Objective To investigate the effects of perampanel on the C-C chemokine receptor 5(CCR5)/cAMP-dependent protein kinase A(PKA)/cyclic-AMP response binding protein(CREB)pathway and hippocampal neuronal damage in epileptic rats.Methods Seventy-two male SPF-grade SD rats were randomly divided into epilepsy group,perampanel group,CCR5 inhibitor(maraviroc)group,recombinant CCL5 protein(rCCL5,CCR5 activator)group,perampanel+rCCL5 group,and a control group,with 12 rats in each group.The duration and frequency of epi-leptic seizures were detected in above groups.HE staining was used to observe the morphology of the hippocampal CA1 region.ELISA was employed to measure the contents of cyclooxygenase-2(COX-2),TNF-α,and IL-18 in the hippocampal CA1 region.Western blotting was conducted to measure the expression levels of CCR5,PKA,and p-CREB in the hippocampal CA1 region.Results Compared with the control group,the epilepsy group demonstrated badly-arranged and swollen neurons in the hippocampal CA1 region,longer duration of epilepsy,higher seizure frequency,increased COX-2,TNF-α and IL-18 contents in the CA1 region,elevated apoptotic rate and CCR5 protein level,and prolonged escape latency,while less number of crossing platforms and reduced protein levels of PKA and p-CREB(P＜0.05).While,both perampanel and maraviroc treatment could reverse above indicators when compared with the levels of the epilepsy group(P＜0.05).In the rCCL5 group,the neural injury was significantly aggravated,the duration of epilepsy and the frequency of epileptic seizures were increased,the contents of COX-2,TNF-α and IL-18 in the hip-pocampal CA1 region were enhanced,the rate of neuronal apoptosis and the expression of CCR5 protein were significantly enhanced,the escape latency was prolonged,and the number of crossed platforms,PKA,and the expression of p-CREb protein were declined(P＜0.05).When compared with the perampanel group,addition of rCCL5 resulted prolonged duration of epilepsy and escape latency,increased frequency of epileptic seizures and protein levels of COX-2,TNF-α,IL-18 and CCR5,more severe neuronal injury in the CA1 region,less platforms crossed,and decreased pro-tein expression of PKA and p-Creb(P＜0.05).The neural apoptotic rate in the hippocampal CA1 region was significantly higher in the perampanel+rCCL5 group than the perampanel group[(10.58±0.43)％vs(6.36±0.31)％,P＜0.05].Conclusion Perampanel may inhibit neuroin-flammation and neuronal apoptosis in epileptic rats by down-regulating CCR5 and then activating the PKA/CREB pathway,and thus attenuate hippocampal neuronal damage.

Objective To investigate the effects of perampanel on the C-C chemokine receptor 5(CCR5)/cAMP-dependent protein kinase A(PKA)/cyclic-AMP response binding protein(CREB)pathway and hippocampal neuronal damage in epileptic rats.Methods Seventy-two male SPF-grade SD rats were randomly divided into epilepsy group,perampanel group,CCR5 inhibitor(maraviroc)group,recombinant CCL5 protein(rCCL5,CCR5 activator)group,perampanel+rCCL5 group,and a control group,with 12 rats in each group.The duration and frequency of epi-leptic seizures were detected in above groups.HE staining was used to observe the morphology of the hippocampal CA1 region.ELISA was employed to measure the contents of cyclooxygenase-2(COX-2),TNF-α,and IL-18 in the hippocampal CA1 region.Western blotting was conducted to measure the expression levels of CCR5,PKA,and p-CREB in the hippocampal CA1 region.Results Compared with the control group,the epilepsy group demonstrated badly-arranged and swollen neurons in the hippocampal CA1 region,longer duration of epilepsy,higher seizure frequency,increased COX-2,TNF-α and IL-18 contents in the CA1 region,elevated apoptotic rate and CCR5 protein level,and prolonged escape latency,while less number of crossing platforms and reduced protein levels of PKA and p-CREB(P＜0.05).While,both perampanel and maraviroc treatment could reverse above indicators when compared with the levels of the epilepsy group(P＜0.05).In the rCCL5 group,the neural injury was significantly aggravated,the duration of epilepsy and the frequency of epileptic seizures were increased,the contents of COX-2,TNF-α and IL-18 in the hip-pocampal CA1 region were enhanced,the rate of neuronal apoptosis and the expression of CCR5 protein were significantly enhanced,the escape latency was prolonged,and the number of crossed platforms,PKA,and the expression of p-CREb protein were declined(P＜0.05).When compared with the perampanel group,addition of rCCL5 resulted prolonged duration of epilepsy and escape latency,increased frequency of epileptic seizures and protein levels of COX-2,TNF-α,IL-18 and CCR5,more severe neuronal injury in the CA1 region,less platforms crossed,and decreased pro-tein expression of PKA and p-Creb(P＜0.05).The neural apoptotic rate in the hippocampal CA1 region was significantly higher in the perampanel+rCCL5 group than the perampanel group[(10.58±0.43)％vs(6.36±0.31)％,P＜0.05].Conclusion Perampanel may inhibit neuroin-flammation and neuronal apoptosis in epileptic rats by down-regulating CCR5 and then activating the PKA/CREB pathway,and thus attenuate hippocampal neuronal damage.

