Altered brain iron deposition in patients with minimal hepatic encephalopathy: an MRI quantitative susceptibility mapping study.

AIM: To explore the use of quantitative susceptibility mapping (QSM) in assessing changes in brain iron deposits and their association with cognitive function in patients with minimal hepatic encephalopathy (MHE). MATERIALS AND METHODS: The study cohort comprised 27 cases with hepatitis B-associated cirrhosis with MHE (MHE group), 25 with hepatitis B-associated cirrhosis without MHE (NMHE group), and 25 healthy controls (HC group). Iron deposits in the bilateral frontal white matter, caudate nucleus (CN), putamen, globus pallidus, thalamus, red nucleus, substantia nigra (SN), hippocampus, and dentate nucleus were measured by QSM. The associations between iron deposition with the time taken to complete number connection tests A (NCT-A) and the score on digital-symbol test (DST) were analysed. RESULTS: Susceptibility values differed significantly in the bilateral CN, left thalamus, right SN, and left hippocampus in the MHE group compared with the other groups and were positively associated with the times taken to complete the NCT-A in the bilateral CN, left thalamus, and right SN and negatively associated with DST scores in the bilateral CN, left TH, and left HP. CONCLUSION: Reduced cognitive function in MHE patients was significantly associated with abnormally increased iron deposition in certain brain areas. The quantification of brain iron deposition by QSM may thus be an objective and accurate means of evaluating MHE.

[Immunogenicity, safety and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years].

Objective: To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years. Methods: An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster. Results: The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A's 44.79 (36.94-54.30) (P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A's 15.71 (13.24-18.63) (P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion: Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

[Pulmonary nuclear protein of the testis midline carcinoma:a case report].

Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare malignant epithelial tumor that typically occurs in the midline regions such as the head, neck, and mediastinum. This tumor is characterized by rapid development, aggressive growth, and strong invasiveness. Due to its short duration, most patients are diagnosed at advanced stages, often leading to rapid mortality. Although reports on pulmonary NUT carcinoma are uncommon, this article presents a case of pulmonary NUT carcinoma in which the patient repeatedly expectorated bronchial casts and tumor tissue. Additionally, a comprehensive review of relevant literature from recent years is provided to enhance understanding of this disease.

[Recommendations for the diagnosis and treatment of connective tissue disease associated pulmonary arterial hypertension in China].

Pulmonary arterial hypertension (PAH) is a clinicopathological syndrome caused by the increase of pulmonary artery, and it is the most serious complication of connective tissue disease (CTD). In recent years, a lot of progress has been made in the diagnosis, treatment and evaluation of PAH. Chinese Rheumatology Association formulated this recommendation on the basis of current experience and guidelines, in order to promote early screening, early diagnosis and early intervention of CTD-PAH, as well as patient follow-up and management, to improve the prognosis of CTD-PAH patients.

[Clinical efficacy evaluation of minimally invasive cardiac surgery coronary artery bypass grafting in patients with multivessel coronary artery disease].

