Shuying Li

Objective: To investigate the effects of earthworm fibrinolytic enzyme (EFE) on proliferation, migration, and apoptosis of Caski cells. Methods: A visual analysis was conducted based on CiteSpace and VOSviewer using 257 studies related to EFE. The optimum concentration of EFE on Caski cells was screened by CCK-8 assay in vitro. The effects of EFE on Caski cell migration, tumorigenicity, protein expression, and apoptosis were determined by cell scratch assay, soft AGAR cloning assay, immunohistochemistry, and flow cytometry. Results: The antitumor activity of EFE has been a hot topic in recent years. EFE significantly inhibited the proliferation of Caski cells compared with the control group, and the difference was statistically significant ( P < .0001). The scratch distance of low, medium, and high concentration cells was significantly increased compared with the control group in the cell scratch test, and showed a certain concentration dependence, and the difference was statistically significant ( P < .05). The results of soft AGAR cloning showed that tumorigenicity of low, medium, and high concentration was significantly decreased compared with control group, and the difference was statistically significant ( P < .001). Immunohistochemical assay showed that the positive rate of low, medium, and high concentration decreased significantly compared with the control group, and the expression of protein was downregulated. Flow cytometry showed that low, medium, and high concentration promoted apoptosis compared with the control group, and the difference was statistically significant ( P < .01). Conclusion: EFE can inhibit the proliferation and migration of Caski cells and promote cell apoptosis.

Human papillomavirus (HPV) is a double-stranded circular DNA virus with a genome of approximately 7–8 kb. This study aimed to establish an overlapping extension polymerase chain reaction method for the amplification of the entire genome of HPV16.

Persistent human papillomavirus (HPV) infection drives cervical carcinogenesis, yet regional variations in genotype distribution and viral load dynamics remain understudied in Beijing, China. This study investigated HPV prevalence, genotype‐specific patterns, and viral load correlations with cervical disease severity among women outpatient clinics from Peking University First Hospital in Beijing. In a retrospective study of 25 197 women undergoing cervical ThinPrep cytology (TCT) and HPV testing from October 2023 to October 2024, colposcopy results from 714 cases were also analyzed. HPV genotyping and quantitative for HPV types (16, 18, 33, 52, 58) were performed. Overall HPV positivity was 16.50% (4157/25 197), peaking in women aged 31~40 years (30.05%). Dominant genotypes were HPV 52 (18.89%), 16 (18.55%), and 58 (12.10%). HR‐HPV prevalence and viral load escalated with disease severity (p < 0.001), notably HPV16 and HPV33. HPV11, 43, 45, and 68 were absent in severe lesions. Single infections (76.35%) predominated, but multi‐infections showed genotype synergism (e.g., HPV51 + 42). The study highlights specific HPV epidemiology and genotype dominance in China, indicating gaps in vaccine coverage. Viral load is a key biomarker for risk assessment, suggesting the need for tailored vaccination programs and viral load monitoring in clinical practice.

Considering the absence of a widely utilized EBV vaccine, we have developed an EBV gL-gH344-Ferritin nanoparticle vaccine utilizing ferritin as a carrier. The gL-gH344-Ferritin fusion gene was synthesized and inserted into the pET30a plasmid. The expression of the fusion protein in the recombinant plasmid was verified by Western blot. Then, the gL-gH344-Ferritin subunit nanoparticle vaccine was obtained by purification of the fusion protein. BALB/c mice were immunized using a two-dose protocol. The titers of EBV specific antibodies were determined using enzyme-linked immunosorbent assay at 4, 8, and 12 weeks after the initial immunization. Moreover, the levels of EBV gL-gH344 specific splenocytes secreting interferon (IFN)-γ and interleukin (IL)-6 were determined using an enzyme-linked immunospot assay. The pET30a-gL-gH344-Ferritin prokaryotic expression plasmid was successfully constructed. gL-gH344-Ferritin was efficiently expressed in E. coli. Following immunization with gL-gH344-Ferritin, the mice sera demonstrated elevated titers of EBV specific immunoglobulin G. Moreover, after stimulating with EBV gL-gH344 specific peptides, the splenocytes of the immunized mice showed a marked tendency to secrete large amounts of IFN-γ and IL-6. The gL-gH344-Ferritin nanoparticle vaccine carrying the EBV gL-gH344 fusion protein induced robust and sustained specific humoral and cellular immune responses in mice.

