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Introducción: Los diabéticos muestran una disminuida función del sistema inmune. Su complicación más temida es la aparición de las úlceras del pie. El Heberprot-P® tiene efectos beneficiosos en la curación de estas úlceras. Objetivo: Evaluar el efecto de la inmunidad celular en el tratamiento de las úlceras del pie diabético con Heberprot-P®. Métodos: Se realizó un estudio observacional, prospectivo, de serie de casos, en 30 pacientes con úlcera de pie diabético, ingresados en el Instituto Nacional de Angiología y Cirugía Vascular. Se administraron 75 µg de Heberprot-P®, tres veces por semana, a través de vías peri- e intralesional, durante ocho semanas. Se evaluaron las variables edad, sexo, glucemia en ayunas, creatinina, urea, ácido úrico, prueba de hipersensibilidad retardada, porcentaje de granulación, tiempo de cierre de la lesión y localización de la úlcera, antes de comenzar el tratamiento, a las 4 y 8 semanas. Resultados: Se precisó un predominio del 60 por ciento en el sexo femenino y del color de piel blanca. Los niveles de glucemia y creatinina se comportaron más elevados en los anérgicos; la urea fue similar tanto en anérgicos como en reactivos; y el ácido úrico resultó mayor en hombres reactivos y en mujeres anérgicas. Hubo mayor proporción de reactivos (63,6 por ciento), que en la cuarta semana presentaron un tejido de granulación igual o mayor al 50 por ciento; y a la octava, igual o mayor al 70 por ciento. Conclusiones: La condición en los pacientes diabéticos de ser reactivo a las pruebas de hipersensibilidad retardada con úlcera de pie diabético de tipo neuropática, tratados con Heberprot-P®, está asociada directamente con una mejor respuesta en la cicatrización de sus lesiones, mediante la formación del tejido de granulación, que favorece el cierre total o parcial de la lesión. Esto no ocurrió con los pacientes anérgicos a dicha prueba(AU)
Introduction: Diabetics show decreased immune system function. Its most feared complication is the appearance of foot ulcers. Heberprot-P® has beneficial effects in healing these ulcers. Objective: To assess the effect of cellular immunity in the treatment of diabetic foot ulcers with Heberprot-P®. Methods: An observational, prospective, case series study was conducted in 30 patients with diabetic foot ulcer admitted to the National Institute of Angiology and Vascular Surgery. 75 µg of Heberprot-P®, three times a week, were administered through peri- and intralesional routes, during eight weeks. The variables age, sex, fasting blood glucose, creatinine, urea, uric acid, delayed hypersensitivity test, percentage of granulation, time of closure of the lesion and location of the ulcer, before starting treatment, at 4 and 8 weeks were evaluated. Results: A predominance of 60 % in females and white skin color were specified. Blood glucose and creatinine levels behaved higher in the anergics; urea was similar in both anergics and reagents; and uric acid was higher in reactive men and anergic women. There was a higher proportion of reagents (63.6 por ciento), which in the fourth week presented a granulation tissue equal to or greater than 50 por ciento; and at the eighth week, it was equal to or greater than 70 por ciento. Conclusions: The condition of being reactive to delayed hypersensitivity tests in diabetic patients with diabetic foot ulcer of neuropathic type, treated with Heberprot-P® is directly associated with a better response in the healing of their lesions, through the formation of granulation tissue, which favors the total or partial closure of the lesion. This did not occur with patients who were anergic to this test(AU)
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Humans , Diabetic Foot/epidemiology , Prospective Studies , Observational Studies as TopicABSTRACT
Objective:To investigate the incidence of immune reconstitution inflammatory syndrome (IRIS) in patients with HIV (HIV) and tuberculosis (TB) infection, and analyze the relationship between Th17/Treg cytokines, CD4 + T lymphocytes and IRIS. Methods:HIV patients with TB infection admitted to Public Health Clinical Center of Chengdu from June 2020 to June 2022 were divided into IRIS group (31 cases) and non IRIS group (93 cases) according to whether IRIS occurred after highly active antiretroviral therapy (HAART). The Demography data, clinical data and laboratory indicators of the two groups were compared. Multivariate logistic regression analysis was conducted to investigate the influencing factors of IRIS in HIV patients with TB infection.Results:There was no significant difference in Demography data between the two groups ( P>0.05). There was a statistically significant difference in the history of opportunistic infection between the IRIS group and the non IRIS group (χ 2=5.194, P<0.05). The levels of HIV RNA, interleukin (IL)-17, and IL-23 in the IRIS group were higher than those in the non IRIS group (all P<0.05). The levels of the γ interferon (IFN- γ), the transforming growth factor-β (TGF- β) and baseline CD4 + T lymphocyte count were lower than those in the non IRIS group (all P<0.05). The results of multivariate logistic regression analysis showed that IL-17 ( OR: 1.266, 95% CI: 1.095-1.464), IL-23( OR: 1.384, 95% CI: 1.120-1.710), and TGF- β( OR: 0.589, 95% CI: 0.436-0.797) were influencing factors for the occurrence of IRIS in HIV patients with TB infection (all P<0.05). Conclusions:For patients with high IL-17 levels, high IL-23 levels, and low TGF- β level of HIV complicated with TB infection, clinical prevention and control should be carried out as soon as possible to prevent the occurrence of IRIS.
