Lipoprotein(a) as a risk factor for atherosclerotic cardiovascular disease in patients in non-metropolitan areas of Brandenburg, Germany.

Background and aims: In the non-metropolitan region of Brandenburg (Germany), which is characterized by high rates of cardiovascular diseases and underserved medical care, there is a lack of awareness regarding lipoprotein(a) [Lp(a)] as a risk factor. In addition, data from patients with atherosclerotic cardiovascular disease (ASCVD) in diverse regional backgrounds, including the understudied Brandenburg cohort, and various healthcare statuses remain insufficient. Methods: In this WalkByLab study, Lp(a) levels were monitored in a non-metropolitan cohort (n = 850) in Brandenburg, Germany, comprising 533 patients at high cardiovascular risk and 317 healthy controls. Patients underwent a comprehensive angiological screening, which included blood serum analysis, assessment of medical and family history, cardiovascular risk, and disease status, and evaluation of lifestyle and quality of life. All parameters were evaluated with regard to two groups based on Lp(a) levels: low (<50 mg/dl) and high (≥50 mg/dl). Results: Brandenburg patients with cardiovascular diseases showed higher Lp(a) levels than healthy controls (24.2% vs. 14.8%, p = 0.001). Logistic regression analysis with different characteristics revealed that Lp(a) was an independent risk factor significantly associated with ASCVD (OR 2.26, 95% CI 1.32-3.95, p = 0.003). The high-Lp(a) group showed a higher proportion of patients with coronary artery disease, peripheral artery disease, or cerebrovascular disease compared to the low-Lp(a) group (50% vs. 36.8%; 57.7% vs. 45.8%; 17.6% vs. 9.2%; p = 0.004); also, a higher percentage of patients in the high-Lp(a) group had heart failure (72.8% vs. 53.2%, p = 0.014) and myocardial infarction (24.7% vs. 13.9%, p = 0.001). The high-Lp(a) group exhibited higher rates of statins (63.1% vs. 50.4%, p = 0.003), ezetimibe (14.8% vs. 5.5.%, p = 0.001), and beta-blockers (55.7% vs. 40.7%, p = 0.001) use. Lp(a) levels were found to be independent of physical activity or smoking behavior and did not change over time (12 months). Conclusions: Our study highlights the significance of elevated Lp(a) levels in Brandenburg cardiovascular patients and identifies them as an independent risk factor for ASCVD, which has implications for addressing cardiovascular health of non-metropolitan populations.

[Effects of Land Use Types on Water Quality at Different Buffer Scales: Tianjin Section of the Haihe River Basin as an Example].

It is important to explore the relationship between land use types and water quality to improve the surface water environment. Based on monthly water quality monitoring data from 16 nationally controlled surface water quality monitoring stations in Tianjin and land use data in 2021, GIS spatial analysis and mathematical and statistical methods were used to study the influence of land use types on surface water quality in buffer zones at different scales. The results showed that:① the land use types in the study area were mainly construction land, farmland, and water areas, which had significant effects on river water quality. Except for water temperature (WT) and pH, the farmland, construction land, and water areas were negatively correlated with each water quality indicator; forest land and grassland were positively correlated with dissolved oxygen (DO) and total nitrogen (TN) and negatively correlated with other water quality indicators. ② The water quality indicators showed obvious spatial differences in different seasons. The pH, DO and TN concentrations were higher in the dry season, whereas the permanganate index, ammonia nitrogen (NH4+-N), and total phosphorus (TP) concentrations were higher in the rainy season. ③ The results of the RDA analysis showed that the 800 m buffer zone land use had the greatest explanatory power for water quality changes in the dry season (50.4%), whereas the 3 000 m buffer zone land use could explain the water quality changes in the rainy season to the greatest extent (49.6%); from the average explanation rate of the dry and rainy seasons, the 3 000 m buffer zone was the best impact scale (50.0%) on water quality indicators in Tianjin. ④ The partial least squares regression (PLSR) analysis showed that the most important variables affecting surface water quality changes were construction land, farmland, and water areas. The predictive ability of the PLSR model of most water quality indicators was stronger in the dry season than that in the rainy season. In the dry season, all water quality indicators, except WT and pH, were most influenced by farmland. In the rainy season, construction land had the greatest influence on WT and NH4+-N concentrations, and the most important influencing factor for the remaining water quality indicators was still farmland. This study showed that the rational planning of land use types within 3 000 m of rivers or lakes was beneficial to improving the water quality of surface water.

