Objectives:Fenofibric acid is extracted from the widely used hypolipemic fenofibrate,nowadays being approved for marketing around numerous nations and regions,nonetheless not in China.Present trial evaluated the efficacy and safety in the Chinese hypertriglyceridemia population. Methods:This is a multi-center,randomized,double-blind,placebo-controlled phase Ⅲ clinical trial.Patients from 3 different cohorts,including severe hypertriglyceridemia(HTG),moderate HTG and mixed-dyslipidemia(MD),were randomized at 1:1 ratio to receive fenofibric acid 135 mg or placebo daily for 12 weeks.The primary endpoint was the percentage change of triglyceridemia(TG)from baseline at week 12.Secondary endpoints were the percentage changes of other blood lipid indexes.At the same time,the incidence of medical adverse events was observed. Results:Among the three cohorts of patients with severe HTG(n=52),moderate HTG(n=23)and MD(n=52),the TG levels in the fenofibric acid-treated group decreased by(49.12±29.19)%,(49.95±25.19)%and(49.79±19.28)%,respectively from baseline to 12 weeks,while the corresponding placebo groups decreased by(18.88±40.69)%,(8.11±29.86)%and increased by(10.42±73.04)%,respectively from baseline to 12 weeks.The differences between treatment and placebo groups were statistically significant(P<0.017 for severe HTG cohort,P<0.05 for moderate and MD cohort).The high-density lipoprotein cholesterol(HDL-C)in the fenofibric acid-treated group increased by(25.51±21.45)%,(24.55±24.73)%,and(23.60±27.38)%,and the placebo group increased by(1.91±20.42)%,(2.40±9.32)%and(7.13±19.12)%,respectively,the differences between the two groups were statistically significant(all P<0.05).In the fenofibric acid group,adverse events with incidence>5%included upper respiratory tract infection(10.9%),abdominal pain(6.3%),and increased serum creatinine levels(6.3%),rates of adverse events were similar between the two groups(P>0.05). Conclusions:Fenofibric acid can significantly reduce triglycerides and elevate HDL-C levels safely in Chinese patients with severe to moderate HTG without statin or MD patients on top of statin therapy.

Objective　To explore the effect of Mp1p on host macrophages through transcriptomics combined with metabolomics. Methods Firstly, a THP-1 macrophage strain (THP-1-Mp1p+) stably expressing Mp1p was constructed using lentivirus. Secondly, using high-throughput RNA sequencing (RNA Seq) technology, the expression level of intracellular mRNA was detected in transcriptomics analysis to determine differentially expressed genes; In metabolomics analysis, metabolite identification was performed through database comparison, and pathway analysis was performed on differential metabolites to reveal potential mechanisms of action. Finally, the results of metabolomics and transcriptomics were combined for analysis, and differential metabolites and genes were analyzed to further elucidate the mechanism of action of Mp1p on macrophages. Results Transcriptome analysis showed that, compared with the negative control group, the THP-1-Mp1p+ group had a total of 1 180 differentially expressed genes (DEGs), with 345 upregulated genes and 835 downregulated genes. GO enrichment analysis of DEGs showed that there were 135 differentially expressed genes, including 105 in biological processes (BP), 28 in cellular components (CC), and 2 in molecular functions (MF). The KEGG analysis results showed that the effect of Mp1p on THP-1 macrophages was highly correlated with the TNF pathway. The metabolomic analysis found that both the blank control group and the THP-1-Mp1p+ macrophage group achieved good separation between QC samples in both positive and negative ion modes. The threshold for significant differential metabolites was set at: VIP≥1 and T-test P<0.05, resulting in the identification of 488 differential metabolites, with 230 in the positive ion mode and 258 in the negative ion mode. Pathway enrichment analysis of the identified metabolites pointed to significant enrichment in metabolic pathways. The combined analysis confirmed that the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and NF-kappaB signaling pathway were important metabolic pathways involved. Conclusions The virulence factor Mp1p may affect host macrophages by modulating the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and NF-kappaB signaling pathway. The findings contribute to a better understanding of the mechanisms of action of Mp1p and may offer potential directions for the selection of relevant diagnostic and therapeutic targets in the future.

