Abstract: Hyperuricemia is a metabolic disease caused by elevated uric acid in the body, and is closely related to the increased risk of cardiovascular disease, metabolic disorders, and renal complications. In the development process of uric acid-lowering drugs, activity evaluation is a crucial step. At present, the activity screening methods of uric acid-lowering drugs can be roughly divided into two categories: in vitro and in vivo. In vitro screening is mainly for such targets as xanthine oxidase, urate transporters, and purine nucleoside phosphorylase, etc.; while in vivo screening is achieved by rodent, poultry and organoid models. In this article, the activity evaluation methods for uric acid-lowering compounds are comprehensively summarized both in vitro and in vivo, aiming to provide some insight for the development of uric acid-lowering drugs.

BACKGROUND: Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules. METHODS: Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model. RESULTS: In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53-24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06-1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16-2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25-2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36-14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08-3.91). No significant difference in the risk for SAEs was found in any comparisons. CONCLUSIONS: Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted. REGISTRATION PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42021278149.
Adult ; Humans ; BNT162 Vaccine ; 2019-nCoV Vaccine mRNA-1273 ; Network Meta-Analysis ; Immunization Schedule ; COVID-19/prevention & control* ; COVID-19 Vaccines/adverse effects* ; Viral Vaccines ; mRNA Vaccines ; Antibodies, Neutralizing ; Antibodies, Viral

Objective: To investigate the functions of FABP5 in the carcinogenesis and development of cervical cancer. Methods: The expression of FABP5 was detected in several cervical cancer cell lines (C33A, Siha, Caski, HeLa and HCC94), 206 cases of cervical cancer tissues with stage Ⅰa2-Ⅱa2 and 40 cases of normal cervical tissues by real-time PCR and Western blotting. Then, the cells were infected with lentivirus-mediated siRNA-targeting FABP5. CCK-8 cell proliferation, colony formation, wound healing and transwell assays were used to investigate the effects of FABP5 on in vitro cell proliferation, migration and invasion. And in vivo xenograft model and lung metastasis model were used to observe the transplanted tumor growth and metastasis in female athymic nude mice. Furthermore, the total protein and RNA were extracted from the primary xenografts to determine the expression levels of FABP5, metalloproteinase-2 and metalloproteinase-9 using Enzyme linked immunosorbent assay (ELISA), real-time PCR and Western blotting. Results: FABP5 expression was found to be significantly unregulated in cervical cancer tissues than that in normal cervical tissues (P<0.05). Compared with the Siha-NC group and uninfected group, the expression of FABP5 mRNA and protein in Siha-FABP5-RNAi group was significantly inhibited along with the decrease of cell proliferation, colony formation, wound healing and invasion ability. The clone formation rates of Siha cells in uninfected group, Siha-NC group and Siha-FABP5-RNAi group were (84.6±4.5)%, (84.6±5.1)% and (21.2±2.6)%, respectively. Moreover, the transwell assay showed that invasive cells in three groups were (72.8±4.7)/HPF, (72.6±3.3)/HPF and (21.4±2.3)/HPF, respectively. All of the difference was statistically significant (P<0.05). Furthermore, FABP5 silencing significantly reduced tumor growth and lung metastases in nude mice in vivo (P<0.001). The subcutaneously xenografted volume in uninfected group, Siha-NC group and Siha-FABP5-RNAi group was (921.4±63.0) mm^3, (1 021.4±56.0) mm³ and (139.6±36.0) mm^3, respectively. The real-time quantitative PCR results showed that the relative expression levels of MMP-2 and MMP-9 mRNA were 1.00±0.10 and 1.00±0.10, 1.00±0.10 and 1.00±0.10 as well as 0.34±0.13 and 0.38±0.17 in xenografted tumor tissues of uninfected group, Siha-NC group and Siha-FABP5-RNAi group, respectively. MMP-2 and MMP-9 was significantly downregulated after FABP5 inhibition(P<0.05). Additionally, the protein expression trend of MMP-2 and MMP-9 in three groups was consistent with the mRNA levels. Conclusion FABP5 might promote the carcinogenesis and metastasis of cervical cancer via up-regulating MMP-2 and MMP-9.

Objective To explore the significance of core-needle biopsy ( CNB) in the diagnosis of thyroid lymphoma. Methods A case of Hashimoto's thyroiditis for several decades, showed a thickening of the neck for several months, and no abnormalities were found by the method of fine-needle aspiration( FNA), then we performed CNB and flow cytology. Results Thyroid lymphoma was finally diagnosed through CNB and flow cytology. Conclusion Thyroid lymphoma should be considered when the neck became thickened in short time in patients with chronic Hashimoto's thyroiditis. Core-needle biopsy accompanied with flow cytometry and immunohistochemistry analysis should be suggested as routine diagnostic method especilly when fine-needle aspiration was negative.