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Objective:To explore the influencing factors of severe pneumonia in children with respiratory syncytial virus (RSV) infection.Methods:A retrospective case-control study was used to collect 210 children with RSV infected pneumonia admitted to Hebei Children′s Hospital from October 2017 to October 2020. Among them, 70 children with severe pneumonia were included in the severe pneumonia group, and 140 children with common pneumonia were included in the common pneumonia group; the baseline data and relevant laboratory indicators of the two groups were compared; Logistic regression was used to analyze the influencing factors of severe pneumonia in children infected with RSV.Results:The proportions of wheezing, congenital heart disease, respiratory failure, heart failure and pleural effusion of children in severe pneumonia group were higher than those in common pneumonia group, and the forced vital capacity (FVC) and forced expiratory volume in the first second (FEV 1) were lower than those in common pneumonia group (all P<0.05); the levels of C-reactive protein (CRP), CD8 + cells, RSV load and Beclin-1 in severe pneumonia group were higher than those in common pneumonia group, and the levels of CD4 + cells and 1, 25-dihydroxyvitamin D [1, 25-(OH) 2D] were lower than those in common pneumonia group (all P<0.05). After treatment, the levels of CRP, CD8 + cells and Beclin-1 in children with severe pneumonia were lower than those before treatment, and the levels of CD4 + cells and 1, 25-(OH) 2D were higher than those before treatment (all P<0.05). Multiple regression model analysis was established. The results showed that congenital heart disease, high CRP level, high CD8 + cells, high RSV load and high Beclin-1 level were risk factors for severe pneumonia in children with RSV infected pneumonia (all OR>1, P<0.05), and high CD4 + cells and 1, 25-(OH) 2D level were protective factors (all OR<1, P<0.05). Conclusions:Severe pneumonia in children with RSV infected pneumonia may be affected by congenital heart disease, CRP, CD4 + cells, CD8 + cells, 1, 25-(OH) 2D, RSV load and Beclin-1.
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Objective:To investigate the risk factors of diabetes mellitus complicated by pulmonary tuberculosis.Methods:The clinical data of 83 patients with diabetes mellitus complicated by pulmonary tuberculosis who received treatment in Taiyuan Fourth People's Hospital from March 2020 to March 2022 were collected. These patients were divided into sensitive group ( n = 45) and resistant group ( n = 38 ) according to the results of drug sensitivity test. Univariate and multivariate non-conditional logistic regression was performed to analyze the influential factors of drug resistance. Results:Univariate logistic regression results revealed that there were significant differences in blood CD4 +T lymphocyte count ( χ2 = 11.73, P = 0.001) and diabetic complications ( χ2 = 4.94, P = 0.026). Multivariate non-conditional logistic regression analysis was performed taking whether blood CD4 +T lymphocyte count was lower than the average level and whether patients with diabetes mellitus had complications as independent variables, and taking whether drug resistance was a dependent variable. The results showed that the OR (95% CI) value of the decreased blood CD4 +T lymphocyte count was 4.909 (1.926-12.514). It is a risk factor for drug resistance of diabetes mellitus complicated by pulmonary tuberculosis. Conclusion:The decrease of blood CD4 +T lymphocyte count is a risk factor of drug resistance in diabetes mellitus complicated by pulmonary tuberculosis, and it should be intervened early in the clinic.
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Objective:To investigate the efficacy of Zhibitai capsules combined with low-dose atorvastatin in the treatment of cervical arteriosclerosis and its effects on high-sensitivity C-reactive protein and regulatory T cells in the peripheral blood. Methods:A total of 104 patients with carotid arteriosclerosis admitted to Fenyang Hospital from January 2021 to April 2022 were retrospectively included in this study. They were divided into a control group ( n = 52) and an observation group ( n = 52) according to different treatment methods. The control group was orally given atorvastatin calcium tablets 20 mg once a day. The observation group was orally given atorvastatin calcium tablets 10 mg once a day, and Zhibitai capsules 0.24 g, one capsule in the morning and one capsule in the evening. After 8 weeks of treatment, changes in total cholesterol, triacylglycerol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and regulatory T cell proportion in the peripheral blood were evaluated. Results:After treatment, high-density lipoprotein cholesterol level and regulatory T cell proportion in the observation group were (1.53 ± 0.29) mmol/L and (5.52 ± 1.38)%, respectively, which were significantly higher than (1.19 ± 0.21) mmol/L and (4.48 ± 0.86)% respectively in the control group ( t = 6.84, 4.61, both P < 0.05). Total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein levels in the observation group were (2.88 ± 0.27) mmol/L, (1.21 ± 0.15) mmol/L, (2.01 ± 0.19) mmol/L, (2.58 ± 0.43) mg/L, respectively, which were significantly lower than (3.68 ± 0.41) mmol/L, (1.33 ± 0.19) mmol/L, (2.69 ± 0.31) mmol/L, (3.70 ± 0.25) mg/L, respectively in the control group ( t = 11.75, 3.57, 12.31, 17.23, all P < 0.05). There was no significant difference in carotid plaque size pre-treatment between the two groups, but the plaque size decreased after treatment compared with before treatment. The efficacy of Zhibitai capsules combined with low-dose atorvastatin in the treatment of cervical arteriosclerosis in the observation group was superior to that in the control group ( P < 0.05). Conclusion:Oral administration of Zhibitai capsules combined with low-dose atorvastatin for the treatment of cervical arteriosclerosis is safe and has few adverse reactions. The combined therapy can decrease serum high-sensitivity C-reactive protein levels, increase the proportion of regulatory T cells in the peripheral blood, help stabilize plaques, and reduce plaque size.
