Objective:To investigate and analyze the relationship between genotype and phenotype in patients with early-onset high myopia (eoHM) associated with hereditary eye diseases.Methods:A family-based study was conducted among 30 families diagnosed with eoHM at Department of Ophthalmology of People's Hospital of Ningxia Hui Autonomous Region from January 2022 to June 2023. Seven families (23.3%, 7/30), all probands, and their 14 parents were included. These seven families were unrelated. Detailed patient and family histories were collected. All participants underwent comprehensive ophthalmic examinations, including best-corrected visual acuity, color vision testing, fundus color photography, optical coherence tomography, fluorescein fundus angiography, and fundus autofluorescence imaging. Full-field electroretinography was performed in four cases. Peripheral venous blood samples were collected from patients and their parents for whole-genome DNA extraction and whole-exome sequencing. Potential pathogenic variants were identified, and their pathogenicity was analyzed and confirmed by Sanger sequencing. The pathogenicity of newly discovered gene variants was evaluated according to the guidelines of the American College of Medical Genetics and Genomics (ACMG). Literature on previously reported eoHM associated with hereditary eye diseases was reviewed to analyze the relationship between variant genes and clinical phenotypes.Results:Among the seven families, three exhibited X-linked inheritance, two showed autosomal recessive inheritance, and two demonstrated autosomal dominant inheritance. All the patients were male. Among the seven patients, one case each was identified with congenital stationary night blindness (CSNB), Bornholm eye disease, X-linked retinitis pigmentosa (XL-RP), cone-rod dystrophy, Knobloch syndrome, familial exudative vitreoretinopathy (FEVR), and Stickler syndrome. Genetic testing revealed nine gene variants highly correlated with the observed phenotypes. The genetic testing results revealed that all patients were found to carry nine gene variants highly associated with the phenotype, including: a hemizygous missense variant NYX c.647A>T (p.N216I) (M1), an OPN1LW LIAVA haplotype variant (M2), a hemizygous frameshift variant RPGR c.3096_3097del (p.E1033RfsTer45) (M3), compound heterozygous variants TTLL5 c.1588_1589del (p.L531EfsTer24) and c.850G>C (p.D284H) (M4, M5), compound heterozygous variants COL18A1 c.2118dup (p.G707RfsTer23) and c.3523_3524del (p.L1175VfsTer72) (M6, M7), a heterozygous missense mutation FZD4 c.1499C>T (p.T500I) (M8), and a heterozygous frameshift variant COL11A2 c.966dup (p.T323HfsTer19) (M9). Among them, M2, M4, M5, M8 and M9 were newly discovered mutation sites, and M1, M3, M6 and M7 were known mutation sites. According to the classification standards and guidelines of genetic variation issued by ACMG, M2, M3, M4, M6, M7, and M9 were judged to be pathogenic variants, while M1, M5, and M8 were of unknown clinical significance. Through literature review, it was found that eoHM was more common among the clinical phenotypes of 4 types of hereditary retinal diseases, including CSNB, Stickler syndrome, FEVR and XL-RP. Conclusion:eoHM is intricately associated with inherited eye diseases and may serve as the earliest indicator of such conditions.

Objective:To investigate and analyze the relationship between genotype and phenotype in patients with early-onset high myopia (eoHM) associated with hereditary eye diseases.Methods:A family-based study was conducted among 30 families diagnosed with eoHM at Department of Ophthalmology of People's Hospital of Ningxia Hui Autonomous Region from January 2022 to June 2023. Seven families (23.3%, 7/30), all probands, and their 14 parents were included. These seven families were unrelated. Detailed patient and family histories were collected. All participants underwent comprehensive ophthalmic examinations, including best-corrected visual acuity, color vision testing, fundus color photography, optical coherence tomography, fluorescein fundus angiography, and fundus autofluorescence imaging. Full-field electroretinography was performed in four cases. Peripheral venous blood samples were collected from patients and their parents for whole-genome DNA extraction and whole-exome sequencing. Potential pathogenic variants were identified, and their pathogenicity was analyzed and confirmed by Sanger sequencing. The pathogenicity of newly discovered gene variants was evaluated according to the guidelines of the American College of Medical Genetics and Genomics (ACMG). Literature on previously reported eoHM associated with hereditary eye diseases was reviewed to analyze the relationship between variant genes and clinical phenotypes.Results:Among the seven families, three exhibited X-linked inheritance, two showed autosomal recessive inheritance, and two demonstrated autosomal dominant inheritance. All the patients were male. Among the seven patients, one case each was identified with congenital stationary night blindness (CSNB), Bornholm eye disease, X-linked retinitis pigmentosa (XL-RP), cone-rod dystrophy, Knobloch syndrome, familial exudative vitreoretinopathy (FEVR), and Stickler syndrome. Genetic testing revealed nine gene variants highly correlated with the observed phenotypes. The genetic testing results revealed that all patients were found to carry nine gene variants highly associated with the phenotype, including: a hemizygous missense variant NYX c.647A>T (p.N216I) (M1), an OPN1LW LIAVA haplotype variant (M2), a hemizygous frameshift variant RPGR c.3096_3097del (p.E1033RfsTer45) (M3), compound heterozygous variants TTLL5 c.1588_1589del (p.L531EfsTer24) and c.850G>C (p.D284H) (M4, M5), compound heterozygous variants COL18A1 c.2118dup (p.G707RfsTer23) and c.3523_3524del (p.L1175VfsTer72) (M6, M7), a heterozygous missense mutation FZD4 c.1499C>T (p.T500I) (M8), and a heterozygous frameshift variant COL11A2 c.966dup (p.T323HfsTer19) (M9). Among them, M2, M4, M5, M8 and M9 were newly discovered mutation sites, and M1, M3, M6 and M7 were known mutation sites. According to the classification standards and guidelines of genetic variation issued by ACMG, M2, M3, M4, M6, M7, and M9 were judged to be pathogenic variants, while M1, M5, and M8 were of unknown clinical significance. Through literature review, it was found that eoHM was more common among the clinical phenotypes of 4 types of hereditary retinal diseases, including CSNB, Stickler syndrome, FEVR and XL-RP. Conclusion:eoHM is intricately associated with inherited eye diseases and may serve as the earliest indicator of such conditions.

