Acquired immunity and Alzheimer's disease

Alzheimer’s disease(AD) is an age-related neurodegenerative disease characterized by progressive cognitive defects. The role of the central immune system dominated by microglia in the progression of AD has been extensively investigated. However, little is known about the peripheral immune system in AD pathogenesis.Recently, with the discovery of the meningeal lymphatic vessels and glymphatic system, the roles of the acquired immunity in the maintenance of central homeostasis and neurodegenerative diseases have attracted an increasing attention. The T cells not only regulate the function of neurons, astrocytes, microglia, oligodendrocytes and brain microvascular endothelial cells, but also participate in the clearance of β-amyloid(Aβ) plaques. Apart from producing antibodies to bind Aβ peptides, the B cells affect Aβ-related cascades via a variety of antibodyindependent mechanisms. This review systemically summarizes the recent progress in understanding pathophysiological roles of the T cells and B cells in AD.

Evolution of Acquired Humoral Immunity after Full Vaccination against SARS-CoV-2. IgG Levels in Healthcare Workers at 6 and 9 Months

Background: The COVID-19 pandemic continues to be a major worldwide health problem. The present study aims to contribute to surveillance of the immune and clinical response of vaccines to SARS-CoV-2. Methods: Observational medication study on acquired immunity and effectiveness of vaccines. Population: 620 workers in the health service of Almansa (Spain). Representative sample of 150 individuals. Sociodemographic, clinical, and epidemiological data and samples were recorded to determine anti-SARS-CoV-2 serum IgG levels 6 and 9 months after vaccination with Pfizer. Results: Mean age 46.45 years;76% women;85.1% working in a hospital. 19.3% had had COVID-19 in the year prior to vaccination. 96.7% were fully vaccinated with Pfizer/BioNTech. At 6 months, 100% seropositivity and mean IgG levels of 3017.2 AU/ml. Significant variations in IgG levels in individuals with prior COVID-19 infection and smokers. At 9 months, 99.3% remained seropositive;2.8% infected after vaccination. The repeated measures analysis showed a difference in means of 669.0 AU/ml (significant decrease in IgG levels of 28.9%). Conclusion: Antibody levels remained positive 6 and 9 months after vaccination, although IgG levels were found to decay.

Factors Associated with Antiretroviral Therapy Defaulting among Adult Patients Receiving Care at Chikankata Mission Hospital, Chikankata District, Zambia

Background: Defaulting on antiretroviral therapy has been identified as the most important factor contributing to the antiretroviral therapy failure rate. This study aimed to investigate factors associated with defaulting on antiretroviral therapy among adult patients receiving care at Chikankata Mission Hospital antiretroviral therapy clinic. Method: Cross-sectional analytical study on 385 participants selected by a computer generated random numbers technique of simple random sampling from among the patients receiving antiretroviral therapy at Chikankata Mission Hospital. Data collected were processed and analysed using Statistical Package for Social Science version 27. Univariate and backward multivariable logistic regression analysis was performed to identify factors associated with antiretroviral therapy defaulting. The level of significance was set at 5% with a confidence level of 95%. Results: Over half (58.4%) of the study participants defaulted on antiretroviral therapy. About 65.8% of study participants indicated improved health as the reason they defaulted on antiretroviral therapy. Most participants indicated that it was important to always go for antiretroviral therapy services (Adjusted Odds Ratio 1.95;95% Confidence Interval: [1.14 - 3.33], p = 0.015). Very few participants indicated poor family support for antiretroviral therapy services (Adjusted Odds Ratio 4.08;95% Confidence Interval: [2.02 - 8.23], p Conclusion: Defaulting on antiretroviral therapy continues to be a significant problem and needs to be addressed as a matter of priority. More counselling and awareness-raising programmes are required to improve knowledge and understanding on the importance of attending scheduled antiretroviral therapy clinics and services as well as the consequences of defaulting on antiretroviral therapy.

