OBJECTIVE To investigate the effect of bs-5-YHEDA iron chelating peptide combined with semaglutide on the cognitive ability and pathological characteristics of D-Gal-induced Alzheimer's disease(AD) model mice. METHODS Forty mice were randomly divided into 5 groups, namely the healthy control group, PBS group, bs-5-YHEDA iron chelating peptide group, combined treatment group and positive control group, with 8 mice in each group, half of each sex. Except for the healthy control group, D-galactose was injected to induce the AD mice model for 6 weeks. For 3 consecutive weeks starting from the 4th week, the bs-5-YHEDA iron chelating peptide group was injected with bs-5-YHEDA(1 mg·mL–1) once every other day at 200 µL in the tail vein; the bs-5-YHEDA iron chelating peptide(1 mg·mL–1) and semaglutide(25 nmol·kg–1·d–1) were given alternately once a day in the combination treatment group; the positive control group was given memantine(3.3 mg·kg–1·d–1) by gavage every other day. The healthy control group and PBS group were injected with the equal dose of PBS. At the end of treatment, the learning memory ability of mice was detected by the Morris water maze method, whole brain and whole blood were dissected, and pathological changes in hippocampal region were observed by HE staining, and Aβ expression and Tau protein phosphorylation levels were detected by immunohistochemistry, enzyme-linked immunosorbent assay and immunoblotting. RESULTS In the Morris water maze spatial exploration experiment, the differences in the number of times the mice traversed the platform, the ratio of swimming distance to the target quadrant, and the time ratio were statistically significant in each group(P<0.05); compared with the PBS group, the ratio of swimming distance to the target quadrant increased in the combined treatment group, and the differences were statistically significant(P<0.05). The results of HE staining showed that compared with the healthy control mice, the hippocampal area in the PBS group showed reduced levels of pyramidal cells, disorganized arrangement, cell edema, and deep staining of nuclei consolidation. Cellular disorganization, deep staining of nuclei and apoptosis in the hippocampus were significantly improved in each treatment group after drug treatment. Immunohistochemistry and Western blotting results showed that the Aβ expression levels and Tau protein phosphorylation levels were significantly higher in the PBS-administered mice compared with the healthy control mice, and the Aβ expression levels and Tau protein phosphorylation levels were reduced in each group after drug treatment, with statistically significant differences(P<0.01 or P<0.001 ). CONCLUSION The combination of bs-5-YHEDA iron chelating peptide and semaglutide can effectively improve the learning and memory ability and pathological characteristics of AD mice, but from the results of immunohistochemistry and immunoblotting experiments, the improvement of pathological characteristics of AD mice in the combination treatment group is not obvious compared with the single bs-5-YHEDA iron chelating peptide group, suggesting that there may be a threshold effect of our designed dual-target combination treatment on the cognitive improvement of AD mice, and the optimization and validation of the effect of multi-target combination treatment need further study.

Objective:To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP).Methods:In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS).Results:A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions:CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.

Objective:To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP).Methods:In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS).Results:A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions:CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.

