Opportunistic infections (OIs) remain a major clinical challenge in people living with HIV/AIDS (PLWHA), and CD4⁺ T-cell counts alone may not fully reflect immune dysfunction. This study aimed to establish predictive cut-off values for lymphocyte subsets to improve the assessment of OIs risk in PLWHA. Peripheral blood samples were collected to assess lymphocyte subsets using flow cytometry between August 17, 2021, and April 19, 2023. Correlation analysis was performed to identify lymphocyte subset indicators strongly associated with CD4+ T-cell counts. Receiver operating characteristic (ROC) analysis was then performed to determine cut-off values for predicting OIs. Finally, the performance of cut-off values was tested in hospitalized PLWHA. Even when CD4 cell counts were above 200 cells/µl or close to normal, patients with abnormal immunological phenotypes had a higher prevalence of OIs. Other lymphocyte subsets have a high positive correlation with CD4+ T-cell counts, with the exception of CD3+CD8+/CD3+, CD3+HLA-DR+/CD3+, and CD3+CD8+HLA-DR+/CD8+, which are strongly negatively correlated. The correlation coefficients of CD4+CD28+ cells were particularly close to 1.0. Furthermore, CD4+CD28+ T lymphocytes demonstrated an AUC of 0.819 with a cut-off of 129 cells/µl, second only to CD4⁺ T cells in terms of AUC. Furthermore, the AUCs for CD3+CD4+CD45RA+, CD3+CD4+CD45RO+, CD3+CD4+CD25+CD127low, CD45RA+CD3+CD4+CD25+CD127low, and CD45RO+CD3+CD4+CD25+CD127low T cells were all > 0.800, with sensitivities exceeding 90

To develop a risk prediction model for hepatocellular carcinoma (HCC) by screening differentially expressed proteins (DEPs) in HIV/HBV coinfected patients with HCC and liver cirrhosis using proteomic techniques. DEPs were identified in plasma from HIV/HBV co-infected patients with HCC and liver cirrhosis using quantitative liquid chromatography-mass spectrometry (LC-MS). Mapping discovered proteins to the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Disease Ontology (DO) databases yielded annotation information for DEPs. Differential plasma apolipoprotein A-1(APOA1) and transthyretin (TTR) expression levels were validated in 88 HIV/HBV co-infected individuals with HCC and liver cirrhosis. In total, 150 DEPs were discovered. The GO entries were primarily enriched for cutaneous immunological response mediated by circulating immunoglobulin and complement activation, as well as lipoprotein particle. The KEGG pathway enrichment was dominated by complement and coagulation cascades. Six of the 15 items enriched in the DO entries were related to lipid metabolism. APOA1, TTR, Prothrombin (F2), Antithrombin-III (SERPINC1), Alpha-2-HS-glycoprotein (AHSG), Alpha-2-macroglobulin (A2M) and Haptoglobin-related protein (HPR) were finally identified as hub proteins. Finally, a visual logistic model using immunoglobulin heavy variable 3-13 (IGHV3-13) and A2M to predict HCC were constructed. Significant variations in plasma APOA1 and TTR levels were found in HIV/HBV co-infected patients with HCC and liver cirrhosis. The screened hub proteins from DEPs can be employed as possible markers for early HCC detection. The developed HCC prediction model can be used to assess the risk of HCC in HIV/HBV co-infected cirrhotic individuals.

