Clinical analysis of patients with early gastric cancer undergoing non-curative endoscopic resection followed by additional surgical procedures / 中华消化内镜杂志

Objective:To analysis the necessity of additional surgical intervention for non-curative endoscopic resection patients with early gastric cancer.Methods:A retrospective analysis was conducted on 73 patients with early gastric cancer who underwent additional surgical procedures after non-curative endoscopic resection at Chinese PLA General Hospital from July 2009 to May 2023. The main outcome measures included pathological classification, positive horizontal margins, positive vertical margins, invasion depth, vascular and lymphatic invasion, eCura grade, lymph node metastasis, and overall survival rate.Results:A total of 73 patients with early gastric cancer who were determined to have non-curative endoscopic resection underwent additional surgical procedures, including 58 males and 15 females with a mean age of 61 (53-67) years. In terms of the site of onset, 37 cases were located in the upper part of the stomach, 24 cases in the lower part, 11 cases in the middle part, and 1 case had multiple lesions. In terms of pathological classification, 43 cases were highly differentiated tubular adenocarcinoma, 16 cases were mucinous/signet ring cell carcinoma, 10 cases were poorly differentiated tubular adenocarcinoma, and 4 cases were high-grade intraepithelial neoplasia. In terms of morphological classification, 22 cases were type 0-Ⅱa, 43 cases were type 0-Ⅱb, and 8 cases were type 0-Ⅲ. In terms of invasion depth, 17 cases were mucosal cancer, 23 cases had submucosal invasion less than 500 μm, and 33 cases had submucosal invasion more than 500 μm. In terms of vascular and lymphatic invasion, 8 cases had lymphatic vessel invasion and 8 cases had venous invasion. Among the 73 patients, 4 were diagnosed as having eCura A, 5 as eCuraB, 4 as eCura C1, and 60 as eCura C2. Among the 60 patients diagnosed as having eCura C2, only 2 cases (3.3%) were found to have lymph node metastasis around the stomach based on postoperative pathological evaluation. Among the 73 endoscopic specimens, 7 patients had positive horizontal margins, 21 had positive vertical margins, and 2 had positive margins in both directions, totaling 30 patients with positive horizontal or vertical margins. According to postoperative pathological evaluation, 9 cases (30.0%) had residual tumors in the original site. Among the 73 patients, 5 were lost to follow-up and 4 died, resulting in an overall survival rate of 94.12% (64/68) and disease-specific survival rate of 98.53% (67/68). The follow-up time of patients was 61.37 (10-166) months.Conclusion:For early gastric cancer patients with eCura C2 following non-curative endoscopic resection, additional surgery is feasible. However, the proportion of patients with actual lymph node metastasis is relatively low.

Liver targeting of compound liposomes mediated by glycyrrhetinic acid derivative receptor and its effect on hepatic stellate cells / 中国中药杂志

The 3-succinate-30-stearyl glycyrrhetinic acid(18-GA-Suc) was inserted into glycyrrhetinic acid(GA)-tanshinone Ⅱ_A(TSN)-salvianolic acid B(Sal B) liposome(GTS-lip) to prepare liver targeting compound liposome(Suc-GTS-lip) mediated by GA receptors. Next, pharmacokinetics and tissue distribution of Suc-GTS-lip and GTS-lip were compared by UPLC, and in vivo imaging tracking of Suc-GTS-lip was conducted. The authors investigated the effect of Suc-GTS-lip on the proliferation inhibition of hepatic stellate cells(HSC) and explored their molecular mechanism of improving liver fibrosis. Pharmacokinetic results showed that the AUC_(Sal B) decreased from(636.06±27.73) μg·h·mL~(-1) to(550.39±12.34) μg·h·mL~(-1), and the AUC_(TSN) decreased from(1.08±0.72) μg·h·mL~(-1) to(0.65±0.04) μg·h·mL~(-1), but the AUC_(GA) increased from(43.64±3.10) μg·h·mL~(-1) to(96.21±3.75) μg·h·mL~(-1). The results of tissue distribution showed that the AUC_(Sal B) and C_(max) of Sal B in the liver of the Suc-GTS-lip group were 10.21 and 4.44 times those of the GTS-lip group, respectively. The liver targeting efficiency of Sal B, TSN, and GA in the Suc-GTS-lip group was 40.66%, 3.06%, and 22.08%, respectively. In vivo imaging studies showed that the modified liposomes tended to accumulate in the liver. MTT results showed that Suc-GTS-lip could significantly inhibit the proliferation of HSC, and RT-PCR results showed that the expression of MMP-1 was significantly increased in all groups, but that of TIMP-1 and TIMP-2 was significantly decreased. The mRNA expressions of collagen-I and collagen-Ⅲ were significantly decreased in all groups. The experimental results showed that Suc-GTS-lip had liver targeting, and it could inhibit the proliferation of HSC and induce their apoptosis, which provided the experimental basis for the targeted treatment of liver fibrosis by Suc-GTS-lip.