OBJECTIVES: Long-term treatment of olanzapine, the most widely-prescribed second-generation antipsychotic, remarkably increases the risk of non-alcoholic fatty liver disease (NAFLD), whereas the mechanism for olanzapine-induced NAFLD remains unknown. Excessive hepatic fat accumulation is the basis for the pathogenesis of NAFLD, which results from the disturbance of TG metabolism in the liver. Apolipoprotein A5 (ApoA5) is a key regulator for TG metabolism in vivo that promotes TG accumulation in hepatocytes, thereby resulting in the development of NAFLD. However, there are no data indicating the role of apoA5 in olanzapine-induced NAFLD. Therefore, this study aims to investigate the role of apoA5 in olanzapine-induced NAFLD. METHODS: This study was carried out via animal studies, cell experiment, and ApoA5 gene knockdown experiment. Six-week-old male C57BL/6J mice were randomized into a control group, a low-dose group, and a high-dose group, which were treated by 10% DMSO, 3 mg/(kg·d) olanzapine, and 6 mg/(kg·d) olanzapine, respectively for 8 weeks. The lipid levels in plasma, liver function indexes, and expression levels of ApoA5 were detected. HepG2 cells were treated with 0.1% DMSO (control group), 25 μmol/L olanzapine (low-dose group), 50 μmol/L olanzapine (medium-dose group), and 100 μmol/L olanzapine (high-dose group) for 24 h. HepG2 cells pretreated with 100 μmol/L olanzapine were transfected with siRNA and scrambled siRNA (negative control), respectively. We observed the changes in lipid droplets within liver tissues and cells using oil red O staining and fat deposition in liver tissues using HE staining. The mRNA and protein levels of ApoA5 were determined by real-time PCR and Western blotting, respectively. RESULTS: After intervention with 3 and 6 mg/(kg·d) olanzapine for 8 weeks, there was no significant difference in body weight among the 3 groups (P>0.05). Olanzapine dose-dependently increased the plasma TG, ALT and AST levels, and reduced plasma ApoA5 levels (all P<0.05), whereas there was no significant difference in plasma cholesterol (HDL-C, LDL-C, and TC) levels among the 3 groups (all P>0.05). Olanzapine dose-dependently up-regulated ApoA5 protein levels in liver tissues (all P<0.05), but there was no significant change in ApoA5 mRNA expression among groups (P>0.05). In the control group, the structure of liver tissues was intact, the morphology of liver cells was regular, and only a few scattered lipid droplets were found in the cells. In the olanzapine-treated group, there was a large amount of lipid deposition in hepatocytes, and cells were balloon-like and filled with lipid droplet vacuoles. The nucleus located at the edge of cell, and the number of lipid droplets was increased significantly, especially in the high-dose group. Likewise, when HepG2 cells were treated with olanzapine for 24 h, the number and size of lipid droplets were significantly elevated in a dose-dependent manner. Moreover, olanzapine dose-dependently up-regulated ApoA5 protein levels in HepG2 cells (all P<0.05), but there was no significant difference in ApoA5 mRNA expression among groups (P>0.05). Compared with the HepG2 cells transfected with scrambled siRNA, the number and size of lipid droplets in HepG2 cells transfected with ApoA5 siRNA were significantly reduced. CONCLUSIONS The short-term intervention of olanzapine does not significantly increase body weight of mice, but it can directly induce hypertriglyceridemia and NAFLD in mice. Olanzapine inhibits hepatic apoA5 secretion but does not affect hepatic apoA5 synthesis, resulting in the pathogenesis of NAFLD. Inhibition of apoA5 secretion plays a key role in the development of olanzapine-related NAFLD, which may serve as an intervention target for this disease.
Animals ; Apolipoprotein A-V/genetics* ; Body Weight ; Dimethyl Sulfoxide/metabolism* ; Liver/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/chemically induced* ; Olanzapine/metabolism* ; RNA, Messenger/metabolism* ; RNA, Small Interfering ; Triglycerides

Objective:To investigate epidemic status of avian influenza virus (AIV) in live poultry market (LPM) and evaluate its potential public health threat and develop control measures in Nanchang city.Methods:Forty-seven LPM in 10 counties/districts of Nanchang city were selected as surveillance sites by using cluster random sampling. Poultry swabs and environmental samples were obtained from LPM. Real time RT-PCR was used for AIV typing and subtyping. Excel 2016, SPSS 24.0 and Prism Version 7 (GraphPad) software were used for statistical analysis.Results:Total of 9 248 poultry swabs and environmental samples were collected. 1 525 specimens(16.49%) were positive for AIV. H7 and H9 were the dominant subtypes, and H9 positive rate was highest (17.44%). Sewage (21.46%) and throat swabs (20.46%) had higher positive rates than the other types of samples. Chicken and duck were dominant hosts for AIV, the corresponding positive rates were 22.80% and 13.95%. The positive rates of Honggutan district, Anyi county and Xinjian district were 25.52%, 24.31% and 22.35%, which were higher than that of the other counties/districts. Each county/district had its unique subtype composition of AIV.Conclusions:The coexistence of H7, H9 and other subtypes of AIV in LMP was identified in Nanchang city. Continuing active surveillance and comprehensive control measures should be taken to reduce the potential risk of human infection.

