Intensive phototherapy don't affect cellular immune function and short-term reactions after discharge in neonatal hyperbilirubinemia / 基础医学与临床

Objective To investigate the effect of intensive phototherapy for neonatal hyperbilirubinemia on cellular immune function and short-term immune-related adverse effects.Methods Totally 180 infants with hyperbilirubi-nemia were treated with different light intensity,the efficacy,cellular immune function and immune adverse effects were followed up for six months after discharge.Results After phototherapy,serum interleukin-6(IL-6)in both groups were decreased and CD4+(%)and CD4+/CD8+were increased than that before phototherapy.The decrease rate of total bilirubin in the intensive phototherapy group was significantly faster than that in the conventional photo-therapy group,at the same time,the total duration of phototherapy and hospital stay were significantly shorter than that in the conventional phototherapy group(P＜0.05).No statistical significance in the incidence of diarrhea,rash,fever and hypo-calcemia during hospitalization and no immune-related adverse effects in 6 months after discharge were recorded.Conclusions Compared with conventional phototherapy,intensive phototherapy reduces serum bilirubin level more quickly and shorten the duration of phototherapy and hospital stay.No common adverse effects nor immune-related adverse effects are recorded during hospitalization and the period of six months after discharge.

Cellular and cytokine immune responses during varicella zoster virus reactivation of herpes zoster infection / 西安交通大学学报(医学版)

Objective To study changes in immune cells and cytokines during the reactivation stage of varicella-zoster virus(VZV)in patients with herpes zoster.Methods A total of 50 patients with herpes zoster and 30 healthy individuals were selected from Xi'an Ninth Hospital between May 2022 and October 2022.Flow cytometry was used to detect the proportion of peripheral blood CD3+cells,CD4+cells,CD8+T cells,B cells and NK cells,as well as levels of cytokines IL-2,IFN-γ,IL-10 and IL-6.We analyzed the immune mechanism of VZV reactivation stage in herpes zoster patients.Results Compared with the healthy control group,the proportion of CD3+cells and CD4+T cells in herpes zoster patients decreased significantly;the proportion of NK cells significantly increased;the levels of IFN-γ,IL-10 and IL-6 significantly increased;the proportion of CD8+T cells,B cells and IL-2 content showed an increasing trend,but there was no significant difference.In addition,the severity of neurological involvement in herpes zoster patients might affect changes in cytokine levels.Conclusion During the reactivation period of VZV,changes in the proportion of immune cells and cytokine expression levels are closely related to the occurrence and development of herpes zoster.

The effects of attenuated Salmonella carrying IL-2/NK4 double gene on immune function in mice / 中国生物制品学杂志

@#Objective To study the effects of attenuated Salmonella(Ty21a-pIRES-IL-2-NK4,TPIN)carrying interleukin-2(IL-2)/4-kringle antagonist of hepatocyte growth factor(NK4)double gene on humoral and cellular immune function.Methods Eighteen BALB/c mice,half male and half female,were randomly divided into control group(1. 5 mL 10%NaHCO3 by gastric tube feeding),Ty21a group(0. 1 mL Ty21a by gastric tube feeding)and TPIN group(0. 1 mL TPIN by gastric tube feeding),with 6 mice in each group. The immunization was boosted twice 7 d after the initial immunization. At 21d after administration,the blood samples were collected from eyeballs and the serum was separated,which was detected for the serum IgG antibody level by ELISA. The thymus and spleen of mice were isolated aseptically,and the spleen cells were stimulated by Ty21a and TPIN respectively in vitro. After 72 h,the proliferation ability of spleen cells was measured by CCK-8 assay,and the expression level of cytokines in spleen cells was detected by ELISA. The spleen and thymus were weighed,the spleen and thymus indexes were analyzed,and HE staining was performed.Results Compared with the control group and Ty21a group,the serum IgG level(F = 111. 74,P < 0. 01)and the contents of IFNγ,IL-4 and IL-10 in spleen cell supernatant(F = 38. 21,11. 37 and 26. 92,respectively,each P < 0. 05)increased significantly,as well as the spleen and thymus indexes(F = 10. 419 and 5. 859,respectively,each P < 0. 05)showed significant increase. In mice of Ty21a and TPIN group,the thymus cortex widened,lymphocytes increased,and there was mild inflammatory reaction;the white pulp and lymphocytes in spleen increased with neutrophil infiltration.Conclusion TPIN has a good immune protective effect,and can significantly stimulate the body to produce humoral immunity and cellular immunity,which may have a good therapeutic effect on tumors.

Immunogenicty and immunoprotective effect of Mycobacterium tuberculosis Ag85B-Fc2a DNA vaccine / 中国生物制品学杂志

