The potential of biofortification technologies for wheat and rice to fill the nutritional Zn intake gap in China.

BACKGROUND: Zinc (Zn) deficiency in humans is of worldwide concern. The objective of this study was to investigate the Zn intake gap in Chinese adults and identify the potential role of biofortification technologies for wheat and rice, including crop nutrient management and breeding, in filling the gap. RESULTS: We use data from the China Health and Nutrition Survey in 2011 to identify food consumption patterns and dietary Zn intake of 4512 adults to define and quantify the Zn intake gap in the population. The dietary Zn intake gap of surveyed adults ranged from -0.8 to 6.53 mg day-1 across nine provinces and differences were associated with differences in food consumption patterns. Both dietary Zn intake and Zn gap for males were higher than for females. The potential of changes in five management strategies (improved nitrogen fertilization, improved phosphorus fertilization, foliar Zn fertilization, improved water management and growing varieties reaching the grain Zn breeding target) was analyzed. Breeding and foliar Zn fertilization were shown to be the two most effective management strategies that could increase dietary intake by 1.29 to 5 mg Zn day-1 dependent on sex and province. CONCLUSION: This study shows that the Zn gap varied across regions in China, with some large enough to warrant interventions. Wheat and rice as two major Zn sources could be targeted without a direct need for dietary diversification. By promoting both biofortification breeding of wheat and rice and Zn fertilization, dietary Zn intake could be enhanced to contribute to human health improvement in China. © 2023 Society of Chemical Industry.

A Practical Risk Classification of Early Recurrence in Hepatocellular Carcinoma Patients with Microvascular invasion after Hepatectomy: A Decision Tree Analysis.

PURPOSE: This study was designed to establish risk classifications for early recurrence in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) after hepatectomy. METHODS: The data of 563 HCC patients with MVI after hepatectomy from two hospitals were retrospectively reviewed. Kaplan-Meier curves and Cox proportional hazards regression models were used to analyse early recurrence. The risk classification for early recurrence was established by using classification and regression tree (CART) analysis and validated by using two independent validation cohorts from two hospitals. RESULTS: Multivariate analysis revealed that four indices, namely, infection of chronic viral hepatitis, MVI classification, tumour size, and serum alpha-fetoprotein (AFP), were independent prognostic factors for early recurrence in HCC patients with MVI. By CART analysis, MVI classification and serum AFP became the nodes of a decision tree and 3-stratification classifications that satisfactorily determined the risk of early recurrence were established. The area under the time-dependent receiver operating characteristic curve (AUC) values of the classification for early recurrence at 0.5, 1.0, and 2.0 years were 0.75, 0.73, and 0.71, respectively, which were all significantly higher than three common classic HCC stages (BCLC stage, Chinese stage, and TNM stage). The calibration curves showed good agreement between predictions by classification for early recurrence and actual survival outcomes. These prediction results also were confirmed in the independent internal and external validation cohorts. CONCLUSIONS: The 3 stratification classifications enabled satisfactory risk evaluation of early recurrence in HCC patients with MVI after hepatectomy.

Inactivation Kinetics and Replication Cycle Inhibition of Coxsackievirus B5 by Free Chlorine.

The kinetics of coxsackievirus serotype B5 (CVB5) inactivation with free chlorine is characterized over a range of pH and temperature relevant to drinking water treatment with the primary goal of selecting experimental conditions used for assessing inactivation mechanisms. The inactivation kinetics identified in our study is similar to or slower than experimental data reported in the literature and thus provides a conservative representation of the kinetics of CVB5 inactivation for free chlorine that could be useful in developing future regulations for waterborne viral pathogens including adequate disinfection treatment for CVB5. Untreated and free chlorine-treated viruses, and host cells synchronized-infected with these viruses, are analyzed by a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) method with the goal of quantitatively investigating the effect of free chlorine exposure on viral genome integrity, attachment to host cell, and viral genome replication. The inactivation kinetics observed results from a combination of hindering virus attachment to the host cell, inhibition of one or more subsequent steps of the replication cycle, and possibly genome damage.

Improving Surgical Excellence: Can Coaching Surgeons Improve Patient Engagement?

