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 study the detection performance of HBsAg single-ELISA-reactive samples of blood donors. 【Methods】 Two kinds of ELISA reagents from different manufacturers (named as reagents A and B) were used for HBsAg screening. A total of 276 samples, from January 2017 to May 2021, with HBsAg single-ELISA-reactive results were collected for further nucleic acid detection technology (NAT) and chemiluminescence immunoassay (CLIA) testing, to undergo HBV-DNA and five hepatitis B tests, respectively. The relationship between HBsAg single-ELISA-reactivity, NAT and CLIA was statistically analyzed. 【Results】 Among the 276 HBsAg single-ELISA-reactive samples, 14 were NAT reactive, with the positive rate of 5.07% (14/276). Fisher′s exact test was used to compare the compliance of reagents A and B with NAT reactivity, and the difference was not statistically significant (P<0.05). Among 14 HBsAg+ /NAT+ samples retested by CLIA, 2 were HBsAg reactive(14.29%, 2/14), 13 were anti-HBc reactive (92.86%, 13/14), 9 had the quantitative value of anti-HBs <10 mIU/mL, 5 had the quantitative value of anti-HBs between 10 to 100mIU/ mL. A total of 5 serological patterns were detected, and anti-HBe+ /anti-HBc+ pattern was the dominant. There were 262 cases of HBsAg+ /NAT- samples, but only 1 (0.38%, , 1/262) case was HBsAg reactive by CLIA, 100 were anti-HBc reactive (38.17%, 100/262), 144 (54.96%, 144/262) were anti-HBs reactive, and 1 was HBeAg reactive. A total of 8 serological patterns were detected. 【Conclusion】 Most of HBsAg single-ELISA-reactive results are false, and NAT could effectively reduce the residual risk of transfusion transmitted diseases.

HIV infection is a serious challenge to global public health. Timely and accurate early diagnosis and early initiation of antiretroviral therapy can effectively resist the spread of the virus, and improve the immune function of HIV-infected patients, thereby improve patients′ outcomes and reduce patients′ hospitalization and mortality. Efficient and sensitive testing is a prerequisite for early diagnosis of HIV infection and is also a focus in the prevention and control of HIV epidemics. Serologic testing has been the most widely used HIV detection technology till now. However, it has been difficult for the traditional antibody detection technology to detect HIV acute infection in a timely and accurate manner and therefore restricted the early diagnosis of HIV infection. In recent years, a variety of new detection technologies, such as HIV antigen/antibody combined detection and biosensors, with their high sensitivity, have significantly shortened the window period for the diagnosis of HIV infection, bringing new hope for early diagnosis of HIV. This paper reviews the principle, scope of application, and application prospect of serological detection technology for HIV infection and provides a reference for the development of new HIV testing strategies.

Objective:To verify the accuracy and feasibility of radioactive 125I seed implantation assisted by an optical navigation system and a 3D-printing non-coplanar template in the treatment of recurrent head and neck cancers. Methods:A total of 12 patients with recurrent head and neck cancer treated with radioactive 125I seed implantation assisted by an optical navigation system and 3D-printing non-coplanar template were enrolled from Dec 2018 to Dec 2019.The pre-plan and post-implant implantation needle number and implanted seed number were recorded.Meanwhile, their dosimetric parameters were compared, including D90, minimum peripheral dose (MPD), V100, V150, V200, conformity index (CI), external index (EI), and the homogeneity index (HI) of the target volume. Results:The median lesion volume was 31.5 cm 3, the median number of seeds was 61.5, and the median prescription dose was 130 Gy.The means of the pre-plan D90, MPD, V100, V150 and V200 were 134.2, 64.6, 93.3, 75.3 and 39.3 Gy, respectively, while those of post-implant D90, MPD, V100, V150, and V200 were 146.7, 68.94, 97.47, 80.40 and 48.30 Gy, respectively, with no statistically significant difference ( P>0.05). Meanwhile, there was no statistically significant difference between the pre-plan and post-implantation needle number, implanted seed number, CI, HI, and EI ( P>0.05). In terms of postoperative dose quality assessment, eight cases were rated excellent (66.6%) and four cases were rated good (33.3%). Conclusions:Radioactive 125I seed implantation assisted by an optical navigation system and 3D-printing non-coplanar template can be accurately performed in the treatment of recurrent head and neck cancer, with good consistency between pre-plan and post-implant dosimetric parameters and thus of prospective potential in clinical application.

