Tegoprazan is a novel potassium-competitive acid blocker with long-lasting and potent acid-suppressing effects,showing favorable efficacy in many acid-related diseases.In eradicating Helicobacter pylori(Hp)infections,tegoprazan-based regimens are noninferior to proton pump inhibitor(PPI)regimens in terms of efficacy,and are well tolerated and safe.In this article,we review the pharmacological mechanism,clinical studies on Hp eradication regimens,and safety of tegoprazan to provide a reference for the selection of Hp e-radication regimens.

Objective To screen Coxsackievirus A16(CA16)vaccine candidate strains and provide preliminary basis for the development of vaccine against hand,foot and mouth disease(HFMD).Methods Cell inoculation and continuous passage were performed on the 35 clinical specimens of patients with hand,foot,and mouth disease from different areas of Kunming.The harvested solution with cytopathic effects was identified using CA16 standard serum.Positive samples were screened for vaccine strains through the virus titer determination,plaque purification,VP1 sequence homology and evolutionary analysis.Results Among the 35 collected clinical oropharyngeal swab samples,23 showed cellular lesions,and 10 were identified as CA16 virus by serology,with a positive rate of 43.5%.After the adaptive cultivation,the virus titers of 10 strains gradually increased,but stabilized at 7.0 lgCCID50 from 48 hours onwards.The plaque of the strain showed that all strains can form plaques of 0.2～0.8 cm,showing the regular differences,and the size of KM/M08 plaques was relatively uniform.All strains were B1b type,with nucleotide homology ranging from 93.3～100%.Among them,KM/M08 had the highest homology with other strains,ranging from 95.2～100%.Conclusion Through the analysis of virus proliferation kinetics curve,gene homology,and evolution,KM/M08 meets the expected screening criteria in all aspects of evaluation and is proposed as a vaccine candidate strain for further researches.

Objective To construct a uricase-deficient mouse model with stable inheritance using the CRISPR/Cas9 system,and evaluate its ability to simulate the disease characteristics of patients with hyperuricemia.Methods Double single guide RNAs(sgRNAs)were designed on both sides of exon 2～4 of the Uox gene.sgRNA and Cas9 mRNA for gene knockout were microinjected into the fertilized eggs of mice.After culture for 2～4 h,the embryos were transferred to surrogate mother mice to produce an F0 generation.Uox-knockout mice were identified by polymerase chain reaction and sequencing analysis.Positive mice were then mated with wild-type(WT)mice to produce an F1 generation,and heterozygous female and male F1 mice were then selected to obtain homozygous F2 mice.Serum and urine levels of uric acid,creatinine,and urea,and serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were detected and compared between homozygous and wild-type mice.Pathological changes in kidney and liver tissues were observed by hematoxylin and eosin and Masson staining.Results Urine levels of serum uric acid(male:(4116.8±1928.1)μmol/L,P＜0.001;female:(2998.0±547.7)μmol/L,P＜0.01)and serum levels of uric acid(male:(478.4±114.6)μmol/L,P＜0.001;female:(507.7±129.6)μmol/L,P＜0.001),creatinine((91.8±55.6)μmol/L,P＜0.001),urea((28.6±13.9)mmol/L,P＜0.05),ALT((53.3±23.3)U/L,P＜0.01),and AST((203.3±70.3)U/L,P＜0.001)were significantly increased in Uox-/-mice compared with WT mice.Histopathological examination showed moderate hepatocyte degeneration in the liver,moderate-to-severe tubular cystic dilation,degeneration,and fibrosis in the kidney,glomerular hypertrophy and hyperplasia,small-vessel dilation and congestion,and infiltration of stromal monocytes and lymphocytes in Uox-/-mice.Conclusions We successfully established a homozygous uricase-deficient mouse strain using CRISPR/Cas9 technology,as a suitable animal model for research in the field of hyperuricemia.