@#Objective To evaluate the immunogenicity and protective effect of Mycobacterium tuberculosis(M.tb) Ag85B-Fc2a DNA vaccine in mice,so as to provide experimental basis for the development of the vaccine.Methods The recombinant plasmid pcD-Ag85B-Fc2a was identified by double digestion and sequencing,and then transfected into CHO-K1 cells.The expression of fusion protein Ag85B-Fc2a was detected by Western blot.Vector pcDNA3.1(+) and recombinant plasmid pcDAg85B-Fc2a were injected into female C57BL/6J mice through thigh muscle respectively(control group and immunization group),with 10 mice in each group,and booster immunization was carried out two weeks after the initial immunization.At14 d,28 d and 42 d after the initial immunization,serum samples was separated,and the titers of IgG antibody in the serum were detected by indirect ELISA.At 42 d after the initial immunization,the spleen of mice was taken aseptically and made into single cell suspension,and the proportions of CD4~+and CD8~+T cells were detected by flow cytometry.The remaining mice were injected with M.tb H37Ra through the tail vein 42 d after the initial immunization at a dose of 10~6 CFU/mouse.After 28 d of challenge,the lung and spleen of mice were collected aseptically.The number of bacteria in the left lung and spleen was measured by plate method,and the bacteria in the right lung was detected by auramine O fluorescence staining.Results Double digestion and sequencing results showed that the recombinant plasmid pcD-Ag85B-Fc2a was constructed correctly.After transfection into CHO-K1 cells,the fusion protein Ag85B-Fc2a with a relative molecular mass of about 70 000was detected.The Ag85B-specific IgG antibody titer in serum of mice in the immunization group was 1:3 200,1:12 160,and 1:12 800 at 14 d,28 d,and 42 d after the initial immunization,respectively,but no antibody titer was detected in the serum samples of control group.At 42 d after the initial immunization,the percentages of CD4~+ T cells in mouse spleen of control group and immunization group were(23.61±0.64)% and(26.92±0.80)%,and the percentages of CD8~+T cells were(14.12±0.87)% and(18.78±0.94)%,respectively,with significant differences(t=3.23 and 3.64,respectively,each P <0.05).After infection with M.tb H37Ra for 28 d,the numbers of bacteria were(4.73±0.13) and(3.81±0.14)CFU in the left lung,and(5.02±0.19) and(4.30±0.13) C.FU in the spleen of control group and immunization group,respectively,with significant differences(t=4.65 and 3.12,respectively,each P <0.01).The bacteria loading in the right lung was consistent with that in the left lung.Conclusion Ag85B-Fc2a DNA vaccine can induce specific humoral and cellular immune effects in mice,and can produce good protective effect against M.tb H37Ra infection.

Assessment of serum granulysin and cathepsin-L levels in vitiligo patients

SUMMARY OBJECTIVE: Cellular and humoral immunity plays a role in the pathogenesis of vitiligo. T lymphocytes and natural killer cells involved in cellular immunity carry out their cytotoxic activities through perforin/granzyme-dependent granule exocytosis, in which granulysin and cathepsin-L are also involved. The aim of this study was to investigate the possible role of serum granulysin and cathepsin-L in the etiopathogenesis of vitiligo and their association with disease activity and severity. METHODS: This randomized, prospective case-control study was conducted with 46 vitiligo patients admitted to the hospital for vitiligo between January and November 2021 and 46 healthy volunteers of similar age and gender. Serum levels of granulysin and cathepsin-L were measured by the enzyme-linked immunosorbent assay method. RESULTS: The mean serum levels of granulysin and cathepsin-L were statistically significantly higher in vitiligo patients compared with the control group (p=0.048 and p=0.024, respectively). There was no statistically significant correlation between serum granulysin and serum cathepsin-L levels and disease severity in the patient group (r=0.30, p=0.062 and r=0.268, p=0.071, respectively). Disease activity also showed no significant association with serum granulysin and cathepsin-L levels (p=0.986 and p=0.962, respectively). CONCLUSION: Although granulysin and cathepsin-L are molecules involved in the pathogenesis of vitiligo, the use of these molecules may not be helpful in assessing disease activity and severity. It may be helpful to conduct comprehensive and prospective studies to find new molecules to fill the gap in this area.

Efecto de la inmunidad celular en el tratamiento de las úlceras del pie diabético con Heberprot-P® / Effect of cellular immunity in the treatment of diabetic foot ulcers with Heberprot-P®

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)

Effect of endoscopic inflation-free thyroid surgery on patient-specific immune function and inflammatory response / 中国综合临床