INTRODUCTION: Non-technical skills complement technical skills in surgeons to provide best possible care for patients. The former is essential to promote patient engagement. Coaching has been introduced to surgeons as a method to improve non-technical skills. We aimed to investigate the impact of coaching for surgeons on patient engagement in the outpatient consultation setting. METHODS: This was a single-centre cohort study conducted in South Australia. Consultant surgeons, suitable coaches, and patients were recruited. Coaches underwent further training by a human factors psychologist on being an effective coach. Outpatient consultations were recorded in an audio-visual format and analysed by investigators. Patient talking time, mutual eye gaze between surgeon and patient, and number of questions asked by the patient were measured as outcomes for patient engagement. RESULTS: 182 patients, 12 surgeons, and 4 coaches participated in the study. Each surgeon underwent 3 coaching sessions, 5 to 6 weeks apart. There were 62 pre-coaching patient consultations, 63 patient consultations after one coaching session, and 57 patient consultations after two coaching sessions. The mean talking time of the patient increased significantly after a single coaching session (P < 0.05) without making significant difference to the total consultation time (p = 0.76). Coaching sessions did not have a significant effect on mutual eye gaze or mean number of questions asked by the patient. CONCLUSION: Coaching of non-technical skills for surgeons appears to objectively improve patient engagement during the outpatient consultation. This would suggest that tailored coaching programs should be developed and delivered to surgeons to improve care delivery.

Farmers perceive diminishing ecosystem services, but overlook dis-services in intensively used agricultural landscapes in the North China Plain.

The UN sustainable development goals ask countries to advance sustainable production methods in agriculture. While the need for a transition to sustainable agricultural production is widely felt, there is little insight into local stakeholders' perceptions regarding agroecosystem (dis)services in areas with intensive production methods. The North China Plain is an agricultural production area with intensive production systems and simplified agricultural landscapes. We conducted a survey with 267 farmers in Quzhou county in the North China Plain in 2020 to measure the perceived level of agroecosystem (dis)services supply and the changes therein between 2015 and 2020. We analyzed which explanatory factors were associated with farmers' perceptions. Provisioning services were at a high level, while the regulating and supporting ecosystem services were considered to be in low supply, as evidenced by low scores for the presence of natural enemies and earthworms, and for natural habitats such as hedgerows and windbreaks. Most of the participants did not perceive dis-services from agriculture. Differences in perception between villages with contrasting biophysical and socio-economic conditions highlight the relevance of contextualized policy development for agricultural landscape composition and configuration to manage ecosystem (dis)services.

Comparison of the Effects of Metformin and Thiazolidinediones on Bone Metabolism: A Systematic Review and Meta-Analysis.

OBJECTIVES: Studies have shown that people with diabetes have a high risk of osteoporosis and fractures. The effect of diabetic medications on bone disease cannot be ignored. This meta-analysis aimed to compare the effects of two types of glucose-lowering drugs, metformin and thiazolidinediones (TZD), on bone mineral density and bone metabolism in patients with diabetes mellitus. METHODS: This systematic review and meta-analysis were prospectively registered on PROSPERO, and the registration number is CRD42022320884. Embase, PubMed, and Cochrane Library databases were searched to identify clinical trials comparing the effects of metformin and thiazolidinediones on bone metabolism in patients with diabetes. The literature was screened by inclusion and exclusion criteria. Two assessors independently assessed the quality of the identified studies and extracted relevant data. RESULTS: Seven studies involving 1656 patients were finally included. Our results showed that the metformin group had a 2.77% (SMD = 2.77, 95%CI [2.11, 3.43]; p < 0.00001) higher bone mineral density (BMD) than the thiazolidinedione group until 52 weeks; however, between 52 and 76 weeks, the metformin group had a 0.83% (SMD = -0.83, 95%CI: [-3.56, -0.45]; p = 0.01) lower BMD. The C-terminal telopeptide of type I collagen (CTX) and procollagen type I N-terminal propeptide (PINP) were decreased by 18.46% (MD = -18.46, 95%CI: [-27.98, -8.94], p = 0.0001) and 9.94% (MD = -9.94, 95%CI: [-16.92, -2.96], p = 0.005) in the metformin group compared with the TZD group.

Glibenclamide alleviates ß adrenergic receptor activation-induced cardiac inflammation.

