The National Institute for Health and Care Excellence(NICE)first updated its 2013 Health Technology Evaluations Guidelines in 2022,followed by further minor adjustments in 2023.This round of updates primarily focuses on five key areas:mea-suring the value of health technologies,understanding and improving the evidence base,structured decision-making,addressing challenging diseases and technologies,and ensuring consistency in methods across evaluation and review projects.It outlines the up-date process and major changes,providing an analysis of these key points with the aim of offering valuable insights and methodologi-cal references for health technology assessment in China.

Geminiviruses cause substantial crop yield losses worldwide. The replication initiator protein (Rep) encoded by geminiviruses is indispensable for geminiviral replication. The Rep protein encoded by beet severe curly top virus (BSCTV, genus Curtovirus, family Geminiviridae) induces VARIANT IN METHYLATION 5 (VIM5) expression in Arabidopsis leaves upon BSCTV infection. VIM5 functions as a ubiquitination-related E3 ligase to promote the proteasomal degradation of methyltransferases, resulting in reduction of methylation levels in the BSCTV C2-3 promoter. However, the specific domains of Rep responsible for VIM5 induction remain poorly characterized. Although Rep proteins from several geminiviruses act as viral suppressors of RNA silencing (VSRs), whether BSCTV Rep also possesses VSR activity remains to be illustrated. In this study, we employed a transient expression system in the 16c-GFP transgenic and the wild-type Nicotiana benthamiana plants to analyze the VSR and the VIM5-inducing activities of different truncated Rep proteins haboring distinct domains. We found that the N-terminal domain (amino acids 1-180) of Rep suppressed GFP silencing in 16c-GFP transgenic N. benthamiana leaves. The minimal N-terminal fragment (amino acids 1-104) induced VIM5 expression upon co-infiltration, while C-terminal truncations lacked VIM5-inducing activity. Our results indicate that the N-terminal domain of Rep encoded by BSCTV mediates the suppression of RNA silencing and induces VIM5 expression. Thus, our findings contribute to a better understanding of interactions between geminiviral Rep and plant hosts.
Geminiviridae/genetics* ; Nicotiana/metabolism* ; Arabidopsis/metabolism* ; RNA Interference ; Viral Proteins/metabolism* ; Arabidopsis Proteins/metabolism* ; Plants, Genetically Modified/metabolism* ; Protein Domains ; Plant Diseases/virology* ; Methyltransferases/metabolism* ; Ubiquitin-Protein Ligases/metabolism* ; DNA Helicases/genetics*

The National Institute for Health and Care Excellence(NICE)first updated its 2013 Health Technology Evaluations Guidelines in 2022,followed by further minor adjustments in 2023.This round of updates primarily focuses on five key areas:mea-suring the value of health technologies,understanding and improving the evidence base,structured decision-making,addressing challenging diseases and technologies,and ensuring consistency in methods across evaluation and review projects.It outlines the up-date process and major changes,providing an analysis of these key points with the aim of offering valuable insights and methodologi-cal references for health technology assessment in China.

Background: The incidence rate and mortality of colorectal cancer (CRC) in China are increasing, and the age of onset is tending to be younger. Aims: To analyze the results of colonoscopy in patients positive for CRC screening, and to explore the significance of a CRC screening protocol that combines risk assessment questionnaire with fecal occult blood test (FOBT) in early diagnosis of colorectal neoplasms. Methods: Individuals who were positive for the first stage of screening (questionnaire + FOBT) in a community CRC screening program in Shanghai Huangpu District from May 2013 to October 2019 and then received the second stage of screening (colonoscopy) in Ruijin Hospital Luwan Branch were enrolled consecutively. Biopsy or polypectomy specimens were taken for pathological examination if any lesions were found endoscopically. Patients who underwent colonoscopy due to changes in bowel habits in the same period were served as controls. The detection rates of colorectal neoplasms in these two groups and the disease characteristics in the screening positive group were analyzed. Results: The screening positive group included 1 329 residents positive for the first stage of screening. The overall detection rate of colorectal lesions was 63.3%, and the detection rates of CRC, colorectal polyps and adenomatous polyps were 2.6% (34 cases), 60.7% (807 cases) and 35.2% (468 cases), respectively. While in control group (n=22 438), the rates were 43.6%, 1.8%, 41.5%, and 21.6%, respectively, all were significantly lower than those in screening positive group (all P<0.05). In screening positive group, the overall detection rate of colorectal lesions was higher in male than in female (73.7% vs. 54.2%, P<0.05) and increased with aging (P<0.05). Most of the CRC cases were in 60-79 years old age group with no gender difference. All CRC and most of the adenomas with dysplasia were greater than or equal to 1 cm in diameter, while most of the adenomas without dysplasia, hyperplastic polyps and inflammatory polyps were less than 1 cm in diameter. Conclusions: The community CRC screening program practiced in China can increase the detection rates of CRC and precancerous lesions effectively.