Objective:To investigate the effect of inflation-free thyroid surgery on patient-specific immune function and inflammatory response.Methods:Sixty patients who underwent axillary endoscopic thyroid surgery at the First Affiliated Hospital of Bengbu Medical College from January 2021 to May 2023 were selected and randomly divided into an observation group and a control group using a random number table method, with 30 patients in each group. The control group underwent unilateral lobectomy and isthmus resection under transareola carbon dioxide inflation endoscopy, while the observation group underwent unilateral lobectomy and isthmus resection under transareola non inflation endoscopy. Compare the cellular immune related indicators, humoral immune related indicators, inflammatory response related indicators, as well as arterial blood partial pressure of carbon dioxide (PaCO 2) and end-expiratory carbon dioxide (PetCO 2) levels at T 1, T 2, and T 3 time points before anesthesia induction (T 1), during adenoidectomy (T 2), at the end of surgery (T 3), on the first postoperative day (T 4), and on the second postoperative day (T 5) in two groups of patients. The measurement data is represented by xˉ±s, and independent sample t-test is used for comparison between the two groups; The comparison between two groups at multiple time points was conducted using two factor analysis of variance, and the pairwise comparison was conducted using LSD- t test; Counting data is represented as an example (%), and inter group comparisons are made using χ 2 Inspection. Results:At time point T 1, there was no statistically significant difference between the two groups of patients in terms of cellular immune related indicators, humoral immune related indicators, and inflammatory response related indicators (all P>0.05). At time points T 2, T 3, T 4, and T 5, the CD3 +, CD4 +, CD4 +/CD8 + values and serum IgA, immunoglobulin A, immunoglobulin IgM The levels of immunoglobulin IgG were all lower than the T 1 time point in this group [control group: (31.49±5.37)%, (26.76±6.11)%, (34.75±5.99)%, (38.92±5.37)%, (51.78±5.90)%, (25.37±8.23)%, (19.12±7.13)%, (29.15±9.85)%, (33.49±8.03)%, (40.12±6.05)%, (0.97±0.28), (0.71±0.30), (1.11±0.36), (1.21±0.39)%, (1.69±0.41), (0.95±0.13), (0.91±0.14) (0.82±0.13), (0.96±0.16) g/L vs (1.21±0.20) g/L, (7.74±1.26), (7.33±1.31), (7.16±1.28), (7.82±1.31) g/L vs (9.18±1.52) g/L, (0.87±0.14), (0.86±0.13), (0.73±0.16), (0.88±0.15) g/L vs (1.16±0.22) g/L; Observation group: (35.82±5.71)%, (30.85±5.86)%, (39.43±5.68)%, (42.53±5.64)% vs (51.36±6.28)%, (30.39±9.76)%, (23.34±8.64)%, (34.68±11.37)%, (38.92±9.82)% vs (40.75±5.68)%, (1.15±0.35a), (0.89±0.38), (1.31±0.33), (1.52±0.37) vs (1.63±0.35), (1.04±0.17), (0.98±0.17) 0), (0.91±0.11a) (1.07±0.14) g/L vs (1.24±0.18) g/L, (8.51±1.35), (8.07±1.32), (7.93±1.34), (8.56±1.39) g/L vs (9.12±1.47) g/L, (0.95±0.11), (0.93±0.12), (0.83±0.18), (0.97±0.14) g/L vs (1.19±0.21) g/L], The CD8+values of both groups of patients were higher than those of the T 1 time point in this group, and at the T 4 time point, the control group was higher than the observation group [(29.89±8.99)% vs (25.70±6.91)%], with statistically significant differences (both P<0.05). At time points T 2, T 3, T 4, and T 5, both groups of patients had serum IL-interleukin-1 levels β、Interleukin IL-6, TNF tumor necrosis factor α The levels of CRP and CRPC reactive protein were higher than those at T 1 time point in this group [control group: (3.92±1.80), (4.16±1.86), (5.81±2.14), (4.46±1.87) ng/L vs (1.36±0.61) ng/L, (5.76±2.78), (6.68±3.12), (9.73±3.12), (4.65±2.78) ng/L vs (0.92±0.60) ng/L, (1.02±0.42), (1.30±0.61), (7.82±2.28), (6.65±2.16) mg/L vs (0.57±0.16) mg/L, (4.48±2.04) (4.48±2.04), (6.45±2.52), (5.33±2.15) ng/L vs (2.86±1.03) ng/L; Observation group: (3.04±1.09), (3.29±1.14), (4.56±2.01), (3.52±1.34) ng/L vs (1.65±0.63) ng/L, (4.12±2.11), (5.07±2.98), (8.07±3.15), (3.22±2.69) ng/L vs (0.98±0.53) ng/L, (0.81±0.34), (1.00±0.50), (6.65±2.03), (5.43±1.93) mg/L vs (0.56±0.12) mg/L, (3.39±1.81), (3.89±1.81) 4±1.93), (5.11±2.10) (3.96±2.03) ng/L vs (2.91±1.09) ng/L], and the control group was higher than the observation group, with statistically significant differences (all P<0.05). At time point T 1, there was no statistically significant difference in PaCO 2 and PetCO 2 between the two groups of patients (both P>0.05); At time points T 2 and T 3, the levels of PaCO 2 [(44.1±4.1), (45.8±4.0) mmHg] and PetCO 2 [(40.8±4.0), (42.1±3.5) mmHg] in the control group were higher than those at time points T 1 [(38.4±1.8), (36.3±1.9) mmHg] and observation group [PaCO 2: (38.3±2.0), (38.6±2.6) mmHg; PetCO 2: (36.3±1.9), (36.5±2.9) mmHg] (all P<0.05), There was no statistically significant difference between the observation group and this group at T 1 time point (all P>0.05). Conclusions:Inflation-free lumpectomy thyroid surgery is worthwhile as it has less suppressive effect on specific immunity and causes less inflammatory response compared to inflatable lumpectomy thyroid surgery.

Chronic infection of hepatitis B virus and cellular immunity / 中华微生物学和免疫学杂志

The persistent infection of hepatitis B virus (HBV) is the result of lacking specific immunity against the virus. This state is also called immune tolerance to HBV. In most cases, acute HBV infection in adults can induce specific immune response which can clear the virus. Perinatal HBV infection, however, usually progresses to chronic infection, indicating a defect in HBV-specific immune response. A typical specific immune response includes four processes, which were antigen presentation, specific CD4 + T cell activation, specific CD8 + T cell activation and B cell activation. There must be some dysfunctions in some or all of the four processes during chronic HBV infection. This article discussed the relationship between chronic HBV infection and cellular immunity, hoping to provide a reference for further study on the reconstitution of specific immunity against HBV.