ß-Adrenergic receptor (ß-AR) overactivation is a major pathological factor associated with cardiac diseases and mediates cardiac inflammatory injury. Glibenclamide has shown anti-inflammatory effects in previous research. However, it is unclear whether and how glibenclamide can alleviate cardiac inflammatory injury induced by ß-AR overactivation. In the present study, male C57BL/6J mice were treated with or without the ß-AR agonist isoprenaline (ISO) with or without glibenclamide pretreatment. The results indicated that glibenclamide alleviated ISO-induced macrophage infiltration in the heart, as determined by Mac-3 staining. Consistent with this finding, glibenclamide also inhibited ISO-induced chemokines and proinflammatory cytokines expression in the heart. Moreover, glibenclamide inhibited ISO-induced cardiac fibrosis and dysfunction in mice. To reveal the protective mechanism of glibenclamide, the NLRP3 inflammasome was further analysed. ISO activated the NLRP3 inflammasome in both cardiomyocytes and mouse hearts, but this effect was alleviated by glibenclamide pretreatment. Furthermore, in cardiomyocytes, ISO increased the efflux of potassium and the generation of ROS, which are recognized as activators of the NLRP3 inflammasome. The ISO-induced increases in these processes were inhibited by glibenclamide pretreatment. Moreover, glibenclamide inhibited the cAMP/PKA signalling pathway, which is downstream of ß-AR, by increasing phosphodiesterase activity in mouse hearts and cardiomyocytes. In conclusion, glibenclamide alleviates ß-AR overactivation-induced cardiac inflammation by inhibiting the NLRP3 inflammasome. The underlying mechanism involves glibenclamide-mediated suppression of potassium efflux and ROS generation by inhibiting the cAMP/PKA pathway.

Identification of Non-Volatile Compounds That Impact Flavor Disliking of Whole Wheat Bread Made with Aged Flours.

Whole wheat flour has a shorter shelf life than refined wheat flour due to off-flavor development. An untargeted liquid chromatography/mass spectrometry (LC/MS) flavoromics approach was applied to identify compounds that negatively impact the flavor liking in whole wheat bread made from aged flours. The chemical profiles of thirteen breads made from aged flours were obtained using LC/MS and modeled by orthogonal partial least squares (OPLS) to predict flavor liking. Top predictive chemical features (negatively correlated) were identified as pinellic acid (9S,12S,13S-trihydroxy-10E-octadecenoic acid), 12,13-dihydroxy-9Z-octadecenoic acid, and 1-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine. The sensory analysis confirmed the three compounds increased the bitterness intensity of the bread samples. The formation of the trihydroxy fatty acid bitter compound, pinellic acid (9S,12S,13S-trihydroxy-10E-octadecenoic acid), was impacted by the lipoxygenase activity of the flour; however, there was no influence on the formation of 12,13-dihydroxy-9Z-octadecenoic acid or 1-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine. Additionally, the concentrations of all bitter compounds were significantly higher in bread made from aged flour versus non-aged flour.

Phosphoglucomutase 1 inhibits hepatocellular carcinoma progression by regulating glucose trafficking.

Glycogen metabolism commonly altered in cancer is just beginning to be understood. Phosphoglucomutase 1 (PGM1), the first enzyme in glycogenesis that catalyzes the reversible conversion between glucose 1-phosphate (G-1-P) and glucose 6-phosphate (G-6-P), participates in both the breakdown and synthesis of glycogen. Here, we show that PGM1 is down-regulated in hepatocellular carcinoma (HCC), which is associated with the malignancy and poor prognosis of HCC. Decreased PGM1 expression obstructed glycogenesis pathway, which leads to the increased flow of glucose into glycolysis, thereby promoting tumor cell proliferation and HCC development. The loss of forkhead box protein J2 (FOXJ2), at least partly due to low genomic copy number in HCC, releases cellular nucleic acid-binding protein (CNBP), a nucleic acid chaperon, to bind to and promote G-quadruplex formation in PGM1 promoter and therefore decreases PGM1 expression. In addition, integrated analyses of PGM1 and FOXJ2 expression provide a better prediction for the malignance and prognosis of HCC. This study establishes a tumor-suppressive role of PGM1 by regulating glucose trafficking and uncovers a novel regulatory mechanism of PGM1 expression.