Objective: To investigate the clinical efficacy of minimally invasive cardiac surgery coronary artery bypass grafting (MICS CABG) in the treatment of patients with multivessel coronary artery disease. Methods: A total of 147 patients with multi-vessel coronary artery disease and coronary heart disease who underwent surgical treatment in Henan Provincial People's Hospital from March 2016 to March 2019 were retrospectively selected. Of which, 69 patients were treated by MICS CABG (minimally invasive group) and 78 patients were treated using the traditional thoracotomy (traditional group). The perioperative indexes, serum myocardial enzyme indexes and renal function indexes of patients before and after operation were compared between the two groups; Two groups of patients were followed up for 2 years; the incidence of adverse cardiovascular events (MACE) was recorded, and survival analysis was performed. Results: The age of the patients in the minimally invasive group and the traditional group were (66.9±5.8) and (68.2±7.0) years old, respectively, and the proportions of males were 60.9% (42 cases) and 51.3% (40 cases) (all P>0.05). All patients in the two groups successfully completed the operation, and no patients in the minimally invasive group were converted to thoracotomy. Before surgery, there was no significant difference in serum cTnI, CK-MB, BUN, Scr, and creatinine clearance between the minimally invasive group and the traditional group (all P>0.05). After re-examination 48 hours after operation, the serum cTnI in the minimally invasive group was (3.109±0.664) µg/L, and the CK-MB was (18.03±3.27) U/L, which were lower than those in the traditional group (3.438±0.715) µg/L, (20.63±4.28) U/L; the difference was statistically significant (all P<0.05). During the 2-year follow-up, there was no statiscally significant difference in the incidence of recurrent myocardial infarction, postoperative atrial fibrillation, postoperative stroke, arrhythmia, heart failure, thrombosis, cardiac death, and MACE events between the minimally invasive group and the traditional group. Statistical significance (all P>0.05). The survival curve analysis showed that the cumulative rates of MACE events in the minimally invasive and traditional groups were 17.39% and 26.92%, respectively (P=0.171). Conclusions: The effect of MICS CABG in the treatment of patients with multivessel coronary artery disease and coronary heart disease is not much different from that of traditional open thoracotomy, but the former is less traumatic, quicker after surgery, and has clinical significance for the recovery of patients' myocardial function.

[The value of preservation of subvalvular structures in patients with mitral and aortic valve replacement surgery and its effect on left ventricular contractility].

Objective: To discuss the clinical value of preserving subvalvular structure in mitral and aortic valve replacement surgery and its effect on left ventricular contractility. Methods: A total of 97 patients who underwent mitral valve replacement surgery in the Adult Cardiac Surgery of Heart Center of Henan Provincial People's Hospital, Central China Fuwai Hospital from June 2016 to December 2018 were selected as the research subjects, of whom 45 cases were preserved subvalvular structure and 52 cases were in the total resection group (intraoperative total resection of the mitral valve and subvalvular chordae tendineae). General cardiac function indexes and left ventricular function quantitative indexes were compared before and in 3 months and 6 months after the operation of the two groups; The changes of the overall longitudinal strain of the long axis of the apex and the overall circumferential strain of the short axis of the left ventricle determined by the two-dimensional speckle tracking technology were compared before and after the operation. Results: The ages of the patients in the preservation group and the total resection group were (41.8±11.3) and (43.3±10.6) years old, respectively, and the male proportions were 58.0% (26 cases) and 44.0% (23 cases), respectively, with no significant difference (all P>0.05). The aortic occlusion time and cardiopulmonary bypass time of the patients in the preservation group were (57.8±4.5) and (78.6±6.7) min, respectively, which were longer than those in the total resection group [(48.1±4.4) and (48.1±4.4) min, respectively] (all P<0.05). The left atrial pressure of the patients in the preservation group at shutdown was (8.4±1.8) mmHg (1 mmHg=0.133 kPa), which was lower than that of the total resection group (11.3±2.5) mmHg (P<0.001). There were interaction effects between groups and time in regards to the left ventricular end-diastolic diameter ( LVEDD ), left ventricular ejection fraction ( LVEF ) and Tei index, as well as the strain rate of mitral annulus and left ventricular wall of interventricular septum of the preservation group and the total resection group (all P<0.05). LVEDD and LVEF of patients in the preservation group at 3rd month after operation were (44.7±4.0) mm and (45.5±4.2) mm, and at 6th months were (56.5±4.9)% and (58.8±5.0)%, respectively, all larger than (42.7±3.6) mm and (42.7±3.6) mm, (54.5±4.6)% and (56.3±4.8)% of the total resection group. The measured value of LVESD in the preservation group at 3rd month after surgery was (32.6±3.2) mm, which was greater than that in the total resection group (31.2±3.4) mm (P<0.05). The Tei index of patients in the preservation group at 3rd and 6th months after surgery were 1.0±0.2 and 0.8±0.2, respectively, which were lower than those in the total resection group 1.2±0.3 and 0.9±0.2 (all P<0.05). Conclusion: Preserving the subvalvular structure during mitral valve replacement surgery can better improve the patient's left ventricular function and left ventricular systolic capacity.