Effects of dexmedetomidine on intestinal stress response and cellular immune function in patients with gynecologic malignancies undergoing laparoscopic surgery / 肿瘤研究与临床

Objective:To explore the effects of dexmedetomidine (DEX) on intestinal stress response and cellular immune function in patients with gynecologic malignancies undergoing laparoscopic surgery.Methods:A total of 60 patients with gynecologic malignancies who scheduled to undergo laparoscopic surgery under general anesthesia in the Second Hospital of Shanxi Medical University from March 2021 to March 2022 were selected. All patients were divided into the DEX group and the control group according to the random number table method, with 30 cases in each group. The DEX group included 12 cases of cervical cancer, 10 cases of endometrial cancer and 8 cases of ovarian cancer; the control group included 14 cases of cervical cancer, 9 cases of endometrial cancer and 7 cases of ovarian cancer. The DEX group: intravenous anesthesia was induced with a dose of DEX 0.5 μg/kg (infusion was completed within 10 min), general anesthesia was maintained with DEX 0.2 μg·kg -1·h -1 pumped intravenously, and the drug was stopped 30 min before surgery. The control group: equal amount of 0.9% sodium chloride solution was pumped intravenously. The venous blood was drawn at the time points of 10 min before general anesthesia (T 0), at the end of operation (T 1) and 1 d after the operation (T 2) to detect the stress response indicators such as cortisol (COR), epinephrine (E), norepinephrine (NE) levels, and immune indicators such as CD4 +, CD8 + proportions and CD4 +/CD8 + at T 0, T 1,and T 2. In addition, the pneumoperitoneum time, general anesthesia time, operation time and intestinal function recovery time were recorded. Results:At T 0, there were no statistically significant differences in the levels of COR, E and NE between the DEX group and the control group (all P > 0.05). At T 1, the levels of COR, E and NE were (146±12) μg/L, (158±14) ng/L, (265±12) ng/L, respectively in the control group, and (136±18) μg/L, (149±15) ng/L, (158±12) ng/L, respectively in the DEX group; the levels of COR, E and NE in the DEX group were lower than those in the control group ( t values were -2.51, -2.37, -2.08, all P < 0.05). At T 2, the levels of COR, E and NE were (124±12) μg/L, (131±16) ng/L, (234±8) ng/L, respectively in the control group, and (116±15) μg/L, (123±12) ng/L, (228±10) ng/L, respectively in the DEX group; the levels of COR, E and NE in the DEX group were also lower than those in the control group ( t values were -2.35, -2.23, -2.17, all P < 0.05). At T 0, there were no statistically significant differences in the proportions of CD4 +, CD8 + and CD4 +/CD8 + between the DEX group and the control group (all P > 0.05). At T 1, the proportions of CD4 +, CD8 + and CD4 +/CD8 + were (23±3)%, (20±3)%, 1.12±0.16, respectively in the control group, and (27±4)%, (23±4)%,1.22±0.19, respectively in the DEX group; the proportions of CD4 +, CD8 + and CD4 +/CD8 + in the DEX group were higher than those in the control group ( t values were -3.43, -2.29, 2.13, all P < 0.05). At T 2, the proportions of CD4 +, CD8 + and CD4 +/CD8 + were (26±3)%, (23±4)%, 1.17±0.16, respectively in the control group, and (31±5)%, (25±4)%, 1.26±0.19, respectively in the DEX group; the proportions of CD4 +, CD8 + and CD4 +/CD8 + in the DEX group were higher than those in the control group ( t values were -4.32, -2.02, 2.02, all P < 0.05). In addition, the time of first exhaust in the DEX group was shorter than that in the control group ( P<0.05). Conclusions:DEX can reduce the intestinal stress response of gynecologic malignancies patients undergoing laparoscopic surgery, thereby improving the immunosuppression of patients. It is also of great significance to protect intestinal mucosal barrier and recover the intestinal function, and DEX has a high safety.

Effects of Jianpi Huaji Fuzheng Decoction supplemented with conventional chemotherapy on cellular immunity and coagulation-fibrinolysis function in patients with primary hepatic carcinoma of spleen-deficiency syndrome / 国际中医中药杂志

Objective:To explore the effects of Jianpi Huaji Fuzheng Decoction supplemented with conventional chemotherapy on Traditional Chinese Medicine (TCM) syndromes scores, cellular immunity and coagulation-fibrinolysis function in patients with primary hepatic carcinoma of spleen-deficiency syndrome.Methods:Prospective cohort study. A total of 85 patients with primary hepatic carcinoma of spleen-deficiency syndrome who met the inclusion criteria in the hospital between March 2018 and March 2021 were divided into 42 cases in control group and 43 cases in observation group according to the random number table method. The control group was given conventional western medicine chemotherapy, and the observation group was given Jianpi Huaji Fuzheng Decoction on the basis of the control group. Both groups were treated for 3 months. Before and after treatment, the TCM syndromes were scored. The levels of CD4 + and CD8 + were detected by flow cytometry with indirect immunofluorescence, and the ratio of CD4 +/CD8 + was calculated. The plasma prothrombin time (PT), fibrinogen (Fg) and coagulation factor Ⅶ (CFⅦ) were detected by automatic blood coagulation analyzer. The toxic and side effects of chemotherapy during treatment were recorded and the clinical efficacy was evaluated. Results:The total effective rate of syndrome efficacy was 95.35% (41/43) in observation group and 78.57% (33/42) in control group ( χ2=3.92, P=0.047). After treatment, the scores of flank pain, lumps, fatigue and jaundice and total score in observation group were significantly lower than those in the control group ( t=2.60, 2.64, 2.85, 2.91, 3.79, P<0.01). The level of CD4 + [(37.68±3.72)% vs. (35.92±3.61)%, t=2.21] and CD4 +/CD8 + [(1.44±0.22) vs. (1.31±0.23), t=2.66] in observation group were significantly higher than those in the control group ( P<0.05), while the level of CD8 + [(26.20±2.72)% vs. (27.44±2.16)%, t=2.32] was significantly lower than that of the control group ( P<0.05). The levels of Fg [(3.11±0.85) g/L vs. (2.74±0.72) g/L, t=2.16] and CFⅦ [(1.76±0.44) mg/L vs. (1.58±0.37) mg/L, t=2.04] were significantly higher than those in the control group ( P<0.05). PT [(14.65±2.72) s vs. (15.91±3.03) s, t=2.02] was significantly shorter than that of the control group ( P<0.05). During treatment, the incidence rate of toxic and side effects of chemotherapy was 11.63% (5/43) in observation group and that in control group was 30.95% (13/42) ( χ2=4.75, P=0.029). Conclusion:Jianpi Huaji Fuzheng Decoction supplemented with conventional chemotherapy can improve the clinical symptoms, promote the recovery of cellular immune function and coagulation-fibrinolysis function, reduce the incidence rates of toxic and side effects of chemotherapy, and enhance the clinical efficacy of patients with primary hepatic carcinoma.