Objective:To explore the ability of sequential immunization regimen inducing neutralizing antibodies against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) Wuhan-Hu1 and Omicron variants in mice.Methods:Groups of 6-8-week-old BALB/c mice were primed with two doses of Wuhan-Hu-1 inactivated vaccine, and then boosted with Omicron or Wuhan-Hu-1 inactivated vaccine, respectively. Binding antibodies were tested by enzyme linked immunosorbent assay; and neutralizing antibodies against Wuhan-Hu1 and Omicron variants were analyzed by vesicular stomatitis virus pseudovirus assay system; SARS-CoV-2 specific cellular immune responses were quantified by enzyme-linked immunosorbent spot assay.Results:IgG antibodies against Wuhan-Hu1, Delta and Omicron RBD were enhanced after the second dose of Wuhan-Hu1 inactivated vaccine. Compared with Wuhan-Hu1 inactivated vaccine, the group boosted with Omicron inactivated vaccine improved Wu-RBD and Omic-RBD specific IgG antibodies 1.41 and 1.26 times, and serum neutralizing antibodies against BA.1, BA.2, BA.4/5 and BF.7 were elevated 4.5, 3.4, 12.1 and 6.5 folds, respectively, by sequential immunization. After booster immunization with inactivated Wuhan-Hu1 or Omicron vaccines, Wu-RBD IgA titer was significantly higher than that of one dose inactivated Wuhan-Hu1 vaccine ( P=0.005 7, P=0.006 1). Conclusions:Neutralizing antibodies against Omicron variants were enhanced by sequential immunization with Omicron inactivated vaccine. Specific IgA was significantly enhanced after the third dose of inactivated vaccine.

Objective:To automatically synthesize Al 18F-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-fibroblast activation protein inhibitor (FAPI)-04, perform PET/CT imaging in vivo, and evaluate its diagnostic efficacy on tumors. Methods:Al 18F-NOTA-FAPI-04 was produced in All-in-one automatic synthesis module and its quality control was conducted by high performance liquid chromatography (HPLC) equipped with a radioactive detector. Al 18F-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice ( n=3) and 4T1 breast cancer models ( n=3) to determine its biodistribution. Then Al 18F-NOTA-FAPI-04 and 18F-FDG PET/CT imaging were performed in a hepatocellular carcinoma patient (male, 51 years old). Results:The synthesis time of Al 18F-NOTA-FAPI-04 was about 35 min, and the radiochemical yield was (25.2±1.9)% (attenuation correction, n=3). The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was (46.11±3.07) GBq/μmol (attenuation correction, n=3). The radiochemical purity was above 99.0% and was still above 98.0% at room temperature after 6 h. PET/CT imaging in mice showed that physiological uptake of Al 18F-NOTA-FAPI-04 was mainly in biliary system and bladder, and Al 18F-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that Al 18F-NOTA-FAPI-04 obtained high tumor background ratio (TBR) values of 4.1, 8.9, 5.4, 4.8, 2.2 in parasternal lymph nodes, anterior diaphragmatic lymph nodes, hilar lymph nodes, pancreaticoduodenal ligament lymph nodes, abdominal aortic lymph nodes, respectively, while TBR values were 1.0, 2.8, 5.0, 2.1, 1.1 by 18F-FDG. Conclusions:Al 18F-NOTA-FAPI-04 can be synthesized with short time, high radiochemical yield and good stability using All-in-one module. Al 18F-NOTA-FAPI-04 PET/CT imaging has high contrast and excellent diagnostic efficacy on tumors.

Objective To explore the effect of budesonide suspension for inhalation in the treatment of childhood asthma and its influence on growth and development in 1-2 years. Methods The 68 children with asthma admitted to our hospital from October 2016 to January 2017 were selected. Every patient had acute attacks and received continued medication. 34 patients treated with salbutamol sulfate inhaled aerosol were used as the control group. 34 patients treated with budesonide suspension combined with salbutamol sulfate aerosol were classified as the observation group. The interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), high-sensitivity-C-reactive protein (hs-CRP), maximum respiratory flow, IS maximum expiratory volume, regulatory B cell ratio, wheezing disappearance time, shortness of breath relief time, wet rales disappearing time, cough disappearing time, and the two year follow-up indicators of growth and development were compared. Results After medication, IL-6, TNF-α, hs-CRP, regulatory B cell ratio, wheezing disappearance time, shortness of breath relief time, moist rales disappearance time, and cough disappearance time were lower in the observation group(P<0.05). The maximum respiratory flow and IS maximum expiratory volume in the observation group were higher than those in the control group (P<0.05). The GH level, height, and weight obtained from two year follow up in the observation group were lower than those in the control group (P<0.05). Conclusion Budesonide suspension combined with salbutamol sulfate aerosol inhalation therapy can alleviate the inflammatory reaction, improve the lung function and immune function of children, and accelerate the disappearance of clinical symptoms, but it will affect the growth and development of children to a certain extent.