Analysis on Characteristics of Typical Syndromes of Acquired Immune Deficiency Syndrome Based on the Feature Selection Method

Objective:To discover the population characteristics of the syndrome types of Acquired Immune Deficiency Syndrome.Methods:Data mining method for feature selection was used.Results:Main symptoms based on feature selection are as follows,deficiency of both qi and blood(pale complexion,fear of cold,easy to catch a cold,pale tongue,weak pulse);liver depression and qi stagnation with effulgent fire(anxiety,insomnia,chest and hypochondrium,irregular menstruation,thin and whitish coating on the tongue,stringy pulse);dual deficiency of qi and yin(low-grade fever and night sweating,yellow urine,pale complexion,dysphoria with feverish sensation in chest,dry cough with less phlegm,weakness,dizziness,dry and red tongue,little coating,thread and rapid pulse);deficiency of spleen and kidney,dampness pathogen blockage(diarrhea,loose stool,eat less and abdominal nausea,abdominal pain,sallow complexion,nausea,vomiting,loss of hair,deafness and tinnitus,pale tongue with whitish coating,deep and thready pulse,slippery and rapid pulse);qi deficiency with blood stasis(weakness,spontaneous sweating,dry mouth without desire to drink,easy to catch a cold,shortness of breath,sallow complexion,eat less and loose stools,dim tongue quality,hesitant pulse).Conclusion:Based on the feature selection method,we can find the main characteristics of Acquired Immune Deficiency Syndrome,and provide objective reference for clinical diagnosis and treatment.

Investigation of perceived stigma among people living with human immunodeficiency virus/ acquired immune deficiency syndrome in Henan Province, China

Purpose:To investigate the level of and factors influencing perceived stigma and discrimination among people living with human immunodeficiency virus(HIV)/acquired immune deficiency syndrome(PLWHA)in Henan Province.Methods:In total,161 PLWHA from Zhengzhou and Zhenping were investigated using the Berger HIV stigma scale.Results:The mean Berger stigma scale score was 105.70±15.20,indicating a middle stigma level.Among the four subscales of the Berger stigma scale,the disclosure concerns score was highest,while the negative self-image score was lowest.Multivariate analyses showed that factors influencing perceived HIV stigma included the level of education and route of infection.Conclusion:The level of perceived HIV stigma and discrimination among PLWHA in Henan Province is moderate and was affected by the level of education and route of infection.Special intervention should be established to address this problem.

上海市艾滋病防治工作现状及对策建议

艾滋病是我国重点控制的传染病之一。我国政府高度重视艾滋病防治工作,制定发布了系列政策文件,全面加强艾滋病防治工作,以推进联合国2030年终结艾滋病流行可持续发展目标的实现。上海市按照国家相关要求,结合本市特点和工作实际,制定了上海市艾滋病防治工作目标,全面落实艾滋病防治责任与任务,持续推进各项防控措施,取得了明显成效。分析近年来上海市艾滋病防治工作进展及现状,并提出下一步工作对策及建议。

Activation-induced pyroptosis contributes to the loss of MAIT cells in chronic HIV-1 infected patients

Background: Mucosal-associated invariant T(MAIT) cells are systemically depleted in human immunodeficiency virus type 1(HIV-1) infected patients and are not replenished even after successful combined antiretroviral therapy(cART).This study aimed to identify the mechanism underlying MAIT cell depletion.Methods: In the present study, we applied flow cytometry, single-cell RNA sequencing and immunohistochemical staining to evaluate the characteristics of pyroptotic MAIT cells in a total of 127 HIV-1 infected individuals, including 69 treatment-naive patients, 28 complete responders, 15 immunological non-responders, and 15 elite controllers, at the Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.Results: Single-cell transcriptomic profiles revealed that circulating MAIT cells from HIV-1 infected subjects were highly activated, with upregulation of pyroptosis-related genes. Further analysis revealed that increased frequencies of pyroptotic MAIT cells correlated with markers of systemic T-cell activation, microbial translocation, and intestinal damage in cART-naive patients and poor CD4+ T-cell recovery in long-term cART patients. Immunohistochemical staining revealed that MAIT cells in the gut mucosa of HIV-1 infected patients exhibited a strong active gasdermin-D(GSDMD, marker of pyroptosis) signal near the cavity side, suggesting that these MAIT cells underwent active pyroptosis in the colorectal mucosa. Increased levels of the proinflammatory cytokines interleukin-12(IL-12) and IL-18 were observed in HIV-1 infected patients. In addition, activated MAIT cells exhibited an increased pyroptotic phenotype after being triggered by HIV-1 virions, T-cell receptor signals, IL-12 plus IL-18, and combinations of these factors, in vitro.Conclusions: Activation-induced MAIT cell pyroptosis contributes to the loss of MAIT cells in HIV-1 infected patients,which could potentiate disease progression and poor immune reconstitution.