An antigen self-assembled and dendritic cell-targeted nanovaccine for enhanced immunity against cancer

The rise of nanotechnology has opened new horizons for cancer immunotherapy. However, most nanovaccines fabricated with nanomaterials suffer from carrier-related concerns, including low drug loading capacity, unpredictable metabolism, and potential systemic toxicity, which bring obstacles for their clinical translation. Herein, we developed an antigen self-assembled nanovaccine, which was resulted from a simple acryloyl modification of the antigen to induce self-assembly. Furthermore, a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid (Zol) were integrated or absorbed onto the nanoparticles (denoted as MEAO-Z) to intensify the immune response. The synthesized nanovaccine with a diameter of around 70 nm showed successful lymph node transportation, high dendritic cell internalization, promoted costimulatory molecule expression, and preferable antigen cross-presentation. In virtue of the above superiorities, MEAO-Z induced remarkably higher titers of serum antibody, stronger cytotoxic T lymphocyte immune responses and IFN-γ secretion than free antigen and adjuvants. In vivo, MEAO-Z significantly suppressed EG7-OVA tumor growth and prolonged the survival time of tumor-bearing mice. These results indicated the translation promise of our self-assembled nanovaccine for immune potentiation and cancer immunotherapy.

Orchestrating antigen delivery and presentation efficiency in lymph node by nanoparticle shape for immune response

Activating humoral and cellular immunity in lymph nodes (LNs) of nanoparticle-based vaccines is critical to controlling tumors. However, how the physical properties of nanovaccine carriers orchestrate antigen capture, lymphatic delivery, antigen presentation and immune response in LNs is largely unclear. Here, we manufactured gold nanoparticles (AuNPs) with the same size but different shapes (cages, rods, and stars), and loaded tumor antigen as nanovaccines to explore their disparate characters on above four areas. Results revealed that star-shaped AuNPs captured and retained more repetitive antigen epitopes. On lymphatic delivery, both rods and star-shaped nanovaccines mainly drain into the LN follicles region while cage-shaped showed stronger paracortex retention. A surprising finding is that the star-shaped nanovaccines elicited potent humoral immunity, which is mediated by CD4+ T helper cell and follicle B cell cooperation significantly preventing tumor growth in the prophylactic study. Interestingly, cage-shaped nanovaccines preferentially presented peptide-MHC I complexes to evoke robust CD8+ T cell immunity and showed the strongest therapeutic efficacy when combined with the PD-1 checkpoint inhibitor in established tumor study. These results highlight the importance of nanoparticle shape on antigen delivery and presentation for immune response in LNs, and our findings support the notion that different design strategies are required for prophylactic and therapeutic vaccines.

Immunogenicity of mucosal COVID-19 vaccine candidates based on the highly attenuated vesicular stomatitis virus vector (VSVMT) in golden syrian hamster

COVID-19 is caused by coronavirus SARS-CoV-2. Current systemic vaccines generally provide limited protection against viral replication and shedding within the airway. Recombinant VSV (rVSV) is an effective vector which inducing potent and comprehensive immunities. Currently, there are two clinical trials investigating COVID-19 vaccines based on VSV vectors. These vaccines were developed with spike protein of WA1 which administrated intramuscularly. Although intranasal route is ideal for activating mucosal immunity with VSV vector, safety is of concern. Thus, a highly attenuated rVSV with three amino acids mutations in matrix protein (VSVMT) was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern. It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently. VSVMT indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein. With a single-dosed intranasal inoculation of rVSVΔGMT-SΔ21, potent SARS-CoV-2 specific neutralization antibodies could be stimulated in animals, particularly in term of mucosal and cellular immunity. Strikingly, the chimeric VSV encoding SΔ21 of Delta-variant can induce more potent immune responses compared with those encoding SΔ21 of Omicron- or WA1-strain. VSVMT is a promising platform to develop a mucosal vaccine for countering COVID-19.