Postoperative adjuvant transcatheter arterial chemoembolization improves the prognosis of patients with huge hepatocellular carcinoma.

BACKGROUND: Surgical resection of huge hepatocellular carcinoma (HCC, ≥ 10 cm) is potentially curative. More adjuvant treatments are needed to reduce relapses in these patients. We evaluated the influence of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) on the prognosis of huge HCC. METHODS: Data from consecutive patients who underwent curative resection for huge HCC in our center were retrospectively collected. Recurrence-free survival (RFS) and overall survival (OS) were compared between patients who did and did not undergo PA-TACE. Propensity score matching (PSM) was used. RESULTS: Among the 255 enrolled patients, 93 underwent PA-TACE. The clinical outcomes were significantly better in the PA-TACE group than those in the non PA-TACE group (5-year RFS rate: 33.5% vs. 18.0%; 5-year OS rate: 47.0% vs. 28.0%, all P < 0.001). After PSM, similar results were obtained (5-year RFS rate: 28.8% vs. 17.6%, P < 0.001; 5-year OS rate: 42.5% vs. 25.0%, P = 0.004). PA-TACE decreased the possibility of early recurrence (< 2 years, crude cohort: P < 0.001, PSM cohort: P < 0.001) but not late recurrence (≥ 2 years, crude cohort: P = 0.692, PSM cohort: P = 0.325). Multivariable Cox regression analysis suggested that PA-TACE was an independent protective factor prolonging early RFS, RFS and OS. CONCLUSIONS: PA-TACE is a safe intervention for huge HCC patients after liver resection and improves outcomes.

α1-AR overactivation induces cardiac inflammation through NLRP3 inflammasome activation.

Acute sympathetic stress causes excessive secretion of catecholamines and induces cardiac injuries, which are mainly mediated by ß-adrenergic receptors (ß-ARs). However, α1-adrenergic receptors (α1-ARs) are also expressed in the heart and are activated upon acute sympathetic stress. In the present study, we investigated whether α1-AR activation induced cardiac inflammation and the underlying mechanisms. Male C57BL/6 mice were injected with a single dose of α1-AR agonist phenylephrine (PE, 5 or 10 mg/kg, s.c.) with or without pretreatment with α-AR antagonist prazosin (5 mg/kg, s.c.). PE injection caused cardiac dysfunction and cardiac inflammation, evidenced by the increased expression of inflammatory cytokine IL-6 and chemokines MCP-1 and MCP-5, as well as macrophage infiltration in myocardium. These effects were blocked by prazosin pretreatment. Furthermore, PE injection significantly increased the expression of NOD-like receptor protein 3 (NLRP3) and the cleavage of caspase-1 (p20) and interleukin-18 in the heart; similar results were observed in both Langendorff-perfused hearts and cultured cardiomyocytes following the treatment with PE (10 µM). Moreover, PE-induced NLRP3 inflammasome activation and cardiac inflammation was blocked in Nlrp3-/- mice compared with wild-type mice. In conclusion, α1-AR overactivation induces cardiac inflammation by activating NLRP3 inflammasomes.

An Eastern Hepatobiliary Surgery Hospital Microvascular Invasion Scoring System in Predicting Prognosis of Patients with Hepatocellular Carcinoma and Microvascular Invasion After R0 Liver Resection: A Large-Scale, Multicenter Study.