Leukocyte telomere length and mitochondrial DNA copy number associate with endothelial function in aging-related cardiovascular disease.

Background: We investigated the association between leukocyte telomere length, mitochondrial DNA copy number, and endothelial function in patients with aging-related cardiovascular disease (CVD). Methods: In total 430 patients with CVD and healthy persons were enrolled in the current study. Peripheral blood was drawn by routine venipuncture procedure. Plasma and peripheral blood mononuclear cells (PBMCs) were collected. Cell-free genomic DNA (cfDNA) and leukocytic genomic DNA (leuDNA) were extracted from plasma and PBMCs, respectively. Relative telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) were analyzed using quantitative polymerase chain reaction. Endothelial function was evaluated by measuring flow-mediated dilation (FMD). The correlation between TL of cfDNA (cf-TL), mtDNA-CN of cfDNA (cf-mtDNA), TL of leuDNA (leu-TL), mtDNA-CN of leuDNA (leu-mtDNA), age, and FMD were analyzed based on Spearman's rank correlation. The association between cf-TL, cf-mtDNA, leu-TL, leu-mtDNA, age, gender, and FMD were explored using multiple linear regression analysis. Results: cf-TL positively correlated with cf-mtDNA (r = 0.1834, P = 0.0273), and leu-TL positively correlated with leu-mtDNA (r = 0.1244, P = 0.0109). In addition, both leu-TL (r = 0.1489, P = 0.0022) and leu-mtDNA (r = 0.1929, P < 0.0001) positively correlated with FMD. In a multiple linear regression analysis model, both leu-TL (ß = 0.229, P = 0.002) and leu-mtDNA (ß = 0.198, P = 0.008) were positively associated with FMD. In contrast, age was inversely associated with FMD (ß = -0.426, P < 0.0001). Conclusion: TL positively correlates mtDNA-CN in both cfDNA and leuDNA. leu-TL and leu-mtDNA can be regarded as novel biomarkers of endothelial dysfunction.

Percutaneous Magnetic Resonance Imaging-Guided Coaxial Cutting Needle Biopsy of Pancreatic Lesions: Diagnostic Accuracy and Safety.

PURPOSE: To appraise the diagnostic performance of magnetic resonance imaging-guided percutaneous coaxial cutting needle biopsy of pancreatic lesions using a 0.4-T open magnetic resonance imaging scanner with optical tracking navigation. MATERIALS AND METHODS: This retrospective study included 158 patients who underwent magnetic resonance imaging-guided pancreatic lesion biopsy procedures from May 2019 to December 2020. Two to four specimens were collected from each patient. Pathological diagnosis and clinical follow-ups were conducted to establish the final diagnosis. The procedures were evaluated for sensitivity, specificity, positive and negative predictive values, diagnostic accuracy, and complications. The Cardiovascular and Interventional Radiological Society of Europe guidelines were used to classify complications. RESULTS: Biopsy pathology revealed 139 pancreatic tumor malignancies and 19 benign pancreatic lesions. Finally, 151 patients were diagnosed with pancreatic malignancy and 7 with benign disease confirmed by surgery, re-biopsy, and clinical follow-up. The sensitivity, specificity, positive and negative predictive value, and accuracy for diagnosis of pancreatic diseases were 92.1%, 100%, 100%, 36.8%, and 92.4%, respectively. The biopsy accuracy was significantly related to the size (≤ 2 cm, 76.2%; 2-4 cm, 94.0%; > 4 cm, 96.2%, P = .02) and not the lesion's location (head of pancreas, 90.7%; neck of pancreas, 88.9%; body of pancreas, 94.3%; tail of pancreas, 96.7%, P = .73). Minor complications included two patients experiencing mild abdominal pain and two with a minor occurrence of hemorrhage. CONCLUSIONS: Percutaneous magnetic resonance imaging-guided pancreatic lesion biopsy combined with optical navigation has high diagnostic accuracy and is safe for clinical practice. Level of Evidence Level 4, Case-series.

Autophagy-related genes analysis reveals potential biomarkers for prediction of the impaired walking capacity of peripheral arterial disease.