Reactive oxygen species (ROS)-responsive drug delivery systems (DDSs) have garnered significant attention in cancer research because of their potential for precise spatiotemporal drug release tailored to high ROS levels within tumors. Despite the challenges posed by ROS distribution heterogeneity and endogenous supply constraints, this review highlights the strategic alliance of ROS-responsive DDSs with photodynamic therapy (PDT), enabling selective drug delivery and leveraging PDT-induced ROS for enhanced therapeutic efficacy. This review delves into the biological importance of ROS in cancer progression and treatment. We elucidate in detail the operational mechanisms of ROS-responsive linkers, including thioether, thioketal, selenide, diselencide, telluride and aryl boronic acids/esters, as well as the latest developments in ROS-responsive nanomedicines that integrate with PDT strategies. These insights are intended to inspire the design of innovative ROS-responsive nanocarriers for enhanced cancer PDT.

Objective:To investigate pediatric colonoscopy procedures and the associated changes in the disease spectrum.Methods:The clinical data of 1 087 children who underwent pediatric colonoscopy at the Second Affiliated Hospital of Nanjing Medical University and Yili Prefecture Friendship Hospital Affiliated to Nanjing Medical University from January 2012 to December 2022 were retrospectively collected. Patients were divided into 0-3 ( n=165), 4-6 ( n=307), 7-10 ( n=275) and 11-14 ( n=340) years groups according to their age, and also divided into two time periods according to the examination time point, 2012-2017 ( n=302) and 2018-2022 ( n=785) groups. Indicators that were observed and analyzed included the primary reasons for colonoscopy, types and proportions of abnormalities, distribution of cases and symptoms by period and age group, and disease diagnosis and treatment before and after colonoscopy. Results:A total of 1 238 colonoscopies were completed in 1 087 children. Blood in the stool was the most common cause (337/1 087, 31.00%). The most abnormalities were found in intestinal polyps (190/1 087, 17.48%) and inflammatory bowel disease (IBD) (181/1 087, 16.65%), as well as in 95 cases (95/1 087, 8.74%) who were confirmed autism and requested colonoscopy placement for fecal microbiota transplantation (FMT). There were differences in case distribution and symptoms among different age groups: polyps were most common in the 0-3 years group (75/165, 45.45%), and IBD was most common in the 11-14 years group (97/340, 28.53%). Compared with 2012-2017, during 2018-2022, the proportion of colonoscopies for polyps in children decreased [from 49.67% (150/302) to 5.10% (40/785), P<0.001], while the proportion for IBD increased [from 12.25% (37/302) to 18.34% (144/785), P=0.016], and autism requiring colonoscopic duct placement for FMT increased [from 2.32% (7/302) to 11.21% (88/785), P<0.001]. Conclusion:Pediatric colonoscopy plays an important role in the diagnosis and treatment of pediatric diseases. With the increasing clinical application demands, diversified procedures such as pre-FMT colonoscopic duct placement are becoming important directions for the future development of pediatric colonoscopy.