The default mode network is affected in the early stage of simian immunodeficiency virus infection:a longitudinal study

Acquired immune deficiency syndrome infection can lead to cognitive dysfunction represented by changes in the default mode network.Most recent studies have been cross-sectional and thus have not revealed dynamic changes in the default mode network following acquired immune deficiency syndrome infection and antiretroviral therapy.Specifically,when brain imaging data at only one time point are analyzed,determining the duration at which the default mode network is the most effective following antiretroviral therapy after the occurrence of acquired immune deficiency syndrome.However,because infection times and other factors are often uncertain,longitudinal studies cannot be conducted directly in the clinic.Therefore,in this study,we performed a longitudinal study on the dynamic changes in the default mode network over time in a rhesus monkey model of simian immunodeficiency virus infection.We found marked changes in default mode network connectivity in 11 pairs of regions of interest at baseline and 10 days and 4 weeks after virus inoculation.Significant interactions between treatment and time were observed in the default mode network connectivity of regions of interest pairs area 31/V6.R and area 8/frontal eye field(FEF).L,area 8/FEF.L and caudal temporal parietal occipital area(TPOC).R,and area 31/V6.R and TPOC.L.ART administered 4 weeks after infection not only interrupted the progress of simian immunodeficiency virus infection but also preserved brain function to a large extent.These findings suggest that the default mode network is affected in the early stage of simian immunodeficiency virus infection and that it may serve as a potential biomarker for early changes in brain function and an objective indicator for making early clinical intervention decisions.

Role of STAT3 in inflammatory bowel disease

Signal transducers and activators of transcription 3 (STAT3) play an important role in various autoimmune disorders including inflammatory bowel disease (IBD). Recent studies have revealed that STAT3 activation plays distinctly different roles between innate immune responses and acquired immune responses in colitis. STAT3-mediated activation of acquired immune re-sponses plays a pathogenic role in colitis by enhancing the survival of pathogenic T cells. In contrast, STAT3-mediated activation of innate responses contributes to the suppression of colitis. This review will summarize the current understanding of the roles of STAT3 in IBD and the potential of targeting STAT3 for the treatment of IBD, emphasizing recent observations.

Current progress of China’s free ART program

China’s Free ART Program was initiated in 2002 as an emergency response to save and improve the lives of AIDS patients living mainly in impoverished rural regions of central China. With little experience in HIV/AIDS treatment and care and resource limitations, China’s efforts to provide widespread access to free antiretroviral therapy has been a process fraught with difficulty. However, the Free ART Program is progressing from an emergency response to a standardized treatment and care system. The development of national guidelines, training programs, a laboratory sup- port network, a national patient database, programs for special populations such as children and patients living with co- infections, and operational research has improved the scope and quality of the free treatment program. As of June 30, 2005, a total of 19,456 patients in 28 provinces, autonomous regions, and special municipalities had received free ART. Challenges stemming from the nature of China’s health system and patient population persist, but with strong govern- ment support and a diverse set of resources, China has the capacity to overcome these challenges and to provide nationwide access to high quality treatment and care.

Vanishing bile duct syndrome in human immunodeficiency virus: Nevirapine hepatotoxicity revisited

Vanishing bile duct syndrome (VBDS) refers to a group of disorders characterized by prolonged cholestasis as a result of destruction and disappearance ofintrahepatic bile ducts. Multiple etiologies have been indentifi ed including infections, neoplastic disorders, autoimmune conditions and drugs. The natural history of this condition is variable and may involve resolution of cholestasis or progression with irreversible damage. VBDS is extremely rare in human immunodeficiency virus (HIV)-infected patients and anti-retroviral therapy has never been implicated as a cause. We encountered a young pregnant female with HIV and VBDS secondary to anti-retroviral therapy. Here, we report her clinical course and outcome.

Lack of Response in Severe Pneumocystis Pneumonia to Combined Caspofungin and Clindamycin Treatment: a Case Report

PNEUMOCYSTIS pneumonia (PCP) is among the most common opportunistic infections in patients with acquired immune deficiency syndrome (AIDS).Although trimethoprim-sulfamethoxazole (TMP-SMX) is the first line therapy for that condition given its efficacy,approximately one third of patients experienced dose-limiting toxicity.1 For cases of severe to moderate PCP,if TMP-SMX treatment fails or is contraindicated,primaquine combined with clindamycin or intravenous pentamidine is recommended as second line therapy.2 However,both primaquine and pentamidine are associated with severe adverse reactions and often unavailable at hospitals in China.3 As a result,other treatment options have been explored.