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Objective:To explore the relevant predictive indicators of fever course > 7 days in children with infectious mononucleosis.Methods:The clinical data of 163 children with infectious mononucleosis who received treatment in Xi'an Children's Hospital from January 2018 to October 2020 were retrospectively analyzed. According to the heat duration, the children were divided into the fever course > 7 days group ( n = 55) and the fever course ≤ 7 days group ( n = 108). The clinical manifestations and laboratory indexes on admission were compared between the two groups. A logistic regression model was used to analyze the influential factors of fever course in children. A receiver operating curve was used to evaluate the predictive value of heat course > 7 days for infectious mononucleosis. Results:The majority of children with infectious mononucleosis had a heat course of 7 days (21.5%). There were no significant differences in clinical manifestations between the fever course > 7 days group and the fever course ≤ 7 days group (all P > 0.05). Neutrophil count, the proportion of monocytes, aspartate aminotransferase, and the proportion of suppressor T (Ts) cells in the fever course > 7 days group were (15.97 ± 7.60) × 10 9/L, 7.75 (4.93, 10.75)%, 53.00 (22.00, 91.50) U/L, 70.00 (57.00, 75.00)%, respectively, which were significantly higher than (15.21 ± 5.29) × 10 9/L, 5.40 (3.40, 9.60)%, 40.00 (30.00, 63.75) U/L, 63.50 (55.00,70.75)% in the fever course ≤ 7 days group ( t = -5.10, Z = -2.31, Z = -2.26, Z = -2.12, all P < 0.05). The proportion of helper T (Th) cells and the ratio of Th/Ts cells in the fever course > 7 days group were 13.00 (9.00, 17.00)% and 0.19 (0.12, 0.30)%, respectively, which were significantly lower than 16.00 (12.25, 20.75)%, 0.26 (0.18, 0.37)% in the fever course ≤ 7 days group ( Z = 2.44, 2.48, both P < 0.05). Multivariate logistic regression analysis showed that the increased proportion of Ts cells ( OR = 0.96, 95% CI 0.922-0.978, P < 0.05) was an influential factor of the prolonged course of fever. The area under the receiver operating characteristic curve of the proportion of Ts cells was 0.637. The cut-off value, sensitivity, and specificity were 67.50%, 61.3%, and 64.3%, respectively. Conclusion:Children with infectious mononucleosis with a longer heat course have more severe immune responses. The proportion of Ts cells > 67.5% can be used as a risk factor for the fever course > 7 days in children with infectious mononucleosis.
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Objective:To analyze the value of cytotoxic T lymphocyte and natural killer cell levels in prognosis evaluation of patients with ST-elevation myocardial infarction (STEMI).Methods:A total of 158 patients with STEMI who underwent percutaneous coronary intervention in The Second People's Hospital of Liaocheng from September 2020 to August 2021 were included in this study. The ratio of cytotoxic T lymphocytes to natural killer cells was measured immediately after admission and 48 hours after surgery. These patients were followed up for 1 month after treatment. They were divided into the adverse cardiovascular event group (occurrence group) and no adverse cardiovascular event group (non-occurrence group) according to the occurrence of cardiovascular adverse events. The influential factors of the prognosis of STEMI and the correlation between the influential factors and STEMI were analyzed.Results:Among 158 patients with STEMI, 27 patients had adverse cardiovascular events, accounting for 17.09%. There were significant differences in systolic blood pressure, left ventricular ejection fraction, and low-density lipoprotein levels between the occurrence and non-occurrence groups ( t = 2.82, 4.27, 2.32, all P < 0.05). At 48 hours after surgery, the levels of cytotoxic T lymphocytes [(22.75 ± 8.39)%, (29.23 ± 4.61)%] and natural killer cells [(13.73 ± 4.64)%, (20.64 ± 4.52)%] in the peripheral blood in the occurrence and non-occurrence groups were significantly decreased compared with before surgery [ t = -5.05, -83.68, -142.71, -7 084.80, all P < 0.001]. Before and 48 hours after surgery, the levels of cytotoxic T lymphocytes [(27.47 ± 3.35)%, (22.75 ± 8.39)%] and natural killer cells [(21.42 ± 4.36)%, (13.73 ± 4.64)%] in the peripheral blood in the occurrence group were significantly lower than those in the non-occurrence group ( t = 7.68, 13.10, 4.16, 5.76, all P < 0.001). Univariate analysis showed that preoperative cytotoxic T lymphocytes < 27.47%, preoperative natural killer cells < 21.42%, left ventricular ejection fraction, and low-density lipoprotein may be the risk factors that affect the prognosis of patients with STEMI ( P < 0.000, 0.012, 0.019, 0.033). Cox regression analysis showed that preoperative cytotoxic T lymphocytes < 27.47% and preoperative natural killer cells < 21.42% were independent risk factors affecting the prognosis of patients with STEMI (both P < 0.001). Conclusion:Reduced levels of baseline cytotoxic T lymphocytes and natural killer cells in patients with STEMI suggest an increased risk of poor prognosis.