Objective: To systematically evaluate the clinical efficacy of immunonutrition support in perioperative period of hepatectomy. Methods: Literatures were researched using CNKI，CBM，Wanfang database，VIP databases，PubMed (Medline)，Embase，Web of science，Science Direct，Cochrane Center from January 1996 to March 2018 with the key words including "肝切除术，免疫营养，hepatectomy，hepatic resection，immunonutrition，immunoenhanced nutrition" . The randomized controlled trials (RCTs) on comparison of efficacy of immunonutrition support versus routine nutritional support in perioperative period of hepatectomy. Patients in the immunonutrition group received immunonutrition support in perioperative period of hepatectomy，and patients in the routine nutrition group received routine nutritional support in perioperative period of hepatectomy. Outcome measures：overall incidence of postoperative complications，incidence of postoperative infectious complications，incidence of postoperative liver failure，perioperative mortality，hospital stay，and hospitalization expenses. Literatures screening，data extraction and quality assessment of methodology were conducted by two researchers separately. Count data were represented as risk ratio (RR) and 95% confidence interval (CI). Measurement data were represented as mean difference (MD) or weighted mean difference (WMD) and 95%CI. Heterogeneity of the included studies was analyzed with I². Funnel plot was used to test potential publication bias if the number of studies included ≥ 10，and funnel plot was used to test potential publication bias for the outcome measures with the maximum number of studies if the number of studies included <10. Results: (1) Document retrival: 12 RCTs were enrolled in the Meta analysis, and the total sample size was 1 136 patients, including 568 patients in the immunonutrition group and in the routine nutrition group, respectively. (2) Results of Meta-analysis: the that immunonutrition group had lower overall incidence of postoperative complications, incidence of postoperative infectious complications, incidence of postoperative liver failure, and hospital stay (RR=0.57, 0.49, 0.30, MD=-3.28, 95%CI: 0.46-0.71, 0.37-0.65, 0.12-0.74, -4.45 to -2.11, P<0.05), and higher hospital expenses (MD=11.86, 95%CI: 10.96-12.77, P<0.05) compared with the routine nutrition group. There was no significant difference in the perioperative mortality between the two groups (RR=0.26, 95%CI: 0.07-1.05, P>0.05). The bilateral symmetry was presented in the funnel plot based on the 9 studies comparing incidence of postoperative infectious complications between the immunonutrition group and routine nutrition group, suggesting that publication bias had little influence on results of Meta-analysis. Conclusions Perioperative immunonutrition support for hepatectomy is safe and feasible. Compared with routine nutritional support, immunonutrition support can significantly reduce overall incidence of postoperative complications, incidence of postoperative infectious complications, incidence of postoperative liver failure, and shorten the hospital stay without increasing postoperative mortality.

Objective:To investigate the role of apolipoprotein A5 (apoA5) in the pathogenesis of obesityrelated hypertriglyceridemia and the related therapeutic effects of metformin.Methods:The ob/ob mice were treated with regular chow diet and metformin for 4 weeks,and the levels of hepatic triglyceride (TG) and apoA5 were measured.Hepatic IAR20 cells were treated with metformin and/or apoA5 siRNAs,and then cellular TG contents and apoA5 expression were determined.Results:High plasma and hepatic levels of apoA5 and TG were found in ob/ob mice.The plasma levels of apoA5 were positively correlated with plasma TG in these mice.Metformin could dosedependently decrease the plasma and hepatic levels of apoA5 and TG in ob/ob mice.Metformin could also dose-dependently reduce cellular TG contents and apoA5 expression,these effects were attenuated by knockdown of apoA5.Conclusion:Hepatic apoA5 is up-regulated in ob/ob mice,which contributes to the elevation of plasma TG.Metformin could inhibit hepatic apoA5 expression,leading to the reduction of the plasma level of TG.