BACKGROUND: The role of autophagy and autophagy-related genes in peripheral arterial disease (PAD) remains unknown and may be of diagnostic and prognostic value. The aim of this study is to investigate the relationship between autophagy and PAD, and identify potential diagnostic or prognostic biomarkers for medical practice. METHODS: Differentially expressed autophagy-related genes in PAD were explored from GSE57691 and validated in our WalkByLab registry participants by quantitative real-time polymerase chain reaction (qRT-PCR). The level of autophagy in peripheral blood mononuclear cells (PBMCs) of WalkByLab participants was assessed by analyzing autophagic marker proteins (beclin-1, P62, LC3B). Single sample gene set enrichment analysis (ssGSEA) was used to evaluate the immune microenvironment within the artery wall of PAD patients and healthy persons. Chemokine antibody array and enzyme-linked immunosorbent assay were used to assess the chemokines in participants' plasma. Treadmill testing with Gardner protocol was used to evaluate participants' walking capacity. Pain-free walking distance, maximum walking distance, and walking time were recorded. Finally, a nomogram model based on logistic regression was built to predict impaired walking performance. RESULTS: A total of 20 relevant autophagy-related genes were identified, and these genes were confirmed to be expressed at low levels in our PAD participants. Western blotting demonstrated that the expression of autophagic marker proteins beclin-1 and LC3BII were significantly reduced in PAD patients' PBMCs. ssGSEA revealed that most of the autophagy-related genes were strongly correlated with immune function, with the largest number of associated genes showing interaction between cytokine-and-cytokine receptors (CCR). In this context, the chemokines growth-related oncogene (GRO) and neutrophil activating protein2 (NAP2) are highly expressed in the plasma of WalkByLab PAD patients and were significantly negatively correlated with the walking distance assessed by Gardner treadmill testing. Finally, the plasma NAP2 level (AUC: 0.743) and derived nomogram model (AUC: 0.860) has a strong predictive potential to identify a poor walking capacity. CONCLUSIONS: Overall, these data highlight both the important role of autophagy and autophagy-related genes in PAD and link them to vascular inflammation (expression of chemokines). In particular, chemokine NAP2 emerged as a novel biomarker that can be used to predict the impaired walking capacity in PAD patients.

The Association Between Antidiabetic Agents and Clinical Outcomes of COVID-19 Patients With Diabetes: A Bayesian Network Meta-Analysis.

Aims: This study aimed to assess the impact of different antidiabetic agents on individuals with diabetes and COVID-19. Methods: We searched PubMed, Web of Science, Embase, and Cochrane Library databases from inception to October 31, 2021 and included seven antidiabetic agents. The data were pooled via traditional pairwise meta-analysis and Bayesian network meta-analysis. Results: The pairwise meta-analysis included 35 studies. Metformin (odds ratio (OR), 0.74; P=0.001), dipeptidyl peptidase-4 inhibitors (DPP4i) (OR, 0.88; P=0.04), sodium-glucose cotransporter-2 inhibitors (SGLT2i) (OR, 0.82; P=0.001), and glucagon-like peptide-1 receptor agonists (GLP1RA) (OR, 0.91; P=0.02) treatment were associated with lower COVID-19 mortality in individuals with diabetes compared to respective non-users. However, insulin treatment resulted in higher mortality (OR, 1.8; P=0.001). Mortality did not significantly differ in sulfonylurea (OR, 0.97; P=0.56) and thiazolidinediones (TZDs) (OR, 1.00; P=0.96) users. Furthermore, due to limited data, we analyzed five antidiabetic agents (metformin, DPP4i, sulfonylurea, insulin, and SGLT2i) and found no association between them and severe disease risk (all P>0.05). The Bayesian network meta-analysis included 18 studies. GLP1RA and SGLT2i had the highest first and second rank probability (67.3% and 62.5%, respectively). Insulin showed the maximum probability of ranking seventh (97.0%). Metformin had the third and fourth highest rank probability of 44.8% and 38.9%, respectively. Meanwhile, DPP4i had the fifth-highest rank probability of 42.4%, followed by sulfonylurea at 45.1%. Conclusion: Metformin, DPP4i, SGLT2i, and GLP1RA treatments were highly possible to reduced COVID-19 mortality risk in individuals with diabetes, while insulin might be related to increased mortality risk. Sulfonylurea and TZDs treatments were not associated with mortality. None of the antidiabetic agents studied were associated with the risk of severe disease. Additionally, GLP1RA probably had the most significant protective effect against death, followed by SGLT2i and metformin. Systematic Review Registration: PROSPERO (CRD42021288200).

