Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.
Animals ; Haplorhini ; Axons ; Motor Neurons ; Interneurons ; Macaca ; Dependovirus/genetics* ; Genetic Vectors

With the increasing life expectancy and lifestyle changes of patients with chronic hepatitis B (CHB), the significance of comorbidities of chronic non-communicable diseases (NCDs) in disease progression and health prognosis of CHB patients is gaining prominence. This study aims to explore the association between CHB and NCDs comorbidities, focusing on the impact of common metabolism-related diseases, such as metabolic syndrome and diabetes, on the health outcomes of CHB patients. We also summarize studies on integrating the management of comorbidities in CHB patients and provide relevant recommendations for effective management. The findings of this study serve as a foundation for understanding the clinical characteristics and prevalence trends, reducing the disease burden of comorbidities among CHB patients, and establishing a comprehensive and coordinated management system for comorbidities.

At present,some studies have identified gain-of-function(GOF)mutations in phosphoinositide 3-kinase(PI3K)genes PIK3CD(which encodes p110δ)lead to activated PI3Kδ syndrome(APDS),which can cause immune deficiency,immune dis-order and even tumor by multiple mechanisms of internal immune system defects,such as reduction/senescence/depletion of T cells,impaired development of B cells,and reduced toxicity of NK cells.Here,we review clinical characteristics of APDS induced by PI3Kδ GOF and molecular mechanism of immune deficiency,focusing on molecular mechanism of lymphocyte development,differentiation and functional defects caused by GOF mutation.

Thioredoxin-interacting protein (TXNIP), which mainly regulates glucose homeostasis in pancreatic β cells, is a novel target in the treatment of diabetes.In this study, 4-hydroxybenzopyrimidine was used as the raw material, four nitrogen-containing rings (imidazole, methylpiperazine, pyrazole, morpholine) were introduced, benzopyrimidine skeleton with nitrogen-containing rings derivatives targeting TXNIP was designed and synthesized, and the protective effect of compounds on palmitic acid-stimulated islet β cells was investigated.A total of 20 benzopyrimidine derivatives were designed and synthesized, and the structures were confirmed by 1H NMR and ESI-MS.Pharmacological studies showed that most of the compounds exhibited protective effects on islet β cells, with better axtivity for compounds C-1, C-2, C-4 and D-2 (cell survival rate > 70%) compared with PA model group (38.3%), Among the four compounds, D-2 had the highest activity of 87.2%, so it could become a potential new anti-diabetic chemical entity.

Objective:To understand the infection status and characteristics of 2019-nCoV infection in different areas in China after the adjustment of the national prevention and control strategy of 2019-nCoV infection.Methods:The online questionnaire survey was conducted among staff and students of 39 public health schools in 23 provinces (municipalities) in China from 12: 00 on December 20 to 9: 00 on December 23, 2022. The infection rates in staff and students in all the provinces were estimated. The risk factors, demographic and clinical characteristics of 2019-nCoV infections were explored.Results:A total of 28 901 valid questionnaires were obtained (26 355 from students and 2 546 from staff) with a qualified rate of 94.3%. The infection rates varied greatly among provinces and cities; the infection rates in students and staff in Beijing reached 78.55% and 76.40%, respectively. Infection rates in students and staff in Tianjin and Hebei also exceeded 65.00%, and 96.76% of infections occurred on and after December 1, 2022. Students had lower risk for the infection compared with staff ( OR=0.72, 95% CI: 0.60-0.86). Compared with age group ≤20 years, the OR of age groups 21-30, 31-40, 41-50, 51-60 and > 60 years were 1.22 (95% CI: 1.14-1.30), 1.54 (95% CI: 1.30-1.84), 1.25 (95% CI: 0.99-1.58), 1.29 (95% CI: 0.94-1.78) and 1.19 (95% CI: 0.51-2.80), respectively. The longer the period after the last vaccination, the higher the risk for the infection. Compared with those who received the last vaccination in the past 3 months, the OR of those who received the last vaccination in the past 4-6 months, 7-9 months, 10-12 months, 13-15 months and ≥16 months were 1.56 (95% CI: 1.34-1.82), 1.59 (95% CI: 1.36-1.86), 1.67 (95% CI: 1.45-1.93), 1.86 (95% CI:1.58-2.19) and 2.46 (95% CI: 2.09-2.90), respectively. Compared with those living alone, the OR of those living with 1-2, 3-4 and ≥5 roommates were 17.55 (95% CI: 15.91-19.39), 20.22 (95% CI: 18.25-22.43) and 11.78 (95% CI: 10.40-13.36), respectively. Only 5.94% of the staff and 7.19% of the students reported asymptomatic infections. Among those with symptoms, 88.18% of students and 85.65% of staff reported symptom of fever. Conclusions:The transmission dynamics of 2019-nCoV infection varied significantly across the country. The speed of transmission of 2019-nCoV and clinical severity of the infection were far beyond our knowledge. Organized epidemiological survey should be regularly carried out to provide reliable data support for more accurate prediction of the epidemic and medical resource allocation.