[Diffuse midline gliomas with H3K27 alteration in children: a clinicopathological analysis of forty-one cases].

Objective: To investigate the clinicopathological features of pediatric diffuse midline glioma with H3K27 alteration and to analyze their relationship with prognosis. Methods: Forty-one cases of childhood diffuse midline glioma with H3K27 alteration were collected at Children's Hospital of Fudan University (39 cases) and Xi'an Children's Hospital (2 cases), from July 2016 to July 2020. The clinical manifestations, imaging data, histopathology, immunohistochemical phenotype and molecular genetics features, tumor size, site and histological grading were evaluated. Results: Among the 41 cases, 21 were males and 20 females, the age of onset was 3-14 years, the average and median age was 7.6 years and 7.0 years, respectively. The tumor sites were brain stem (n=36) and other locations (n=5). The clinical manifestations were dizziness, gait disturbance, and limb weakness, etc. The MRI features were variable. The histology varied from low-grade to high-grade glioma with neuron differentiation. Immunohistochemistry showed that the tumor cells expressed H3K27M, GFAP, and Olig2. Genetic study showed that 76% (16/21) of tumors had H3F3A gene mutation, mostly accompanied by TP53 (62%, 13/21) missense mutation; five tumors (24%, 5/21) had HIST1H3B gene mutation, accompanied by missense mutations in ACVR1 and PI3K pathway-related gene PIK3CA (4/5) and PIK3R1 (1/5) mutations. The prognosis was dismal with only one alive and others died. The average and median overall survival time was 7 months and 4 months, respectively. Cox multivariate regression analysis showed that age, tumor location, radiologically maximum tumor diameter, histologic grading, and surgical methods were not significantly associated with overall survival rate (P>0.05). Conclusions: Pediatric diffuse midline gliomas with H3K27 alteration have unique clinicopathological and genetic characteristics. The prognosis is poor. The tumor location and histopathologic grading are not related to prognosis. New specific drugs and comprehensive treatment are needed to improve the prognosis.

[Analysis of differences and influencing factors of liver injury associated with different strains of 2019-nCoV infection].

Objective: To analyze whether there are differences and related influencing factors in liver injury associated with different strains of 2019-nCoV/SARS-CoV-2 infection. Methods: Data of epidemiology, clinical symptoms, laboratory tests, and treatment outcomes of patients with COVID-19 infection confirmed with Alpha and Delta virus strain in Zhejiang Province were retrospectively collected. Statistical analysis was performed using independent samples t-test or Mann-Whitney U test, χ2 test or Fisher's exact test, and logistic regression analysis. Results: A total of 788 and 381 cases with Alpha and Delta virus strain were included. Vaccination ratio was 0% in Alpha and 85.30% in Delta group (P<0.001), The proportion of patients with fever (80.71% vs. 40.94%, P<0.001) was significantly higher in Alpha than Delta strain group. The proportion of critical ill patients was significantly higher in Delta group (9.90% vs. 1.57%, respectively, P<0.001). The virus negative conversion time was significantly longer in Delta than Alpha group (22 d vs. 11 d, P<0.001), but the incidence of liver injury was significantly higher in Alpha than Delta group (20.05% vs. 13.91%, P=0.011). Univariate analysis showed that Alpha virus strain infection, male sex, body mass index, chronic liver disease, fever, diarrhea, shortness of breath, severe/critical illness, elevated creatine kinase (CK), elevated international normalized ratio (INR) and an elevated neutrophil/lymphocyte ratio was significantly associated with an increased risk of liver injury occurrence, and in patients with pharyngeal pain the risk of liver injury occurrence was significantly reduced. Multivariate analysis showed that shortness of breath [OR, 2.667 (CI: 1.389-5.122); P=0.003], increased CK [OR, 2.544 (CI: 1.414-4.576); P=0.002] and increased INR [OR, 1.721] (CI: 1.074-2.758); P=0.024] was significantly associated with an increased risk of liver injury occurrence, and in patients with pharyngeal pain the risk of liver injury occurrence was significantly reduced [OR, 0.424 (CI: 0.254-0.709); P=0.001]. Conclusion: Although the virulence of the Delta is stronger than Alpha strain, most patients infected with Delta strain vaccinated against COVID-19 in Zhejiang province had milder clinical symptoms and a lower incidence and degree of liver injury. Notably, the infection risk even remains after vaccination; however, symptoms and the incidence of severe and critical illness can be significantly reduced.

