Objective To analyze the status of persistent human papillomavirus (HPV) infection and the distribution of viral subtypes in the Zhengzhou region. Methods Clinical data of 55239 patients who underwent HPV-DNA genotyping tests from 2018 to 2024 were collected. On the basis of HPV follow-up results, patients were divided into three groups: 849 cases of infection with the same HPV type, 255 cases of persistent infection with different HPV types, and 857 cases of transient HPV infection. Results Among the 9232 initially-screened patients who were positive with HPV, the high-risk HPV (HR-HPV) positive rate was 84.6% (7813/9232), and predominant subtypes were HPV-16 (20.8%), HPV-52 (17.2%), and HPV-53 (9.6%). The low-risk HPV (LR-HPV) positive rate was 15.4% (1419/9232), mainly HPV-81 (28.1%) and HPV-42 (27.0%). Among the 1961 follow-up cases, the rates of persistent and non-persistent infections with the same HPV type were 35.7% (701/1961) and 7.5% (148/1961), respectively. The rates of persistent and non-persistent infections with different HPV types were 10.9% (214/1961) and 2.1% (41/1961), respectively. Meanwhile, 43.7% (857/1961) tested negative upon follow-up. Among the 701 cases of persistent infection with the same HPV type, HR-HPV accounted for 85.7% (601/701), and LR-HPV accounted for 14.3% (100/701). Among the 214 cases of persistent infection with different HPV types, 89.7% (192/214) were high-risk transitions, and 10.3% (22/214) were low-risk transitions. Regardless of HPV types, HR-HPV was more likely to cause persistent infection than LR-HPV. In addition, over 60% of HR-HPV persistent infections resolved within 18 months, 30% developed into persistent infections, and only 15% of patients had persistent infections that last more than 24 months. Conclusion Persistent HPV infections are predominantly high-risk types. Most patients clear the infection within 18 months, approximately 30% develop persistent infections, and about 15% of patients have persistent infections that last more than 24 months. However, the HR-HPV persistent infection rates across different age groups slightly differ.

Background::T-cell-mediated immunity is crucial for the effective clearance of viral infection, but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with human immunodeficiency virus (PLWH) remain unclear.Methods::Forty-five PLWH who had received antiretroviral therapy (ART) for more than two years and 29 healthy controls (HCs) at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose (week 0) and 4 or 12 weeks (week 4 or week 12) after receiving the third dose of inactivated SARS-CoV-2 vaccine. Flow cytometry, enzyme-linked immunospot (ELISpot), and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this study.Results::The results of the ELISpot and activation-induced marker (AIM) assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine, and a similar magnitude of immune response was induced against the Omicron (B.1.1.529) variant compared to the wild-type strain. In detail, spike-specific T-cell responses (measured by the ELISpot assay for interferon γ [IFN-γ] release) in both PLWH and HCs significantly increased in week 4, and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third vaccination. In the AIM assay, spike-specific CD4 + T-cell responses peaked in both PLWH and HCs in week 12. Additionally, significantly higher spike-specific CD8 + T-cell responses were induced in PLWH than in HCs in week 12. In PLWH, the release of the cytokines interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), and IL-22 by peripheral blood mononuclear cells (PBMCs) that were stimulated with spike peptides increased in week 12. In addition, the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week 12. Interestingly, the magnitude of SARS-CoV-2-specific T-cell responses in PLWH was negatively associated with the extent of CD8 + T-cell activation and exhaustion. In addition, positive correlations were observed between the magnitude of spike-specific T-cell responses (determined by measuring IFN-γ release by ELISpot) and the amounts of IL-4, IL-5, IL-2 and IL-17F. Conclusions::Our findings suggested that SARS-CoV-2-specific T-cell responses could be enhanced by the booster dose of inactivated COVID-19 vaccines and further illustrate the importance of additional vaccination for PLWH.