Objective:To understand the characteristics of sexualized drug use (SDU) among men who have sex with men (MSM) in Chengdu and classify their behavioral patterns by applying the two-step cluster (TSC) algorithm and by exploring the association between SDU patterns and high risk sexual behaviors, in order to provide a reference basis for the development of HIV prevention interventions.Methods:Supported by an MSM-friendly organization in Chengdu from December 2021 to February 2022, MSM were recruited by on-site survey and peer referral to collect information on sociodemographics, SDU characteristics, sexual behaviors, STD diagnosis, and HIV status. TSC was performed to classify the characteristics of SDU, and the differences between groups were compared. Chi-square test and multiple binary logistic regressions were used to identify the relationship between SDU clusters and HIV-related risk sexual behaviors.Results:A total of 727 MSM were surveyed, and 39.8% (289/727) of the respondents reported SDU experience with a same-sex partner in the last six months. TSC clustered SDU-MSM into three behavioral pattern groups. There were significant differences in monthly income, types of drugs used for SDU, mode, frequency, polydrug use, multiple sexual partners, non-adherence to condom use, and group sex among the three groups of SDU-MSM ( P<0.05). Multivariate binary logistic regression analysis showed that the third category of SDU-MSM was 2.22 (95% CI: 1.06-4.66) times more likely than the first category not to use condoms consistently; the third and second categories were 2.82 (95% CI: 1.18-6.77) times and 8.78 (95% CI: 3.42-22.42) times. Conclusions:The prevalence of SDU among MSM in Chengdu was more than 1/3, and different SDU clustering pattern was associated with high-risk sexual behaviors. MSM with higher SDU frequency, drug use, and polydrug abuse are more difficult to adhere to condom use and more likely to have group sex and high risk sexual behaviors, increasing the risk of STD and HIV infection, and need to strengthen SDU surveillance and intervention.

Objective:To evaluate the clinical efficacy and safety of adalimumab combined with acitretin in the treatment of childhood generalized pustular psoriasis.Methods:Five children with generalized pustular psoriasis were collected from Department of Dermatology, Tianjin Children′s Hospital from October 2019 to August 2020. After admission, the patients received oral acitretin at a dose of 0.5 mg·kg -1·d -1. After relevant laboratory examinations, these patients additionally received subcutaneous injections of 20- or 40-mg adalimumab at weeks 0 (the initial dose) , 1, and every 2 weeks thereafter; when patients obtained a 50% improvement in the Japanese Dermatology Association (JDA) severity index score, the dose of acitretin would be reduced to 0.3 mg·kg -1·d -1, and acitretin would be discontinued after a 75% improvement. The disease condition was evaluated at weeks 0, 1, 2, 4, 8, 12 and 24 after the start of adalimumab treatment, and adverse reactions were monitored during treatment. Results:All the 5 patients received drug treatment for at least 40 weeks. After 2-week treatment, 3 patients achieved a 50% reduction in JDA severity index score (JDA50) ; after 4-week treatment, 4 achieved JDA75, and 1 achieved JDA100; after 8-week treatment, all the 5 patients achieved JDA100. By June 2021, all the 5 children received follow-up for at least 40 weeks, no recurrence was observed during the treatment period, and no infections, malignant tumors or other serious adverse reactions occurred.Conclusion:Adalimumab combined with acitretin shows rapid onset of action and high safety in the treatment of childhood generalized pustular psoriasis.