Therapeutic effects of probiotic Clostridium butyricum WZ001 on bacterial vaginosis in mice.

AIMS: To observe the therapeutic effects of vaginal infusion of probiotic Clostridium butyricum WZ001 on bacterial vaginosis (BV) in mice. METHODS AND RESULTS: Female ICR mice were used to establish the model of BV by infecting oestrogen-treated mice with Escherichia coli, and then treated with high- and low dose of C. butyricum. Clinical indexes of mice in the C. butyricum-treated groups were significantly improved and comparable to those in the antibiotic group. Pap staining showed that neutrophil count was significantly increased after modelling and largely decreased after C. butyricum treatment (P < 0·01). Dynamic observation of E. coli and Lactobacillus showed that the number of E. coli significantly decreased in the C. butyricum-treated groups or in the antibiotic group with prolonged treatment (P < 0·01). Besides, the number of E. coli in the low-dose C. butyricum group was higher than that in either its high-dose counterpart or the antibiotic group respectively (P < 0·01). The number of Lactobacillus decreased evidently in the antibiotic group (P < 0·01), while that in the C. butyricum groups remained consistent. Moreover, C. butyricum inhibited the proliferation of E. coli by the experiment in vitro. The phosphorylation of nuclear factor-kappa B (NF-κB) p65 in vaginal tissue and the serum levels of inflammatory cytokines, IL-1ß, TNF-α and IL-6, increased after modelling and significantly decreased after treated with C. butyricum (P < 0·01), with no difference found when compared with the antibiotic group. CONCLUSION: Clostridium butyricum inhibits the growth of pathogenic bacteria as well as the inflammatory response induced by E. coli and promotes the growth of Lactobacillus to maintain the vaginal micro-ecological balance. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results suggest that probiobitc C. butyricum WZ001 has a great potential in the clinical treatment of BV.

[Quantitative evaluation of intravoxel incoherent motion diffusion-weighted imaging and three-dimensional arterial spin labeling in Ki-67 labeling index and grading of brain gliomas].

Objective: To investigate the value of multiple parameters derived from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and three-dimensional arterial spin labeling (3D-ASL) in Ki-67 labeling index (Ki-67 LI) and grading of human brain gliomas. Methods: From December 2015 to May 2018, 45 patients of gliomas confirmed by surgical pathology in Li Huili Hospital, Ningbo Medical Center were divided into low-grade group (20 cases of WHO grade Ⅱ) and high-grade group (12 cases of WHO grade Ⅲ, 13 cases of WHO grade Ⅳ), and the Ki-67 LI of glioma was obtained by immunohistochemistry. All patients, 24 males and 21 females, aged 25-83 years, mean(53±12)years, underwent conventional magnetic resonance imaging (MRI), IVIM-DWI and 3D-ASL before operation, then measured the true water diffusion coefficient (D), microcirculation perfusion coefficient (D(*)), perfusion fraction (f) and cerebral blood flow (CBF) in the tumor solid area and the contralateral normal white matter area. Those parameters and the Ki-67 LI were compared between the low-and high-grade groups with Mann-Whitney U test. Spearman's correlation was used to analyze the correlation between the quantitative parameters and Ki-67 LI. The ROC curve was used to assess the diagnostic efficacy of parameters in the grading assessment of brain gliomas. Results: The D(0.791×10(-3)mm(2)/s) and f (0.261) of the high-grade group were lower than those of the low-grade group, whereas D(*) (4.153×10(-3) mm(2)/s), CBF(102.027 ml·min(-1)·100 g(-1)) and Ki-67 LI (0.25) were higher (P<0.05). There was a moderate negative correlation between D, f and Ki-67 LI(r=-0.513,-0.457, all P<0.05). There was no significant correlation between D(*) and Ki-67 LI (P=0.571). The area under the curve (AUC) for identifying high-and low-grade gliomas by D, D(*), f and CBF values was 0.965, 0.745, 0.842, and 0.830 respectively (all P<0.05). Conclusion: D and f can be used for quantitative prediction of Ki-67 LI. IVIM-DWI and 3D-ASL are helpful in the grading assessment of gliomas, and the diagnostic efficiency of D is the highest.