Objective:To investigate the mechanisms of interleukin-17A (IL-17A) regulating the expressions of IL-1β and IL-23 in mouse keratinocytes (KCs).Methods:Primary KCs were isolated from the skin of 400 newborn male and female wild type C57BL/6 mice and cultured in 24-well plates with Roswell Park Memorial Institute 1640 medium containing fetal bovine serum in the volume fraction of 10% for the following experiments. (1) The cells were divided into phosphate buffer solution (PBS) control group and IL-17A stimulation group according to the random number table (the same grouping method below), which were cultured with 10 μL PBS or 10 μL IL-17A in the mass concentration of 100 ng/mL for 6 hours, respectively. The expression levels of IL-1β and IL-23 mRNA in cells were detected by real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-PCR), with 3 samples in each group. (2) The cells were divided into dimethyl sulfoxide (DMSO) control group, IL-17A+ DMSO group, IL-17A+ nuclear factor κB (NF-κB) inhibitor group, IL-17A+ signal transduction and activator of transcription 3 (STAT3) inhibitor group, IL-17A+ extracellular signal-regulated kinase 1 (ERK1) inhibitor group, IL-17A+ ERK2 inhibitor group, and IL-17A+ c-Jun N-terminal kinase (JNK) inhibitor group. The reagents were added to cells in corresponding groups respectively and cultured for 6 hours. The volume of each reagent was 10 μL, the mass concentration of IL-17A was 100 ng/mL, and the molarity concentrations of NF-κB, STAT3, ERK1, ERK2, JNK signal pathway inhibitors PDTC, S3I-201, SCH772984, SCH772984, SP600125 were 5 μmol/L, 100 μmol/L, 4 nmol/L, 1 nmol/L, and 10 μmol/L, respectively. The expression levels of IL-1β mRNA and IL-23 mRNA in cells were detected by real-time fluorescence quantitative RT-PCR, with 3 samples in each group. (3) The cells were grouped and treated the same as those in experiment (1). The levels of NF-κB phosphorylation, STAT3 phosphorylation, ERK phosphorylation, and JNK phosphorylation were detected by Western blotting, with 3 samples in each group. Data were statistically analyzed with two-tailed Student t test, one-way analysis of variance, t test, and Bonferroni correction. Results:(1) After culture of 6 hours, compared with those in PBS control group, the expression levels of IL-1β and IL-23 mRNA in cells in IL-17A stimulation group were significantly increased ( t=13.46, 6.72, P<0.01). (2) After culture of 6 hours, the expression levels of IL-1β and IL-23 mRNA in cells in DMSO control group, IL-17A+ DMSO group, IL-17A+ NF-κB inhibitor group, IL-17A+ STAT3 inhibitor group, IL-17A+ ERK1 inhibitor group, IL-17A+ ERK2 inhibitor group, and IL-17A+ JNK inhibitor group were 1.00±0.11, 4.01±0.32, 0.32±0.06, 1.76±0.43, 3.62±0.24, 3.80±0.43, 4.26±0.74 and 1.03±0.29, 4.08±0.34, 4.76±0.38, 4.70±0.21, 1.06±0.42, 0.92±0.21, 0.39±0.05, respectively. Compared with those in DMSO control group, the expression levels of IL-1β and IL-23 mRNA in cells in IL-17A+ DMSO group were significantly increased ( t=9.24, 12.60, P<0.01). Compared with that in IL-17A+ DMSO group, the expression level of IL-1β mRNA was significantly decreased in cells in IL-17A+ NF-κB inhibitor group and IL-17A+ STAT3 inhibitor group ( t=11.34, 6.91, P<0.01). Compared with that in IL-17A+ DMSO group, the expression level of IL-23 mRNA was significantly decreased in cells in IL-17A+ ERK1 inhibitor group, IL-17A+ ERK2 inhibitor group, and IL-17A+ JNK inhibitor group ( t=12.44, 13.03, 15.21, P<0.01). (3) After culture of 6 hours, compared with those in PBS control group, the levels of NF-κB phosphorylation, STAT3 phosphorylation, ERK phosphorylation, and JNK phosphorylation in cells in IL-17A stimulation group were significantly increased. Conclusions:IL-17A promotes the transcription of IL-1β in mouse KCs through the phosphorylation of NF-κB and STAT3 pathways and IL-23 through the phosphorylation of ERK and JNK pathways.

