The expression of CTLA-4 in hepatic alveolar echinococcosis patients and blocking CTLA-4 to reverse T cell exhaustion in Echinococcus multilocularis-infected mice.

Alveolar echinococcosis (AE) is a zoonotic parasitic disease caused by the infection of Echinococcus multilocularis (E. multilocularis) larvae. Cytotoxic T-lymphocyte antigen 4 (CTLA-4) produces inhibitory signals and induces T cell exhaustion, thereby inhibiting the parasiticidal efficacy of the liver immune system. Therefore, the purpose of this study is to explore how T-cell exhaustion contributes to AE and whether blocking CTLA-4 could reverse T cell exhaustion. Here we discovered that the expression of CTLA-4 was increased in the infiltrating margin around the lesion of the liver from AE patients by using western blot and immunohistochemistry assay. Multiple fluorescence immunohistochemistry identified that CTLA-4 and CD4/CD8 molecules were co-localized. For in vitro experiments, it was found that the sustained stimulation of E. multilocularis antigen could induce T cell exhaustion, blocking CTLA-4-reversed T cell exhaustion. For in vivo experiments, the expression of CTLA-4 was increased in the liver of E. multilocularis-infected mice, and the CTLA-4 and CD4/CD8 molecules were co-localized. Flow cytometry analysis demonstrated that the percentages of both CD4+ T cells and CD8+ T cells in the liver and peripheral blood were significantly increased and induced T exhaustion. When the mice were treated with anti-CTLA-4 antibodies, the number and weight of the lesions decreased significantly. Meanwhile, the flow cytometry results suggested that blocking CTLA-4 could effectively reverse T cell exhaustion and reactivate immune function. Our work reveals that blocking CTLA-4 could effectively reverse the T cell exhaustion caused by E. multilocularis and could be used as a novel target for the treatment of AE.

Effects of the Chinese herbal formula San-Huang Gu-Ben Zhi-Ke treatment on stable chronic obstructive pulmonary disease: a randomized, double-blind, placebo-controlled trial.

Objective: The aim of this study was to evaluate the efficacy and safety of the Chinese herbal formula San-Huang Gu-Ben Zhi-Ke (SHGBZK) as a treatment for patients with stable chronic obstructive pulmonary disease (COPD) diagnosed with lung-spleen Qi deficiency. Method: A randomized, double-blind, placebo-controlled trial was designed. 98 adults aged between 40 and 80 years with stable COPD diagnosed with lung-spleen Qi deficiency were included. All participants received basic treatment for COPD. Patients in the experimental group took SHGBZK, while the control group took placebo. The primary outcome was the frequency of acute exacerbation. The secondary outcomes were lung function, symptom score, exercise capacity and quality of life. Results: Of 98 patients who underwent randomization, 50 patients in the SHGBZK group and 48 in the placebo group were included in the full analysis set. After 24-week therapy and 28-week follow-up, patients in treatment group had significant improvements in symptom, exercise capacity and quality of life. After Subgroup analysis, the frequency of acute exacerbation in patients with a COPD Assessment Test (CAT) score of at least 10 or a modified Medical Research Council (mMRC) score of at least 2 was significantly lower in the SHGBZK group than in the placebo group. Lung function in patients with frequent exacerbation was significantly higher in the SHGBZK group than in the placebo group. The incidence of adverse events was generally similar in the two groups. Conclusion: SHGBZK had beneficial effects on symptom, exercise capacity and quality of life in stable COPD patients. SHGBZK also had the potential to reduce the frequency of exacerbation and improve lung function in specific groups of COPD patients. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=26933, identifier ChiCTR1800016349.

The Investigation of the Effect and Mechanism of Sophora moorcroftiana Alkaloids in Combination with Albendazole on Echinococcosis in an Experimental Rats Model.