Background::Total human immunodeficiency virus (HIV) DNA and integrated HIV DNA are widely used markers of HIV persistence. Droplet digital polymerase chain reaction (ddPCR) can be used for absolute quantification without needing a standard curve. Here, we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA.Methods::The limit of detection, dynamic ranges, sensitivity, and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat (LTR) and human CD3 gene (for total HIV DNA) and ACH-2 cells (for integrated HIV DNA). Forty-two cases on stable suppressive antiretroviral therapy (ART) were assayed in total HIV DNA and integrated HIV DNA. Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive (CD4 +) T-cell counts, CD8 + T-cell counts and CD4/CD8 T-cell ratio, respectively. The assay linear dynamic range and lower limit of detection (LLOD) were also assessed. Results::The assay could detect the presence of HIV-1 copies 100% at concentrations of 6.3 copies/reaction, and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction (95% confidence intervals [CI]: 3.6-6.5 copies/reaction) with linearity over a 5-log 10-unit range in total HIV DNA assay. For the integrated HIV DNA assay, the LLOD was 8.0 copies/reaction (95% CI: 5.8-16.6 copies/reaction) with linearity over a 3-log 10-unit range. Total HIV DNA in CD4 + T cells was positively associated with integrated HIV DNA ( r = 0.76, P <0.0001). Meanwhile, both total HIV DNA and integrated HIV DNA in CD4 + T cells were inversely correlated with the ratio of CD4/CD8 but positively correlated with the CD8 + T-cell counts. Conclusions::This ddPCR assay can quantify total HIV DNA and integrated HIV DNA efficiently with robustness and sensitivity. It can be readily adapted for measuring HIV DNA with non-B clades, and it could be beneficial for testing in clinical trials.

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

Objective To investigate the expression of autophagy marker in peripheral blood T and B lymphocytes of patients with autoimmune hepatitis (AIH) and its clinical significance. Methods Peripheral blood samples were collected from 62 AIH patients who were treated in Beijing YouAn Hospital affiliated to Capital Medical University from October 2019 to October 2020 who were treated in Beijing YouAn Hospital affiliated to Capital Medical University from October 2019 to October 2020 and 8 healthy controls to detect autophagy of T and B lymphocyte subsets, and then subgroup analyses were performed based on treatment, diagnostic type, and presence or absence of liver cirrhosis and liver failure. The t -test was used for comparison of normally distributed continuous data between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Mann-Whitney U test was used for comparison between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results Compared with the healthy control group, the AIH group had a significantly higher mean fluorescence intensity (MFI) of the autophagy marker LC3B in CD4 + T, CD8 + T, CD19 + B, and CD4 + CD25 + T lymphocytes (all P < 0.05), especially in CD19 + B lymphocytes. The non-treatment group and the partial remission group had a significantly higher MFI of autophagy marker in CD19 + B lymphocytes than the complete remission group ( P =0.037 and 0.040); the idiopathic AIH (I-AIH) group and the drug-induced AIH(DI-AIH) group had a significantly higher MFI than the primary biliary cholangitis (PBC)-AIH overlap syndrome group ( P =0.037 and 0.031); the non-cirrhosis group and the decompensated cirrhosis group had a significantly higher MFI than the compensated cirrhosis group ( P =0.009 and 0.003); the liver failure group had a significantly higher MFI than the non-liver failure group ( P =0.042). The PBC-AIH group had a significantly higher MFI of autophagy marker in CD4 + CD25 + T lymphocytes than the I-AIH group and the DI-AIH group ( P =0.042 and 0.044), the compensated cirrhosis group had a significantly lower MFI than the non-cirrhosis group ( P =0.037), and the non-liver failure group had a significantly higher MFI than the liver failure group ( P =0.043). Conclusion AIH patients have a significant increase in the expression of autophagy marker in peripheral blood T and B lymphocyte subsets compared with healthy individuals, and the level of autophagy is associated with treatment, diagnostic type, and disease severity.