The course evaluation scheme oriented ability cultivation was established. The for-mative evaluation indexes which were practiced in information retrieval course were divided into two indicators:classroom learning and performance including five secondary indexes(classroom discipline, classroom learning, homework, questions and answer questions online, personal essay and group dis-cussion reports) with the and seven observation points(pre-class preparation, teacher-student interac-tions, classroom discussions and classroom reports, experimental class performance, homework com-pletion, the utilization of network teaching platform, personal essay and group discussion), and these were practiced in the teaching of “information retrieval” curriculum, the usual results was composed with the usual academic performance and utilization of the network teaching platform. Finally, the practice results were discussed and summarized in order to cultivate the ability of the students who major in information management and to improve the teaching quality.

Objective To explore the peripheral blood microRNA (miRNA) expression of patients with gastric cancer,and to establish specific peripheral blood miRNA expression profile of gastric cancer,which would provide the evidencc for investigating the role of miRNA in the genesis and development of gastric cancer and looking for new molecular markers of gastric cancer.MethodsA total of 6 gastric cancer patients and 6 healthy volunteers were selected.The totat RNA of peripheral blood was extracted for miRNA expression profile examination and hioinformation analysis. The results of microarray were verified by real-time PCR. The online miRNA target gene pr(e)diction software was used to predict and screen miRNA differentially expressed target genes. Results Compared with control group,there were 54 differentially expressed miRNA in gastric cancer group,of which the expression of 35 miRNA (miRNA-504,mi RNA-183,miRNA- 938,miRNA-1285,miRNA- 576-3p,miRNA-663,etc) were up-regulated and 19 miRNA (miRNA-433,miRNA-193b,miRNA-329,miRNA 409-3p,miRNA 154,el(e)) were down-regulated.The results of real-time PCR indicated that there was a good consistency between PCR verificd results and microarray results in 2 up-regulated miRNA (miRNA 504 and miRNA-183) and 2 down-regulated miRNA (miRNA-443 and miRNA- 193b).ConclusionThere is specific peripheral blood miRNA expression profile of patients with gastric cancer,and these differentially cxpressed miRNA will likely become new diagnostic biomarkers of gastric cancer.

Gastric precancerous lesion refers to epithelial dysplasia(atypical hyperplasia or intraepithelial neoplasias),which is associated with increased risk of gastric cancer.It happens to be controlled by multiple factors and/or polygene such as the H.pylori infection,diet and environment which play an important role in the development of gastric precancerous lesions.This article describes the pathogenesis of gastric precancerous lesions as many scholars have studied some of it.

Objective To investigate the effects of ginsenoside Rg3 on growth and apoptosis of gastric cancer cell line MKN-45 and SGC-7901 in vitro. Methods MKN-45 and SGC-7901 cells at logarithmic growth phase were obtained, and were cultured with ginsenoside Rg3 of different concentrations (20, 30, 40, 50 μg/mL) for 24, 48 h or 24, 48 and 72 h. Cells cultured without ginsenoside Rg3 were served as controls. The inhibition rates of ginsenoside Rg3 on MKN-45 and SGC-7901 cells were detected by MTT assay, apoptosis rate of SGC-7901 cells was determined by Annexin V/PI double staining flow cytometry, cell cycles of SGC-7901 cells were analysed by flow cytometry, and morphological changes of SGC-7901 cells in 50 μg/mL ginsenoside Rg3 treatment group were observed by transmission electron microscopy. Results The inhibition rates on MKN-45 and SGC-7901 cells in each ginsenoside Rg3 treatment group were significantly higher than those in control group (P < 0.05), and the inhibition rates increased with the concentrations of ginsenoside Rg3 and time of culture ( P < 0.05). Compared with control group, the apoptosis rates of SGC-7901 cells and percentages of cells in G_1/G_1 cell cycle in each ginsenoside Rg3 treatment group were significantly increased in a concentration and time dependent manner. Typical morphology of SGC-7901 cell apoptosis was observed by transmission electron microscopy in 50 μg/mL ginsenoside Rg3 treatment group. Conclusion Ginsenoside Rg3 has significant inhibition effect on gastric cancer cell lines in vitro with a concentration and time dependent manner, the mechanism of which may involve the induction of gastric cell line apoptosis.

Objective To study the effects of matrine in combination with 5-fluorouracil (5-FU) on inhibiting transplanted gastric cancer (cell line SGC-7901) in the nude mice and their myelotoxicity effects. Methods The two dosages of matrine (50 mg/kg and 100 mg/kg) combined respectively with 50 mg/kg of 5-fluorouracil (5-FU) were injected intra-abdominally, and 50 mg/kg or 100 mg/kg matrine or 5-FU injection alone groups served as controls. The relative tumor volume (RTV) and tumor inhibition rate (IR) were calculated. The nude mice bone marrow was taken, the number of the nucleated cells were calculated, and bone marrow colony was cultured. Results The tumor-inhibiting effect in the combined group of 100 mg/kg of matrine +50 mg/kg of 5-FU was significantly increased as compared with those in all the control group ( P