In 2014, The Cancer Genome Atlas firstly classified gastric cancer into four types according to genotype. Epstein-Barr virus (EBV) positive gastric cancer or EBV-associated gastric cancer (EBVaGC) is attracting attention because it is a possibly suitable group for immunotherapy. Among the mutations observed in tumors, such as gastric cancer, p53 mutations are the most frequent. In particular, it occurs more frequently in EBVaGC than in EBV-negative gastric cancer (EBVnGC). Meanwhile, EBV infection is considered as an early event of tumorigenesis. The interactions between wild-type p53 proteins and BZLF1 (Z) proteins are essential in maintaining the latent state of EBV infection and promoting early replication. In the latter stages of replication, wild-type p53 proteins are degraded through the ubiquitination of some viral molecules. These findings may indicate the importance of wild-type p53 genes in EBVaGC formation. Inflammatory responses induced by EBV infection, tumor with a large number of lymphocyte infiltration, genome high mutation, and PD-L1 amplification make it possible to become the appropriate group of immunotherapy, which also illustrate that the important role of immune microenvironment during tumor progression. In EBVnGC, extremely high levels of p53 mutation were observed because of several associated factors, and the p53 protein encoded by the mutant p53 gene lost its antitumor function after tumorigenesis. In this review, the possible mechanisms of rare p53 mutation in EBVaGC are summarized.

Objective To investigate the relationship between the expression of Toll-like receptor 4 (TLR4) on mononuclear cells in peripheral blood and changes of serum vitamin D level in children with bronchiolitis.Methods The children who were diagnosed as bronchiolitis and received treatment in the Second Affiliated Hospital of Harbin Medical University from October 2013 to January 2014 were chosen as the pre-treatment group,and then divided them into moderate group and severe group according to the clinical symptoms,20 cases for each group.Then the cases in pre-treatment group who recovered after treatment were recruited as the after-treatment group,and the children who were healthy and medical examination in the Second Affiliated Hospital of Harbin Medical University in the same period were recruited as the healthy control group.The expressions of TLR4 on CD14 labeled mononuclear cells in the periphera were measured by flow cytometry.The level of 25 (OH) D in serum was detected by enzyme linked immunosorbent assay (ELISA).Results (1) The expression level in children with bronchiolitis of TLR4:the mode-rate group [(18.98 ±2.29)％] and severe group [(30.13 ±2.13)％] increased significantly (P ＜0.05) compared with control group [(1.17 ± 0.57) ％].And the expression level of moderate group [(2.02 ± 0.48) ％] and severe group [(11.43 ± 1.52) ％] decreased significantly after treatment (P ＜0.05).(2) Serum vitamin D level in children with bronchiolitis of the moderate group[(17.16 ± 3.34) μg/L] and severe group [(6.56 ± 2.28) μg/L] were lower than healthy control group [(53.69 ± 20.18) μg/L] before treatment (P ＜ 0.05),especially the severe group [(6.56 ±2.28) μg/L].The level of moderate group [(9.59 ± 2.31) μg/L] and severe group [(4.70 ± 0.67) μg/L] became lower after treatment (P ＜ 0.05).(3) Both severe group (r =-0.491,P ＜ 0.05) before treatment and moderate group (r =-0.436,P ＜ 0.05) after treatment showed negative correlation between TLR4 on mononuclear cells in peripheral blood and serum 25 (OH)D level in children with bronchiolitis.And no correlation was found among healthy control group,moderate group before treatment and severe group after treatment (P ＞ 0.05).Conclusions The conditions of children with bronchiolitis was positively correlated with the expression level of TLR4,and negatively correlated with the vitamin D level.The serum 25 (OH) D decreased steadily during the treatment.The expression of TLR4 in monocytes has a certain correlation with the level of vitamin D in children with bronchiolitis.