Objective To investigate the functions of FABP5 in the carcinogenesis and development of cervical cancer. Methods The expression of FABP5 was detected in several cervical cancer cell lines (C33A, Siha, Caski, HeLa and HCC94), 206 cases of cervical cancer tissues with stageⅠa2?Ⅱa2 and 40 cases of normal cervical tissues by real?time PCR and Western blotting. Then, the cells were infected with lentivirus?mediated siRNA?targeting FABP5. CCK?8 cell proliferation, colony formation, wound healing and transwell assays were used to investigate the effects of FABP5 on in vitro cell proliferation, migration and invasion. And in vivo xenograft model and lung metastasis model were used to observe the transplanted tumor growth and metastasis in female athymic nude mice. Furthermore, the total protein and RNA were extracted from the primary xenografts to determine the expression levels of FABP5, metalloproteinase?2 and metalloproteinase?9 using Enzyme linked immunosorbent assay ( ELISA ), real?time PCR and Western blotting.Results FABP5 expression was found to be significantly unregulated in cervical cancer tissues than that in normal cervical tissues ( P＜0.05). Compared with the Siha?NC group and uninfected group, the expression of FABP5 mRNA and protein in Siha?FABP5?RNAi group was significantly inhibited along with the decrease of cell proliferation, colony formation, wound healing and invasion ability. The clone formation rates of Siha cells in uninfected group, Siha?NC group and Siha?FABP5?RNAi group were (84.6± 4.5)%, (84.6±5.1)% and (21.2±2.6)%, respectively. Moreover, the transwell assay showed that invasive cells in three groups were (72.8±4.7)／HPF, (72.6± 3.3)／HPF and ( 21.4± 2.3)／HPF, respectively. All of the difference was statistically significant (P＜0.05). Furthermore, FABP5 silencing significantly reduced tumor growth and lung metastases in nude mice in vivo ( P＜0.001). The subcutaneously xenografted volume in uninfected group, Siha?NC group and Siha?FABP5?RNAi group was (921.4±63.0) mm3, (1 021.4±56.0) mm3 and (139.6±36.0) mm3, respectively. The real?time quantitative PCR results showed that the relative expression levels of MMP?2 and MMP?9 mRNA were 1.00±0.10 and 1.00±0.10, 1.00±0.10 and 1.00±0.10 as well as 0.34±0.13 and 0.38±0.17 in xenografted tumor tissues of uninfected group, Siha?NC group and Siha?FABP5?RNAi group, respectively. MMP?2 and MMP?9 was significantly downregulated after FABP5 inhibition(P＜0.05). Additionally, the protein expression trend of MMP?2 and MMP?9 in three groups was consistent with the mRNA levels. Conclusion FABP5 might promote the carcinogenesis and metastasis of cervical cancer via up?regulating MMP?2 and MMP?9.

Objective To investigate the functions of FABP5 in the carcinogenesis and development of cervical cancer. Methods The expression of FABP5 was detected in several cervical cancer cell lines (C33A, Siha, Caski, HeLa and HCC94), 206 cases of cervical cancer tissues with stageⅠa2?Ⅱa2 and 40 cases of normal cervical tissues by real?time PCR and Western blotting. Then, the cells were infected with lentivirus?mediated siRNA?targeting FABP5. CCK?8 cell proliferation, colony formation, wound healing and transwell assays were used to investigate the effects of FABP5 on in vitro cell proliferation, migration and invasion. And in vivo xenograft model and lung metastasis model were used to observe the transplanted tumor growth and metastasis in female athymic nude mice. Furthermore, the total protein and RNA were extracted from the primary xenografts to determine the expression levels of FABP5, metalloproteinase?2 and metalloproteinase?9 using Enzyme linked immunosorbent assay ( ELISA ), real?time PCR and Western blotting.Results FABP5 expression was found to be significantly unregulated in cervical cancer tissues than that in normal cervical tissues ( P＜0.05). Compared with the Siha?NC group and uninfected group, the expression of FABP5 mRNA and protein in Siha?FABP5?RNAi group was significantly inhibited along with the decrease of cell proliferation, colony formation, wound healing and invasion ability. The clone formation rates of Siha cells in uninfected group, Siha?NC group and Siha?FABP5?RNAi group were (84.6± 4.5)%, (84.6±5.1)% and (21.2±2.6)%, respectively. Moreover, the transwell assay showed that invasive cells in three groups were (72.8±4.7)／HPF, (72.6± 3.3)／HPF and ( 21.4± 2.3)／HPF, respectively. All of the difference was statistically significant (P＜0.05). Furthermore, FABP5 silencing significantly reduced tumor growth and lung metastases in nude mice in vivo ( P＜0.001). The subcutaneously xenografted volume in uninfected group, Siha?NC group and Siha?FABP5?RNAi group was (921.4±63.0) mm3, (1 021.4±56.0) mm3 and (139.6±36.0) mm3, respectively. The real?time quantitative PCR results showed that the relative expression levels of MMP?2 and MMP?9 mRNA were 1.00±0.10 and 1.00±0.10, 1.00±0.10 and 1.00±0.10 as well as 0.34±0.13 and 0.38±0.17 in xenografted tumor tissues of uninfected group, Siha?NC group and Siha?FABP5?RNAi group, respectively. MMP?2 and MMP?9 was significantly downregulated after FABP5 inhibition(P＜0.05). Additionally, the protein expression trend of MMP?2 and MMP?9 in three groups was consistent with the mRNA levels. Conclusion FABP5 might promote the carcinogenesis and metastasis of cervical cancer via up?regulating MMP?2 and MMP?9.

