Epilepsy is a chronic neurological disorder affecting ~65 million individuals worldwide. Abnormal synaptic plasticity is one of the most important pathological features of this condition. We investigated how ubiquitin-specific peptidase 47 (USP47) influences synaptic plasticity and its link to epilepsy. We found that USP47 enhanced excitatory postsynaptic transmission and increased the density of total dendritic spines and the proportion of mature dendritic spines. Furthermore, USP47 inhibited the degradation of the ubiquitinated α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit glutamate receptor 1 (GluR1), which is associated with synaptic plasticity. In addition, elevated levels of USP47 were found in epileptic mice, and USP47 knockdown reduced the frequency and duration of seizure-like events and alleviated epileptic seizures. To summarize, we present a new mechanism whereby USP47 regulates excitatory postsynaptic plasticity through the inhibition of ubiquitinated GluR1 degradation. Modulating USP47 may offer a potential approach for controlling seizures and modifying disease progression in future therapeutic strategies.
Animals ; Receptors, AMPA/metabolism* ; Neuronal Plasticity/physiology* ; Seizures/physiopathology* ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice ; Ubiquitin Thiolesterase/genetics* ; Male ; Excitatory Postsynaptic Potentials/physiology* ; Ubiquitination ; Dendritic Spines/metabolism* ; Hippocampus/metabolism*

Objective:To investigate the impact of inserting an exogenous gene, NanoLuc (Nluc), at different sites in the influenza virus genome on viral properties and analyze the expression stability of the exogenous gene both in vitro and in vivo. Methods:Using molecular cloning techniques and reverse genetics, eight recombinant influenza viruses were constructed by inserting the exogenous Nluc gene into the gene segments encoding hemagglutinin (HA), neuraminidase (NA), non-structural protein (NS), and polymerase basic protein 1 (PB1). Viral replication capacity was evaluated by hemagglutination and plaque assays. Nluc expression in infected cells was monitored by fluorescence imaging. The potential impact of the exogenous gene insertion on viral infectivity was examined in a mouse infection model. Independent samples t-test were used for statistical analysis. Results:The recombinant viruses with insertions in the HA, NA, and NS gene segments generated fluorescent signals in the first generation of rescued viruses and demonstrated replication capabilities in plaque and hemagglutination assays. The recombinant viruses based on the NA and NS genes were capable of stably expressing Nluc across different generations, and exhibited correct fluorescent distribution patterns in mouse infection experiments. Meanwhile, the NS gene-based recombinant virus demonstrated superior stability in the mouse model.Conclusions:This study demonstrates that the NS gene segment of influenza virus can serve as an effective insertion site for exogenous genes without impairing the viral replication or infectivity, and the recombinant virus constructed based on it exhibits high integration stability and substantial application potential.

Human papillomavirus (HPV) can cause various tumors such as cervical cancer in women. Further study of HPV infection and its pathogenic mechanism, as well as the development of vaccines and anti-tumor drugs, have been hindered due to the strong host specificity and tissue affinity of HPV, along with the challenges in in vitro culture and the lack of animal infection models. To advance the study of HPV infection and its pathogenic mechanism and to development better prevention and treatment measures, it is important to establish an animal model that closely resembles the infection and pathogenesis pathways in humans. This article reviews previous research on HPV-related animal models using mice, rabbits, macaques, and Drosophila, including infectious models, tumor models, and transgenic models, aiming to provide reference for the selection of appropriate animal models for HPV-related research.

Objective:To investigate the impact of inserting an exogenous gene, NanoLuc (Nluc), at different sites in the influenza virus genome on viral properties and analyze the expression stability of the exogenous gene both in vitro and in vivo. Methods:Using molecular cloning techniques and reverse genetics, eight recombinant influenza viruses were constructed by inserting the exogenous Nluc gene into the gene segments encoding hemagglutinin (HA), neuraminidase (NA), non-structural protein (NS), and polymerase basic protein 1 (PB1). Viral replication capacity was evaluated by hemagglutination and plaque assays. Nluc expression in infected cells was monitored by fluorescence imaging. The potential impact of the exogenous gene insertion on viral infectivity was examined in a mouse infection model. Independent samples t-test were used for statistical analysis. Results:The recombinant viruses with insertions in the HA, NA, and NS gene segments generated fluorescent signals in the first generation of rescued viruses and demonstrated replication capabilities in plaque and hemagglutination assays. The recombinant viruses based on the NA and NS genes were capable of stably expressing Nluc across different generations, and exhibited correct fluorescent distribution patterns in mouse infection experiments. Meanwhile, the NS gene-based recombinant virus demonstrated superior stability in the mouse model.Conclusions:This study demonstrates that the NS gene segment of influenza virus can serve as an effective insertion site for exogenous genes without impairing the viral replication or infectivity, and the recombinant virus constructed based on it exhibits high integration stability and substantial application potential.

Human papillomavirus (HPV) can cause various tumors such as cervical cancer in women. Further study of HPV infection and its pathogenic mechanism, as well as the development of vaccines and anti-tumor drugs, have been hindered due to the strong host specificity and tissue affinity of HPV, along with the challenges in in vitro culture and the lack of animal infection models. To advance the study of HPV infection and its pathogenic mechanism and to development better prevention and treatment measures, it is important to establish an animal model that closely resembles the infection and pathogenesis pathways in humans. This article reviews previous research on HPV-related animal models using mice, rabbits, macaques, and Drosophila, including infectious models, tumor models, and transgenic models, aiming to provide reference for the selection of appropriate animal models for HPV-related research.