Construction of a novel bivalent DNA vaccine against SARS-CoV-2 and influenza A virus H3N2 and evaluation of its immunogenicity in mice / 中华微生物学和免疫学杂志

Objective:To construct a bivalent DNA vaccine against SARS-CoV-2 and influenza A virus H3N2 and to evaluate its immunogenicity in mice.Methods:The coding sequences for spike 1 (S1) protein of SARS-CoV-2 Beta variant and hemagglutinin (HA) of influenza A virus Cambodia (H3N2) strain were codon-optimized and synthesized. The two coding genes were ligated by the self-cleaving 2A peptide using over-lapping PCR to construct S1-2A-HA fragment, which was inserted into pVRC vector to construct the bivalent DNA vaccine, named as pVRC-S1-2A-HA. Indirect immunofluorescence assay (IFA) and Western blot were performed to detect the expression of S1 and HA proteins. BALB/c mice were immunized with pVRC-S1-2A-HA by intramuscular injection and electroporation. The humoral immune responses induced in mice were detected by indirect ELISA, pseudovirus neutralization assay and hemagglutination inhibition assay. Cellular immune responses were detected by IFN-γ ELISPOT, intracellular cytokine staining (ICS) and cytometric bead array (CBA).Results:The bivalent DNA vaccine pVRC-S1-2A-HA could express S1 and HA proteins in vitro. Specific cellular immune responses against S1 protein and specific IgG antibody against HA protein were significantly induced in mice with single-dose immunization. The antigen-specific immunity was significantly enhanced after booster immunization. The geometric mean titer (GMT) of specific IgG antibody increased to 3 251 for S1 protein and 45 407 for HA protein after two-dose immunization. Moreover, the S1-specific T cells increased to 1 238 SFC/10 6 cells. ICS results indicated that the booster vaccination induced CD4 + T and CD8 + T cells to produce IL-2, IFN-γ and TNF-α in mice. The secretion of various cytokines including IL-2, IL- 4, IL-6, IL-10 and IFN-γ in mouse splenocytes was induced after single-dose immunization. Conclusions:A bivalent DNA vaccine against SARS-CoV-2 and influenza A virus H3N2 was constructed and could induce S1- and HA-specific humoral and cellular immune responses in mice, suggesting the great potential of it for further development and application.

Effect of Jiedu Huayu Granules on Inflammatory State of Patients with Chronic Hepatic Failure with Toxic Heat and Stasis Syndrome / 中国实验方剂学杂志

ObjectiveTo evaluate the curative effect of Jiedu Huayu granules （JDHY） in the treatment of chronic liver failure （CLF） with the syndrome of toxic heat and stasis and investigate the influence on the inflammatory state. MethodA total of 136 patients were randomly divided into a control group and an observation group with 68 cases in each group. In addition to the comprehensive western medicine treatment， patients in the control group received Yinchen Haotang granules orally at 1 dose/day and those in the observation group received JDHY at 10 g/time，3 times/day. The treatment lasted for eight weeks. The endotoxin （ET），diamine oxidase （DAO），aromatic amino acids （AAA），branched chain amino acids （BCAA），blood ammonia，calcitonin （PCT），tumor necrosis factor-α （TNF-α），interleukin （IL）-1，IL-6，IL-17，regulatory T cells （Treg cells），helper T cells 17 （Th17），Th17/Treg ratio，total bilirubin （TBil），albumin （Alb），alanine aminotransferase （ALT），aspartate aminotransferase （AST），prothrombin activity （PTA）， and D-dimer （D-D） levels before and after treatment were detected. The Child-Pugh grading scores of liver function， toxic heat and stasis syndrome scores， and the model scores of end-stage liver disease（MELD） before and after treatment were recorded. The fatality rate and survival were recorded at the follow-up for 48 weeks. ResultCompared with the control group after treatment， the observation group showed decreased ET，DAO， and blood ammonia， increased BCAA/AAA ratio （P<0.01）， reduced PCT，TNF-α，IL-1，IL-6， and IL-17 （P<0.01）， elevated Treg cells， dwindled Th17 and Th17/Treg ratio （P<0.01）， diminished TBil，ALT，AST， and D-D levels， and up-regulated Alb and PTA（P<0.01）. The Child-Pugh grading score，MELD score， and toxic-heat and stasis syndrome score of the observation group were lower than those of the control group （P<0.01）. The total response rate in the observation group was 93.65% （59/63），which was higher than 79.03% （49/62） in the control group （χ2=5.683，P<0.05）. The fatality rate of the observation group eight weeks after treatment was 6.35% （4/63），which was lower than 19.35% （12/62） of the control group （χ2=4.757，P<0.05）. There was no significant difference in mortality between the two groups 16，24， and 48 weeks after treatment. As revealed by the Log-rank test，the difference in survival curves between the two groups was not statistically significant. ConclusionJDHY can remove toxins from the body，regulate immune function，relieve inflammation，improve liver function， and reduce the severity of the disease in CLF patients with the syndrome of toxic heat and stasis. It is significant in clinical efficacy and worthy of clinical application.