Heme peroxidases are responsible for the dehydrogenation and oxidation metabolism of harmaline into harmine / 中国天然药物

Harmaline and harmine are β-carboline alkaloids with effective pharmacological effects. Harmaline can be transformed into harmine after oral administration. However, enzymes involved in the metabolic pathway remain unclear. In this study, harmaline was incubated with rat liver microsomes (RLM), rat brain microsomes (RBM), blood, plasma, broken blood cells, and heme peroxidases including horseradish peroxidase (HRP), lactoperoxidase (LPO), and myeloperoxidase (MPO). The production of harmine was determined by a validated UPLC-ESI-MS/MS method. Results showed that heme peroxidases catalyzed the oxidative dehydrogenation of harmaline. All the reactions were in accordance with the Hill equation. The reaction was inhibited by ascorbic acid and excess H2O2. The transformation of harmaline to harmine was confirmed after incubation with blood, plasma, and broken blood cells, rather than RLM and RBM. Harmaline was incubated with blood, plasma, and broken cells liquid for 3 h, and the formation of harmine became stable. Results indicated an integrated metabolic pathway of harmaline, which will lay foundation for the oxidation reaction of dihydro-β-carboline. Moreover, the metabolic stability of harmaline in blood should not be ignored when the pharmacokinetics study of harmaline is carried out.

Forensic Analysis of 6 Cases of Sudden Death due to Hyperthyroid Heart Disease / 法医学杂志

Objective To analyse the cases of sudden death due to hyperthyroid heart disease,and explore the general information of deaths and the forensic pathological characteristics to provide reference evidence for forensic identification of such cases.Methods Six cases of sudden death due to hyperthyroid heart disease between 2001 and 2016 were selected from School of Forensic Medicine,China Medical University.The general information (gender and age),clinical manifestations,medical history,anatomical and histopathological findings,biochemical parameters and cause of death were analysed retrospectively.Results Most of the 6 patients had definite history of hyperthyroidism,and they all showed certain degrees of symptoms of cardiovascular disease;had obvious incentive factors of death;histopathological examination of thyroid conformed to the performances of diffuse toxic goiter;with increase of cardiac weight,dilatation of cardiac chambers,myocardial hypertrophy and focal necrosis;postmortem biochemical analyses of pericardial fluid could be used as an additional method for diagnostic of sudden death due to hyperthyroid heart disease.Conclusion The identification of death due to hyperthyroid heart disease should be based on the clinical history and the results of autopsy,histopathological examination,postmortem toxicology tests.The postmortem biochemical detection of thyroid and cardiac function should be performed if necessary.

Development and characterization of a stable cell line expressing respiratory syncytial virus non-structural protein NS1 / 病毒学报

To develop a stable cell line that could express the RSV NS1, the full-length RSV NS1 gene was generated by RT-PCR amplification from respiratory syncytial virus. NS1 gene was ligated with pBABE-puro to construct the recombinant retroviral expression plasmid pBABE-NS1, which was cotransfected into 293FT packaging cells with PIK packaging plasmid by calcium phosphate co-precipitation. The supernatant of 293FT was collected to infect HEp-2 cells, the resulting cell clones stably expressing NS1 were screened by puromycin. Using QPCR, CPE staining method and indirect immunofluorescence assay, the expression of NS1 at both gene and protein levels was identified. The recombinant plasmid pBABE-NS1 was identified by EcoRI and BamHI endonuclease digestion and the sequence analysis. QPCR results showed that the NS1 gene amplification in HEp-2-NS1 cells was 8483 fold higher than that in HEp-2 cells. Although the exogenous interferon was added, all cells were destroyed after 48 hours post infection using CPE staining method, showing that HEp-2-NS1 cells remained sensitive to the VSV virus. The results of RT-PCR and indirect immunofluorescence assay showed that the NS1 gene in HEp-2 cells could not only transcribe mRNA, but also express NS1 protein steadily. We had successfully established HEp-2-NS1 cell lines with stable expression of respiratory syncytial virus non-structural protein NS1.

The effects of a hot water soluble extract (S-03) isolated from Isatis indigotica root on influenza A and B viruses in vitro / 病毒学报

This study was to investigate the antiviral effects of a hot water soluble extract S-03 isolated from Isatis indigotica root on different subtypes of influenza A and B viruses in MDCK cell cultures, using plaque reduction, immunofluorescence and hemo-agglutination inhibition (HAD) assays. Chemical analysis of the extract S-03 showed that it contained high proportion of polysaccharides. The antiviral effects in vitro showed that the S-03 had no effect on different influenza viruses if the drug was used before virus adsorption, but S-03 showed obvious activities against influenza viruses if treatment after virus adsorption or direct reaction of drug and virus before virus adsorption. Hemagglutination inhibition assay showed that S-03 inhibited HA activities of different human influenza viruses (inhibition concentration ranged from 3.12 to 25 mg/mL), avain influenza viruses (inhibition concentration ranged from 25 to 50 mg/mL). The antiviral effects of S-03 on different influenza A and B viruses in vitro might be through the inhibition of the HA to prevent infection.