Objective To construct a uricase-deficient mouse model with stable inheritance using the CRISPR/Cas9 system,and evaluate its ability to simulate the disease characteristics of patients with hyperuricemia.Methods Double single guide RNAs(sgRNAs)were designed on both sides of exon 2～4 of the Uox gene.sgRNA and Cas9 mRNA for gene knockout were microinjected into the fertilized eggs of mice.After culture for 2～4 h,the embryos were transferred to surrogate mother mice to produce an F0 generation.Uox-knockout mice were identified by polymerase chain reaction and sequencing analysis.Positive mice were then mated with wild-type(WT)mice to produce an F1 generation,and heterozygous female and male F1 mice were then selected to obtain homozygous F2 mice.Serum and urine levels of uric acid,creatinine,and urea,and serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were detected and compared between homozygous and wild-type mice.Pathological changes in kidney and liver tissues were observed by hematoxylin and eosin and Masson staining.Results Urine levels of serum uric acid(male:(4116.8±1928.1)μmol/L,P＜0.001;female:(2998.0±547.7)μmol/L,P＜0.01)and serum levels of uric acid(male:(478.4±114.6)μmol/L,P＜0.001;female:(507.7±129.6)μmol/L,P＜0.001),creatinine((91.8±55.6)μmol/L,P＜0.001),urea((28.6±13.9)mmol/L,P＜0.05),ALT((53.3±23.3)U/L,P＜0.01),and AST((203.3±70.3)U/L,P＜0.001)were significantly increased in Uox-/-mice compared with WT mice.Histopathological examination showed moderate hepatocyte degeneration in the liver,moderate-to-severe tubular cystic dilation,degeneration,and fibrosis in the kidney,glomerular hypertrophy and hyperplasia,small-vessel dilation and congestion,and infiltration of stromal monocytes and lymphocytes in Uox-/-mice.Conclusions We successfully established a homozygous uricase-deficient mouse strain using CRISPR/Cas9 technology,as a suitable animal model for research in the field of hyperuricemia.

Humans ; Early Detection of Cancer ; Endoscopy ; Esophageal Neoplasms/epidemiology* ; Risk Factors ; Mass Screening

Non-human primates(NHP)are becoming increasingly important laboratory animals,especially in the field of neuroscience,where many significant breakthroughs have been made,including research on brain development,neurodegenerative diseases,and psychiatric disorders.However,as their breeding and use grows,biosafety and animal ethics issues should be considered.This review summarizes the application and challenges of NHP laboratory animals in the neuroscience field from the aspects of an NHP overview,feeding and operation,biosafety,and animal ethics.

Objective To establish a human α-synuclein nuclear localization signal transgenic mouse model and investigate the effects of α-synuclein nuclear localization on the behavior of mice.Methods Human α-synuclein nuclear localization signal and EGFP lentiviral vectors were constructed.Transgenic mice were created with the microinjection method.Using PCR and Western Blot method to identify the genotypes and protein expression of the transgenic founder mice and their offsprings.The immunofluorescence was used to examine the localization of human α-synuclein in the mouse brain tissue.The behavioral changes of the transgenic mice were evaluated by the open field test,rotarod test,and O maze test.Results The h SNCA-NLS gene was successfully inserted into the mouse genome,the human α-syn was successfully expressed,and the human α-syn has localized with the nuclear.Further studies found that human α-synuclein nuclear localization signal transgenic mice had significant motor dysfunction,astrocyte proliferation and inflammatory response at 2 months of age and exhibited significant anxiety-like symptoms and reduced expression of the γ-aminobutyric acid(GABA)gene at 9 months of age,which persisted until 12 months of age.Conclusions A human α-synuclein nuclear localization signal transgenic mouse model has been successfully established.The mice exhibit significant motor dysfunction and anxiety-like symptoms.The successful establishment of this model provides a foundation for studying the role of α-syn nuclear localization in Parkinson's disease.