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Objective:To investigate the effects of the timing of chemotherapy after breast cancer surgery on patient's immune function and quality of life.Methods:A total of 100 patients who underwent modified radical mastectomy for breast cancer from January 2017 to January 2019 in Jining No. 1 People's Hospital were included in this study. These patients were randomly divided into a control group and an early chemotherapy group ( n = 50/group). Patients in the control group underwent chemotherapy 4-6 weeks after surgery. Patients in the early chemotherapy group received chemotherapy 2 weeks after surgery. The chemotherapy regimens were the same in the two groups. The levels of CD 4+, CD 8+, CD 4+/CD 8+, immunoglobulin A (IgA), and immunoglobulin G (IgG) were measured before and after chemotherapy in each group. Chemotherapy-related reverse reactions and infections were recorded. The quality of life was evaluated in each group at the last follow-up. Results:Before chemotherapy, there were no significant differences in CD 4+, CD 8+, CD 4+/CD 8+, IgA, and IgG levels between the two groups (all P > 0.05). After chemotherapy, CD 4+ and CD 4+/CD 8+ levels in the early chemotherapy group were (51.76 ± 5.21)% and (2.00 ± 0.25), respectively, which were significantly higher than (48.21 ± 4.78)% and (1.70 ± 0.21) in the control group ( t = 3.55, 4.98, both P < 0.05). After chemotherapy, the CD 8+ level in the early chemotherapy group was (25.93±2.43)%, which was significantly lower than (28.29 ± 2.31)% in the control group ( t = 6.50, P < 0.05). Serum IgA and IgG levels in the early chemotherapy group were (3.24 ± 0.38) g/L and (9.27 ± 1.04) g/L, respectively, which were significantly higher than (2.75 ± 0.37) g/L and (8.43 ± 0.97) g/L in the control group ( t = 6.53, 4.18, both P < 0.05). During chemotherapy, there was no significant difference in the incidence of reverse reactions between the two groups (all P > 0.05). The incidence of infections was significantly lower in the early chemotherapy group than the control group ( P < 0.05). At the last follow-up, generic quality of life inventory-74 scores in the early chemotherapy group were significantly higher than those in the control group (all P < 0.05). Conclusion:Early chemotherapy can markedly reduce the effects of chemotherapy on the immune function of patients after breast cancer surgery, decrease the incidence of infections, and improve quality of life.
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Objective:To investigate the effect of T-lymphocyte and subpopulation counts on the prognosis of severe acute pancreatitis (SAP) patients.Methods:The clinical data of 90 patients with SAP diagnosed at the Shanghai General Hospital between January 2019 and June 2022 were retrospectively analyzed, and the patients were divided into good prognosis and poor prognosis group according to whether they were diagnosed for 28 d. The general information of the patients was recorded, including blood-related immunological indicators within 24 h of diagnosis, including leukocytes, neutrophils, lymphocytes, monocytes, CD 3+ , CD 4+ , CD 8+ T-lymphocyte count and CD 4+ /CD 8+ T-lymphocyte ratio, IgG4 level; blood inflammation index procalcitonin, albumin level and APACHEⅡ score at admission; survival and complication status of patients at 28 d of diagnosis. Non-parametric Mann-Whitney U test was used to analyze the correlation between each index and the prognosis of the patients. The subject operating characteristic curve (ROC) of patients was plotted, and area under curve (AUC) was calculated to assess the value of CD 3+ and CD 4+ T-lymphocytes in predicting the prognosis of SAP. Results:The majority of SAP patients were male (65.6%). The main cause of SAP was gallstone (56.7%), followed by hyperlipidemia (35.6%). At 28 days after diagnosis, 85(94.4%) patients survived, and 39 of them were cured and included in the good prognosis group. Forty-six cases were complicated with infection, multiple organ dysfunction syndrome (MODS) and local pancreatic complications, and 5 cases (5.56%) died; and a total of 51 cases were included in the poor prognosis group. Compared with the good prognosis group, the number of CD 3+ T-lymphocytes [366(268, 498) cells /μl vs 709(578, 999) cells /μl], CD 4+ T-lymphocytes [209(120, 298) cells /μl vs 486(303, 548) cells /μl] and albumin level (33.9 g/L vs 35.9 g/L) within 24 hours in the poor prognosis group were significantly lower, while the level of procalcitonin (1.02 ng/ml vs 0.43 ng/ml) and APACHEⅡ score [7(4, 10) vs 5(3, 8)] were significantly increased, and all the differences were statistically significant (all P value <0.05). ROC curve analysis showed that the AUC values for CD 3+ and CD 4+ T-lymphocyte counts within 24 hours for predicting poor prognosis of SAP were 0.857 (95% CI 0.696-1.000) and 0.867 (95% CI 0.708-1.000), respectively. The cut-off values were 524 cells /μl and 301 cells /μl, the sensitivity were both 85.7%, and the specificity were 78.6% and 85.7%, respectively. Conclusions:The significant decrease of peripheral blood CD 3+ and CD 4+ T-lymphocyte count within 24 h of SAP diagnosis has a certain predictive value for the prognosis of patients with SAP.
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Primary sclerosing cholangitis （PSC） is an immune-mediated chronic cholestatic liver disease and can progress to end-stage liver diseases such as liver cirrhosis and liver failure， and there are still no effective treatment methods at present. Studies have found that T lymphocytes are closely associated with the development and progression of PSC. This article reviews the role of T lymphocytes in PSC， so as to provide new ideas for research on the pathogenesis of PSC and the clinical diagnosis and treatment of PSC.