Angiotensin receptor-neprilysin inhibitor improves coronary collateral perfusion.

Background: We investigated the pleiotropic effects of an angiotensin receptor-neprilysin inhibitor (ARNi) on collateral-dependent myocardial perfusion in a rat model of coronary arteriogenesis, and performed comprehensive analyses to uncover the underlying molecular mechanisms. Methods: A rat model of coronary arteriogenesis was established by implanting an inflatable occluder on the left anterior descending coronary artery followed by a 7-day repetitive occlusion procedure (ROP). Coronary collateral perfusion was measured by using a myocardial particle infusion technique. The putative ARNi-induced pro-arteriogenic effects were further investigated and compared with an angiotensin-converting enzyme inhibitor (ACEi). Expression of the membrane receptors and key enzymes in the natriuretic peptide system (NPS), renin-angiotensin-aldosterone system (RAAS) and kallikrein-kinin system (KKS) were analyzed by quantitative polymerase chain reaction (qPCR) and immunoblot assay, respectively. Protein levels of pro-arteriogenic cytokines were measured by enzyme-linked immunosorbent assay, and mitochondrial DNA copy number was assessed by qPCR due to their roles in arteriogenesis. Furthermore, murine heart endothelial cells (MHEC5-T) were treated with a neprilysin inhibitor (NEPi) alone, or in combination with bradykinin receptor antagonists. MHEC5-T proliferation was analyzed by colorimetric assay. Results: The in vivo study showed that ARNis markedly improved coronary collateral perfusion, regulated the gene expression of KKS, and increased the concentrations of relevant pro-arteriogenic cytokines. The in vitro study demonstrated that NEPis significantly promoted MHEC5-T proliferation, which was diminished by bradykinin receptor antagonists. Conclusion: ARNis improve coronary collateral perfusion and exert pro-arteriogenic effects via the bradykinin receptor signaling pathway.

The effect of prophylactic balloon occlusion in patients with placenta accreta spectrum: a Bayesian network meta-analysis.

OBJECTIVES: Placenta accreta spectrum (PAS) can induce severe life-threatening obstetric hemorrhage. Herein, we conducted a Bayesian network meta-analysis of previous studies to evaluate the relative benefits of different prophylactic balloon occlusion (PBO) procedures. METHODS: PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to July 2021. Blood loss volume, blood transfusion volume, and hysterectomy rate were regarded as the primary endpoints. The data were pooled using a Bayesian network and traditional pairwise meta-analysis. RESULTS: Fifty-nine articles with a total sample size of 5150 patients were included. Compared with no PBO (non-PBO) intervention, PBO of the abdominal aorta (PBOAA, mean difference(MD) - 1.02, 95% credible interval (CrI) - 1.4 to - 0.67), common iliac artery (PBOCIA, MD - 0.84; 95%CrI - 1.36 to - 0.06) and internal iliac artery (PBOIIA, MD - 0.42; 95%CrI - 0.72 to - 0.13) significantly lowered blood loss volume, with PBOAA being more effective than PBOIIA (MD - 0.60; 95%CrI - 1.05 to - 0.17). PBOAA and PBOIIA also significantly decreased blood loss volume (MD - 2.33; 95%CrI - 3.74 to - 0.94, MD - 1.57; 95%CrI - 2.77 to - 0.47 respectively) and hysterectomy rate (OR 0.31; 95%CrI 0.16 to 0.54, OR 0.53; 95%CrI 0.29 to 0.92 respectively). PBOAA has the highest probability of being more effective in reducing the blood loss volume, blood transfusion volume, and hysterectomy rate. CONCLUSIONS: Performing PBOAA, PBOCIA, or PBOIIA in PAS patients is an effective way to minimize blood loss volume, while PBOAA and PBOIIA also reduce blood transfusion volume and hysterectomy rate. PBOAA is a notably more effective strategy to reduce blood loss volume than PBOIIA. KEY POINTS: • PBOAA, PBOCIA, and PBOIIA procedures can significantly reduce the blood loss volume compared to non-PBO intervention in PAS patients, of which PBOAA was more effective than the PBOIIA procedure. • PBOAA and PBOIIA could significantly reduce the blood transfusion volume and hysterectomy rate in contrast to the non-PBO intervention in patients with PAS. • According to our statistical treatment ranking, PBOAA was statistically superior in reducing blood transfusion volume, blood transfusion volume, and hysterectomy rate than other PBO procedures.