BackgroundThe burden of hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis coinfections remains disproportionately high among people living with HIV/AIDS. Hubei province is located in central China, where there are distinct regional characteristics of the distribution of people living with HIV/AIDS acquired via diverse transmission routes and the AIDS epidemic itself. ObjectiveWe aimed to estimate the magnitude of HBV, HCV, or syphilis coinfections among people living with HIV/AIDS with blood-borne transmission, which includes former paid blood donors, contaminated blood recipients, and intravenous drug users, as well as among people with sex-borne HIV transmission (including heterosexual people and men who have sex with men) and people with mother-to-child HIV transmission. MethodsFrom January 2010 to December 2020, people living with HIV/AIDS were tested for hepatitis B surface antigen (HBsAg), HCV antibodies, and syphilis-specific antibodies. The positive patients were further tested for HBV markers, HBV DNA, and HCV RNA, and received a rapid plasma reagin circle card test. All people living with HIV/AIDS were first divided into transmission groups (blood, sex, and mother-to-child); then, people with blood-borne HIV transmission were divided into former paid blood donors, contaminated blood recipients, and intravenous drug users, while people with sex-borne HIV transmission were divided into heterosexual people and men who have sex with men. ResultsAmong 6623 people living with HIV/AIDS, rates of chronic HCV infection were 80.3% (590/735) in former paid blood donors, 73.3% (247/337) in intravenous drug users, 57.1% (444/777) in contaminated blood recipients, 19.4% (21/108) in people with mother-to-child HIV transmission, 8.1% (240/2975) in heterosexual people, and 1.2% (21/1691) in men who have sex with men. Chronic HBV infection rates were similar among all people with blood-borne HIV transmission. However, compared to heterosexual people, the chronic HBV infection rate was greater in men who have sex with men (213/1691, 12.6% vs 308/2975, 10.4%; χ21=5.469; P=.02), although HBV exposure was less common (827/1691, 48.9% vs 1662/2975, 55.9%; χ21=20.982; P<.001). Interestingly, the combination of HBsAg and hepatitis B e antigen (HBeAg) was found in 11 patients with sex-borne HIV transmission, but in 0 people with blood-borne HIV transmission (11/196, 5.6% vs 0/521, 0%; χ21=29.695, P<.001). In people with sex-borne HIV transmission, the proportions of patients with a syphilis titer ≥1:16 and neurosyphilis were 8.6% (105/1227) and 7.8% (37/473), respectively, whereas these values were 0 in people with blood-borne HIV transmission. ConclusionsIn people living with HIV/AIDS, HCV transmission intensity was significantly associated with specific exposure modes of blood or sexual contact. The rate of chronic HBV infection among men who have sex with men was higher than in any other population. Attention should be paid to the high prevalence of neurosyphilis in people living with HIV/AIDS who contract HIV by sexual intercourse.

目的 探讨 HIV 对大脑颞叶皮层神经元中次黄嘌呤核苷酸脱氢酶 Ⅱ(inosine monophosphate dehydrogenase 2,IMPDH2)蛋白表达的影响.方法 应用MoCA分数和磁共振成像手段评估HIV感染者轻度认知障碍情况.利用中国恒河猴SHIV KU-1神经艾滋病模型,HE染色观察猴颞叶皮层细胞结构的变化;采用免疫组化方法和Western blot方法检测IMPDH2 在猴颞叶皮层神经元内的表达;以及借助在线数据库预测IMPDH2 相关信号通路的关键信号分子.结果 HIV感染者颞叶皮质较健康对照萎缩.与健康对照相比,SHIV KU-1 感染恒河猴颞叶皮层神经元中IMPDH2 蛋白表达显著降低(P<0.0001).HNRNPA1 等 8 个基因与IMPDH2 有潜在的相互作用.结论 IMPDH2 在HIV患者颞叶皮层神经元中的表达下调,其可能参与了HIV相关神经认知障碍发生.

To evaluate clinical value of metagenomic next-generation sequencing (mNGS) in people living with HIV/AIDS (PLWHA) who had CNS disorders. Cerebrospinal fluid (CSF) samples from 48 PLWHA presenting with CNS disorders were sequenced using mNGS and compared with clinical conventional diagnostic methods. In total, 36/48 ss(75%) patients were diagnosed with pathogen(s) infection by mNGS, and the positive detection proportion by mNGS was higher than that by clinical conventional diagnostic methods (75% vs 52.1%, X 2 = 5.441, P = 0.020). Thirteen out of 48 patients (27.1%) were detected with 3–7 pathogens by mNGS. Moreover, 77 pathogen strains were detected, of which 94.8% (73/77) by mNGS and 37.0% (30/77) by clinical conventional methods ( X 2 = 54.206, P < 0.001). The sensitivity and specificity of pathogens detection by mNGS were 63.9% (23/36) and 66.7% (8/12), respectively, which were superior to that by clinical conventional methods (23/36 vs 9/25, X 2 = 4.601, P = 0.032; 8/12 vs 5/23, X 2 = 5.029, P = 0.009). The application of mNGS was superior for its ability to detect a variety of unknown pathogens and multiple pathogens infection, and relatively higher sensitivity and specificity in diagnosis of CNS disorders in PLWHA.

