all predicted to be hydrophilic and in nucleus. Furthermore, the full-length cDNA sequence of GeERF2B-1 was cloned from the leaves of G. elegans. Subcellular localization suggested that GeERF2B-1 was located in the nucleus. According to the quantitative reverse-transcription PCR(qRT-PCR), GeERF2B-1 showed constitutive expression in roots, stems, and leaves of G. elegans, and the expression was the highest in roots. In terms of the response to 4 ℃ treatment, the expression of GeERF2B-1 was significantly higher than that in the control and peaked at 12 h, suggesting a positive response to low temperature. This study lays a scientific basis for the functional study of GeERF transcription factors and provides gene resources for the improvement of stress resistance of G. elegans.
DNA, Complementary ; Gene Expression Regulation, Plant ; Phylogeny ; Plant Proteins/metabolism* ; Temperature ; Transcription Factors/metabolism*

ObjectiveTo explore the effects of metformin （Met） on amyloid-β （Aβ） in AD cell model M146L and the underlying mechanism. MethodsMTT assay was performed to determine the optimal concentration of Met. Western blotting was performed to measure the protein levels of Aβ₄₂， amyloid precursor protein （APP） ， β-site APP-cleaving enzyme （BACE）and proteolytic enzymes including insulin-degrading enzyme （IDE）， neprilysin （NEP）， and light chain 3 Ⅱ/Ⅰ （LC3 Ⅱ/Ⅰ）； Immunofluorescence was performed to visualize how Aβ₄₂ peptides and IDE were affected by Met. Western blotting was performed to test levels of IDE and Aβ₄₂ after treatment of Met and Bacitracin （Bac）， a special inhibitor of IDE. ResultsIn this study， we showed that the levels of Aβ₄₂ were down-regulated by the Met treatment （P<0.05）. No effect was observed on the expression of APP and BACE， both of which are related to the production of Aβ， after Met treatment in M146L cells （P＞0.05）. Furthermore， levels of proteolytic enzymes including IDE， NEP， and LC3Ⅱ/Ⅰ levels were markedly decreased in the M146L cells compared to the CHO cells （P<0.05） ， and only the level of IDE was reversed after the Met treatment for 24 h （P<0.05）. Importantly， Met-mediated Aβ₄₂ degradation in M146L cells was completely blocked by the Bac （P<0.05）. ConclusionsThis study clarifies the ameliorating effect of Met on the abnormal accumulation of Aβ₄₂ in M146L cells， and that the underlying mechanism is mediated by the increased expression of IDE in the Aβ degradation pathway， providing an experimental basis for the T2DM drug metformin as a potential therapeutic target for AD.

OBJECTIVE: To observe the neurotoxicity and hematotoxicity of maternal exposure to 1-bromopropane(1-BP) on the offspring rats by the breast-feeding route. Method A total of eight specific pathogen free female rats and their 64 male newborn rats were divided into the control group and the exposure group, with four lactation female rats and their 32 male newborn rats in each group. The female rats in exposure group were intragastrically administered with 700.00 mg/kg body mass of 1-BP during lactation, and the control group was given equal volume of corn oil for 21 days, once a day. The body mass of female rats and their offspring rats were measured during the exposure period. After exposure, the Morris water maze and the open field tests were performed in male offspring. The blood samples of offspring were collected for blood routine and blood biochemical indexes detection. The histopathological examination was performed in the hippocampus in the male offspring. RESULTS: A litter of eight pups in the exposure group began to die one day after the mother rat was exposed to 1-BP, and all rats died on the ninth day after exposure. There was no significant difference in the body mass of female rats between the exposure group and the control group(P>0.05). The body mass of offspring rats in the exposure group was lower than that in the control group at the same time point from the first day to the 21 st day of the female rats exposed to 1-BP(all P<0.05). In the orientation navigation experiment, the escape latency time on the first, the second day and the total distance on the first day in the offspring of the exposure group were significantly prolonged than those in the control group at the same time points(all P<0.05). The number of times of crossing the platform of offspring rats in the exposure group was less than that in the control group in the spatial exploration test(P<0.01). In the open field test, there was not statistical significance of the activity, rest time ratio, total distance, the distance ratio and time ratio in the central region in the offspring between the two groups(all P>0.05). The counts of white blood cells, neutrophils, lymphocytes, and average red blood cell width, platelet ratio and average platelet volume of the offspring of the exposure group decreased(all P<0.05), the serum levels of globulin, total protein, triacylglycerol and total bilirubin decreased(all P<0.05), and the albumin/globulin ratio and serum glucose level increased(all P<0.05), when compared with that of the control group. Histopathological examination results showed that the nerve fibers were loose in the hippocampal dentate gyrus area, and there were necrotic neurons and loss of nerve fibers in the CA1 area of the offspring rats. CONCLUSION: Maternal exposure to 1-BP during lactation can induce neurotoxicity and hematotoxicity to offspring rats. The neurotoxicity mainly caused damage to the central nerve system, which affected the learning and memory function of the offspring rats. The reason may be related to the damage caused by 1-BP on the hippocampal function.

Arthropod-borne diseases, such as malaria and dengue fever, have frequently beset five countries(Cambodia, Vietnam, Laos, Myanmar, and Thailand) in the tropical rainy Lancang-Mekong region, which pose a huge threat to social production and daily life. As a resort to such diseases, chemical drugs risk the resistance in plasmodium, non-availability for dengue virus, and pollution to the environment. Traditional medicinal plants have the multi-component, multi-target, and multi-pathway characteristics, which are of great potential in drug development. Exploring potential medicinals for arthropod-borne diseases from traditional medicinal plants has become a hot spot. This study summarized the epidemiological background of arthropod-borne diseases in the Lancang-Mekong region and screened effective herbs from the 350 medicinal plants recorded in CHINA-ASEAN Traditional Medicine. Based on CNKI, VIP, and PubMed, the plants for malaria and dengue fever and those for killing and repelling mosquitoes were respectively sorted out. Their pharmacological effects and mechanisms were reviewed and the material basis was analyzed. The result is expected to serve as a reference for efficient utilization of medicinal resources, development of effective and safe drugs for malaria and dengue fever, and the further cooperation between China and the other five countries in the Lancang-Mekong region.
Animals ; Culicidae ; Malaria ; Plants, Medicinal ; Plasmodium ; Thailand