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ObjectiveTo investigate whether cytotoxic T lymphocyte （CTL）－derived exosomes can downregulate HBx expression and inhibit hepatic stellate cell （HSC） activation. MethodsThe supernatants of HepG2， HepGA14， and CTL cells were collected to extract exosomes， which were referred to as NC－exo， HBV－exo， and CTL－exo， respectively）. Transmission electron microscopy was used to observe their morphology， and Western Blot was used to measure the expression of the markers of exosomes CD63 and TSG101. NC－exo， HBV－exo， and CTL－exo labeled by BODIPY dye were mixed with HBV－exo at different ratios and were then co－cultured with HSC LX－2 （HSC－LX2）. A fluorescence microscope was used to observe whether exosomes could enter LX－2 cells， and an fluorescence microscope was used to observe cell morphological changes； quantitative real－time PCR （qPCR） was used to measure the expression of the activated biomarkers such as transforming growth factor－β1 （TGF－β1）， ɑ－smooth muscle actin （ɑ－SMA）， and collagen type I （Collagen I） in LX－2 cells. CTL－exo was added to the HepGA14 culture system； then qPCR was used to measure the mRNA expression level of HBV DNA， cccDNA， and HBx in exosomes in HepGA14 cells， and Western Blot was used to measure the protein expression level of HBx in exosomes. The t-test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe exosomes were all microcysts with a double－layer membrane structure and were circular or elliptical in shape， with the expression of the signature proteins CD63 and TSG101， and the vesicles had a diameter of 50－100 nm. The fluorescence microscope showed that exosomes could enter LX－2 cells， and HSC were enlarged with extended cell processes. The results of qPCR showed that there were significant differences in the expression levels of TGF－β1， ɑ－SMA， and Collagen I genes between the NC－exo， HBV－exo， NC－exo+HBV－exo， and Con groups （F=444.678， 417.144， and 571.508， all P<0.05）. After the intervention of HepGA14 cells with CTL－exo， qPCR results showed that compared with the control group， there were significant reductions in the expression levels of HBV DNA and cccDNA in HepGA14 cells （all P<0.05）， the relative mRNA expression level of HBx in exosomes （P<0.05）， and the protein expression level of HBx （P<0.05）. CTL－exo and HBV－exo were mixed at different ratios （2∶1， 5∶1， 10∶1） and were then used for the intervention of LX－2 cells， and qPCR results showed that the expression levels of TGF－β1， ɑ－SMA， and Collagen I genes in LX－2 cells gradually decreased with the increase in the ratio of CTL－exo between groups （P<0.05）. ConclusionCTL－exo can downregulate the protein expression of HBx in HBV－exo to inhibit HSC activation， suggesting that CTL－exo has an anti－hepatitis B liver fibrosis effect.
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Objective:To investigate the changes of T helper cell (Th), regulatory T-cell (Treg cell) related cytokines in vaginal lavage fluid of patients with high risk-human papilloma virus 16 (HR-HPV16) positive and its predictive effect on the development of cervical neoplasms.Methods:A total of 200 cases of HR-HPV16 positive patients who admitted to Xingtai People's Hospital from January 2022 to December 2022 were selected as the experimental group. According to the results of pathological examination, all patients in the experimental group were divided into non pathological group (78 cases), low grade squamous intraepithelial lesion (LSIL) group (49 cases), high grade squamous intraepithelial lesion (HSIL) group (39 cases) and cervical cancer group (34 cases); and 100 healthy people undergoing the physical examination in the same period were taken as the healthy control group. Enzyme-linked immunosorbent assay (ELISA) double-antibody sandwich method was used to detect the levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-17, tumor necrosis factor α (TNF-α), interferon γ (IFN-γ) and transforming growth factor β (TGF-β) in vaginal lavage fluid of patients in different groups. Multivariate logistics regression was used to analyze the risk factors of cervical cancer, and a nomogram model was established. The receiver operating characteristics (ROC) curve was drawn with pathological results as the gold standard, and the area under the curve (AUC) was calculated to evaluate the predictive ability of the nomogram model.Results:The levels of IL-6, IL-10, IL-17, TNF-α, TGF-β in vaginal lavage fluid of patients in the experimental group were higher than those in the healthy control group, while the levels of IL-2, IL-12 and IFN-γ in the experimental group were lower than those in the healthy control group, and the differences were statistically significant (all P < 0.05); the difference in IL-4 level of both groups was not statistically significant ( P > 0.05). There were statistically significant differences in IL-6, IL-10, IL-17, TNF-α, TGF-β, IL-2, IL-12 and IFN-γ among non pathological group, LSIL group, HSIL group and cervical cancer group (all P < 0.05); the levels of IL-6, IL-10, IL-17, TNF-α, TGF-β in cervical cancer group were the highest, the levels of IL-2, IL-12 and IFN-γ were the lowest; the level of IL-4 in non pathological group, LSIL group, HSIL group and cervical cancer group had no statistically significant difference ( P > 0.05). Logistics regression analysis showed that low IL-2, high IL-4, high IL-6, high IL-10, low IL-12, high IL-17, high TNF-α, low IFN- γ and low TGF-β expressions in vaginal lavage fluid of patients with HR-HPV16 positive were independent risk factors for the development of cervical cancer (all P < 0.05). The results of nomogram analysis showed that IL-6, IL-10, IL-17, TNF-α, TGF-β in vaginal lavage fluid were the factors predicting the development of cervical cancer in HR-HPV16 positive patients. The ROC curve analysis showed that the AUC of nomogram model in predicting the development of cervical cancer in HR-HPV16 positive patients was 0.945 (95% CI 0.901-0.988), and the predictive efficacy was good. Conclusions:Th and Treg cell related cytokines levels in vaginal lavage fluid of patients with HR-HPV16 positive show pathological changes in cervical cancer patients and the above indicators have a high value in predicting the development of cervical cancer.