Coronavirus disease 2019 (COVID-19) was first reported three years ago, when a group of individuals were infected with the original SARS-CoV-2 strain, based on which vaccines were developed. Here, we develop six human monoclonal antibodies (mAbs) from two elite convalescents in Wuhan and show that these mAbs recognize diverse epitopes on the receptor binding domain (RBD) and can inhibit the infection of SARS-CoV-2 original strain and variants of concern (VOCs) to varying degrees, including Omicron strains XBB and XBB.1.5. Of these mAbs, the two most broadly and potently neutralizing mAbs (7B3 and 14B1) exhibit prophylactic activity against SARS-CoV-2 WT infection and therapeutic effects against SARS-CoV-2 Delta variant challenge in K18-hACE2 KI mice. Furthermore, post-exposure treatment with 7B3 protects mice from lethal Omicron variants infection. Cryo-EM analysis of the spike trimer complexed with 14B1 or 7B3 reveals that these two mAbs bind partially overlapped epitopes onto the RBD of the spike, and sterically disrupt the binding of human angiotensin-converting enzyme 2 (hACE2) to RBD. Our results suggest that mAbs with broadly neutralizing activity against different SARS-CoV-2 variants are present in COVID-19 convalescents infected by the ancestral SARS-CoV-2 strain, indicating that people can benefit from former infections or vaccines despite the extensive immune escape of SARS-CoV-2.

BackgroundHBV coinfection is frequent in people living with HIV (PLWH) and is the leading cause of hepatocellular carcinoma (HCC). While risk prediction methods for HCC in patients with HBV monoinfection have been proposed, suitable biomarkers for early diagnosis of HCC in PLWH remain uncommon.MethodsLiquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to examine serum protein alterations in HCC and non-HCC patients with HIV and HBV co-infection. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Disease Ontology (DO) enrichment analysis were performed on the differentially expressed proteins (DEPs). The risk prediction model was created using five-cross-validation and LASSO regression to filter core DEPs.ResultsA total of 124 DEPs were discovered, with 95 proteins up-regulated and 29 proteins down-regulated. Extracellular matrix organization and membrane component were the DEPs that were most abundant in the categories of biological processes (BP) and cellular components (CC). Proteoglycans in cancer were one of the top three DEPs primarily enriched in the KEGG pathway, and 60.0% of DEPs were linked to various neoplasms in terms of DO enrichment. Eleven proteins, including GAPR1, PLTP, CLASP2, IGHV1-69D, IGLV5-45, A2M, VNN1, KLK11, ANPEP, DPP4 and HYI, were chosen as the core DEPs, and a nomogram was created to predict HCC risk.ConclusionIn HIV/HBV patients with HCC, several differential proteins can be detected in plasma by mass spectrometry, which can be used as screening markers for early diagnosis and risk prediction of HCC. Monitoring protease expression differences can help in the diagnosis and prognosis of HCC.

Background:To analyze the changing characteristics of continuous monitoring of refined lymphocyte subsets in people living with HIV/AIDS (PLWHA) during ART period.Methods:Refined lymphocyte subsets was continuously monitored using flow cytometry for 173 PLWHA, who were hospitalized in Zhongnan Hospital of Wuhan University from August 17, 2021 to September 14, 2022. The effect of ART status and duration of ART on changes of refined lymphocyte subsets were compared in different groups. Then, the levels of refined lymphocyte subsets in PLWHA treated for more than 10 years were compared to those of 1086 healthy individuals.Results:In addition to conventional CD4+ T lymphocytes and CD4+/CD8+ ratio, gradually increasing in numbers of CD3+CD4+CD45RO cells, CD3+CD4+CD45RA cells, CD45RA+CD3+CD4+CD25+CD127low and CD45RO+CD3+CD4+CD25+CD127low cells were found with the increase of ART duration. The number of CD4+CD28+ cells and CD8+CD28+ cells were 174/ul and 233/ul at 6 months post-ART, which gradually increased to 616/ul and 461/ul after ART initiation more than 10 years. Moreover, in ART ≤ 6 months, 6 months-3years, 3-10 years and >10 years groups, the percentage of CD3+CD8+HLA-DR+/CD8 were 79.66%, 69.73%, 60.19% and 57.90%, respectively, and the differences between groups showed statistical significance (F=5.727, P=0.001). For those PLWHA with ART more than 10 years, the levels of CD4+ T lymphocytes, CD3+CD4+CD45RO cells, CD3+CD4+CD45RA cells, CD4+CD28+ cells and CD8+CD28+ cells can increase to levels similar to those of healthy control. However, for those PLWHA with ART more than 10 years, CD4+/CD8+ ratio was 0.86 ± 0.47, which was lower than that of healthy control (0.86 ± 0.47 vs 1.32 ± 0.59, t=3.611, P=0.003); absolute counts and percentage of CD3+CD8+HLA-DR+ cells were 547/ul and 57.90%, which were higher than those of healthy control(547/ul vs 135/ul, t=3.612, P=0.003; 57.90% vs 22.38%, t=6.959, P<0.001).Conclusion:Persistent ART can gradually improve the immune status of PLWHA, which is manifested in the increase of lymphocytes, function recovery of lymphocytes and reduction of aberrant activation status of the immune system. After 10 years of standardized ART, most lymphocytes could return to levels of healthy persons, although it may take longer to complete recovery for CD4+/CD8+ ratio and CD3+CD8+HLA-DR+ cells.