Sonodynamic therapy (SDT) is an emerging noninvasive treatment modality that utilizes low-frequency and low-intensity ultrasound (US) to trigger sensitizers to kill tumor cells with reactive oxygen species (ROS). Although SDT has attracted much attention for its properties including high tumor specificity and deep tissue penetration, its anticancer efficacy is still far from satisfactory. As a result, new strategies such as gas-assisted therapy have been proposed to further promote the effectiveness of SDT. In this review, the mechanisms of SDT and gas-assisted SDT are first summarized. Then, the applications of gas-assisted SDT for cancer therapy are introduced and categorized by gas types. Next, therapeutic systems for SDT that can realize real-time imaging are further presented. Finally, the challenges and perspectives of gas-assisted SDT for future clinical applications are discussed.

Recently, monkeypox has become a global concern amid the ongoing COVID-19 pandemic. Monkeypox is an acute rash zoonosis caused by the monkeypox virus, which was previously concentrated in Africa. The re-emergence of this pathogen seems unusual on account of outbreaks in multiple nonendemic countries and the incline to spread from person to person. We need to revisit this virus to prevent the epidemic from getting worse. In this review, we comprehensively summarize studies on monkeypox, including its epidemiology, biological characteristics, pathogenesis, and clinical characteristics, as well as therapeutics and vaccines, highlighting its unusual outbreak attributed to the transformation of transmission. We also analyze the present situation and put forward countermeasures from both clinical and scientific research to address it.
COVID-19 ; Disease Outbreaks/prevention & control* ; Humans ; Monkeypox/epidemiology* ; Monkeypox virus ; Pandemics/prevention & control*

Since the outbreak of COVID-19 caused by the 2019-nCoV (SARS-CoV-2), with its high pathogenicity and contagiousness, it has posed a serious threat to global public health security. Up to now, the pathogenesis of 2019-nCoV is unclear, and there is no effective treatment. Vaccine as one of the most effective strategies to prevent virus infection has become a hot area. Based on the current understanding of 2019-nCoV, the development of 2019-nCoV vaccines covers all types: inactivated virus vaccine, recombinant protein vaccine, viral vector-based vaccine, mRNA vaccine, and DNA vaccine, etc. In this review, we focus on the candidate targets of the novel coronavirus, and the types, development status and progress of 2019-nCoV vaccines in order to provide information for further research and prevention.

According to the new biopsychosocial medical model,status and burden of diseases should be evaluated comprehensively,and health-related quality of life can be an important measurement index of the burden of diseases.Conventional assessment methods for health-related quality of life include interval-based assessment methods and preference-based assessment methods (health utilities and willingness-to-pay).This review introduces willingness-to-pay,and summarizes its applications in skin diseases.However,at present,only a small quantity of small-scale studies are available on willingness-to-pay,with only a few kinds of skin diseases involved.In the application of health-economic assessment of skin diseases,willingness-to-pay can serve as an approximate index of benefit gains,and be more valuable in practice than health utilities (the index of utility gains).With the increase in health-economic researches on skin diseases,more attention is paid to the willingness-to-pay for skin diseases and other health-economic assessment methods,and large-scale health-economic assessment-related researches are expected to be conducted on more kinds of skin diseases.

Objective A state quo survey of laboratory animal resource in Guangdong province is performed to provide reference data for government management decision-making and market assessment of laboratory animals. Methods We used questionnaires focusing on the laboratory animal facilities with authorization by Guangdong Province Government, which mainly included the production and use of laboratory animals,the qualification of employees and the facilities space. Results The total production and use of laboratory animals(except for the eggs)had been increasing in the last four years. 1.57 million laboratory animals were produced and 0.754 million laboratory animals were used in 2016. There were 2352 employees,roughly the same as in 2015. The facilities space for breeding was 121008 m2,and for animal experiment was 73470 m2,which were rising in the past three years. Conclusions In order to reinforce the industry development of laboratory animals in Guangdong province,some suggestions were given in our study,such as facilitating the application of superiority resource including non-human primate and aquatic laboratory animals,supporting the standardization production of several scarce mice and rats, improving relevant employees' overall level and constructing laboratory animal facilities sharing platform.