[Liver transplantation for polycystic liver disease: 11 cases report and literature review].

Objective: To explore the indications and safety of orthopedic liver transplantation for polycystic liver disease (PLD). Methods: Data of 11 patients with PLD who underwent orthotopic liver transplantation between 2004 and 2013 was retrospectively analyzed. Demographic, clinical and follow-up data were collected for statistical analysis. The survival rate was calculated by Kaplan-Meier method. Results: Over a period of 10 years, the patients received modified piggyback orthopedic liver transplantation (n=9) or combined liver-kidney transplantation (n=2) for PLD. The recipients' median age was 56 years. Seven patients were classified as Gigot type Ⅱ PLD, and four were classified as Gigot type Ⅲ PLD. Eight patients had severe decreased mobility (Eastern Cooperative Oncology Group, ECOG≥3). Only three cases were Child-Pguh Class C patients and the model for end-stage liver disease (MELD) score was>20. The mean hospitalization duration was (45.4±15.3) days, and the mean length of stay in intensive care unit was (4.1±1.9) days. The perioperative mortality was 18.2% and morbidity of complications was 63.6%. The median follow-up period was 111 months. Two patients died of severe complications after combined liver-kidney transplantation. One patient died of ischemia cholangitis during follow-up. The actuarial 1-, 5-and 10-year survival rate during the follow-up period was 82.2%, 81.8%, and 65.5%, respectively. Conclusions: Liver transplantation is the only curative and safe procedure for PLD, and it provides a good long-term prognosis and high quality of life for PLD patients. Liver transplantation could be a primary option in treating progressive or advanced PLD.

Measurement of the spin temperature of optically cooled nuclei and GaAs hyperfine constants in GaAs/AlGaAs quantum dots.

Deep cooling of electron and nuclear spins is equivalent to achieving polarization degrees close to 100% and is a key requirement in solid-state quantum information technologies. While polarization of individual nuclear spins in diamond and SiC (ref. ) reaches 99% and beyond, it has been limited to 50-65% for the nuclei in quantum dots. Theoretical models have attributed this limit to formation of coherent 'dark' nuclear spin states but experimental verification is lacking, especially due to the poor accuracy of polarization degree measurements. Here we measure the nuclear polarization in GaAs/AlGaAs quantum dots with high accuracy using a new approach enabled by manipulation of the nuclear spin states with radiofrequency pulses. Polarizations up to 80% are observed-the highest reported so far for optical cooling in quantum dots. This value is still not limited by nuclear coherence effects. Instead we find that optically cooled nuclei are well described within a classical spin temperature framework. Our findings unlock a route for further progress towards quantum dot electron spin qubits where deep cooling of the mesoscopic nuclear spin ensemble is used to achieve long qubit coherence. Moreover, GaAs hyperfine material constants are measured here experimentally for the first time.

Impact of an intervention programme on knowledge, attitudes and practices of population regarding severe fever with thrombocytopenia syndrome in endemic areas of Lu'an, China.