Purpose-Immunotherapy has revolutionized cancer therapy, becoming the standard of care for various malignancy treatments. Human immunodeficiency virus (HIV) patients, however, are an underserved group with limited access to clinical trials and cancer therapy. This study was to evaluate the safety and efficacy of programmed cell death 1 (PD - 1) inhibitors in patients with advanced cancer and HIV/acquired immunodeficiency syndrome (AIDS). Methods and Materials-We performed a prospective, open-label, nonrandomized, phase 1 single center study. Patients with advanced cancer and HIV/AIDS received the treatment of PD - 1 inhibitors (camrelizumab, 200 mg, administered intravenously every 3 weeks), along with combination antiretroviral therapy (cART) for HIV. Results-Sixteen participants (12 men and 4 women; median age, 46.5 (29 - 78) years) were enrolled; 1 had non - Hodgkin lymphoma (NHL), and 15 had non - AIDS - defining cancers. Safety was observed over 130 cycles of treatment with camrelizumab. Most treatment-emergent adverse events at least possibly attributed to camrelizumab were grade 1 or 2, including reactive cutaneous capillary endothelial proliferation (RCCEP) (9 participants), hearing loss (1 participant), hypophysitis (1 participant). 3 participants experienced hemorrhage due to poor performance status. HIV was controlled in all participants. Best tumor responses included 3 complete response, 5 partial response, 2 stable disease, and 6 progressive disease. The 2 years progression-free survival (PFS) was 67.0% (95% CI: -0.05, 0.00) and overall survival (OS) was 55.3% (95% CI: -0.05, 0.01) for the 16 patients who had received camrelizumab. Conclusions-This study demonstrates that camrelizumab treatment in patients with advanced cancers and HIV/AIDS was feasible and the clinical outcomes were acceptable.

To establish a plasma model to predict the risk of liver fibrosis in HIV/HBV co-infected individuals. Quantitative liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to identify differentially expressed proteins (DEPs) in plasma collected from HIV/HBV co-infected individuals with and without liver fibrosis. In total, 97 DEPs were identified, among which 11 were further validated as potential biomarkers, with immunoglobulin and complement components being the most common proteins. These markedly altered proteins were found to mediate pathophysiological pathways, including humoral immune response, complement and coagulation cascades, and complement activation. A visual logistic model, in which immunoglobulin heavy variable 3-20 (IGHV3-20), immunoglobulin heavy variable 1-24 (IGHV1-24), and macrophage colony-stimulating factor 1 receptor (CSF1R) proteins were included, has been established to predict liver fibrosis in HIV/HBV co-infected individuals. The preliminary conclusion showed that the combination of IGHV3-20, IGFHV1-24, and CSF1R is expected to become a predictive model for liver fibrosis in the context of HIV/HBV co-infection and a further validation should be performed.