Effect of antidepressant therapy on cellular immunity and quality of life of patients with depression after thoracoscopic radical resection of esophageal cancer / 中华胸心血管外科杂志

Objective:To investigate the effect of antidepressant therapy on cellular immunity and quality of life of patients with depression after thoracoscopic radical resection of esophageal cancer.Methods:Between June 2015 to March 2019, our hospital during the period of line thoracoscope comorbid depressive patients, 186 cases of esophageal cancer radical, according to the indicator method were randomly divided into treatment group and the control group (n=93), the treatment group after surgery for antidepressant treatment, the control group did not give any postoperatively in patients with depressive drugs treatment, routine for psychological counseling. Self-rating Depression Scale SDS and Generic Quality of Life Inventory-74 (GQoli-74) were used to evaluate the changes of depression status and Quality of Life in 2 groups before and after treatment. Flow cytometry was used to detect the levels of CD 4+ and CD 8+ subsets in peripheral blood to evaluate the changes of immune system function in 2 groups before and after treatment. Results:After treatment, the SDS score of the treatment group was significantly lower than that before treatment, the difference was statistically significant( P<0.05), while the SDS score of the control group was not significantly changed before and after treatment, the difference was not statistically significant( P>0.05). After antidepressant treatment, CD 4+ and CD 4+ /CD 8+ levels in the immune system in the treatment group were significantly increased, and CD 8+ levels were significantly decreased, with statistical significance ( P<0.05), while CD 4+ , CD 8+ and CD 4+ /CD 8+ levels in the control group were not significantly changed before and after treatment. There was no significant difference ( P>0.05). After treatment, the body function, psychological function, social function, material state and total score of quality of life of patients in the treatment group were significantly improved compared with before treatment, the difference was statistically significant ( P<0.05), while the score of quality of life of patients in the control group was not significantly changed before and after treatment, the difference was not statistically significant ( P>0.05). Conclusion:Antidepressant therapy can significantly improve the depression status of postoperative esophageal cancer patients, and improve the immune system function and quality of life.

Vitamina D intralesional em múltiplas verrugas plantares recorrentes - Um estudo cego, prospectivo e controlado por placebo / Intralesional vitamin D in multiple recurrent plantar warts - A single, blind, prospective, placebo-controlled study

Introdução: As verrugas, são proliferações epidérmicas benignas da pele. A maioria dos pacientes procura orientação médica, pois as verrugas são cosmeticamente inaceitáveis e podem ser dolorosas. As verrugas plantares, em particular, são tipicamente refratárias ao tratamento que requer várias sessões. As modalidades terapêuticas disponíveis são limitadas pela alta taxa de recorrência, dor e cicatrizes. Em contraste, as abordagens imunoterapêuticas estimulam o sistema imunológico do hospedeiro, aumentando a imunidade celular para eliminar o vírus. Objetivo: Avaliar a segurança e eficácia da injeção intralesional de vitamina D3 no tratamento de múltiplas verrugas plantares recorrentes. Métodos: Um total de 60 pacientes com verrugas plantares múltiplas recorrentes, foram divididos em dois grupos de 30. No grupo 1, 0,5ml de vitamina D intralesional foi injetado na base da maior verruga e no grupo 2, injetou-se 0,5ml de solução salina normal. As sessões foram repetidas a cada 2 semanas por no máximo 4 sessões e os pacientes foram acompanhados por um período de 12 meses. Resultados: No grupo de estudo, a eliminação completa foi observada em 73,3% (22) e nos controles, 70% dos pacientes não apresentaram resposta. Conclusão: A vitamina D3 intralesional é uma opção de tratamento segura e eficaz em verrugas plantares.

Introduction: Warts or verrucae, caused by the human papillomavirus (HPV), are a benign epidermal proliferation of the skin. Most patients seek medical advice as warts are cosmetically unacceptable and can be painful. Plantar warts, in particular, are typically refractory to treatment requiring multiple treatment sessions. High recurrence rates, pain, and scarring limit the available therapeutic modalities. In contrast, immunotherapeutic approaches stimulate the host immune system by enhancing cellular immunity to eliminate the virus. Objective: To assess the safety and efficacy of intralesional vitamin D3 injection to treat multiple recurrent plantar warts. Methods: 60 patients with multiple recurrent warts were divided into two groups of 30 each. Group 1 received 0.5 ml intralesional vitamin D in the base of the largest wart, and Group 2 received 0.5 ml of normal saline. The sessions were repeated every two weeks for a maximum of four sessions, and patients were followed up for 12 months to detect any recurrences. Results: The study group showed complete clearance in 73.3% (22) individuals, while most controls (70%) showed no response. Conclusion: Intralesional vitamin D3 is a safe and effective treatment option for multiple recurrent plantar warts.