Knowledge, attitudes and practices (KAP) of the population regarding severe fever with thrombocytopenia syndrome (SFTS) in endemic areas of Lu'an in China were assessed before and after an intervention programme. The pre-intervention phase was conducted using a sample of 425 participants from the 12 selected villages with the highest rates of endemic SFTS infection. A predesigned interview questionnaire was used to assess KAP. Subsequently, an intervention programme was designed and applied in the selected villages. KAP was re-assessed for each population in the selected villages using the same interview questionnaire. Following 2 months of the programme, 339 participants had completed the re-assessed survey. The impact of the intervention programme was evaluated using suitable statistical methods. A significant increase in the KAP and total KAP scores was noted following the intervention programme, whereas the proportion of correct knowledge, the positive attitudes and the effective practices toward SFTS of respondents increased significantly. The intervention programme was effective in improving KAP level of SFTS in populations that were resident in endemic areas.

MRI-measured myocardial iron load in patients with severe diabetic heart failure.

AIM: To investigate whether a correlation exists between abnormal myocardial iron status and cardiac lipid deposition as well as other biomarkers in patients with diabetic heart failure (DHF). MATERIALS AND METHODS: Seventeen volunteers (Group 1), 26 patients with non-severe DHF (Group 2), and 25 patients with severe DHF (Group 3) were recruited for this study. Myocardial middle-section T2* mapping and septal 1H magnetic resonance spectroscopy (1H-MRS) were performed using a 3 T magnetic resonance imaging (MRI) machine to assess the iron status and lipid deposition individually. Fasting venous blood was used to examine serum biomarkers. RESULTS: Cardiac T2* (ms) of the three groups were 22.8±2.1, 21.7±1.8, and 18.6±1.3, respectively. The value of Group 3 was significantly lower than that of the other two groups (p<0.001). Myocardial triglyceride (%) levels differed among the three groups (Group 1, 0.53±0.13; Group 2, 1.11±0.29; Group 3, 1.47±0.12; p<0.001). Cardiac T2* was inversely correlated with both cardiac triglycerides and left ventricular ejection fraction (LVEF) in overall participants (Groups 1-3) or Group 3 (each p<0.001). CONCLUSIONS: Abnormal myocardial iron status was found in patients with severe diabetic heart failure. Myocardial lipotoxicity may be responsible for this process.

RNA interference-mediated silencing of aquaporin (AQP)-5 hinders angiogenesis of colorectal tumor by suppressing the production of vascular endothelial growth factor.

Aquaporin (AQP)-5 is an essential member of AQP family involved in the tumorigenesis of various malignant tumors. However, its role in the angiogenesis of colorectal cancer is unclear and requires further investigation. In this study, a pRNA-H1.1 vector containing the short hairpin RNA (shRNA) targeting AQP5 mRNA was constructed to inhibit the endogenous expression of AQP5 in human umbilical vein endothelial cells (HUVECs). We found that the AQP5-silenced HUVECs acquired decreased proliferation, migration and tube formation ability. AQP5 shRNA also inhibited the enzyme activity of matrix metalloprotease (MMP)-9 in HUVECs without affecting the MMP-2. Further, two colorectal cancer cell lines (HT29 and HCT116) stably transfected with scrambled or AQP5 shRNA were established. The expression and secretion of vascular endothelial growth factor (VEGF)-A (a pro-angiogenic factor) in colorectal cancer cells were downregulated by AQP5 shRNA. HUVECs cultured in low-VEGF conditioned media (CM) obtained from cancer cells developed less vessel-like tubes and had decreased proliferation and migration. The growth and angiogenesis of xenograft tumors were suppressed when the endogenous AQP5 in HT29 cells was knocked down. Tumor samples were additionally collected from patients with colorectal cancer to analyze the expression of AQP5. The immunofluorescence data indicated that AQP5 was expressed in both inner cancer areas and CD31-positive vessels. Taken together, our study suggests AQP5 as a novel anti-angiogenesis target for colorectal cancer.

Effects of oxidative stress induced by high dosage of dietary iron ingested on intestinal damage and caecal microbiota in Chinese Yellow broilers.