Objective:To investigate the accuracy and feasibility of 3D-printing individualized template-guided and CT-guided 192Ir interstitial brachytherapy in the central recurrent gynecologic tumors by comparing pre-plan and intraoperative physical dosimetric parameters. Methods:This study involved 38 patients with central recurrent gynecologic tumors who underwent 3D printing individual template (3D-PIT)-assisted and CT-guided 192Ir interstitial brachytherapy in the Department of Radiation Oncology of the Peking University Third Hospital from Jan 2018 to Dec 2019.The prescription doses for the target tumor areas were 10-36 Gy to be delivered at 5-6 Gy/fraction for 2-6 fractions.The pre-plan and intraoperative dosimetric parameters were compared, including the minimum prescription doses delivered to 90% and 100% of target volume( D90, D100)and the mean percentage of volume receiving 100% of the prescription doses ( V100). Meanwhile, the doses delivered to 2 cm 3 ( D2 cm 3) of organs at risk (bladders, rectums, and colons) were analyzed.The quality parameters of the brachytherapy were studied, including conformity index (CI), homogeneity index (HI), and external index (EI) of the target volume.Perioperative complications were also observed. Results:A total of 194 treatments were included.During the treatment, 5-13 (median 6) needles were inserted, with a prescription dose of 5-6 Gy per fraction.There were no statistical differences between pre-plan and intraoperative D90, D100, V100, CI, HI, and EI as well as the D2 cm 3 of bladders and colons at risk ( P>0.05). In contrast, for the D2 cm 3 of rectums, the intraoperative dose was slightly higher than the pre-plan dose, showing a statistical difference ( t=-0.335, P=0.027). Conclusions:The 3D-PIT-assisted and CT-guided 192Ir interstitial brachytherapy at a high dose rate is accurate and feasible in the treatment of recurrent gynecologic tumors, meeting the pre-plan dose requirement.

【Objective】 To study and analyze the profile of irregular antibodies among voluntary blood donors in Jiaxing area. 【Methods】 The ABO and RhD blood groups of all voluntary blood donors from November 2018 to November 2020 were detected by DIAGAST QWALYS 3 automatic blood group analyzer. According to routine serological screening program of irregular antibody, the samples reactive to O blood cell were sent to the reference laboratory for further identification of the antibody specificity, and the specificity and distribution characteristics of irregular antibodies were analyzed statistically. 【Results】 A total of 79 samples presenting irregular antibodies were yielded out of 90 854 blood samples, with a positive rate of 0.087%. More female samples (n=44) than male (n=35) (P<0.05). 29 donors aged 18 to 31, 33 aged 32 to 45, and 17 aged over 45 years old (P<0.05). 73 samples were RhD positive and 6 were RhD negative (P< 0.05). 40 only donated once, and 39 donated more than twice (P>0.05). 【Conclusion】 Female, RhD negative and more than 45 years old blood donors are more likely to present irregular antibodies, regardless of the number of blood donations.

Objective:To understand the characteristics of brucellosis in key population in rural areas of Hulunbuir City, Inner Mongolia Autonomous Region, and clarify the influencing factors of brucellosis infection, such as knowledge, belief and behavior, so as to provide scientific basis for the formulation of brucellosis prevention strategies and measures.Methods:A case-control study was used to study the confirmed cases of brucellosis among the key population of brucellosis in Hulunbuir rural areas in 2018. The patients without brucellosis were selected as control group. A questionnaire survey was used to investigated brucellosis related knowledge. The health-related behaviors (including raising livestock, cleaning houses, wells shared by human and livestock, immunizing livestock) were analyzed by single factor variation analysis and logistic regression analysis.Results:This study investigated 892 cases of population, 881 people responded effectively to the questionnaire, including 445 males, accounting for 50.51%, 436 females, accounting for 49.49%; the age range of 5-83 years old, the average age of (51.34 ± 11.87) years old; 153 cases of brucellosis antibody positive. The infection rate of brucellosis in this area was 17.37%, in which the male infection rate was 22.47%(100/445), and the female infection rate was 12.16% (53/436). There was a significant difference between male and female(χ 2=16.331, P < 0.05). Logistic regression analysis showed that raising cattle, cleaning houses, wells shared by human and livestock, using manure from cattle and sheep to fertilize, immunizing livestock were risk factors of brucellosis infection ( OR=1.905, 1.568, 1.320, 1.428, 1.488, P < 0.05). Conclusions:The incidence rate of brucellosis in Hulunbuir is higher than that in females. Close contact with infectious livestock and their excreta is a risk factor for brucellosis infection. According to the results of this survey. It is necessary to strengthen health education and behavior intervention of key population in order to effectively prevent and control brucellosis.