Objective To confirm the diagnosis of a human case with atypical vivax-malaria from Yunnan Province by molecular technique. Methods DNA was extracted from blood films of unidentified sample, and of four known Plasmodium species (P. vivax, P. falciparum, P. knowlesi, and P. cynomolgi). A DNA-based diagnosis with the polymerase chain reaction (PCR) method targeting the small subunit ribosomal RNA (SSU rRNA) genes of genus- and species-specific (two human malaria species and P. knowlesi) was introduced. Results The PCR amplification with primer pair specific for P. knowlesi produced a single fragment of 150 bp. Sequence analysis showed that the amplified fragment was identical to the sequence of P. knowlesi. Conclusion The patient was naturally infected with P. knowlesi.

Objective: To explore the effect of the Epstein-Barr virus (EBV) BZLF1 gene on the biological behavior of EBV-negative gas-tric cancer cells and the underlying molecular mechanism. Methods: Lentiviral overexpressing BZLF1 was used to infect AGS and HGC27 gastric cancer cell lines. And the cell proliferation, apoptosis and migration invasive ability, and expression changes of cell sig-naling pathway were detected by CCK8 assay, apoptosis detection, migration and invasion assay, as well as western blot. HGC27 cells overexpressing BZLF1 were injected into the dorsal of NOD/SCID mice to construct xenografts, and the effect of BZLF1 on tumor growth was observed. Results: The expression of BZLF1 protein was significantly up-regulated in AGS-BZLF1 and HGC27-BZLF1 infected by over-expressing BZLF1 lentivirus. The cell proliferation in vitro and the tumorigenic ability in mice were significantly increased (P<0.05). Apoptosis was inhibited by BZLF1 protein, and the apoptotic rate of AGS-BZLF1 and HGC27-BZLF1 was (2.40±0.14)% and (3.90± 0.14)%, which was significantly lower than (5.75±0.35)% and (9.70 ± 0.42)% of AGS and HGC cells (P<0.05); however, there was no sig-nificant change in cell migration and invasion ability. In-depth molecular mechanism studies found that PI3K/AKT signaling pathway was significantly activated with enhanced pAKT and pS6 expression. After blocking the PI3K/AKT signaling pathway with BEZ235 inhibi-tor, the growth of HGC27-BZLF1 and AGS-BZLF1 cells was inhibited. Conclusions: EBV BZLF1 may promote the growth of gastric cancer cells by activating the PI3K/AKT signaling pathway and targeting PI3K/AKT pathway inhibitors, and serve as a promising treatment op-tion for EBV-associated gastric carcinoma.

Objective To evaluate the immunogenicity and safety of a split-virion influenza vac-cine after its manufacturing process was improved. Methods The immunological non-inferiority of trial to control vaccines was evaluated in 240 subjects aged 3-<18 years. Another 360 subjects aged 18-<60 years were randomly divided into three groups that were respectively given three consecutive lots of trail vaccine to assess the consistency of immunogenicity. Results There were 4. 17% of the subjects aged 3-<18 years showed adverse reactions following immunization with trail vaccine and it was not significantly different from that of the control group (P>0. 05). No significant difference in seroconversion rate, geometric mean titer (GMT) of haemagglutination inhibition antibodies(HIAb) or protection rate was found between trial and control groups (P>0. 05). No significant difference in seroconversion rate or HIAb GMT was found among the three lots (P>0. 05). Conclusion The trial influenza vaccine has good safety, immunogenicity and lot-to-lot consistency after the manufacturing process was improved.