Angiotensin-converting enzyme inhibitors stimulate cerebral arteriogenesis.

AIM: Arteriogenesis constitutes the most efficient endogenous rescue mechanism in cases of cerebral ischaemia. The aim of this work was to investigate whether angiotensin-converting enzyme inhibitors (ACEi) stimulates, and angiotensin II receptor type 1 blockers (ARB) inhibits cerebral collateral growth by applying a three-vessel occlusion (3-VO) model in rat. METHODS: Cerebral collateral growth was measured post 3-VO (1) by assessing blood flow using the cerebrovascular reserve capacity (CVRC) technique, and (2) by assessing vessel diameters in the posterior cerebral artery (PCA) via the evaluation of latex angiographies. A stimulatory effect on arteriogenesis was investigated for ACEi administration ± bradykinin receptor 1 (B1R) and 2 (B2R) blockers, and an inhibitory effect was analysed for ARB administration. Results were validated by immunohistochemical analysis and mechanistic data were collected by human umbilical vein endothelial cell (HUVEC) viability or scratch assay and monocyte (THP-1) migration assay. RESULTS: An inhibitory effect of ARB on arteriogenesis could not be demonstrated. However, collateral growth measurements demonstrated a significantly increased CVRC and PCA diameters in the ACEi group. ACEi stimulates cell viability and migration, which could be partially reduced by additional administration of bradykinin receptor 1 inhibitor (B1Ri). ACEi inhibits the degradation of pro-arteriogenic bradykinin derivatives, but combined ACEi + B1Ri + B1Ri (BRB) treatment did not reverse the stimulatory effect. Yet, co-administration of ACEi + BRB enhances arteriogenesis and cell migration. CONCLUSION: We demonstrate a potent stimulatory effect of ACEi on cerebral arteriogenesis in rats, presumable via B1R. However, results imply a pleiotropic and compensatory effect of ACEi on bradykinin receptor-stimulated arteriogenesis.

Impact of Virtual Dementia Tour on empathy level of nursing students: A quasi-experimental study.

OBJECTIVE: As a developable ability, empathy is significantly associated with patient-centered care. The authors intended to evaluate the effect of Virtual Dementia Tour (VDT) upon nursing students' empathy level and propose practical rationales for optimizing future dementia care. METHODS: A total of 45 second-year undergraduate nursing students were organized to watch a theme movie entitled Still Alice and participate in an 8-min VDT. Jefferson Scale of Empathy-Health Professional Students (JSE-HPS) was employed for evaluating the empathy level of nursing students. After VDT, all nursing students participated in a structured interview. Descriptive statistics and paired t-tests were performed using SPSS 24.0. RESULTS: Their empathy levels demonstrated significant overall improvements (106.69 ± 9.49 vs 115.51 ± 10.16, P < 0.01). During the course of VDT, nursing students experienced varying levels of anxiety and frustration. All of them were satisfied with the program since they had gained a deeper understanding of demented patients and the program could change their attitudes toward demented elders. CONCLUSION: Watching a specially selected movie and participating in VDT may be an effective method for enhancing empathy and caring during nursing student education.

Control of postpartum hemorrhage in women with placenta accreta spectrum using prophylactic balloon occlusion combined with Pituitrin intra-arterial infusion.

OBJECTIVES: The aim of this study is to evaluate the efficacy of prophylactic internal iliac artery balloon occlusion combined with Pituitrin intra-arterial infusion in the control of postpartum hemorrhage in women with placenta accreta spectrum (PAS). METHODS: This is a prospective and non-randomized controlled study. The participants were assigned into three groups: without balloon catheterization (non-BC) group, balloon catheterization (BC) group, and Pituitrin combined with balloon catheterization (PBC) group. The primary outcomes were estimated blood loss (EBL) and the units of transfused packed red blood cells (PRBC). The secondary outcome was the incidence of hysterectomy. RESULTS: A total of 100 participants were recruited between August 2013 and November 2018 and assigned into the respective groups as follows: 27 in the non-BC group, 22 in the BC group, and 51 in the PBC group. No statistical differences were found in demographic characteristics among the three groups. There was a trend of lower EBL, PRBC, and hysterectomy rate in the BC group than those in the non-BC group, while all values showed no significant differences (all p > 0.05). Patients in the PBC group had significantly lower EBL, PRBC, and hysterectomy rate compared with those in the non-BC group (all p < 0.05). Linear regression analysis revealed that the PBC (vs. others) was negatively correlated with EBL and the non-BC (vs. others) independently predicted more EBL. CONCLUSIONS: Balloon occlusion combined with Pituitrin infusion is an effective treatment method which significantly reduced EBL, PRBC, and hysterectomy rate in patients with PAS. KEY POINTS: • Internal iliac artery balloon occlusion combined with Pituitrin intra-arterial infusion can significantly decrease EBL, PRBC, and hysterectomy rate during cesarean section in patients with PAS. • Cesarean section without balloon occlusion and placenta accreta depth are two independent risk factors for EBL in patients with PAS.