Background::Cluster of differentiation 8 (CD8 T) cells play critical roles in eradicating human immunodeficiency virus (HIV)-1 infection, but little is known about the effects of T cells expressing CD8 at low levels (CD8 low) or high levels (CD8 high) on HIV-1 replication inhibition after HIV-1 invasion into individual. Methods::Nineteen patients who had been acutely infected with HIV-1 (AHI) and 20 patients with chronic infection (CHI) for ≥2 years were enrolled in this study to investigate the dynamics of the quantity, activation, and immune responses of CD3 +CD8 low T cells and their counterpart CD3 +CD8 high T cells at different stages of HIV-1 infection. Results::Compared with healthy donors, CD3 +CD8 low T cells expanded in HIV-1-infected individuals at different stages of infection. As HIV-1 infection progressed, CD3 +CD8 low T cells gradually decreased. Simultaneously, CD3 +CD8 high T cells was significantly reduced in the first month of AHI and then increased gradually as HIV-1 infection progressed. The classical activation of CD3 +CD8 low T cells was highest in the first month of AHI and then reduced as HIV-1 infection progressed and entered the chronic stage. Meanwhile, activated CD38 -HLA-DR +CD8 low T cells did not increase in the first month of AHI, and the number of these cells was inversely associated with viral load ( r = -0.664, P = 0.004) but positively associated with the CD4 T-cell count ( r = 0.586, P = 0.014). Increased programmed cell death protein 1 (PD-1) abundance on CD3 +CD8 low T cells was observed from the 1st month of AHI but did not continue to be enhanced, while a significant T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) abundance increase was observed in the 12th month of infection. Furthermore, increased PD-1 and TIGIT abundance on CD3 +CD8 low T cells was associated with a low CD4 T-cell count (PD-1: r = -0.456, P = 0.043; TIGIT: r = -0.488, P = 0.029) in CHI. Nonetheless, the nonincrease in PD-1 expression on classically activated CD3 +CD8 low T cells was inversely associated with HIV-1 viremia in the first month of AHI ( r = -0.578, P = 0.015). Notably, in the first month of AHI, few CD3 +CD8 low T cells, but comparable amounts of CD3 +CD8 high T cells, responded to Gag peptides. Then, weaker HIV-1-specific T-cell responses were induced in CD3 +CD8 low T cells than CD3 +CD8 high T cells at the 3rd and 12th months of AHI and in CHI. Conclusions::Our findings suggest that CD3 +CD8 low T cells play an anti-HIV role in the first month of infection due to their abundance but induce a weak HIV-1-specific immune response. Subsequently, CD3 +CD8 low T-cell number decreased gradually as infection persisted, and their anti-HIV functions were inferior to those of CD3 +CD8 high T cells.

BACKGROUND: T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines. METHODS: Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT + CD4 + and TIGIT + CD8 + T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose. RESULTS: Compared to that in HCs, the frequency of TIGIT + CD8 + T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT + CD8 + T cells also increased. A decrease in the ratio of both T naïve (T N ) and central memory (T CM ) cells among TIGIT + CD8 + T cells and an increase in the ratio of the effector memory (T EM ) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT + CD8 + T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT + CD8 + T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT + CD8 + T cells in PLWH were significantly weaker than those of TIGIT - CD8 + T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT + CD8 + T cells and TIGIT - CD8 + T cells was insignificant at 4W and 12W, except at 0W. CONCLUSIONS TIGIT expression on CD8 + T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8 + T cells, thereby enhancing the effectiveness of vaccination.
Humans ; Antibodies, Viral ; CD8-Positive T-Lymphocytes ; COVID-19/complications* ; COVID-19 Vaccines/immunology* ; HIV Infections/complications* ; Receptors, Immunologic ; SARS-CoV-2

Background::It is controversial whether the apolipoprotein E epsilon 4 allele ( APOE ε4) is a risk gene for human immunodeficiency virus (HIV)-related neurocognitive impairment. This meta-analysis aimed to summarize evidence of the associations between APOE ε4 and cognitive impairment in people living with HIV (PLWH). Methods::Our study conducted a systematic literature search of PubMed, Web of Science, Embase, Google Scholar, and ProQuest for studies published before April 11, 2022 that evaluated associations between APOE ε4 and cognitive impairment in adult PLWH (aged ≥18 years). We calculated pooled odds ratios (ORs) of global cognitive impairment and 95% confidence intervals (CIs) and standardized mean differences (SMDs) for specific cognitive domains between APOE ε4 carriers and non-carriers. Subgroup meta-analyses were used to evaluate the result profiles across different categorical variables. Results::Twenty studies met the inclusion criteria, including 19 that evaluated global cognitive impairment. APOE ε4 was significantly associated with global cognitive impairment in PLWH (OR = 1.36, 95% CI = [1.05, 1.78], number of estimates [ k] = 19, P = 0.02, random effects). Subgroup meta-analysis based percentage of females showed evident intergroup differences in global cognitive performance between ε4 carriers and non-carriers ( P = 0.015). APOE ε4 carriers had lower cognitive test scores than non-carriers in all seven cognitive domains, including fluency (SMD = -0.51, 95% CI = [-0.76, -0.25], P < 0.001, k = 4, I2= 0%), learning (SMD = -0.52, 95% CI = [-0.75, -0.28], P < 0.001, k = 5, I2 = 0%), executive function (SMD = -0.41, 95% CI= [-0.59, -0.23], P < 0.001, k= 8, I2= 0%), memory (SMD=-0.41, 95% CI= [-0.61, -0.20], P < 0.001, k= 10, I2= 36%), attention/working memory (SMD=-0.34, 95% CI= [-0.54, -0.14], P= 0.001, k= 6, I2= 0%), speed of information processing (SMD = -0.34, 95% CI = [-0.53, -0.16], P < 0.001, k = 8, I2 = 0%), and motor function (SMD = -0.19, 95% CI = [-0.38, -0.01], P = 0.04, k = 7, I2 = 0%). Conclusions::Our meta-analysis provides significant evidence that APOE ε4 is a risk genotype for HIV-associated cognitive impairment, especially in cognitive domains of fluency, learning, executive function, and memory. Moreover, the impairment is sex specific. Meta analysis registration::PROSPERO, CRD 42021257775.