Objective:To investigate the effect of acute myocardial infarction (AMI)-activated inflammation on adipokine imbalance and the therapeutic effects of statin.Methods:A total of 32 C57BL/6 mice were divided into 4 groups:a sham group,an AMI group,a low-dose atorvastatin [2 mg/(kg.d)] group and a high-dose atorvastatin [20 mg/(kg.d)] group.AMI models were established by surgical coronary artery ligation.Plasma levels of high sensitive C reaction protein (hs-CRP),adiponectin and resistin were measured.Adiponectin and resistin expressions were determined.In addition,mouse 3T3-L1 preadipocytes in vitro were differentiated and they were stimulated by oxidized low density lipoprotein (ox-LDL).The protein expressions of adiponectin and resistin in adipocytes were detected.The effects of atorvastatin on ox-LDL-induced adipokine imbalance in adipocytes were identified.Results:The plasma levels of hs-CRP and resistin in AMI mice were significantly increased,whereas the plasma levels of adiponectin were remarkably decreased.However,atorvastatin treatment blocked the changes in the plasma levels of hs-CRP,resistin and adiponectin in AMI mice in a dose-dependent manner.Consistent findings regarding the adipose expressions of the two adipokines were obtained.The plasma levels of hs-CRP were positively correlated with resistin but negatively with adiponectin.In vitro study,ox-LDL increased resistin protein and adiponectin expressions in adipocytes,which were dose-dependently reversed by atorvastatin.Conclusion:Inflammation activation in AMI mice leads to adipokine imbalance.Atorvastatin ameliorates the AMI-induced adipokine imbalance via anti-inflammation.

Objective To investigate the levels of nutritional knowledge, attitude and dietary habits and its influential factors of the officers and soldiers in frontier forces to provide the theory basis for nutrition education.Methods Using self-designed nutritional knowledge-altitude-practice (KAP) questionnaires to survey 90 officers and soldiers who lived in plateau for at least 6 months. Questionnaires were handed out and handed over on the spot. According toMilitary Nutrition Survey and Evaluation Methods (GJB 1636A-2016), we measured the physical index of officers and soldiers, including height, weight and skin thickness of triceps. And we also evaluated body mass index (BMI) and upper arm muscle circumference.Results Nutrition knowledge, attitude and practice conditions of plateau forces were at the average, better and average levels respectively. Nutritional knowledge was significantly positively related to the practices (r=0.283,P=0.003), and was also significantly positively related to the age of the soldiers (r=0.228,P=0.04). Nutritional attitude was positively related to source of officers and soldiers (r=0.339,P=0.035), and nutritional practices were positively related to the upper arm muscle circumference (r=0.222,P=0.030). 65.6% of the officers and soldiers would like to know the knowledge about relationship between diet and disease. 25.6% of the officers and soldiers in the plateau were alcohol users.Conclusions Although the nutrition knowledge of plateau forces were poor, and the nutritional practices were influenced by nutritional knowledge, but the soldiers' attitude of changing unhealthy dietary habits was very positive. It is necessary to undertake the dietary nutrition education related to the high altitude nutrition among plateau forces to guild their nutritional practice scientifically.

Objective To evaluate the application value of ultrasound in vascularization of different artificial bones . Methods A total of 15 New Zealand rabbits were utilized for model establishment of classic segmental bone defect in bilateral radius . Recombinant human bonemorphogenic protein-2 ( rhBMP-2 ) coralline hydroxyapatite(CHA) and CHA were implanted into left and right limbs . Each CHA was divided into 4 equal parts which were examined with conventional ultrasonography and contrast-enhanced ultrasonography( CEUS ) on 3 d ,7 d ,11 d ,15 d ,30 d and 45 d respectively . CEUS quantitative was performed by time-intensity curve(TIC) ,which parameters including the basic intensity(BI) ,peak intensity (PI) ,increased signal intensity ( ΔSI) and time to peak ( TTP) . Then the results were analyzed and compared to pathology . Results Within the same duration ,the vascularization degree in rhBMP-2 group was stronger than that in the ordinary group with advanced vascularization time . Positive correlation was detected between ΔSI and time of both groups ( r =0 .938 ,0 .890 ;P =0 .000) ,and negative correlation was found between BI/PI or TTP and time ( BI/PI: r = -0 .798 ,-0 .899 ; P = 0 .000 ;TTP= r -0 .874 ,-0 .868 ;P = 0 .000 ) . No statistical significance was observed among four observation points of both CHA ,which indicated no obvious difference in vascularization degree of each observation point . Conclusions The structure of bone graft can be clearly displayed by conventional ultrasound ,and CEUS is able to show the early blood perfusion in two CHA grafts and to accurately evaluate the difference of CHA microvascular growth before and after rhBMP-2 application . The combination of these two techniques is a promising approach of evaluating bone graft vascularization in clinical practice .