Objective:To explore the cost-effectiveness and cost-benefit of chronic obstructive pulmonary disease (COPD) screening and intervention based on family doctor contract services.Methods:From January 2023 to October 2023, using purposive sampling and a cross-sectional survey method, 1 040 individuals aged 60 to 75 years who underwent physical examinations at community health service centers in Shanghai Minhang district were selected as research subjects. The subjects were divided into a control group ( n=532) and a study group ( n=508). The control group received conventional community health education and participated in a COPD screening and intervention program provided by the examination center. The study group received COPD screening and intervention provided by contracted family doctors under a tightly integrated medical consortium. The screening content for both groups included initial and follow-up risk assessment questionnaires, pulmonary function tests, bronchodilator tests, and CT scans. A comparative analysis was conducted on the screening compliance rate, positive rate, and cost-effectiveness and cost-benefit between the two groups. Results:A total of 251 individuals at high risk for COPD and confirmed COPD patients were identified through initial and re-screening in both groups, accounting for 24.13% of the subjects, including 222 individuals at high risk (21.35%) and 29 confirmed patients (2.79%). The study group had significantly higher compliance rates in questionnaire-based initial screening, questionnaire-based re-screening+pulmonary function tests, bronchodilator experiments, diagnosis, and subsequent CT scans than the control group ( χ2=33.563, 41.425, 24.842, 17.363, all P<0.05).There were significant higher proportions of high-risk individuals and patients identified through screening in the study group than those in the control group ( χ2=44.880, all P<0.05). The study group had significantly higher positive rates of questionnaire-based initial screening, pulmonary function tests, bronchodilator experiments, and CT scans than the control group ( χ2=29.191, 11.313, 12.370, 4.429, all P<0.05). The overall costs of the screening in the control and study groups were 36 100 and 53 900 yuan, respectively. The cost of pulmonary function tests in the screening for the control and study groups was 1.44 million and 2.45 million yuan, respectively, accounting for 43.19% of the total cost, which was the highest proportion among all costs. The per capita cost for identifying one high-risk individual or patient with COPD was 358.46 Yuan, and the cost in study groups was significantly lower than that in the control group (322.75 vs. 429.45 yuan, χ2=20.396, P<0.05). The per capita net benefits and cost-benefit ratios for the overall subjects in the two groups were 0.37 million yuan and 43.50, respectively. The average net benefit of the study group and the control group was 0.49 million yuan and 0.26 million yuan respectively. The average net benefit of the study group was 0.23 million yuan higher than that of the control group. The cost-benefit ratio of the study group and the control group were 46.77 and 38.61, respectively. The cost-benefit ratio of the study group was 8.16 higher than that of the control group. Conclusion:The screening and intervention for COPD based on family doctor contract services have significant effectiveness, with a marked improvement in screening compliance and high cost-effectiveness, and can be used in community medical institutions with relatively sound family doctor and medical consortium services for targeted COPD screening.

Objective To investigate the expression of allograft inflammatory factor-1(AIF-1)in the testicular model of diabetes mellitus(DM)rats as well as its significance.Methods The rat model of DM testis(DMT)was established,which were randomly divided into the DM testis 4-week group(DMT4W),DM testis s 8-week group(DMT8W)and the DM testis 12-week group(DMT12W).The normal control group(NC group)was randomly divided into three subgroups:NC 4-week(NC4W),NC 8-week(NC8W)and NC 12-week(NC12W).The morphologic changes of testis in the different groups was detected by histopathology.The expression of AIF-1 protein was detected by immunohistochemistry.The expression of AIF-1 and NF-κB p65 protein was observed by immunofluorescence.Results The histopathological results suggested that the numbers of spermatogenic cells,sertoli cells,interstitial cells and sperms in the DMT group were significantly decreased,as compared with the NC group.The immunohistochemistry results showed that the expression of AIF-1 protein was significantly increased in the DMT group,as compared with the NC group(P<0.05).The intensity of AIF-1 and NF-κB p65 in the DMT group was significantly increased by immunofluorescence,as compared with the NC group.Conclusion The over expression of AIF-1 protein in DMT tissue suggests that it may play an important role in the pathological process of DMT and may become a new therapeutic target and diagnostic marker in the future.

The metastasis of contralateral adrenal gland and gallbladder following radical nephrectomy is extremely uncommon in clinical practice. We presented one such case. The patient underwent laparoscopic radical right nephrectomy. Postoperative pathology revealed clear cell carcinoma of the right kidney. Five years after operation, CT revealed occupying lesions in the left adrenal gland and gallbladder. Transperitoneal laparoscopic left adrenalectomy and cholecystectomy were performed. Pathological examination showed that the left adrenal tumor and gallbladder tumor were clear cell carcinoma. The patient received targeted therapy and tumor-free survived for 10 months.

Influenza viruses are common pathogens causing respiratory infections in humans. Among the four seasonal influenza viruses, influenza A virus H3N2 has become the leading cause of seasonal influenza illness and death, posing a great threat to public health and the economy. Since it first emerged and caused a pandemic in 1968, H3N2 has been circulating repeatedly in human beings and continually evades host immune attack by antigenic drift, resulting in a decrease in vaccine efficacy. In this paper, the antigenic evolution of influenza A virus H3N2, the impact of antigenic evolution on the selection of vaccine strains and some models for predicting the evolution of influenza viruses were analyzed and reviewed, which paved the road for understanding the antigenic evolution of influenza virus and vaccine development.