The objective of this trial was to test the effects of oxidative stress induced by a high dosage of dietary iron on intestinal lesion and the microbiological compositions in caecum in Chinese Yellow broilers. A total of 450 1-day-old male chicks were randomly allotted into three groups. Supplemental iron (0, 700 and 1,400 mg/kg) was added to the basal diet resulting in three treatments containing 245, 908 and 1,651 mg/kg Fe (measured value) in diet respectively. Each treatment consisted of six replicate pens with 25 birds per pen. Jejunal enterocyte ultrastructure was observed by transmission electron microscopy. The results showed that a high dosage of dietary iron induced oxidative stress in broilers. Dilated endoplasmic reticulum (ER), autophagosome formation of jejunal enterocytes and decreased villi were caused by this oxidative stress. Compared to the control, concentration of the malondialdehyde (MDA) in jejunal mucosa in the 908 and 1,651 mg/kg Fe groups increased by 180% (p < .01) and 155% respectively (p < .01); activity of copper-zinc superoxide dismutase (Cu/ZnSOD) increased in jejunum (p < .01); and the concentration of plasma reduced glutathione (GSH) decreased by 34.9% (p < .01) in birds fed 1,651 mg/kg Fe. Gene expression of nuclear factor, erythroid-derived 2-like 2 (Nrf2) and zonula occludens-1 (ZO-1), in the higher dietary Fe groups was enhanced (p < .05). Species of microbial flora in caecum increased caused by oxidative stress. The PCR-DGGE (denaturing gradient gel electrophoresis) dendrograms revealed different microbiota (65% similarity coefficient) between the control and iron-supplemented groups (p < .05). These data suggest high dosage of iron supplement in feed diet can induce oxidative stress in Chinese Yellow broilers, and composition of microbiota in the caecum changed. It implied there should be no addition of excess iron when formulating diets in Chinese Yellow broilers.

[Influence of UCHL5 on proliferation and apoptosis of SW527 breast cancer cells].

Objective: To investigate the effect of UCHL5 on proliferation and apoptosis of breast cancer cells. Methods: SW527 cells were infected with lentiviral vector carrying short hairpin RNA to delete the expression of UCHL5. 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was used to examine cell proliferation, and subcutaneous transplantation experiments were performed to detect tumor growth. Cell apoptosis was detected using Annexin V/ Propidium iodide (PI) double staining. The correlation between UCHL5 expression and the expressions of proliferation and apoptosis associated genes was analyzed using TCGA breast invasive carcinoma data set. The relationship between UCHL5 expression and breast cancer patients'survival was analyzed using Kaplan-Meier Plotter online tool. Results: After knockdown of UCHL5, A values of SW527 cells on day 2 and day 4 were 0.822±0.017 and 1.045±0.023, respectively, which were significantly lower than 0.976±0.016 and 1.284±0.025 of control cells on day 2 and day 4 (P<0.001). In vivo xenografted mouse model, the volume in UCHL5-suppressed group was (166.90±75.05) mm(3,) significantly smaller than (329.80±35.84) mm(3) in control group (P=0.029). Flow cytometry analysis showed the apoptotic rate of SW527 cells was (8.60±1.13)% after knockdown of UCHL5, significantly higher than (2.95±0.07)% of control group (P=0.020). TCGA database analysis showed that the expression of UCHL5 was positively correlated with the expressions of genes related to cell proliferation, in paralled with the increased expression of UCHL5, the expression of the pro-apoptosis associated genes was decreased. Kaplan-Meier Plotter analysis demonstrated that the overall survival and relapse-free survival of breast cancer patients with high expression of UCHL5 were much shorter (all P<0.001). Conclusions: Down-regulation of UCHL5 inhibits the proliferation and tumor formation and promotes apoptosis of SW527 cells. High expression of UCHL5 may predict poor prognosis of breast cancer patients.

[Correlation between serum HBV DNA level and HBsAg titer in HBeAg-positive pregnant women and impact of genomic variability of hepatitis B virus pre S/S regions on their correlations].