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Objective:To investigate the clinical value of peripheral blood T lymphocytes in the diagnosis and prognosis of patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation.Methods:The clinical and laboratory data of 50 HCC patients, who received liver transplantation and were followed up in the Liver transplantation Center of Beijing Youan Hospital from January 2014 to December 2016, were retrospectively analyzed. The differences on clinical laboratory indicators and five-year survival were compared between HCC recurrence group ( n=29) and non-recurrence group ( n=21). Spearman correlate analysis was used to analyze the correlation between clinical laboratory indicators and HCC recurrence after liver transplantation. Receiver operator characteristic (ROC) curve was used to analyze the diagnostic value of CD4+T lymphocytes in HCC recurrence after liver transplantation. Kaplan-Meier survival curve was used to compare the survival time of patients with different CD4+T lymphocytes levels post liver transplantation. Results:Compared to non-recurrence group, the level of alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, albumin, lymphocytes, alpha-fetoprotein, protein induced by vitamin K deficiency or antagonist-Ⅱ, CD3+, CD4+and CD8+T lymphocytes were significantly different (all P<0.05). The median recurrence time after liver transplantation was 13.0 (6.0, 24.0) months, and the mortality rate was 100%. The 5-year mortality rate was 0 in the non-recurrence group. During 5-year follow-up, the median survival time of patients in the HCC recurrence group was 18.0 (9.0, 36.0) months, which was significantly lower than that of non-recurrence group [60.0 (60.0, 60.0) months, ( P<0.05)]. Compared with non-recurrence group, the CD3+, CD4+, and CD8+T lymphocytes were significantly lower in the recurrence group (all P<0.05). Spearman correlate analysis showed that HCC recurrence after liver transplantation was negatively correlated with the CD3+, CD8+and CD4+T lymphocytes ( r=-0.43, -0.38, -0.44, all P<0.05). ROC analysis showed that CD4+T lymphocytes at cutoff of≤265.50 cells/μl was valuable for the diagnosis of HCC recurrence after liver transplantation (specificity 100%, sensitivity 48.30%). Survival curve analysis showed that the survival time was significantly lower in the CD4≤265.50 cells/μl group [15.0 (10.0, 36.8) months] than that in the CD4>265.50 cells/μl group [53.0 (19.5, 60.0) months] ( P<0.05). Conclusion:There is a significant negative correlation between CD4+T lymphocytes and HCC recurrence after liver transplantation. CD4+T lymphocytes at cutoff value of≤265.50 cells/μl is valuable for the clinical diagnosis and prognosis evaluation of HCC recurrence after liver transplantation.
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Objective:To investigate the expression profile of IL-36 family members in patients with coronary atherosclerotic heart disease (CAHD) and to assess the regulatory effects of exogenous IL-36 on CD8 + T cell function in CAHD patients. Methods:Twenty controls and 82 CAHD patients including 31 with stable angina pectoris (SAP), 27 with unstable angina pectoris (UAP) and 24 with acute myocardial infarction (AMI) were enrolled in this study. Anti-coagulant peripheral blood samples were collected. Plasma and peripheral blood mononuclear cells were isolated. The levels of IL-36α, IL-36β, IL-36γ and IL-36 receptor antagonist (IL-36RA) in plasma were measured by ELISA. CD8 + T cells were enriched. The expression of IL-36 receptor subunits at mRNA level was semi-quantified by real time PCR. Flow cytometry was used to detect the expression of programmed death-1 (PD-1), cytotoxic T lymphocytes associated protein-4(CTLA-4) and lymphocyte-activation gene-3 (LAG-3) in CD8 + T cells. Levels of periforin, granzyme B, granulysin, IFN-γ and TNF-α in the culture supernatants of CD8 + T cells were measured by ELISA. Purified CD8 + T cells from controls and AMI patients were stimulated with recombinant human IL-36RA. Changes in the expression of immune checkpoint molecules and the secretion of cytotoxic molecules and cytokines after IL-36RA stimulation were analyzed. One-way analysis of variance or paired t-test was used for statistical analysis. Results:There were no significant differences in plasma IL-36α, IL-36β or IL-36γ level between the control, SAP, UAP and AMI groups ( P>0.05). Plasma IL-36RA level was significantly down-regulated in the AMI group as compared with that in the control, SAP and UAP groups[(1 159.57±297.83) pg/ml vs (1 773.47±754.29) pg/ml, (1 600.12±740.48) pg/ml and (1 578.72±720.42) pg/ml; P<0.05]. The expression of IL-1 receptor 6 (IL-1R6) and IL-1 receptor accessory protein (IL-1RAcP) at mRNA level, the expression of PD-1 and CTLA-4, and the secretion of IFN-γ and TNF-α by CD8 + T cells showed no significant differences between the four groups ( P>0.05). Periforin, granzyme B and granulysin levels secreted by CD8 + T cells of the AMI group were significantly higherthan those of the control, SAP and UAP groups ( P<0.05). In the control group, recombinant human IL-36RA stimulation did not affect the expression of immune checkpoint molecule or the secretion of cytotoxic molecules and cytokines by CD8 + T cells ( P>0.05). In the AMI group, the percentage of PD-1 + CD8 + T cells increased after recombinant human IL-36RA stimulation ( P=0.033), but no significant change in the percentage of CTLA-4 + CD8 + T cells was observed ( P=0.288). Moreover, recombinant human IL-36RA stimulation suppressed the CD8 + T cells of AMI patients to secrete periforin, granzyme B and granulysin ( P<0.05), but not affect the secretion of IFN-γ and TNF-α ( P>0.05). Conclusions:The reduced IL-36RA level in AMI patients might induce the enhancement of CD8 + T cell activity by promoting CD8 + T cells to secrete cytotoxic molecules, which was involved in the immunopathogenesis of AMI.