Objective: To investigate the epidemiological characteristics and genetic profile of human bocavirus (HBoV) among patients with acute respiratory infection (ARI) in Yucheng, Henan, China.Methods: A total of 1,153 throat swabs were collected from ARI patients between March and June 2023. These samples were tested for 18 pathogens using quantitative chain reaction (qPCR). The VP1 gene were amplified and sequenced from HBoV-positive samples. The viral genetic characterization was analyzed by comparing the HBoV1 sequences with reference sequences.Results: Of the 1,153 samples, the detection rate of HBoV positive was 6.85%, primarily detected in May 2023. The majority of HBoV positive cases were found in children under 5 years old. Clinical manifestations in HBoV-positive patients predominantly were fever and cough, with a clinical diagnosis of lower respiratory tract infection. Other viruses were also detected in 20% of HBoV-positive samples. All HBoV sequences identified in this study belonged to HBoV1, with the Ib sublineage being the predominant strain circulating in Yucheng during March–June 2023.Conclusion: After the implementation of the optimized COVID-19 prevention and control strategy in December 2022, HBoV infection was prevalent in Yucheng, Henan in May-June 2023, mainly among children younger than 5 years old, especially those under 2 years old. The Ib sublineage of HBoV was the dominant circulating strain in Yucheng, Henan during March–June 2023.

In recent years, it has been found that Lycium barbarum can repair liver damage and promote liver regeneration. Additionally, the polysaccharides contained in Lycium barbarum have anticancer properties and can induce apoptosis in cancer cells. Molecular docking, a mature computer-aided method, is widely used in drug discovery. This study aimed to verify the efficacy of active ingredients of Lycium barbarum in the treatment of liver cancer by molecular docking.