A C1976Y missense mutation in the mouse Ip3r1 gene leads to short-term mydriasis and unfolded protein response in the iris constrictor muscles.

Ip3r1 encodes an inositol 1,4,5-trisphosphate-responsive calcium channel. Mutations in the IP3R1 gene in humans may cause Gillespie syndrome (GS) typically presents as fixed dilated pupils in affected infants, which was referred to as iris hypoplasia. However, there is no report of mice with Ip3r1 heterozygous mutations showing dilated pupils. Here, we report a new Ip3r1 allele with short-term dilated pupil phenotype derived from an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. This allele carries a G5927A transition mutation in Ip3r1 gene (NM_010585), which is predicted to result in a C1976Y amino acid change in the open reading frame of IP3R1 (NP_034715). We named this novel Ip3r1 allele Ip3r1C1976Y. Histology and pharmacological tests show that the dilated pupil phenotype is a mydriasis caused by the functional defect in the iris constrictor muscles in Ip3r1C1976Y. The dilated pupil phenotype in Ip3r1C1976Y was referred to as mydriasis and excluding iris hypoplasia. IHC analysis revealed increased expression of BIP protein, the master regulator of unfolded protein response (UPR) signaling, in Ip3r1C1976Y mice that did not recover. This study is the first report of an Ip3r1 mutation being associated with the mydriasis phenotype. Ip3r1C1976Y mice represent a self-healing model that may be used to study the therapeutic approach for Ip3r1-related diseases.

Generation of hepatic spheroids using human hepatocyte-derived liver progenitor-like cells for hepatotoxicity screening.

Rationale: The idiosyncratic drug-induced liver injury (iDILI) is a major cause of acute liver injury and a key challenge in late-stage drug development. Individual heterogeneity is considered to be an essential factor of iDILI. However, few in vitro model can predict heterogeneity in iDILI. We have previously shown that mouse and human hepatocytes can be converted to expandable liver progenitor-like cells in vitro (HepLPCs). However, the limited proliferation potential of human HepLPCs confines its industrial application. Here, we reported the generation of a novel hepatocyte model not only to provide unlimited cell sources for human hepatocytes but also to establish a tool for studying iDILI in vitro. Methods: Human primary hepatocytes were isolated by modified two-step perfusion technique. The chemical reprogramming culture condition together with gene-transfer were then used to generate the immortalized HepLPC cell lines (iHepLPCs). Growth curve, doubling time, and karyotype were analyzed to evaluate the proliferation characteristics of iHepLPCs. Modified Hepatocyte Maturation Medium and 3D spheroid culture were applied to re-differentiate iHepLPCs. Results: iHepLPCs exhibited efficient expansion for at least 40 population doublings, with a stable proliferative ability. They could easily differentiate back into metabolically functional hepatocytes in vitro within 10 days. Furthermore, under three-dimensional culture conditions, the formed hepatic spheroids showed multiple liver functions and toxicity profiles close to those of primary human hepatocytes. Importantly, we established a hepatocyte bank by generating a specific number of such cell lines. Screening for population heterogeneity allowed us to analyze the in vitro heterogeneous responses to hepatotoxicity induced by molecular targeted drugs. Conclusions: In light of the proliferative capacity and the heterogeneity they represented, these iHepLPCs cell lines may offer assistance in studying xenobiotic metabolism as well as liver diseases in vitro.

Hyperoside Attenuates Hepatic Ischemia-Reperfusion Injury by Suppressing Oxidative Stress and Inhibiting Apoptosis in Rats.