Objective:To investigate the feasibility, efficacy and adverse reactions of programmed death-1(PD-1) inhibitors in patients with acquired immunodeficiency syndrome (AIDS) complicated with malignant tumor.Methods:From September 2020 to August 2021, patients with AIDS complicated with malignant tumor in Zhongnan Hospital of Wuhan University were enrolled. Data including basic information, laboratory test results, CD4 + T cell count, human immunodeficiency virus (HIV) viral load were collected. Patients were continuously administered intravenously PD-1 monoclonal antibody until disease progression or intolerant toxicity reaction occurred. Adverse reactions during treatment were recorded.And treatment outcomes were assessed once every 12 weeks after treatment. HIV viral load was measured after treatment once a week for four consecutive times, then once four weeks for two consecutive times, and then once every 12 weeks. Results:Ten patients were included in the study, including seven males and three females, three cases of Hodgkin′s lymphoma, two cases of cervical cancer and hepatocellular carcinoma respectively, one case of non-Hodgkin′s lymphoma, non-small cell lung cancer and anal cancer respectively. There were four patients with CD4 + T cell count of 100 to 200 cells/μL and two patients with CD4 + T cell count lower than 100 cells/μL. All patients had completed at least three cycles of treatment with PD-1 monoclonal antibody, HIV viral load remained lower than 20 copies /mL. Three cases achieved complete response and three cases achieved partial response. Adverse reactions were cutaneous capillary endothelial proliferation (CCEP) (seven cases), major bleeding (three cases), and hearing impairment (one case). Conclusions:PD-1 inhibitor has no adverse effect on the continuous suppression of HIV viral load and has an effect on tumor control, so it is a viable choice in AIDS patients complicated with tumor. However, due to its considerable adverse reactions, multidisciplinary cooperation is needed to reduce the risk of complications and deal with serious complications.

The identification of circulating proteins associated with acquired immunodeficiency syndrome-related non-Hodgkin lymphoma (AIDS-NHL) may help in the development of promising biomarkers for screening, diagnosis, treatment, and prognosis. Here, we used quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify differentially expressed proteins (DEPs) in plasma collected from patients with AIDS-NHL and human immunodeficiency virus (HIV)-infected patients without NHL (HIV+ ). Proteins with a log2 (fold change) in abundance >0.26 and p < 0.05 were considered differentially abundant. In total, 84 DEPs were identified, among which 20 were further validated as potential biomarkers, with immunoglobulin and complement components being the most common proteins. Some of the proteins were further verified in a retrospective analysis of the medical records of patients in a larger cohort. These markedly altered proteins were found to mediate pathophysiological pathways that likely contribute to AIDS-NHL pathogenesis, such as the humoral immune response, complement activation, and complement and coagulation cascades. Our findings provide a new molecular understanding of AIDS-NHL pathogenesis and provide new evidence supporting the identification of these proteins as possible biomarkers in AIDS-NHL.

BACKGROUND:Mental disorders linked with dysfunction in the temporal cortex, such as anxiety and depression, can increase the morbidity and mortality of people living with HIV (PLWHA). Expressions of both nucleobindin 1 (NUCB1) and cannabinoid receptor 1 (CNR1) in the neurons have been found to alter in patients with depressive disorder, but whether it is involved in the development of depression in the context of HIV infection is unknown. Objectives To investigate the effects of NUCB1 on depressive disorder among PLWHA and preliminarily explore the underlying molecular mechanisms.METHODS:Individuals who were newly HIV diagnosed were assessed on the Hospital Anxiety and Depression scale (HADS). Then SHIV-infected rhesus monkeys were used to investigate the possible involvement of the NUCB1 and the CNR1 protein in depression-like behavior.RESULTS:The prevalence rate of depression among PLWHA was 27.33% (41/150). The mechanism results showing elevated NUCB1 levels in cerebrospinal fluid from HIV-infected patients suffering from depression were confirmed compared to those of HIV-infected patients. Moreover, the immunohistochemical analysis indicated the expression of NUCB1 in the temporal cortex neurons of SHIV-infected monkeys was higher than that of the healthy control. Conversely, CNR1 expression was down-regulated at protein levels.CONCLUSIONS:Depression symptoms are common among PLWHA and associate with NUCB1 expression increases, and NUCB1 may be a potential target for depression.