Objective: To analyze the correlation between serum HBV DNA level and HBsAg titer in hepatitis B e antigen positive pregnant women without antiviral therapy, and investigate the impact of genomic variability of preS/S regions on their correlations. Methods: Prenatal serum samples from 882 pregnant women with chronic HBV infection who were positive for HBsAg, HBeAg and HBV DNA and were not on antiviral therapy were included in the analysis. The Abbott i2000 and m2000 systems were used to qualitatively or quantitatively detect HBsAg, HBeAg and HBV DNA levels, respectively. HBV genotyping was performed using a type-specific primer nested polymerase chain reaction (nPCR). In addition, serum samples of pregnant women with HBV DNA levels correlated with HBsAg titer and HBV DNA levels higher than HBsAg titers were used to perform preS/S region amplification by nPCR method. PCR products were directly sequenced and mutation sites were analyzed by MEGA6.0 stasticial software. Mann-Whitney U test was used for the measurement data, and 2-test test for count data. Correlations between variables were analyzed using Spearman's rank correlation. Results: Serum HBsAg titer of HBeAg-positive pregnant women was positively correlated with HBV DNA level (r = 0.754, P < 0.01). Compared with the control group, mutation sites A60V (100% vs. 15.38%, χ(2) = 7.61, P < 0.01), V90A (100% vs. 30.77%, χ(2) = 4.43, P < 0.05) and I161T of HBV preS/S region (80.00% vs. 0, χ(2) = 9.14, P < 0.01) showed a significant decrease in HBsAg titer. Conclusion: Serum HBV DNA levels were positively correlated with HBsAg titer in HBeAg-positive pregnant women. Therefore, serum HBsAg titer may be used as a surrogate marker of serum HBV DNA. Single or multiple amino acid mutations sites A60V, V90A, and I161T in preS/S region may be one of the reasons that lead to a significant drop in HBsAg titer and affect its correlation with HBV DNA levels.

[Clinical results of Mei mini maze procedure for atrial fibrillation patients with previously failed catheter ablation].

Objective: To evaluate the efficacy of Mei mini maze procedure for treating atrial fibrillation (AF) patients with previously failed catheter ablation. Methods: Between August 2010 and May 2016, 48 AF (8 proximal AF, 15 persistent AF and 25 long-standing persistent AF) patients (29 males, 19 females, mean age: (62.5±7.3) years old) with previously 1-3 failed catheter ablation results were treated with Mei mini maze procedure in our department. Under thoracoscopic assistance, the procedure was performed through three ports on left chest wall, pulmonary vein isolation and ablations of the roof and posterior wall of left atrium was made by bipolar radiofrequency ablation. Ganglionic plexus ablation was made by the ablation pen. Left atrial appendage was excluded. Patients were followed at outpatient clinic and per telephone. Electrocardiogram, CT and echocardiography examinations were performed at 1, 3, 6 and 12 months post operation. The success rate of the procedure was analyzed by Kaplan-Meier curves and evaluated by the log-rank test. Results: Mean AF history was (8.1±6.3) years and left atria dimension was (44.1±6.2) mm in this patient cohort. All procedures were performed successfully in these 48 patients. Pericardial adhesions were dissected in 21 patients. Durations of the procedures were (142.3±35.6) minutes.There were no serious complications. The hospital stay was (9.3±1.8) days. Sinus rhythm was documented in 44 patients (91.7%) at discharge. The mean follow-up duration was (28.0±17.2) months. Thirty-eight patients (82.6%) were in sinus rhythm. There was no stroke, thrombus in the left atrium and stenosis of pulmonary vein during the follow-up. Sinus rhythm was achieved in 7 out of 8 paroxysmal AF patients, in 31 out of 38 non-paroxysmal AF patients, and in 13 out of 15 persistent AF patients. Kaplan-Meier curve showed that the success rate in the long-standing persistent AF group was lower than in the other two groups, but there was no statistical difference. Conclusions: Mei mini maze procedure has a high success rate for AF patients with previously failed catheter ablation history, which could completely isolate the bilateral pulmonary vein and left atrial posterior wall with good quality and integrity of ablation line, and left atrial appendage is also resected during the procedure.