Background Tumor is a new organism formed by abnormal hyperplasia of local tissue cells under the action of various tumorigenic factors. Inflammation plays a decisive role in inducing tumorigenesis, promoting tumor development, invasion and migration. More and more evidence indicate that exosomes are involved in regulating the formation of tumor microenvironment in the process of proinflammatory carcinogenesis, leading to the stimulation of anti-tumor immune response or systemic immunosuppression, and exosomes play a crucial role in the development of tumor. Methods The articles on tumor-derived exosomes and inflammatory responses from January 2005 to January 2024 were collected through Web of Science (WOS), and the inclusion criteria were “Article”, “Review Article” and “Early Access”. Articles obtained after excluding “Book Chapters”, “Editorial Material”, “Proceeding Paper”, “Meeting Abstract” and “Retracted Publication”. Bibliometrics and visualization analysis were carried out on the obtained articles using CiteSpace6.2.R6 and VOSviewer1.6.20. Results Total of 703 articles were included. The number of published documents showed a fluctuating growth trend year by year. A total of 61 countries have participated in the research on the effects of exosomes and inflammatory responses on tumors, among which China and the United States have the largest influence in this field. The obtained articles have been published in 60 journals around the world, among which PLOS ONE and NAT REV IMMUNOL are the journals with the most published articles and the highest co-citations respectively. The article from French author THERY C was cited the most (202 times). As a major researcher on the basic function of exosomes, THERY C established the gold standard for extraction, separation and identification of exosomes, and found that exosomes promote tumor metastasis through direct regulation of miRNA. Her research has had a huge impact on the field. Keyword co-occurrence analysis indicate that extracellular vesicles, inflammation, cancer, miRNAs, mesenchymal stem cells, drug delivery, gastric cancer and circulating endothelial microparticles are the research hotspot at present stage. The main keywords of the cluster analysis show that extracellular vesicles, human papilloma virus, myeloid cells, tumor macro-environment are the current research hotspots and frontier. The research hotspots have developed over time from the time chart of keywords and clustering, especially after 2016, exosomes have established extensive links with drug delivery, cancer treatment, inflammatory response and other fields. Tumor-derived exosomes stimulate receptor cells to secrete pro-inflammatory cytokines and growth factors, enabling immune and inflammatory cells to perceive the intracellular environment of cancer cells even when cancer cells do not express any tumor-specific antigens. For example, in anoxic environment, cancer cells can secrete exosomes containing pro-inflammatory factors to promote the invasion and metastasis of cancer cells. In the complex tumor microenvironment, both tumor cells and various stromal cells will secrete specific exosomes, and promote the development of tumors through various ways, so that tumor cells have drug resistance, and bring adverse effects on the clinical treatment of tumor patients. MicroRNAs and long noncoding RNA as hot keywords play important roles in regulating and mediating tumor development, and their specificity makes them important biomarkers for cancer prediction and diagnosis. Highlighting word analysis shows that microRNAs secreted by leukemia patients can effectively promote the proliferation of malignant cells and the development of cardiovascular diseases. At the same time, exosomes can induce the secretion of some microRNAs in patients, leading to cardiac repair and regeneration. Therefore, the detection and screening of microRNAs plays a crucial role in predicting the incidence of cardiovascular diseases in patients. Conclusion Exosomes have attracted increasing attention due to their significant heterogeneity and ability to regulate the tumor immune microenvironment. However, tumor cell-derived exosomes accelerate tumor progression by enhancing immunosuppression and inflammation, increasing oxidative stress, and promoting angiogenesis, which may lead to poor prognosis. Graphical abstract

Objective: To comprehensively evaluate the association between Oral Squamous Cell Carcinoma (OSCC) and Human Papillomavirus (HPV) infection by Meta analysis. Methods: Using oral squamous cell carcinoma and human papillomavirus as search terms, full-text English literatures in PubMed and Web of Science were searched, and the collected data were analyzed statistically by using Review Manager and Stata MP 17.0. To investigate the etiological association between oral squamous cell carcinoma and human papillomavirus infection. Results: A total of 13 literatures were included according to the screening criteria, including 1026 patients with oral squamous cell carcinoma and 966 patients in the control group. Random effects model was used for meta-analysis based on heterogeneity test results. The results showed that the average HPV positive rate of patients with oral squamous cell carcinoma worldwide was 31.48%, OR: 3.58, 95%CI: 1. 98~6.50, Z test results showed a z value of 4.20, P<0.05, which indicated that the occurrence of oral squamous cell carcinoma is correlated with HPV. Subgroup analysis showed that gender, lymph node metastasis, degree of tumor differentiation, tumor grade, tumor site, and personal lifestyle (smoking and alcohol consumption) were not significantly associated with HPV infection in patients with oral squamous cell carcinoma, while location of patients was associated with HPV Infection. Publication bias estimation and sensitivity analysis showed no significant publication bias. Conclusion: Through a Meta analysis of HPV infection in patients with oral squamous cell carcinoma worldwide, it was found that the location of patients with oral squamous cell carcinoma was associated with HPV infection.