BACKGROUND: Microvascular invasion (MVI) is associated with poor postoperative survival outcomes in patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH) MVI scoring system was established to predict prognosis in patients with HCC with MVI after R0 liver resection (LR) and to supplement the most commonly used classification systems. MATERIALS AND METHODS: Patients with HCC with MVI who underwent R0 LR as an initial therapy were included. The EHBH-MVI score was developed from a retrospective cohort from 2003 to 2009 to form the training cohort. The variables associated with overall survival (OS) on univariate analysis were subsequently investigated using the log-rank test, and the EHBH-MVI score was developed using the Cox regression model. It was validated using an internal prospective cohort from 2011 to 2013 as well as three independent external validation cohorts. RESULTS: There were 1,033 patients in the training cohort; 322 patients in the prospective internal validation cohort; and 493, 282, and 149 patients in the three external validation cohorts, respectively. The score was developed using the following factors: α-fetoprotein level, tumor encapsulation, tumor diameter, hepatitis B e antigen positivity, hepatitis B virus DNA load, tumor number, and gastric fundal/esophageal varicosity. The score differentiated two groups of patients (≤4, >4 points) with distinct long-term prognoses outcomes (median OS, 55.8 vs. 19.6 months; p < .001). The predictive accuracy of the score was greater than the other four commonly used staging systems for HCC. CONCLUSION: The EHBH-MVI scoring system was more accurate in predicting prognosis in patients with HCC with MVI after R0 LR than the other four commonly used staging systems. The score can be used to supplement these systems. IMPLICATIONS FOR PRACTICE: Microvascular invasion (MVI) is a major determinant of survival outcomes after curative liver resection for patients with hepatocellular carcinoma (HCC). Currently, there is no scoring system aiming to predict prognosis of patients with HCC and MVI after R0 liver resection (LR). Most of the widely used staging systems for HCC do not use MVI as an independent risk factor, and they cannot be used to predict the prognosis of patients with HCC and MVI after surgery. In this study, a new Eastern Hepatobiliary Surgery Hospital (EHBH) MVI scoring system was established to predict prognosis of patients with HCC and MVI after R0 LR. Based on the results of this study, postoperative adjuvant therapy may be recommended for patients with HCC and MVI with an EHBH-MVI score >4. This score can be used to supplement the currently used HCC classifications to predict postoperative survival outcomes in patients with HCC and MVI.

Microvascular invasion predicts a poor prognosis of solitary hepatocellular carcinoma up to 2 cm based on propensity score matching analysis.

AIM: Microvascular invasion (MVI) is not discussed for solitary hepatocellular carcinoma (HCC) up to 2 cm in the 8th Edition of the American Joint Committee on Cancer Staging Manual. The present study aimed to reappraise the influence of MVI on solitary HCC up to 2 cm in diameter. METHODS: Between January 2010 and December 2012, a retrospective cohort of 496 HCC patients from the Eastern Hepatobiliary Surgery Hospital was analyzed. Propensity score matching was carried out to balance the baseline characteristics. Survival analysis was carried out using the Kaplan-Meier method. Risk factors were evaluated using the Cox proportional hazards model. Multivariate logistic regression was used to identify the risk factors associated with MVI. RESULTS: All patients were classified into either an MVI-negative group (n = 332) or an MVI-positive group (n = 164). The MVI-positive group had poorer recurrence-free survival and overall survival before and after propensity score matching. The multivariate analysis showed that MVI; being male; increased total bilirubin levels, alanine transaminase levels and γ-glutamyl transpeptidase levels; decreased albumin levels; and HBV DNA load >103  IU/mL were risk factors for recurrence-free survival. MVI, older age, lower albumin levels, and cirrhosis were risk factors for overall survival. Age <50 years, alpha-fetoprotein >20 ng/mL, and lack of or an incomplete capsule were significantly independent predictors for MVI. CONCLUSIONS: MVI had a negative impact on the prognosis of solitary HCC up to 2 cm after curative hepatectomy. The 8th edition of the American Joint Committee on Cancer staging system could be improved by subdividing solitary HCC up to 2 cm according to MVI.

Overexpression of MTHFD1 in hepatocellular carcinoma predicts poorer survival and recurrence.

Aim: MTHFD1 was the enzyme providing one-carbon derivatives of tetrahydrofolate. We sought to investigate the impact of MTHFD1 on hepatocellular carcinoma (HCC). Methods: Bioinformatic analysis, western blot and immunohistochemistry were conducted to detect MTHFD1 expression in HCC. The relationships between MTHFD1 and prognosis of 172 HCCs were analyzed by Kaplan-Meier method and Cox proportional hazards model. Results: High MTHFD1 expression in HCC represented poor prognosis (overall survival p = 0.025; time to recurrence p = 0.044). Combining MTHFD1 with serum AFP, survival analysis demonstrated the prognosis of the MTHFD1 low expression and AFP ≤20 ng/ml group was better than that of the MTHFD1 high expression or AFP >20 ng/ml group and the MTHFD1 high expression and AFP >20 ng/ml group (overall survival p < 0.0001; time to recurrence p < 0.0001). Conclusion: High MTHFD1 expression in HCC indicated poorer prognosis. Combining MTHFD1 with serum AFP improved the accuracy of prognostic prediction.