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Dendritic cells are the most powerful antigen-presenting cells in the human body, which are involved in the occurrence and development of multiple sclerosis, neuromyelitis optica, myasthenia gravis and other neuroimmune conditions. Recently, tolerogenic dendritic cells (tolDCs) are gradually becoming the research focus and therapeutic target of neuroimmune conditions. They can reconstruct the balance of T cells by inducing effector T cell anergy/deletion, and producing antigen-specific regulatory T cells, ultimately achieving the goal of maintaining immune tolerance. In this review, the mechanisms that tolDCs reconstruct T cell balance in neuroimmune conditions are analyzed and the research progress related to tolDC therapy is summarized.
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Objective:To investigate changes in expression of plasma soluble CD100 (sCD100) and membrane-bound CD100 (mCD100) on peripheral T cells in patients with herpes zoster, and to observe the regulatory effect of exogenous CD100 on CD8 + T cells. Methods:A total of 53 patients with herpes zoster attending the Zhumadian Central Hospital from July 2019 to April 2021 were enrolled, so were 25 age- and sex-matched healthy controls. Anticoagulated venous blood samples were collected, plasma and peripheral blood mononuclear cells were isolated, plasma sCD100 levels were detected by enzyme-linked immunosorbent assay, and mCD100 expression on CD4 + and CD8 + T cells was determined by flow cytometry. After the purification of CD8 + T cells, the secretion levels of cytotoxic molecules and cytokines by CD8 + T cells were measured and compared between herpes zoster patients and controls. Some purified CD8 + T cells from herpes zoster patients were stimulated with recombinant human CD100 and recombinant varicella-zoster virus glycoprotein, and the effect of recombinant human CD100 on the secretion of cytotoxic molecules and cytokines by CD8 + T cells was investigated. Comparisons between groups were conducted by t test. Results:Plasma sCD100 levels were significantly lower in the herpes zoster group (1.12 ± 0.23 ng/ml) than in the control group (1.31 ± 0.28 ng/ml, t = 2.97, P = 0.004), the proportion of mCD100 + CD8 + T cells was significantly higher in the herpes zoster group (17.41% ± 4.26%) than in the control group (14.69% ± 3.70%, t = 2.52, P = 0.014), and no significant difference in the proportion of mCD100 + CD4 + T cells was found between the two groups (2.52% ± 0.58% vs. 2.32% ± 0.56%, t = 1.27, P = 0.208). The herpes zoster group showed significantly decreased mRNA expression of perforin and granzyme B in, and lower secretion levels of perforin, granzyme B, interferon-γ and tumor necrosis factor-α by CD8 + T cells compared with the control group (all P < 0.05). After stimulation with recombinant human CD100, levels of perforin, granzyme B, interferon-γ and tumor necrosis factor-α in the culture supernatant of CD8 + T cells (43.68 ± 14.12, 126.8 ± 22.92, 12.79 ± 3.66, 310.0 ± 79.90 pg/ml, respectively ) were significantly higher than those in non-stimulated group (34.55 ± 10.78, 99.04 ± 10.44, 9.53 ± 2.00, 275.6 ± 68.04 pg/ml, respectively, all P < 0.05) . Conclusion:There was an imbalance between sCD100 and mCD100 expression in patients with herpes zoster, and exogenous sCD100 may enhance the cytotoxicity of CD8 + T cells in herpes zoster patients.
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Primary liver cancer (PLC) has the features of insidious onset and difficulties in early diagnosis, with limited and ineffective therapeutic options. Chimeric antigen receptor (CAR) T-cell therapy is a genetically modified T-cell therapy that recognizes tumor-specific antigens and activates T cells to exert a tumor-killing effect. CAR T-cell therapy has made great progress in the treatment of hematological tumors and has achieved a good clinical effect in the field of solid tumors in recent years, and although CAR T-cell therapy has developed from the first to the fifth generation, there are still many challenges in the field of solid tumors. This article comprehensively reviews the mechanisms of CAR T-cell therapy for PLC and related research advances, including the main targets such as GPC3, AFP, MUC1, and NKG2D in CAR T-cell therapy for PLC, CAR T-cell therapy for PLC and oncolytic virus, and combined treatment with immune checkpoint inhibitors, as well as the advances in the biological, preclinical, and clinical studies on these targets and treatment modalities and the challenges and solutions for CAR T-cell therapy in the treatment of PLC, so as to provide a reference for the future clinical development of CAR T-cell therapy in liver cancer.