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd

Liver fibrosis can progress to liver cirrhosis and end-stage liver disease, which may lead to poor prognosis. In addition to pathological angiogenesis and hepatic sinusoid remodeling, hepatic lymphangiogenesis also plays an important role in the progression of liver fibrosis. This article briefly describes lymphatic vessel markers and their expression in the liver, introduces the role of lymphangiogenesis in liver fibrosis, and reviews the role of liver macrophages (Kupffer cells) and lymphatic endothelial cells in lymphangiogenesis. It is pointed out lymphangiogenesis may become a potential target for the intervention of liver fibrosis, which plays an important role in the early treatment and reversal of liver fibrosis and the prevention of liver cirrhosis and end-stage liver disease.

Objective To investigate the effectiveness and safety of esophageal covered stent for the treatment of esophagogastric cervical anastomotic fistula. Methods Retrospective analysis of clinical and imaging data of patients with esophageal and gastric anastomotic neck fistula treated by esophageal membrane stent implantation in the Affiliated Tumor Hospital of Zhengzhou University from July 2015 to June 2018. Twenty‐one cases, 15 males and 6 females were enrolled. All patients showed fistula after esophagogastrostomy for esophageal carcinoma. All the fistulas were located in the cervical segment of esophagus and were diagnosed as anastomotic fistula 2 to 13 days after surgery. The length of esophagus residue, the position and size of the fistula were measured by esophagography. We retrospectively analyzed the data of patients with cervical anastomotic fistula treated with esophageal covered stent. Patients were followed up for more than 6 months by review and telephone follow‐up. Results In the 21 patients, 19 (90.5%) were successfully implanted stents at one time, and 2 (9.5%) were placed at a lower position. The esophageal stent was implanted for 10 to 60 days (31±19) days, and the stent was successfully removed after the fistula healed, with a procedure time of 6 to 23 minutes. No recurrence of fistula was found during follow‐up. Four patients had anastomotic scar stenosis, and eating smoothly after balloon dilatation. Conclusion Esophageal covered stent implantation is a safe and effective technique for gastroesophageal cervical anastomotic fistula.

Objective: To evaluate the feasibility and accuracy of deep learning in CT image segmentation and further lesion-volume assessment of spontaneous intracerebral hemorrhage. Methods: A total of 1 223 cases of spontaneous intracerebral hemorrhage including parenchymal hemorrhage, ventricular hemorrhage, subarachnoid hemorrhage and mixture hemorrhage, from April 2016 to April 2018 in Tianjin Medical University General Hospital, were retrospectively enrolled and analyzed. The patients were randomly divided into training set (905 cases), validation set (156 cases) and test set (162 cases), among each group, the number of parenchymal hemorrhage was 498, 107 and 100, respectively. The bleeding area manually outlined by physician was served as the reference standard to build the segmentation model and to evaluate the performance of the validation set. Patients were divided into 3 groups according to the volume calculated by reference standard. The volume of hematoma in group 1 was less than 5 ml, while group 2 was 5-25 ml, and group 3 was more than 25 ml. Comparison of the hematoma volume calculated by segmentation model and that calculated by ABC/2 formula was conducted in 97 simple intraparenchymal hemorrhage cases. Results: In 162 cases of test set, the Dice coefficients of the segmentation model were 0.87, 0.85, 0.67 and 0.77 in parenchymal hemorrhage, intraventricular hemorrhage, subarachnoid hemorrhage and mixture hemorrhage, respectively. The estimated hematoma volume in the 97 intraparenchymal hemorrhage cases calculated by the segmentation model was (29.55±37.69) ml, and that calculated by the ABC/2 formula was (24.04±31.22) ml. Compared with reference standard, the absolute errors of three segmentation model were (0.52±0.54), (1.53±1.22) and (7.93±8.49) ml in group 1, 2 and 3 respectively. The absolute errors of the ABC/2 formula were (0.68±0.60), (3.16±2.90) and (19.31±17.23) ml in group 1, 2 and 3. Conclusion Deep learning based segmentation model improved detection of intraparenchymal hematoma volume, compared with ABC/2 formula.

By reading a large number of literature, this paper summarized the current situation of experiential teaching in geriatric overseas, and pointed out the existing problems, such as the current research results at home and abroad are inconsistent, there was a lack of interdisciplinary team experiential teaching related research, as well as the lack of standardized patient and progressive case application, evaluation indicators and assessment forms need to be reformed and gives the corresponding suggestions.