Objective To investigate the prognostic value of preoperative fibrinogen and albumin ratio (FAR) in patients with gallbladder carcinoma.Methods The clinicopathological data of 100 patients with gallbladder carcinoma who undergoing radical resection at Beijing Hospital from Feb 2007 to Feb 2019were retrospectively analyzed.The receiver operating characteristic (ROC) curve was drawn to determine the optimal cut-off value of FAR,and the prognostic factors were evaluated by Kaplan-Meier method,univariate and multivariate analysis.Results The optimal cut-off value of preoperative FAR for postoperative overall survival was 0.08.FAR was significantly associated with preoperative total bilirubin (TBil)levels,tumor differentiation,T stage,TNM stage,resection margin status,and preoperative CA199 levels (all P＜0.05).Multivariate analysis indicated that TNM staging (HR =3.562,95％ CI:1.075-11.798,P =0.038) and FAR (HR =2.482,95％ CI:1.263-4.875,P =0.008) were independent prognostic factors in patients with gallbladder carcinoma who underwent radical surgery.Conclusion Preoperative FAR is closely related to the prognosis of patients with gallbladder carcinoma and might be useful for the evaluation of prognosis of patients with gallbladder carcinoma.

Objective: To analyze the residual risk of transfusion transmitted hepatitis B virus (HBV) infection by enzyme-linked immunosorbent assay (ELISA) method in hepatitis B surface antigen (HBsAg) negative blood donors, and to assess the infection status. Methods: A total of 45551 samples were collected from blood donors.All samples were tested by 2 different ELISA kids of HBsAg and nucleic acid testing (NAT) individually of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Those ELISA HBsAg negative and NAT single reactive (HBsAg-/HBV DNA+ ) specimens were analyzed by quantitative detection of HBV DNA and by serologic testing of HBV antigen and antibody. Results: A total of 44 HBsAg-/HBV DNA+ samples were detected, including 42 occult HBV infections (OBI) and 2 window period infections (WP). The detection rate of OBI rate was 0.90‰, and 32 samples of OBI sample HBV DNA was less than 20 IU/ml, and the OBI detection rate was significantly different between different genders, ages and blood donation times (P<0.05). In the OBI sample, there were 6 serological models, 92.9%(39/42) OBI samples hepatitis B core antibody (HBcAb) positive, and 76.9%(30/39) HBV DNA in HBcAb positive samples were less than 20 IU/ml; 29.5% (13/42) of OBI blood donors hepatitis B e antigen (HBeAb) and HBcAb were also positive, of whom 84.6% (11/13) were HBV DNA quantitatively <20 IU/ml. Conclusions HBV residual risk of transfusion-transmitted infection may occur through HBsAg- and single NAT reactive blood donors, mainly include OBI, and HBV DNA low level. Blocking of single NAT reactive blood donors could reduce transfusion-transmitted HBV infection.

AIM:To investigate the effect of vitamin D3 up-regulated protein 1 (VDUP1) gene over-expression/knockdown on the proliferation and migration of human breast cancer MCF-7 cells and its related mechanisms.METHODS:Gene over-expression/interference techniques were used to up-regulate/down-regulate the expression of VDUP1 in the MCF-7 cells.The mRNA expression of VDUP1 was detected by qPCR.CCK-8, BrdU and Transwell assays were used to measure the cell viability, proliferation and migration, respectively.The protein levels of Akt, p-Akt, GSK3β and p-GSK3β were determined by Western blot.RESULTS:The mRNA expression of VDUP1 was up-regulated after transfection with VDUP1 over-expression plasmid (P<0.05), and down-regulated after transfection with VDUP1 siRNA (P<0.05).Over-expression of VDUP1 significantly inhibited MCF-7 cell proliferation and migration (P<0.05), while knockdown of VDUP1 enhanced cell proliferation and migration (P<0.05).Furthermore, over-expression of VDUP1 up-regulated the protein levels of p-Akt and p-GSK3β (P<0.05).Inverse results were obtained after knockdown of VDUP1.CONCLUSION:The viability and migration ability of MCF-7 cells are inhibited by over-expression of VDUP1 but enhanced by VDUP1 knockdown, which may be related with Akt/GSK3β pathway.