Blood-brain barrier is a natural barrier between blood and brain tissue that can protect the brain from invasion by infectious pathogens in blood and maintain the homeostasis of the brain environment. However, neurotropic viruses can escape or disrupt blood-brain barrier and then invade the brain, causing serious complications in the central nervous system such as encephalitis and meningitis, which seriously threaten human life. This paper mainly summarized the research progress in the pathogenic mechanisms of common neurotropic viruses crossing blood-brain barrier and invading the central nervous system.

Objective: To analyze the spatiotemporal distribution of life expectancy (LE) and health-adjusted life expectancy (HALE) in Guangzhou from 2010 to 2019, and quantize the comprehensive impact of different causes and sequelae on health. Methods: The LE, HALE, and cause-excluded health adjusted life expectancy (CEHALE) were estimated using cause-of-death surveillance datasets from Guangzhou Municipal Center for Disease Control and Prevention from 2010 to 2019 and open data from the Global Burden of Disease Study. Joinpoint log-linear regression model was used to analyze the temporal trend and described spatial distribution. Results: In 2019, the LE in residents in Guangzhou was 82.9 years (80.1 years in men and 85.9 years in women), and the HALE was 75.6 years (74.0 years in men and 77.3 years in women). Compared with the urban fringe, the central urban area had higher LE and HALE, and the differences between LE and HALE were small. The LE and HALE in Guangzhou showed an increasing trend from 2010 to 2019. The LE increased by 2.8 years (AAPC=0.4, 95%CI: 0.3-0.4), with the increase of 2.8 years in men and 2.9 years in women. The HALE increased by 2.4 years (AAPC=0.3, 95%CI: 0.3-0.4), with the increase of 2.5 years in men and 2.2 years in women. The median healthy life lost due to communicable, maternal, neonatal, and nutritional diseases was 6.2 years (AAPC=-4.2, 95%CI: -5.3--3.1), while the median healthy life lost due to non-communicable diseases was 14.7 years (AAPC=1.6, 95%CI: 0.9-2.3), the median healthy life expectancy reduced by injury was 6.3 years (AAPC=-3.5, 95%CI: -4.5--2.6). Musculoskeletal disorders, skin and subcutaneous diseases, cardiovascular diseases, nutritional deficiencies, diabetes and kidney diseases were the top five diseases causing healthy life expectancy loss. Conclusion: The LE and HALE in residents in Guangzhou increased steadily from 2010 to 2019, but the quality of life in the urban fringe was lower than that of the central urban area. Non-communicable diseases were the leading causes of healthy life expectancy loss. Health policies and prevention measures should be developed according to area specific characteristics, and social medical resources should be rationally allocated to key diseases to reduce their disease burden.
Cost of Illness ; Female ; Health Status ; Humans ; Infant, Newborn ; Life Expectancy ; Male ; Noncommunicable Diseases ; Quality of Life

Exosomes are extracellular vesicles containing a variety of cell membrane molecules and related protein. They have been found to act as important intercellular messengers carrying functional RNAs, proteins and lipids that can induce phenotypic changes in recipient cells and promote cell activation or inhibition effect. In recent years, some studies have shown that exosomes can not only play an immune activation role to trigger antiviral immune response after viral infection, but also help to spread virus among cells, thus contributing to viral immune escape. Exosomes can either spread or limit an infection depending on the type of pathogen and the features of source cells, and can be studied as potential targets for development of antiviral drugs and vaccines. This review summarized the role of exosomes in viral infections with an emphasis on their potential contribution to pathogenesis.