Objective: To analyze the infection status of human papillomavirus (HPV) in women after vaccination by meta-analysis. Methods: The PubMed, Wiley, science direct and web of science databases were searched by computer. The full-text English literatures published since the establishment of the database were collected with HPV and vaccination as key words. The literatures that met the inclusion criteria were selected and used RevMan5.3 analysis. Results: Nine literatures were included, and the number of researchers was 60570. The results showed that the protective effect of HPV16/18 and HPV31/33/45/52/58 related 6-month persistent infection in vaccinated women was higher than that in non vaccinated women, and the protective rate was 95% (RR: 0.05, 95% CI: 0.04 ~ 0.06). The protective effect of 12-month persistent infection related to any type of HPV in the experimental group was higher than that in the control group, and the protective rate was 96% (RR: 0.04, 95% CI: 0.03 ~ 0.06). The incidence of CIN1+ associated with HPV16/18 and (or) HPV6/11/16/18 decreased in women after vaccination in a protocol compliant population (PPE) (RR: 0.12, 95% CI: 0.06 ~ 0.22); The incidence rate of CIN2+ was lower than that of non vaccinated population (RR: 0.06, 95% CI: 0.02 ~ 0.18). The incidence of CIN1+ associated with HPV16/18 and (or) HPV6/11/16/18 in vaccinated women was lower than that in non vaccinated people in the modified intention to analyze population (mITT) (RR: 0.15, 95% CI: 0.07 ~ 0.31). The incidence rate of CIN2+ was lower than that of non vaccinated population (RR: 0.11, 95% CI: 0.04 ~ 0.34). The incidence of HPV6/11/16/18/31/33/45/52/58 related cervical lesions was lower than that of the control group, and the final combined effect value was RR = 0.02 (95% CI: 0.01 ~ 0.04). The incidence rate of hpv6/11/16/18/31/33/45/52/58 related vaginal and vulvar diseases of any grade and high grade was lower than that of the control group, and the final combined effect value was RR=0.06 (95% CI: 0.03 ~ 0.10). Conclusion: The protective effect of HPV vaccine against persistent HPV infection in women is higher, and the incidence rate of related cervical, vaginal and vulvar diseases is lower. Bivalent, tetravalent and ninvalent vaccines all show long-term protection.

Background/Aims: The study aimed to explore the effects of Epstein-Barr virus–-encoded BARF1 in human gastric epithelial cells (GES-1). Materials and Methods: A eukaryotic expression vector carrying BARF1 gene (pcDNA3.1-BARF1) was constructed. The pcDNA3.1-BARF1 was transfected into GES-1 cells, and they were selected by G418. The GES-1 cells lines that expressed BARF1 (GES-1-BARF1) were obtained. The cycle of GES-1-pcDNA3.1 cells (GES-1 cells transfected with empty vector), GES-1-BARF1 cells (GES-1 cells transfected with BARF1), and TPA-GES-1-BARF1(GES-1-BARF1 cells stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) were analyzed by flow cytometry. Colony formation in soft agar and tumorigenicity of the transfected cells in mice with severe combined immunodeficiency (SCID) were also observed. Results: The morphology of GES-1-BARF1 cells were changed from the original shuttle to round, the adhesion between the cells and bottle wall was weakened, and the cells showed overlapping growth. The proliferation rate of GES-1-BARF1 and TPA-GES-1-BARF1 cells were faster than GES-1 and GES-1-pcDNA3.1 cells; the S phase was significantly prolonged for GES-1-BARF1 and TPA-GES-1-BARF1. GES-1-BARF1 and TPA-GES-1-BARF1 cells formed colonies in soft agar, with a cloning rate of 24.2% (58/240) and 40.0% (96/240), respectively; GES-1 and GES-1-pcDNA3.1 cells did not form colonies in soft agar. Tumors were formed in mice with SCID after injecting TPA-GES-1-BARF1 cell groups. Tumor formation did not occur in mice with SCID after injecting GES-1 and GES-1-pcDNA3.1 cell groups, but nodules were formed in the mice with SCID after injecting GES-1-BARF1 cell groups. Conclusion: GES-1-BARF1 cells malignant transformation was induced by transfected BARF1 gene and TPA stimulation. This result indicated that tumor formation not only require oncogenes, but also the stimulation of cancer-promoting substance.