The clustered regulatory interspaced short palindromic repeat-Cas9 (CRISPR-Cas9) system is the part of the prokaryotic immune system, which could recognize and delete the exogenous sequences originated from virus or plasmid. Based on its mechanism, CRISPR-Cas9 system was developed into the new generation of gene editing tool. Compared to the existed technologies such as ES targeting, ZFN or TALEN, CRISPR-Cas9 system is a more efficient, economical and promising approach to manipulate the genome. In this review, we summarize the research progress about CRISPR-Cas9 technology, especially the latest applications in gene therapy studies of human diseases.
CRISPR-Cas Systems ; Clustered Regularly Interspaced Short Palindromic Repeats ; Gene Editing ; Genetic Therapy ; Humans ; Plasmids

Parkinson′s disease(PD)is a common disease caused by multiple factors and characterized by pathological degen?eration in the dopaminergic neural system. Based on its pathogenic factors,PD can be divided into several subtypes,so it is essential to develop therapeutic agents based on the main pathogenic factor of each subtype of PD. Recently it is confirmed that the mutation of leucine-rich repeat kinase 2(LRRK2)gene leads to increased activity of the LRRK2 notably,and then causes neurodegeneration. Thus developing LRRK2 inhibitors to modulate the kinase activity will be a novel therapy for the PD subtype which is caused by LRRK2 gene mutation. LRRK2,either a kinase or a GTPase,has two drug binding sites. Therefore,two types of LRRK2 inhibitors are being studied,one is the kinase inhibitor and the other is GTPase inhibitor. This paper summarizes the recent progress in the dis?covery and development of LRRK2 inhibitors.

[ ABSTRACT] AIM: To explore the relationship between FRAS 1 protein and brain metastases of non-small cell lung cancer (NSCLC).METHODS:The mRNA expression of FRAS1 in the brain metastatic tumor tissues and primary tumor tissues of NSCLC was detected by qPCR .The protein expression of FRAS 1 in the tumor tissues and normal tissues adjacent to tumor tissues of NSCLC was measured by SP method of immunohistochemistry .The protein expression of FRAS 1 in NSCLC primary tumor tissues with or without brain metastases was also determined .RESULTS:The mRNA expression of FRAS1 in the brain metastatic zone was nearly 10 times higher than that in the primary tumor tissues , and there was sig-nificant difference between the 2 groups (P<0.05).FRAS1 protein was expressed in the NSCLC primary tumor tissues , but was not found in the normal tissues adjacent to primary tumor tissues .The protein expression of FRAS 1 in the NSCLC with brain metastases was significantly higher than that without brain metastases ( P<0.01 ) .CONCLUSION: FRAS1 protein may be associated with the occurrence of NSCLC .The over-expression of FRAS1 protein may be related to brain metastases with NSCLC .

BACKGROUND:Studies have shown that human leukocyte antigen (HLA)-A*0206 subtype is related to the abscess of nasopharyngeal carcinoma, but there is no corresponding transgenic animal models that could used to judge the relationship between HLA-A*0206 and nasopharyngeal carcinoma on the overal level and further research of immunotherapy and gene therapy. OBJECTIVE:To construct lentiviral vectors carrying pLVX-CMV-HLA-A*0206-HA-mCMV-ZsGreen and establish HLA-A*0206 transgenic mice. METHODS:The HLA-A*0206 sequence was synthesized. EcoRI recognition site was introduced in the 5’ end by polymerase chain reaction, and influenza virus hemagglutinin labels and BamHI recognition site were introduced in the 3’ end. Eco RI and Bam HI double enzyme digestion target fragments and the pLVX-CMV-mCMV-ZsGreen plasmids were connected to the digested productions and transfected JM109 competent cel s. The positive clones were selected and identified by double enzyme digestion and sequencing. The positive plasmid and packaging plasmids were transfected into 293T cel s, which were human renal epithelial cel line that can express SV40 large T antigen. The lentivirus containing target sequence was produced. RESULTS AND CONCLUSION:Gel electrophoresis and sequencing results showed that, HLA-A*0206 was successful y inserted into pLVX-CMV-mCMV-ZsGreen frame plasmids. Transfection efficiency was 92%after 48 hours of transfecting 293T cel s. The viral suspension titer was 5 × 108 measured by fluorescence method. Experimental findings indicate that, the lentivirus containing cytomegalovirus promoter, HLA-A*0206, influenza virus hemagglutinin label and Zsgreen report gene was successful y constructed.