[Effects of Ramipril on the expression of connexin 43 in cerebral arteries of spontaneously hypertensive rats].

The present study was designed to examine whether Ramipril (an inhibitor of angiotensin-converting enzyme) affected spontaneous hypertension-induced injury of cerebral artery by regulating connexin 43 (Cx43) expression. Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were randomly divided into WKY, WKY + Ramipril, SHR, and SHR + Ramipril groups (n = 8). The arterial pressure was monitored by the tail-cuff method, and vascular function in basilar arteries was examined by pressure myography. Hematoxylin-eosin (HE) staining was used to show vascular remodeling. The expression and distribution of Cx43 was determined by using immunofluorescence and immunohistochemistry analysis. The protein and mRNA levels of Cx43 were examined by Western blot and real-time PCR analysis, respectively. The results showed that chronic Ramipril treatment significantly attenuated blood pressure elevation (P < 0.01, n = 8) and blood vessel wall thickness in SHR (P < 0.01, n = 8). The cerebral artery contraction rate in the SHR group was higher than that in the WKY group (P < 0.05, n = 8). The cerebral artery contraction rate in the SHR + Ramipril group was lower than that in the SHR group (P < 0.05, n = 8). Pretreatment with 2-APB (Cx43 non-specific blocker) or Gap26 (Cx43 specific blocker) significantly decreased the vasoconstriction rate, while pretreatment with AAP10 (Cx43 non-specific agonist) significantly increased the vasoconstriction in the SHR + Ramipril group (P < 0.05, n = 8). In addition, the expression of Cx43 mRNA and protein in cerebral arteries of SHR group was higher than that of WKY group (P < 0.05, n = 8). The mRNA and protein expression of Cx43 in cerebral arteries of SHR + Ramipril group was significantly lower than that of SHR group (P < 0.05, n = 8). These results suggest that Ramipril can down-regulate the expression of Cx43 mRNA and protein in cerebral arterial cells of SHR, lower blood pressure, promote vasodilation, and improve arterial damage and vascular dysfunction caused by hypertension.

Postoperative adjuvant sorafenib improves survival outcomes in hepatocellular carcinoma patients with microvascular invasion after R0 liver resection: a propensity score matching analysis.

BACKGROUND: Microvascular invasion (MVI) is a major determinant of survival outcome for hepatocellular carcinoma (HCC). This study aimed to investigate the efficacy of postoperative adjuvant Sorafenib (PA-Sorafenib) in HCC patients with MVI after R0 liver resection (LR). METHODS: The data of patients who underwent R0 LR for HCC with histologically confirmed MVI at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. The survival outcomes for patients who underwent PA-Sorafenib were compared with those who underwent R0 LR alone. Propensity score matching (PSM) analysis was performed. RESULTS: 728 HCC patients had MVI in the resected specimens after R0 resection, with 581 who underwent LR alone and 147 patients who received in additional adjuvant sorafenib. PSM matched 113 patients in each of these two groups. The overall survival (OS) and recurrence free survival (RFS) were significantly better for patients in the PA-sorafenib group (for OS: before PSM, P = 0.003; after PSM, P = 0.007), (for RFS: before PSM, P = 0.029; after PSM, P = 0.001), respectively. Similar results were obtained in patients with BCLC 0-A, BCLC B and Child-Pugh A stages of disease. CONCLUSIONS: PA-Sorafenib was associated with significantly better survival outcomes than LR alone for HCC patients with MVI.

Chronic inflammation-elicited liver progenitor cell conversion to liver cancer stem cell with clinical significance.