Regulatory Effect of Qingzhenfang on Cellular Immune Function of Patients with Chronic Urticaria / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Qingzhenfang for plasmoby （chronic urticaria）， and to investigate its effect on cellular immune function. Method:One hundred and thirty-two cases patients were divided into control group and observation group evenly according to random number table. The 60 patients in control group finished the study because of 6 cases of dropout， loss of follow-up and withdrawal， and 62 patients in observation group finished the study. Patients in both groups got Yiebastine tablets， 10-20 mg/time， 1 time/day. Patients in control group additionally got Piminxiao capsule， 4 grains/time， 3 times/day， while patients in observation additionally got Qingzhenfang， 1 dose/day. The treatment continued for 8 weeks in both groups. Before the treatment， and at the second， fourth， and eighth week after treatment， scores of urticaria activity for 7 days （USA7） and total symptom score （TSS） were graded. Before and after treatment， scores of chronic urticaria quality of life scale （CU-Q2oL） and syndrome of rheumatic fever were graded. A follow-up of 3 months was conducted for the patients whose score of USA7 was less than 7 to record the recurrence. Complement 3 and 4 （C3， C4）， CD4⁺， CD8⁺ cells were detected， and Th17/ CD4⁺ and Treg/ CD4⁺， CD4⁺/CD8⁺ and Th17/Treg were calculated. Levels of peripheral blood interleukin-10 （IL-10）， IL-17 and IL-23 were detected， and safety was evaluated after the treatment. Result:At the second， fourth and eighth week after the treatment， scores of USA7， TSS， CU-Q2oL and syndrome of rheumatic fever in observation group were lower than those in the control group （<italic>P</italic><0.01）. Levels of C3， C4， CD4⁺， Treg， CD4⁺/CD8⁺and IL-35 in observation group were higher than those levels detected in control group （<italic>P</italic><0.01）， while levels of CD8⁺， Th17， Th17/Treg， IL-10， IL-17 and IL-23 were lower than those in the control group （<italic>P</italic><0.01）. Recurrence rate was 25.58% （11/43） in observation group， lower than 48.48% （16/33） in control group （<inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:msup><mml:mrow><mml:mi>χ</mml:mi></mml:mrow><mml:mrow><mml:mn mathvariant="normal">2</mml:mn></mml:mrow></mml:msup></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/19F4CEA3-4719-4fe6-AFE8-81E481AA497E-M002.jpg"><?fx-imagestate width="3.30199981" height="3.64066648"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/19F4CEA3-4719-4fe6-AFE8-81E481AA497E-M002c.jpg"><?fx-imagestate width="3.30199981" height="3.64066648"?></graphic></alternatives></inline-formula>=4.276， <italic>P</italic><0.05）， and the clinical efficacy in observation group was superior to that in control group （<italic>Z</italic>=2.021， <italic>P</italic><0.05）. Conclusion:Yaoyi Qingzhenfang can control the degree of disease and improve the quality of life for patients with chronic urticaria， with superior clinical efficacy. In addition， it can reduce recurrence rate， increase the levels of C3， C4， regulate cellular immune function， and reduce immune inflammatory response， so it is worthy of further clinical research and use.

Effect of pregnancy malaria on T cells in immune organ of offspring mice / 中华地方病学杂志

Objective:To observe the influence of pregnant mice having malaria on T cell function of offspring mice, and to study the changes of cellular immune response in offspring mice exposed to malaria infection in uterus.Methods:Adult Kunming mice of clean grade were selected after mating, on the 14th day of pregnancy, pregnant mice were randomize assigned into experimental group ( n = 5) and control group ( n = 5) according to the method of random number table. Each mouse in the experimental group was intraperitoneally inoculated with 1 × 10 6 red blood cells infected with Plasmodium berghei ( P.b), and same volume of normal saline was given to control group. After birth, the changes of CD4/CD8 T cell subsets in their thymuses and spleens of the two group neonatal mice were analyzed by flow cytometry at day 0, 1, 3, 5 and 4-week-old. Then the 4-weeks-old neonatal mice were intraperitoneally inoculated with 1 × 10 6P.b. On the third day, the changes of CD4/CD8 T cells subsets in their thymuses and spleens were observed, respectively, and the immune response of spleen cells stimulated by P.b antigen or mitogen [concanavalin A (Con A)] was detected. Results:Compared with the control group, the proportions of CD3 +CD4 +CD8 - T cells in thymus and spleen of the offspring of the experimental group (0, 1, 3, 5 days) were higher ( P < 0.05), while the proportions of CD3 +CD4 -CD8 + T cells in thymus were lower ( P < 0.05). For 4-week-old offspring and after infection of P.b, the proportions of CD3 +CD4 +CD8 - T cells in thymus and spleen of the experimental group were both significantly higher than those of control group ( P < 0.05), in contrast, the proportions of CD3 +CD4 -CD8 + T cells in thymus and spleen were both significantly lower than those of control group ( P < 0.05). The spleen cells of 4-week-old mice were stimulated by P.b antigen or mitogen ConA in vitro, compared with the control group, there were no significant differences in the proportions of CD3 +CD4 +CD8 - T cells and CD3 +CD4 -CD8 + T cells in the experimental group ( P > 0.05). Conclusion:During pregnancy, the maternal infection of P.b could significantly affect the ratio of CD4/CD8 T cell subsets in thymus and spleen of offspring mice; and could change the cellular immune response of offspring to P.b infection.

Detection and significance of immune function in oral mucosa-associated diseases / 口腔疾病防治

@#The evaluation of immune function plays an important role in the diagnosis, treatment and prognosis of many diseases. To date, immune function detection includes cellular immunity, humoral immunity, and inflammatory markers. In this paper, the application of immune function detection in the diagnosis, differential diagnosis and treatment monitoring of various diseases was discussed; then, the application value of immune function detection in the diagnosis and treatment of three common oral mucosa-related diseases, including recurrent aphthous ulcer (RAU), oral lichen planus (OLP), and oral squamous cell carcinoma (OSCC), were reviewed combined with the literature and our research. Our research found that RAU patients present abnormal humoral immune function and obvious inflammatory reactions, whereas OLP and OSCC patients present mild inflammatory reactions and more serious abnormal cellular and humoral immune function, so the combined detection of immune function has a certain guiding value for the diagnosis and treatment of these diseases. Moreover, in the future, it is necessary to carry out a study on large sample, multicenter and multiindex joint detection to better clarify the role of immune dysfunction in the pathogenesis of various diseases and its mechanism, to establish the corresponding diagnostic model and prognostic prediction model, to find more effective treatment methods.