Chronically SHIVSF162P3N-infected cynomolgus monkeys were used to determine the effects of the antibody-mediated acute CD4+ T cell depletion on viral load as well as on the immunological factors associated with disease progression. Compared with the control animals, CD4+ T cell-depleted animals with SHIV infection showed (i) little alteration in plasma viral load over the period of 22 weeks after the depletion; (ii) increased CD4+ T cell proliferation and turnover of macrophages at the early phase of the depletion, but subsequent decline to the basal levels; and (iii) little impact on the expression of the inflammatory cytokines and CC chemokines associated with disease progression. These findings indicate that the antibody-mediated acute CD4+ T cell depletion had minimal impact on plasma viral load and disease progression in chronically SHIVSF162P3N-infected cynomolgus monkeys. Future investigations are necessary to identify the key factor(s) related to the immune activation and macrophage infection during the CD4 deletion in chronic viral infection.

建立了一种培养及大量扩增中国恒河猴外周血γδT细胞的方法.采用Ficoll密度梯度离心法分离中国恒河猴(rhesus macaque)外周血单核细胞(peripheral blood mononuclear cells,PBMCs),用含5％猴自体血清、1 000U·mL-1白介素-2(IL-2)和不同浓度唑来膦酸(1,5,10 μmol·L-1)的OpTmizer细胞培养基进行培养,并使用流式细胞仪进行纯度及表型分析.结果 显示:使用含不同浓度唑来膦酸培养基诱导第8d时,1μmol·L-1和5μ上mol· L-1处理组的猴γδT细胞分别扩增至总细胞的91.4％和93.1％;5μmol·L-1处理组表达CD56、CD69及HLA-DR蛋白的猴γδT细胞占总细胞的比例分别为75.6％、75.5％以及78.0％;5μmol·L-1处理组表达干扰素IFN-γ的猴γδT细胞比例为84.8％.本研究通过优化培养基的组成成分,仅添加猴自体血清和IL-2即能有效诱导猴γδT细胞在体外的大量扩增,且培养得到的猴γδT细胞能够显著表达CD56、CD69、HLA-DR及IFN-γ,并具有较强的免疫激活和细胞杀伤作用.

目的建立中国恒河猴SHIVKU-1艾滋病模型,观察感染SHIVKU-1的中国恒河猴中枢神经系统损伤的病理改变特点。方法用SHIVKU-1感染2只中国恒河猴（编号WSH01和WSH02）,分别于感染后第72周和第70周出现严重艾滋病症状时执行安乐死。取脑组织的不同部位行常规病理切片,进行HE染色检查和免疫组织化学染色检查。结果 WSH01恒河猴感染晚期出现站立困难、行动迟缓、左半身控制能力丧失等明显的神经艾滋临床症状。WSH02恒河猴感染晚期全身耗竭,严重腹泻。HE染色检查WSH01恒河猴小脑、脑干、枕叶中可见多核巨细胞浸润和神经胶质小结形成;大脑皮层小胶质细胞增生;海马回神经元细胞减少、排列无序。病理诊断为艾滋病脑炎。WSH02猴仅在脑组织中观察到部分小胶质细胞结节,未见其他明显的神经病理损伤。免疫组化检查观察到在实验猴脑组织有两种主要的损伤形式,分别为典型的血管周病变和弥散性病变;大量活化巨噬细胞和小胶质细胞浸润和激活,多核巨细胞形成（CD68,CD163,Iba-1）;损伤部位SHIVKU-1病毒蛋白P28强阳性（SIV p28）;WSH01恒河猴海马回神经元细胞明显减少且排列无序（MAP2）。结论中国恒河猴SHIVKU-1感染导致中枢神经系统损伤,脑组织各部位表现出不同程度的病理改变,以大量巨噬细胞/小胶质细胞浸润、激活,并伴有病毒显著增殖为主。

Emerging evidences indicate that hepatitis B virus (HBV) infection is associated with non-Hodgkin lymphoma (NHL), but the mechanisms of HBV-induction lymphomagenesis remain unclear. In this report, retrospective analysis of the prevalence of hepatitis B surface antigen (HBsAg) among NHL cases demonstrated significantly higher HBsAg carrier rate among B-cell NHL cases than controls (other cancers except primary liver cancer) (adjusted odds ratio, 1.56; 95% confidence interval, 1.13-2.16). Furthermore, cells with an immortalization potential existed in the peripheral blood of 4 patients with chronic HBV infection. Characterization of these cells showed their immunophenotypes similar to that of the majority of HBsAg-positive B-cell NHL patients. Immunoglobulin (Ig) gene rearrangements confirmed the clonal Ig gene rearrangements. Cytogenetic analysis revealed abnormal karyotypes of these cells with an immortalization potential. Compared with cells with an immortalization potential that we previously found in B-cell NHL patients by the same way, these cells showed many similar features. In conclusion, cells with an immortalization potential existed in the part of patients with chronic HBV infection before lymphoma development and showed some malignant features. They may be the cellular basis of HBV-associated lymphomagenesis.