Endometriosis, a heterogeneous, inflammatory, and estrogen-dependent gynecological disease defined by the presence and growth of endometrial tissues outside the lining of the uterus, affects approximately 5-10% of reproductive-age women, causing chronic pelvic pain and reduced fertility. Although the etiology of endometriosis is still elusive, emerging evidence supports the idea that immune dysregulation can promote the survival and growth of retrograde endometrial debris. Peritoneal macrophages and natural killer (NK) cells exhibit deficient cytotoxicity in the endometriotic microenvironment, leading to inefficient eradication of refluxed endometrial fragments. In addition, the imbalance of T-cell subtypes results in aberrant cytokine production and chronic inflammation, which contribute to endometriosis development. Although it remains uncertain whether immune dysregulation represents an initial cause or merely a secondary enhancer of endometriosis, therapies targeting altered immune pathways exhibit satisfactory effects in preventing disease onset and progression. Here, we summarize the phenotypic and functional alterations of immune cells in the endometriotic microenvironment, focusing on their interactions with microbiota and endocrine and nervous systems, and how these interactions contribute to the etiology and symptomology of endometriosis.
Female ; Humans ; Endometriosis/metabolism* ; Killer Cells, Natural/metabolism* ; T-Lymphocytes/metabolism* ; Estrogens ; Endometrium/metabolism*

Ischemic stroke has the characteristics of high morbidity, high disability rate, and high fatality rate. There is currently no effective rehabilitation treatment method. With the advancement of basic research and preparation technology of stem cells and the extensive development of animal experiments, stem cell transplantation has shown great potential for application in the treatment of ischemic stroke. This article elaborated on the mechanism, types and sources of stem cell transplantation and transplantation methods. By reviewing the research process of stem cells in ischemic stroke model, we can provide reference for clinical research of stem cell transplantation in the treatment of ischemic stroke.

Objective To observe and analyze the pathological changes in BALB/c mice infected with herpes simplex virus typeⅡ (HSV-2) through nasal and genital inoculation. Methods Six-week old female BALB/c mice were divided into two groups, experimental and control groups. In the experimental group, the mice were infected with HSV-2 (104 CCID50/20μl per mouse) through nasal and genital tract in-oculation. Accordingly, the mice in the control group were injected with equal volume of PBS. Tissue speci-mens were collected from lung, nervous system and reproductive system for pathological analysis and viral load detection at different time points after infection. Lat gene expression in mouse trigeminal and sacral gan-glia was detected through in situ hybridization. In addition, the proliferation of viruses isolated form trigemi-nal and sacral ganglia of the infected mice was observed in vitro. Results Weight loss and histopathological lesions were observed in the mice of the experimental group 6 d after infection. Major pathological changes in the HSV-2-infected mice through nasal tract inoculation involved the lung and central nervous system( CNS) , including alveolar wall congestion, cerebrovascular cuff response and lymphocyte infiltration. How-ever, the major lesions in the infected mice through genital tract inoculation were found in the reproductive ducts, such as sacral ganglion necrosis, eosinophilia in the vagina and uterus, and ovarian congestion. Re-sults of the viral load detection in tissues and organs of the infected mice were consistent with the pathological changes. The mice infected through nasal tract inoculation had significantly higher viral loads in the nerves and lungs than those by genital tract inoculation, but lower viral loads in the genital tracts and sacral ganglia. Positive expression of lat gene at mRNA level was detected in the trigeminal and sacral ganglia of mice with HSV-2 latency 28 d after infection. In addition, both of the tissue fragments from trigeminal and sacral ganglia had cytopathic effects ( CPEs) on Vero cells. Enhanced expression of lat gene at mRNA level and much severer CPEs were induced by genital tract inoculation than by nasal tract inoculation. Conclu-sions HSV-2 could infect and cause histopathological damages in BALB/c mice through both nasal and genital tracts. In addition, the locations of the pathological lesions were closely related to the mode of infection.