Major comorbid disease processes associated with increased incidence of acute kidney injury

Acute kidney injury （AKI） is commonly seen amongst critically ill and hospitalized patients. Individuals with certain co-morbid diseases have an increased risk of developing AKI. Thus, recognizing the co-morbidities that predispose patients to AKI is important in AKI prevention and treatment. Some of the most common co-morbid disease processes that increase the risk of AKI are diabetes, cancer, cardiac surgery and human immunodefciency virus （HIV） acquired immune defciency syndrome （AIDS）. This review article identifies the increased risk of acquiring AKI with given co-morbid diseases. Furthermore, the pathophysiological mechanisms underlying AKI in relation to co-morbid diseases are discussed to understand how the risk of acquiring AKI is increased. This paper reviews the effects of various co-morbid diseases including： Diabetes, cancer, cardiovascular disease and HIV AIDS, which all exhibit a significant increased risk of developing AKI. Amongst these co-morbid diseases, inflammation, the use of nephrotoxic agents, and hypoperfusion to the kidneys have been shown to be major pathological processes that predisposes individuals to AKI. The pathogenesis of kidney injury is complex, however, effective treatment of the co-morbid disease processes may reduce its risk. Therefore, improved management of co-morbid diseases may prevent some of the underlying pathology that contributes to the increased risk of developing AKI.

T-CELL RESPONSE OF ADVANCED AIDS PATIENTS AFTER HIGHLY ACTIVE ANTIRETROVIRAL THERAPY

Objective To investigate the response on late stage Chinese AIDS patients after highly active antiretroviral therapy （HAART）. Methods From October 2002 to March 2004, 20 cases of late stage Chinese AIDS patients were selected to participate in this opened and randomised study, we purposely chose those with CD4＋ T cell counts 〈 100/mm^3. All of them had one or two opportunistic infections and none had been treated with anti-HIV drugs. All patients were tested with CD4＋ （naive CD4＋ T cell defined by CD45RA＋ and CD62L＋, memory CD4＋ T cell defined by CD45RA-）, CD8＋ T cell, plasma HIV viral load, and clinical manifestations on before, during, and after HAART （5 different regimes） on 1, 3, 6, 9, and 12 months. Before HAART mean CD4＋ T cell counts were 32 ± 31 （range 2-91）/mm^3, and plasma HIV viral load were 5.07 ± 0.85（range 2.04-5.70） log copies/mL. In 1 month＇s time patients treated with HAAT had mean CD4＋ and CD8＋ T cell counts increasing rapidly. After 1 month the increasing speed turned to slow down, but HIV viral load decreased predominantly within the first 3 months. The major part of increasing CD4＋ T cells were memory CD4＋ T cells, as for naive CD4＋ T cells increasing low and slow. Clinical symptoms and signs improved, and opportunistic infections reduced. The quality of life will be far much better than before. Each patient was followed for 12 months, and had finished 12 months＇ HAAT. Conclusion This is the first report in China that late stage Chinese AIDS patients after HAART could have their immune reconstitution. The regular pattern is similar to what had been reported in Western countries and also in China. So it is worth to treat late stage Chinese AIDS patients with HAAT.

Retroviral integrase protein and intasome nucleoprotein complex structures

Retroviral replication proceeds through the integration of a DNA copy of the viral RNA genome into the host cellular genome, a process that is mediated by the viral integrase(IN) protein. IN catalyzes two distinct chemical reactions: 3'-processing, whereby the viral DNA is recessed by a di- or trinucleotide at its 3'-ends, and strand transfer, in which the processed viral DNA ends are inserted into host chromosomal DNA. Although IN has been studied as a recombinant protein since the 1980 s, detailed structural understanding of its catalytic functions awaited high resolution structures of functional IN-DNA complexes or intasomes, initially obtained in 2010 for the spumavirus prototype foamy virus(PFV). Since then, two additional retroviral intasome structures, from the α-retrovirus Rous sarcoma virus(RSV) and β-retrovirus mouse mammary tumor virus(MMTV), have emerged. Here, we briefly review the history of IN structural biology prior to the intasome era, and then compare the intasome structures of PFV, MMTV and RSV in detail. Whereas the PFV intasome is characterized by a tetrameric assembly of IN around the viral DNA ends, the newer structures harbor octameric IN assemblies. Although the higher order architectures of MMTV and RSV intasomes differ from that of the PFV intasome, they possess remarkably similar intasomal core structures. Thus, retroviral integration machineries have adapted evolutionarily to utilize disparate IN elements to construct convergent intasome core structures for catalytic function.