Isolation of viable circulating tumor cells (CTC) holds the promise for improving screening, early diagnosis, and personalized treatment of lymphoma. In this study, we isolated and characterized spontaneously immortalized B-lymphocyte (SIBC) lines from HIV-infected patients with and without Non-Hodgkin's Lymphoma (AIDS-NHL). A total of 22 SIBC lines was isolated from peripheral blood mononuclear cells (PBMC) of HIV-infected patients with (n = 40) and without (n = 77) clinically detectable NHL, but not from healthy individuals (n = 34). Of these, 8 SIBC lines named HIV-SIBC were generated from HIV-infected patients without AIDS-NHL (10%, 8/77), while 14 SIBCs named AIDS-NHL-SIBC were from 13 of the AIDS-NHL patients (32.5%, 13/40). Among the 14 AIDS-NHL-SIBCs, 12 were derived from AIDS-NHL patients with poor prognoses (survival time less than 1 year). SIBCs displayed markers typical of memory B cells (CD3(-)CD20(+)CD27(+)) with EBV infection. Moreover, AIDS-NHL-SIBCs were representative of CTC as evidenced by monoclonal Ig gene rearrangement, abnormal chromosomal karyotype, and the formation of xenograft tumors, while HIV-SIBCs generated harbored some features of tumor cells, none had the capacity of xenograft tumor formation, suggesting HIV-SIBC present the precursor of CTC. These results indicate that SIBCs is associated with poor prognosis in AIDS-NHL patients and can be isolated from HIV-infected patients with NHL and without NHL. This findings point to the need for further molecular characterization and functional studies of SIBCs, which may prove the value of SIBCs in the diagnosis, prognoses, and screening for NHL among HIV-infected patients.

Reliable tumor biomarkers for risk assessment, screening, detection, diagnosis, and prognosis remain an unmet need for patients with AIDS-Related Non-Hodgkin’s Lymphoma (AIDS-NHL) and its high risk population–HIV/AIDS patients. In this study, we generated spontaneously immortalized B lymphocyte cell (SIBC) lines by culturing peripheral blood mononuclear cells (PBMCs) derived from AIDS-NHL and HIV/AIDS patients, then evaluated their clinical significance for detection, diagnosis, and prognosis. From 34 AIDS-NHL and 71 HIV/AIDS patients, we generated 14 AIDS-NHL-SIBC and 6 HIV-SIBC lines, respectively. Among 14 AIDS-NHL-SIBC lines, 12 SIBCs were derived from patients with poor prognoses. All SIBCs presented main markers typical of memory B-cells (CD3−CD20+CD27+) and the majority of cells expressed NHL related immunologic proteins (BCL-2, MUM-1. Ki67, etc.). AIDS-NHL-SIBCs exhibited the typical biological characteristics of tumor cells, including monoclonal Ig gene rearrangement, abnormal chromosome, and growth of xenograft tumors in NOD/SCID mice, while HIV-SIBCs possessed partial tumor cell properties, but no xenograft tumors. These findings suggest that the AIDS-NHL-SIBC lines are representative of the malignant B-lymphocytes circulating in AIDS-NHL patients (CTC), while HIV-SIBC might be a CTC precursor in HIV/AIDS patients. These data provide evidence of a potentially valuable diagnostic and prognostic biomarker for AIDS-NHL patients, and present a basis for early screening of NHL among HIV/AIDS patients.

我国重大传染病的防治需要全社会的参与协作,将重大传染病纳入高等教育通识课具有现实意义.通过对重大传染病课程的学习,大学生可以提高自身健康卫生保护意识和能力,并积极关注社会公共健康问题,积极参与重大传染病的防治.这将有助于预防与控制重大传染病的流行.