Objective:To investigate the relationship between serum vascular endothelial growth factor (VEGF) levels and white matter high signal and non-dementia vascular cognitive dysfunction in patients with cerebral small vascular disease (CSVD).Methods:Total 106 patients with CSVD who were admitted to the Department of Neurology of the First Affiliated Hospital of Xinxiang Medical College from April 2019 to December 2020 were enrolled.They were divided into vascular cognitive impairment no dementia group (VCIND group, n=47) and no vascular cognitive impairment group (N-VCI group, n=59)according to mini-mental assessment scale (MMSE), Montreal cognitive assessment (MoCA) scale and activity of daily living scale (ADL). Serum VEGF levels were detected by enzyme-linked immunosorbent assay (ELISA). The baseline data, serum VEGF levels, MoCA score and Fazekas score were compared between the two groups.The correlation between serum VEGF level and white matter high signal and cognitive function was analyzed.SPSS 19.0 software was used for data processing.The statistical methods were t-test, Chi square test, nonparametric test, Logistic regression analysis, Pearson correlation analysis and Spearman correlation analysis. Results:There were significant differences in serum VEGF level((464.18±114.58)pg/mL, (414.17±45.80)pg/mL, F=22.880), MoCA score((13.07±6.48), (20.17±4.06), F=17.920) and Fazekas score (4(3, 5), 3(1, 3), Z=-4.189)between the two groups (all P<0.05). The level of VEGF( β=0.008, OR=1.008, 95% CI=1.001-1.015, P<0.05) was the influencing factor of cognitive function in patients with CSVD .The level of VEGF was negatively correlated with the total score of MoCA, attention and calculation power, and orientation ability ( r=-0.345, -0.373, -0.445, all P<0.05) and it was positively correlated with the total Fazekas score and the Fazekas score of paraventricular and deep white matter ( r=0.392, 0.495, 0.302, all P<0.05). There was a linear trend between the high signal grade of paraventricular and deep white matter and VCIND (both P<0.05). Conclusion:Serum VEGF level is correlated with cognitive function and white matter hyperintensity in patients with CSVD.The increase of VEGF level may be a factor reflecting cognitive dysfunction.In addition, with the increase of white matter hyperintensity level, the risk of VCIND in CSVD is increased.

Objective:To investigate the changes in adaptive phenotypes of Yersinia pestis ( Yp) during successive passages in macrophages. Methods:A Yp strain of 201-MI was induced by 50 successive passages of Yp 201 strain in Raw264.7 cells. Phenotypic characteristics of 201 and 201-MI strains were compared by analyzing their survival rates in macrophages, growth curves, biofilm formation abilities, acid and hydrogen peroxide-stress tolerance, and virulence to mammal cells (Raw264.7 and HeLa cells) and mice. Results:Comparing with 201 strain, 201-MI strain showed various phenotypic changes, including higher survival rate in Raw264.7 cells, faster growth in iron-deficient medium, higher tolerance to acid and hydrogen peroxide, decreased biofilm formation ability, and less damages to Raw264.7 and HeLa cells. More-over, 201-MI strain showed decreased virulence to mice in both subcutaneous and intraperitoneal challenges. Preliminary comparative genomics analysis revealed some indel and nonsense mutations in 201-MI strain, which might account for its phenotype changes.Conclusions:After successive passages in macrophages, Yp showed some phenotypic changes, which might reflect its adaptive evolution under the pressure of macrophages. Detailed multi-omics analysis would be of great help to understand the underlying genetic mechanisms of these changes, and the related Yp-macrophage interaction processes as well.