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Objective To investigate the expression of Sema4D in peripheral blood T cells and serum of patients with hepatitis B cirrhosis and its correlation with clinical indicators. Methods A total of 20 patients with chronic hepatitis B (CHB), 68 patients with hepatitis B cirrhosis, and 20 healthy controls who attended The 940 th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army from October 2020 to November 2021 were enrolled. According to Child-Pugh class, the patients with hepatitis B cirrhosis were divided into Child-Pugh class A group with 24 patients, Child-Pugh class B group with 24 patients, and Child-Pugh class C group with 20 patients. After peripheral blood samples were collected to isolate serum and peripheral blood mononuclear cells (PBMCs), flow cytometry was used to measure the expression of membrane-bound Sema4D (mSema4D) + CD4 + T cells and mSema4D + CD8 + T cells in PBMCs, and ELISA was used to measure the expression of soluble Sema4D (sSema4D) in serum; their correlation with viral replication and liver inflammation markers was analyzed. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t -test was used for further comparison 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 further comparison between two groups; a Spearman correlation analysis was also performed. Results There were significant differences in the expression of mSema4D + CD4 + T cells and mSema4D + CD8 + T cells between the CHB group, the hepatitis B cirrhosis group, and the control group ( F =43.092 and 13.344, both P < 0.001), while there were significant differences between any two groups ( P < 0.05). The expression levels of mSema4D + CD4 + T cells and mSema4D + CD8 + T cells gradually decreased with increasing Child-Pugh class ( F =14.093 and 17.154, both P < 0.05), and there were significant differences between any two groups ( P < 0.05). The content of sSema4D was 1.54(1.42-1.71) ng/mL in the control group, 1.08(1.07-1.38) ng/mL in the CHB group, and 4.87(2.13-14.97) ng/mL in the hepatitis B cirrhosis group, with a significant difference between the three groups ( H =32.366, P < 0.001) and between any two groups ( P < 0.05). The content of sSema4D was 2.42(0.59-5.65) ng/mL in the Child-Pugh class A group, 4.92(2.75-12.73) ng/mL in the Child-Pugh class B group, and 14.18(4.59-18.43) ng/mL in the Child-Pugh class C group, with a significant difference between the three groups ( H =11.889, P =0.003) and between any two groups ( P < 0.05). In patients with hepatitis B cirrhosis, the level of sSema4D was positively correlated with the levels of alanine aminotransferase (ALT) and HBV DNA quantification ( r =0.294 and 0.430, both P < 0.05). Conclusion Sema4D is lowly expressed on T cell membrane and highly expressed in serum of patients with hepatitis B cirrhosis, and sSema4D may be involved in the development and progression of hepatitis B cirrhosis by affecting the levels of ALT and HBV DNA.
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Bronchopulmonary dysplasia(BPD)is a severe complication in premature infants, and the pathogenesis remains complex, potentially involving pulmonary inflammatory injury and faulty reparative response.T-cell immaturity in preterm neonates and the upregulation of related harmful regulatory genes, as well as the imbalance of T-cell homeostasis, have been reported to contribute significantly to the development of inflammatory diseases.Growing evidence suggests that alterations in the levels and functions of T cell subsets may participate in the development of BPD, serving as a new avenue for BPD prevention and treatment.Herein, we summarize recent advancements in understanding the role of T lymphocytes in the pathogenesis of BPD.
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Objective:To investigate the clinical efficacy of lenalidomide combined with bortezomib and dexamethasone (RVd) regimen in treatment of newly diagnosed multiple myeloma (NDMM) patients and its effect on the levels of regulatory T cells (Treg cells) and natural killer (NK) cells.Methods:Thirty-eight NDMM patients who were admitted to the Second Affiliated Hospital of Bengbu Medical College from September 2019 to May 2022 were selected for a prospective study, and were divided into control group (18 cases) and observation group (20 cases) according to random number table method. The control group was treated with bortezomib+epirubicin+dexamethasone (VAd) regimen, and the observation group was treated with RVd regimen. The efficacy and safety were compared between the two groups. The levels of Treg cells (CD4 + CD25 + FOXP3 +) and NK cells (CD3 - CD56 + CD16 +) before and after treatment in the two groups were detected by flow cytometry, and the results were compared. Results:After 4 courses of treatment, the objective response rate (ORR) of the observation group was 95.0% (19/20), which was higher than that of the control group [77.8% (14/18)], and the difference was statistically significant ( P = 0.016). Before treatment, there was no statistical difference in the levels of Treg cells and NK cells between the two groups ( P values were 0.381 and 0.650). After treatment, the level of Treg cells in the control group increased from (1.5±0.5)% before treatment to (4.7±1.3)% ( P = 0.008), while the level of Treg cells in the observation group increased from (1.4±0.5)% before treatment to (6.8±1.5)% ( P = 0.001), and the level in the observation group was higher than that in the control group ( P = 0.027); the level of NK cells in the control group increased from (16±6)% before treatment to (20±5)% ( P = 0.004), while the level of NK cells in the observation group increased from (16±6)% before treatment to (24±6)% ( P = 0.006), and the level in the observation group was higher than that in the control group ( P = 0.032). The incidence rates of thrombocytopenia and neutropenia in the observation group were higher than those in the control group, and the differences were statistically significant ( P values were 0.012 and 0.027), which was reversible after active treatment. There was no statistical difference in the incidence rates of other adverse reactions (all P>0.05). Conclusions:RVd regimen for NDMM is clinically effective, safe and reliable, and the patients' levels of Treg cells and NK cells elevate after treatment.