Hepatic Kaposi sarcoma: A case report and review of the literature

Kaposi sarcoma(KS) is an aggressive cancer caused by human herpesvirus-8, primarily seen in immunocompromised patients. As opposed to the well-described cutaneous manifestations and pulmonary complications of KS, hepatic KS is rarely reported before death as most patients with hepatic KS do not manifest symptoms or evidence of liver injury. In patients with acquired immune deficiency syndrome, hepatic involvement of KS is present in 12%-24% of the population on incidental imaging and in approximately 35% of patients with cutaneous KS if an autopsy was completed after their death. Patients with clinically significant hepatic injury due to hepatic KS usually have an aggressive course of disease with hepatic failure often progressing to multi-organ failure and death. Here we report an unusual presentation of acute liver injury due to hepatic KS and briefly review the published literature on hepatic KS.

Water,electrolytes,and acid-base alterations in human immunodeficiency virus infected patients

The clinical spectrum of human immunodeficiency virus （HIV） infection associated disease has changed significantly over the past decade, mainly due to the wide availability and improvement of combination antiretroviral therapy regiments. Serious complications associated with profound immunodeficiency are nowa-days fortunately rare in patients with adequate access to care and treatment. However, HIV infected patients, and particularly those with acquired immune defciency syndrome, are predisposed to a host of different water, electrolyte, and acid-base disorders （sometimes with opposite characteristics）, since they have a modified renal physiology （reduced free water clearance, and relatively increased fractional excretion of calcium and magnesium） and they are also exposed to infectious, inflammatory, endocrinological, oncological variables which promote clinical conditions （such as fever,tachypnea, vomiting, diarrhea, polyuria, and delirium）, and may require a variety of medical interventions （antiviral medication, antibiotics, antineoplastic agents）, whose combination predispose them to undermine their homeostatic capability. As many of these disturbances may remain clinically silent until reaching an advanced condition, high awareness is advisable, particularly in patients with late diagnosis, concomitant inflammatory conditions and opportunistic diseases. These disorders contribute to both morbidity and mortality in HIV infected patients.

The Role of HIV Replicative Fitness in Perinatal Transmission of HIV

Perinatal transmission of Human immunodeficiency virus(HIV),also called mother-to-child transmission(MTCT),accounts for 90% of infections in infants worldwide and occurs in 30%-45% of children born to untreated HIV-1 infected mothers.Among HIV-1 infected mothers,some viruses are transmitted from mothers to their infants while others are not.The relationship between virologic properties and the pathogenesis caused by HIV-1 remains unclear.Previous studies have demonstrated that one obvious source of selective pressure in the perinatal transmission of HIV-1 is maternal neutralizing antibodies.Recent studies have shown that viruses which are successfully transmitted to the child have growth advantages over those not transmitted,when those two viruses are grown together.Furthermore,the higher fitness is determined by the gp120 protein of the virus envelope.This suggests that the selective transmission of viruses with higher fitness occurred exclusively,regardless of transmission routes.There are many factors contributing to the selective transmission and HIV replicative fitness is an important one that should not be neglected.This review summarizes current knowledge of the role of HIV replicative fitness in HIV MTCT transmission and the determinants of viral fitness upon MTCT.

Testing Point of Care Portable Data Capture in a Hospital HIV Transmission Prevention Programme and Experience from Computerized Patient Management in a Sub-Saharan Clinic Setting

Clinicians involved in HIV/AIDS （Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome） prevention of mother to child transmission （PMTCT） programme and research activities can benefit from the advantages that computerized systems add to medical practice even in resource constrained sub-Saharan clinic settings. Their continued use of paper based systems presents clinical data management and patient care challenges. A portable point of care data capture electronic system and a computerized clinic patient management system （CCPMS） were implemented to remedy these challenges. PMTCT report compilation was easier with the portable data collection system whose data were found to be more complete and accurate with a 0.83% error rate compared to a 4.1% error rate in the paper registers. A resounding majority of clinicians preferred using the new CCPMS with many of the view that it improved drug inventory and general clinic management with a positive effect on patient care.

Peritoneal Tuberculosis in a Patient with HIV： Case Study in the Excellent Center in HIV/AIDS Care in Lubumbashi＇s University, Lubumbashi City

Tuberculosis is a disease of poverty. It is also a disease that prevents escaping poverty. There is a case report of disseminated tuberculosis with peritoneal involvement and peritoneal responsible for the clinical manifestations that may delay diagnosis. This location deserves mention as a share of expansion of tuberculosis in the presence of abdominal pain and bread signs of lung disease at a lower cost balance.