Purpose: The aim of the study was to evaluate the status of psychological resilience among women in their second pregnancy and to investigate the possible influencing factors. Methods: A total of 275 women in their second pregnancy and who met the criteria were surveyed from two public hospitals in China from July 2018 to January 2019. The instruments included the General Self-designed Questionnaire, Connor–Davidson Resilience Scale, Social Support Rate Scale, and 36-item Pregnancy Stress Rating Scale. Results: The total psychological resilience score of second-pregnancy women was relatively low. Multivariate regression analysis identified five factors associated with psychological resilience: intimacy with husbands, social support utilization, gender of the first child, high-risk pregnancy of the first child, and the stress caused by worrying about the health and safety of the mother and fetus. Conclusion Women in their second pregnancy represent a unique population, and their low psychological resilience score deserves attention. Identification of factors contributing to decreased psychological resilience may enable us to design prevention and intervention strategies and to deliver specific psychological supports to pregnant women at high risk of developing negative psychology.

Objective:To investigate the relationship between serum matrix metalloproteinase-9 (MMP-9) level and the location and severity of bleeding in patients with cerebral microbleeds(CMBs).Methods:A total of 60 CMBs patients admitted to the Department of Neurology of the First Affiliated Hospital of the Xinxiang Medical University from January 2019 to August 2020 were selected as subjects as the CMBs group, and 60 healthy controls without nervous system diseases in outpatient physical examination during the same period were selected as the control group. The clinical data and biochemical indicators of the two groups were collected. Serum MMP-9 levels were measured by enzyme linked immunosorbent assay (ELISA). According to susceptibility weighted imaging (SWI), CMBs patients were divided into grade 1 group ( n=24), grade 2 group ( n=19) and grade 3 group ( n=17), and according to the micro analytical rating scale (MARS), the CMBs patients were divided into the lobar group ( n=19), the deep or infratentorial group ( n=17) and the mixed group ( n=24).The relationship between serum MMP-9 level and the location and severity of CMBs was analyzed. SPSS 19.0 software was used for data statistical analysis.One-way ANOVA, t-test and rank sum test were used for comparison. Logistic regression analysis was used to analyze the influencing factors. Pearson correlation analysis and Spearman correlation analysis were used for correlation analysis. Results:The level of MMP-9 in CMBs group was significantly higher than that in control group (208.13(142.25, 285.88) μg/L, 149.50(93.40, 186.51)μg/L), and the difference was statistically significant ( P<0.05). Serum MMP-9 level was a risk factor of CMBs ( β=1.322, OR=3.750, 95% CI=2.038-7.997, P=0.002). The difference of level of MMP-9 in different severity of CMBs was statistically significant (147.55(109.25, 266.47)μg/L, 242.12(147.55, 288.80)μg/L, 270.42(203.43, 364.27)μg/L, P=0.017). Serum MMP-9 level was positively correlated with the number of CMBs ( r=0.371, P=0.003). The difference of MMP-9 level of CMBs in different locations were statistically significant (249.77(158.43, 338.46)μg/L, 188.83(138.52, 243.15)μg/L, 210.65(144.25, 255.78)μg/L, P=0.013). The increased serum MMP-9 level was a risk factor for CMBs( β=0.401, OR=1.122, 95% CI=1.004-1.204, P=0.036). Conclusion:The increased level of serum MMP-9 may be a risk factor of CMBs, especially for CMBs in cerebral lobesand, and the level of MMP-9 is positively correlated with the severity of CMBs.

Purpose: The aim of the study was to evaluate the status of psychological resilience among women in their second pregnancy and to investigate the possible influencing factors. Methods: A total of 275 women in their second pregnancy and who met the criteria were surveyed from two public hospitals in China from July 2018 to January 2019. The instruments included the General Self-designed Questionnaire, Connor–Davidson Resilience Scale, Social Support Rate Scale, and 36-item Pregnancy Stress Rating Scale. Results: The total psychological resilience score of second-pregnancy women was relatively low. Multivariate regression analysis identified five factors associated with psychological resilience: intimacy with husbands, social support utilization, gender of the first child, high-risk pregnancy of the first child, and the stress caused by worrying about the health and safety of the mother and fetus. Conclusion Women in their second pregnancy represent a unique population, and their low psychological resilience score deserves attention. Identification of factors contributing to decreased psychological resilience may enable us to design prevention and intervention strategies and to deliver specific psychological supports to pregnant women at high risk of developing negative psychology.