The substantial heterogeneity and hierarchical organization in liver cancer support the theory of liver cancer stem cells (LCSCs). However, the relationship between chronic hepatic inflammation and LCSC generation remains obscure. Here, we observed a close correlation between aggravated inflammation and liver progenitor cell (LPC) propagation in the cirrhotic liver of rats exposed to diethylnitrosamine. LPCs isolated from the rat cirrhotic liver initiated subcutaneous liver cancers in nonobese diabetic/severe combined immunodeficient mice, suggesting the malignant transformation of LPCs toward LCSCs. Interestingly, depletion of Kupffer cells in vivo attenuated the LCSC properties of transformed LPCs and suppressed cytokeratin 19/Oval cell 6-positive tumor occurrence. Conversely, LPCs cocultured with macrophages exhibited enhanced LCSC properties. We further demonstrated that macrophage-secreted tumor necrosis factor-α triggered chromosomal instability in LPCs through the deregulation of ubiquitin D and checkpoint kinase 2 and enhanced the self-renewal of LPCs through the tumor necrosis factor receptor 1/Src/signal transducer and activator of transcription 3 pathway, which synergistically contributed to the conversion of LPCs to LCSCs. Clinical investigation revealed that cytokeratin 19/Oval cell 6-positive liver cancer patients displayed a worse prognosis and exhibited superior response to sorafenib treatment. CONCLUSION: Our results not only clarify the cellular and molecular mechanisms underlying the inflammation-mediated LCSC generation but also provide a molecular classification for the individualized treatment of liver cancer. (Hepatology 2017;66:1934-1951).

Longitudinal Study of Scar Hyperplasia Formation Following Cleft Lip Wound Healing.

The purpose of this study was to observe the hyperplasia trend of scar after the cleft lip surgery in a rabbit animal model, and determine the time-point of the highest hypertrophic degree of scar after cleft lip repair. Forty New Zealand white rabbits from the same offspring were used to establish a cleft lip wound healing model using Millard surgery procedure. The scar volumes were measured and granulation tissues were observed visually in the 2, 3, 4, and 5 weeks after operation. The scar tissues were harvested at the indicated time-points. Immunohistochemical (IHC) and Western Blot analyses were performed to detect the expression level of α-smooth muscle actin (α-SMA) in the scar tissue. The scars shrunk and the volumes reduced at 3 to 4 weeks after surgery; however, at 5 weeks postsurgery, the volumes increased. IHC and Western blot analyses indicated the expression of α-SMA was significantly enhanced 3 to 4 weeks, but reduced in the 5 weeks after surgery. Overall, the degree of scar hyperplasia after cleft lip surgery in rabbits was normally distributed and the scarring was most severe in the 3 to 4 weeks after cleft lip surgery. The study confirms a novel animal model for the assessment of therapies for the treatment of scar hyperplasia of human cleft lip in future.

Preoperative 3D and 4D-CT imaging using 640-Multislice CT (640-MSCT) in diagnosis of female urethral diverticulum.

OBJECTIVE: To determine the sensitivity and specificity of 640-Multislice CT (640-MSCT) in diagnosing the female UD. MATERIALS AND METHODS: We investigated 16 patients with symptomatic UDs preoperatively in our hospital from August 2010 to March 2016. The patients' average age was 38.8 years. All patients were performed 640-MSCT of pelvis; then, 3D and 4D images were reconstructed preoperatively. RESULTS: In 3D and 4D-CT images, out of 16 patients, thirteen patients had one ostium, two had 2 ostia and one had 3 ostia. Out of those thirteen patients, eight patients' ostia were located at 5 o'clock and five patients' at 7 o'clock. Patients with 2 ostia location were at 5 and 6 o'clock and 5 and 7 o'clock, respectively. Patients with 3 ostia location were at 5, 6 and 7 o'clock. The mean distance from the bladder neck to the ostia was 22.5 mm. The shape of UD was out-pouching in 11 patients (68.8%), U-shaped in four patients (25.0%) and circumferential in 1 patient (6.2%). The CT findings were confirmed by surgical findings. CONCLUSIONS: 640-MSCT is a useful tool in identifying UD's shape and ostium (including number, location) before operation. Preoperative 640-MSCT should be an adaptable modality for clinically suspected UD patients. ADVANCES IN KNOWLEDGE: Several imaging methods have been used to diagnose female UD. 640-MSCT may be more suitable to diagnose it for its higher sensitivity and specificity in diagnosis of female UD, especially in identifying UD's shape and number and location of ostium.