Objectives To evaluate the association between serum cystatin C and carotid atherosclerosis.Methods Medical data,including physical examinations,serum levels of cystatin C,bilirubin,uric acid and other biochemical markers and duplex ultrasonographic scanning for the carotid artery,of 1741 healthy adults (1193 men and 548 women) who sought physical check-up at Peking Union Medical College Hospital during January 2010 and December 2011 were collected,and those with hypertension,diabetes and liver or renal function failure were excluded.Based on the results of carotid duplex uhrasonography,all the adults checked were assigned to two groups,one with thickened intima-media and atherosclerotic plaque (group A),the other with non-thickened intima-media and non-atherosclerotic plaque (group B).Difference in serum cystatin C,bilirubin,uric acid and other biochemical markers between the two groups was analyzed by using Student's t test.The correlation between the markers and carotid plaque was analyzed by using Spearman correlation analysis.The correlated factors of the carotid thickness and plaque appearance were analyzed by using unconditional Logistic regression analysis.Results Serum level of cystatin C was significantly increased in group A (t =-8.85,P ＜ 0.05).Thickness of carotid intima was positively correlated with serum cystatin C (r =0.21,P ＜ 0.05).In multivariate Logistic regression analysis,high level of serum cystatin C was not an independent risk factor of carotid atherosclerosis.Conclusion Relationship between serum cyatatin C and carotid atherosclerosis was not confirmed in our populations,which should be explored further in cohort studies.

OBJECTIVETo evaluate trends of overweight and obesity prevalence between 1996 and 2007 in Yi farmers and Yi migrants.

METHODSAn Yi migrant study was conducted in Liangshan Yi Autonomous Prefecture, Sichuan Province, China from 1996 to 2007. Data were collected with identical methods, including standardized questionnaire and body measurements.

RESULTSAge- and sex-specific body mass index (BMI) significantly increased from 20.02 in 1996 to 22.36 in 2007, among Yi farmers, which was significantly different from those among Yi migrants (23.67 in 2007 and 20.90 in 1996) (P<0.05). Prevalence of obesity rose from 1.21 % in 1996 to 4.55 % in 2007 (OR=1.15, P<0.001) in Yi migrants, while that in Yi farmers from none in 1996 to 0.12 % in 2007 (P>0.05). Prevalence of overweight rose significantly to 26.24 % in 2007 from 17.24 % in 1996 (OR=1.06, P<0.001) in Yi migrants, while that in Yi farmers from 1.29 % in 1996 to 4.45 % in 2007 (OR=1.14, P>0.001). Yi migrants appeared to have a 5.52-fold higher risk on developing overweight and obesity than Yi farmers have.

CONCLUSIONThe Yi migrants had a steeper increase of overweight with year and consequently caused more obesity. Change in lifestyle may contribute most likely to higher prevalence of overweight and obesity in Yi migrants.

Adult ; Agriculture ; statistics & numerical data ; trends ; Body Mass Index ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Obesity ; epidemiology ; Overweight ; epidemiology ; Prevalence ; Rural Population ; statistics & numerical data ; Transients and Migrants ; statistics & numerical data ; Urban Population ; statistics & numerical data ; Young Adult

BACKGROUNDUnhygienic blood collection in the early 1990s led to blood-borne infections in Central China. This study aimed to estimate human immunodeficiency virus (HIV) co-infection with hepatitis C and B viruses (HCV and HBV) and their risk factors in a rural area of Shanxi Province with a history of commercial blood donation.

METHODSA cross-sectional study was conducted in 2004. All adult residents in the target area were invited to participate in the study. Face-to-face interviews were completed and blood specimens were tested for HIV, HCV, and HBV surface antigen (HBsAg).

RESULTSPrevalence rates of HIV, HCV, and HBsAg were 1.3% (40/3 062), 12.7% (389/3 062), and 3.5% (103/2982), respectively. Of the 40 HIV-positive specimens, 85% were HCV positive and 2.5% were HBsAg positive. The history of commercial blood donation was positively associated with HIV, HCV, and HIV/HCV co-infections, but was negatively associated with HBsAg seropositivity. Migration for employment in the last 5 years was positively related to HIV, HBsAg, and HIV/HCV co-infections. Univariate logistic analysis showed that illegal drug use, number of sex partners, extramarital sex behavior, commercial sex behavior, and condom use rate were not related to anti-HIV, anti-HCV, HBsAg seropositivity or their co-infections.

CONCLUSIONThe history of commercial blood donation was the main risk factor for HIV, HCV, and HIV/HCV co-infections in this former commercial blood donation area. HIV and HCV prevention and treatment interventions are important in this area.

Adolescent ; Adult ; Blood Donors ; China ; epidemiology ; Cross-Sectional Studies ; Female ; HIV Infections ; epidemiology ; etiology ; Hepatitis B ; epidemiology ; etiology ; Hepatitis C ; epidemiology ; etiology ; Humans ; Male ; Middle Aged ; Transfusion Reaction ; Young Adult