Echinococcosis is a worldwide anthropozoonosis which is highly endemic over large animal husbandry areas in northwestern China. The current clinical therapeutic medicine against echinococcosis is albendazole, although it caused serious side effects in patients. The component in traditional Chinese herb medicine, Sophora moorcroftiana alkaloids (SA), is thought to be a potential drug to treat echinococcosis. In order to explore the effect and mechanism of SA treatment against echinococcosis, we established animal echinococcosis model and treated rats with albendazole alone, alkaloids alone, and combined therapy. The combined treatment showed effective inhibition against parasite infection due to induction of host response and alleviated liver injury; meanwhile albendazole caused serious liver problem. The proteomics study revealed that the combined therapy might induce complement activation through C3, C4, C5, SERPINA1, and SERPINC1 proteins and cell adhesion by ANXA2, EZR, YWHAB, HSP90AN1, and PRKAR2A proteins, while albendazole treatment could induce liver injury through CRYAB, YWHAZ, SLC25A24, and HSPA1B proteins that were involved in cell death. In all, we consider that the combinational treatment displayed better therapeutic effects against liver echinococcosis as well as alleviated liver injury, which could be considered as an effective strategy to treat echinococcosis clinically.

[An Epidemiological Survey on Echinococcosis in Yushu Prefecture of Qinghai Province].

Objective: To investigate the prevalence of echinococcosis in Yushu Prefecture of Qinghai Province in 2012. Methods: Two to three towns were selected in each of Chengduo, Nangqian, Qu malai, Yushu, Zaduo and Zhiduo Counties from June to August in 2012. Ultrasound examination was conducted for residents aged over 1 year, and ELISA was performed to detect serum antibody against Echinococcus. Visceral dissection was performed to detect hydatid infection in rodents and livestock. ELISA was used to detect Echinococcus antigen in collected dog feces. Results: A total of 7 025 residents received ultrasound examination, of whom 319 showed hydatid cysts with a morbidity rate of 4.54%. ELISA showed a serum antibody positive rate of 16.38% （457/2 790）. The mobidity of hydatid disease was highest in Chengduo County （7.41%, 181/2 444）, and the rate of serum antibody was highest in Yushu County （23.18%, 127/548）. The morbidity and serum antibody in males were 3.91% （118/3 018） and 13.93% （172/1 235） respectively, and those in females were 5.02% （201/4 007） and 18.33% （285/1 555）. In terms of age distribution, the morbidity was relatively higher in residents of 60- （8.39%, 38/453） and 40- years （6.61%, 67/1 014）; and the rate of serum antibody was highest in residents over 70 years （33.93%, 19/56）. In terms of occupation, the morbidity was relatively higher in herdsmen （5.28%, 252/4 777）, Herdsmen-peasants （6.52%, 24/368）, and religious workers（3.37%, 11/326）, while the rate of serum antibody was relatively higher in children（24%, 6/25）, religious workers （18.79%, 31/165） and herdsmen（18.34%, 328/1 788）. In terms of education level, the morbidity and the rate of serum antibody were both highest in the uneducated（5.04%, 41/4 779; 18.34%, 359/1 958, respectively）. In terms of residential pattern, the morbidity and the rate of serum antibody were both highest in those who were settled in winter and nomadic in summer （8.25%, 227/2 753; 19.48%, 158/811, respectively）. There were significant differences in the morbidity and the rate of serum antibody in aspects of residential region, sex, age, occupation, education level and residential pattern (P<0.05 or P<0.01). In 872 rodents detected, the Echinococcus hydatid rate was 0.46% （4/872）, while in 809 cattle and sheep detected, the Echinococcus hydatid rate was 10.14% （82/809）. The fecal antigen positive rate in 838 samples of dog feces was 10.74%（90/838）. Conclusion: It shows a high morbidity of hydatid diesease and serum antibody positive rate in residents, a high Echinococcus hydatid rate in cattle and sheep, and a high fecal antigen positive rate in dogs in Yushu Prefecture.