PURPOSE: Hepatic ischemia-reperfusion (IR) injury is a serious complication of many clinical conditions, which may lead to liver or multiple organ failure. Hyperoside, a flavonoid compound, has been reported to protect against myocardial and cerebral injury induced by IR. This study aimed to investigate the protective effects of hyperoside on hepatic IR injury in rats. METHODS: Using the 70% hepatic IR injury model, we divided 32 male Wistar rats into 4 groups (n = 8): sham-operated, IR+saline (saline/p.o.), IR+vehicle (carboxy methyl cellulose/p.o.), and IR+hyperoside (50 mg/kg/d/p.o.). At 24 hours after reperfusion, blood and liver tissue were collected. The effects of hyperoside on hepatic IR injury were assessed through tests of serum transaminase, hepatic histopathology, and measurement of markers of oxidative stress and apoptosis. RESULTS: Pretreatment with hyperoside protected the liver from IR injury by a reduction in serum aspartate aminotransferase/alanine aminotransferase levels and a decrease in the severity of histologic changes. Hyperoside treatment also decreased the activity of malondialdehyde, increased the activities of superoxide dismutase and glutathione peroxidase, up-regulated the expression of heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1, and reduced the apoptotic index after IR injury. A decrease in the expression of caspase-3 and an increase in the ratio of B cell lymphoma 2 to B cell lymphoma 2-associated X also were observed. CONCLUSION: Hyperoside has a protective effect on hepatic IR injury in rats, which may be due to its antioxidant and antiapoptotic properties.

Navigated magnetic resonance imaging-guided celiac plexus neurolysis using an open magnetic resonance system for pancreatic cancer patients with upper abdominal pain.

AIMS: The study aimed to evaluate the safety and efficacy of navigated magnetic resonance imaging (MRI)-guided celiac plexus neurolysis (CPN) using a 0.4 T open magnetic resonance system. MATERIALS AND METHODS: A retrospective analysis was performed on 23 patients with unresectable pancreatic cancer who underwent MRI-guided CPN between January 2013 and October 2017. Clinical outcomes were evaluated by recording the complications, the opioid intake, and questionnaire before the intervention and at the time point of 1 day, 1 month, and 3 months postprocedure using a numerical visual analog scale (VAS). RESULTS: Navigated MRI guidance allowed the precise placement of needle in the targeted area and the visualization of the injected neurolysis agents for all cases. The VAS scores decreased from 8.8 ± 1.0 to 2.9 ± 0.9, 4.2 ± 1.7, and 4.7 ± 1.8 at 1 day, 1 month, and 3 months postprocedure (P < 0.05). This intervention reduced the dosage of opioid consumption 1 month after the procedure (52.3 ± 10.4 mg before the treatment vs. 28.2 ± 4.9 mg after the treatment; P < 0.001). Treatment-related side effects included hematoma in one patient, short episodes of diarrhea in three patients, and hypotension in four patients. CONCLUSIONS: With the assistance of the navigation system, MRI-guided CPN is a safe and effective treatment approach for managing the upper abdominal pain in patients with unresectable pancreatic cancer.

Pre-cesarean prophylactic balloon placement in the internal iliac artery to prevent postpartum hemorrhage among women with pernicious placenta previa.

OBJECTIVE: To evaluate pre-cesarean prophylactic balloon placement (PBP) in the internal iliac artery among women with pernicious placenta previa. METHODS: The present retrospective study included women with pernicious placenta previa who underwent cesarean delivery at Shanghai Renji Hospital, Shanghai, China, between March 1, 2011, and June 30, 2017. Data were compared between patients who did and did not undergo PBP. RESULTS: Among 42 patients included, 20 underwent PBP and 22 did not. Mean ± SD estimated blood loss was 2900.00 ± 2352.21 mL in the PBP group, and 4549.77 ± 2366.67 mL in the non-PBP group (P=0.025). The amount of transfused red blood cells was 8.40 ± 7.14 U and 13.00 ± 7.93 U (P=0.018), respectively. No patients in the PBP group developed postoperative disseminated intravascular coagulopathy, compared with 3 (14%) in the non-PBP group (P=0.087). In the PBP and non-PBP groups, the hospital stay duration was 7.40 ± 3.07 and 8.68 ± 2.58 days (P=0.029), and there were 1 and 7 patients who had obstetric hysterectomies (P=0.027), respectively. Two patients experienced PBP-related adverse events, including thrombosis and re-bleeding. There were no deaths. CONCLUSION: Pre-cesarean PBP in the internal iliac artery was a safe and effective treatment that could reduce the incidence of both postpartum hemorrhage and hysterectomy among women with pernicious placenta previa.