Objective:To establish the normal values of water-perfused high resolution esophageal manometry (HREM)(GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing in Chinese population.Methods:From September 1, 2019 to June 30, 2020, 91 healthy volunteers receiving water-perfused HREM (GAP-36A) at resting period, water swallowing, semisolid swallowing and solid swallowing were selected from 9 hospitals (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; the First Affiliated Hospital of Dalian Medical University; the Second Hospital of Hebei Medical University; the Second Affiliated Hospital, Naval Medical University; the First Affiliated Hospital, Sun Yat-sen University; the First Affiliated Hospital, University of Science and Technology of China; Aviation General Hospital of China Medical University; the Affiliated Hospital of Medical School of Nanjing University and the First People′s Hospital of Yichang). Parameters included the position of the upper and lower edges of the upper esophageal sphincter (UES) and lower esophageal sphincter (LES), the length of the LES and UES, the position of the pressure inversion point (PIP), the resting pressure of UES and LES and swallow-related parameters such as the distal contraction integral (DCI), 4 s integrated relaxation pressure (IRP), distal latency (DL) and UES residual pressure. One-way analysis of variance, post-hoc test and sum rank test were used for statistical analysis.Results:A total of 87 healthy volunteers were enrolled, including 40 males and 47 females, aged (38.5±14.2) years old (ranged from 19 to 65 years old). The position of the upper and lower edges of the LES was (42.7±2.8) and (45.6±2.8) cm, respectively, the length of the LES was (2.9±0.4) cm, and the position of PIP was (43.3±2.8) cm. The position of the upper and lower edges of the UES was (18.1±3.0) and (22.6±2.0) cm, respectively, and the length of the UES was (4.8±1.0) cm. The resting pressure of LES and UES was (17.4±10.7) and (84.1±61.1) mmHg (1 mmHg=0.133 kPa), respectively. The DCI value at solid swallowing was higher than those at water swallowing and semisolid swallowing ((2 512.4±1 448.0) mmHg·s·cm vs. (2 183.2±1 441.2) and (2 150.8±1 244.8) mmHg·s·cm), and the differences were statistically significant ( t=-4.30 and -3.74, both P<0.001). The values of 4 s IRP at semisolid swallowing and solid swallowing were lower than that at water swallowing ((4.6±4.1) and (4.9±3.9) mmHg vs. (5.4±3.9) mmHg), and the differences were statistically significant ( t=3.38 and 2.09, P=0.001 and 0.037). The DL at water swallowing was shorter than those at semisolid swallowing and solid swallowing ((8.5±1.8) s vs. (9.8±2.2) and (10.6±2.8) s), and the DL at semisolid swallowing was shorter than that at solid swallowing, and the differences were statistically significant ( t=-10.21, -13.91 and -4.68, all P<0.001). The UES residual pressure at water swallowing was higher than those at semisolid swallowing and solid swallowing (9.5 mmHg, 6.5 to 12.3 mmHg vs. 8.0 mmHg, 4.5 to 11.7 mmHg and 5.5 mmHg, 2.0 to 9.3 mmHg), and the UES residual pressure at semisolid swallowing was higher than that at solid swallowing, and the differences were statistically significant ( t=3.48, 10.30 and 6.35, all P<0.001). Conclusions:The normal values of water-perfused HREM (GAP-36A) in Chinese population at resting period, water swallowing, semisolid swallowing and solid swallowing can provide a reference basis for clinical diagnosis and treatment for patients receiving water-perfused HREM examination.

Objective To evaluate the safety of a Chinese thimerosal-free trivalent split influenza virus vaccine after being marketed in a large population. Methods Through the information management system of adverse event following immunization (AEFI), the adverse events in healthy people aged 6 months and above who were vaccinated with split influenza virus vaccine in Hubei Province from October to December 2015 were collected. The data was analyzed by descriptive methodology. Results From October 1, 2015 to June 30, 2016, among the 227 920 people in Hubei Province who were vaccinated with split influenza virus vaccine, the common adverse reactions were mainly fever, redness, irritability, pain and itching. Four cases of AEFI were passively observed and reported in the system, with a reporting rate of 1.76/100 000, among which 3 cases were anaphylactic rash and 1 case was optic neuritis. Conclusion The Chinese thimerosal-free trivalent split influenza virus vaccine used in Hubei Province had a good safety record and is suitable for the general vaccination of people without vaccination contraindications.