Schistosomiasis is a neglected zoonotic parasitic disease. Currently, praziquantel is the drug of choice for the treatment of schistosomiasis, and is the only effective chemical for treatment of schistosomiasis japonica. Since its introduction in the 1970s, praziquantel has been used for large-scale chemotherapy of schistosomiasis for over 40 years. However, there have been reports pertaining to the resistance to praziquantel in schistosomes. Therefore, development of novel antischistosomal agents as alternatives of praziquantel, is of great need. Histone deacetylases and histone acetyltransferases have been recently reported to play critical roles in the growth, development and reproduction of schistosomes, and are considered as potential drug targets for the treatment of schistosomiasis. This review summarizes the latest advances of histone deacetylase and histone acetyltransferase inhibitors in the research on antischistosomal drugs, so as to provide insights into research and development of novelantischistosomal agents.

Teaching evaluation is an important measure to test the teaching quality. In order to better achieve the training objectives among international medical students based on the specific conditions of foreign students and the characteristics of Human Parasitology, a process-based assessment and evaluation system has been established for international medical students. The process assessment highlights the characteristics of assessment process, diversified forms and inquires of test questions. Following implementation of process assessment, the proportion of excellence (examination scores of 90 and higher) improved from 3.25% (10/308) to 13.09% (50/382) (t = 5.995, P < 0.001) and the proportion of good marks (examination scores of 80 to 89) increased from 18.83% (58/308) to 36.13% (138/382) (t = 7.505, P < 0.001) during the semester assessment among international medical students at five grades, while the proportion of failure in examination pass (examination scores of below 60) reduced from 12.34% (38/308) to 3.24% (10/382) (t = 7.303, P < 0.000 1), indicating that the process-based assessment and evaluation system improves the examination score of Human Parasitology among international medical students and the teaching quality of Human Parasitology.

OBJECTIVE: To analyze the effect of mechanical cardiopulmonary resuscitation (CPR) on patients with cardiac arrest with the vertical spatial pre-hospital emergency transport. METHODS: A retrospective cohort study was conducted. The clinical data of 102 patients with out-of-hospital cardiac arrest (OHCA) who were transferred to the emergency medicine department of Huzhou Central Hospital from the Huzhou Emergency Center from July 2019 to June 2021 were collected. Among them, the patients who performed artificial chest compression during the pre-hospital transfer from July 2019 to June 2020 served as the control group, and the patients who performed artificial-mechanical chest compression (implemented artificial chest compression first, and implemented mechanical chest compression immediately after the mechanical chest compression device was ready) during pre-hospital transfer from July 2020 to June 2021 served as the observation group. The clinical data of patients of the two groups were collected, including basic data (gender, age, etc.), pre-hospital emergency process evaluation indicators [chest compression fraction (CCF), total CPR pause time, pre-hospital transfer time, vertical spatial transfer time], and in-hospital advanced resuscitation effect evaluation indicators [initial end-expiratory partial pressure of carbon dioxide (P_ETCO₂), rate of restoration of spontaneous circulation (ROSC), time of ROSC]. RESULTS: Finally, a total of 84 patients were enrolled, including 46 patients in the control group and 38 in the observation group. There was no significant difference in gender, age, whether to accept bystander resuscitation or not, initial cardiac rhythm, time-consuming pre-hospital emergency response, floor location at the time of onset, estimated vertical height, and whether there was any vertical transfer elevator/escalator, etc. between the two groups. In the evaluation of the pre-hospital emergency process, the CCF during the pre-hospital emergency treatment of patients in the observation group was significantly higher than that in the control group [69.05% (67.35%, 71.73%) vs. 61.88% (58.18%, 65.04%), P < 0.01], the total pause time of CPR was significantly shorter than that in the control group [s: 266 (214, 307) vs. 332 (257, 374), P < 0.05]. However, there was no significant difference in the pre-hospital transfer time and vertical spatial transfer time between the observation group and the control group [pre-hospital transfer time (minutes): 14.50 (12.00, 16.75) vs. 14.00 (11.00, 16.00), vertical spatial transfer time (s): 32.15±17.43 vs. 27.96±18.67, both P > 0.05]. It indicated that mechanical CPR could improve the CPR quality in the process of pre-hospital first aid, and did not affect the transfer of patients by pre-hospital emergency medical personnel. In the evaluation of the in-hospital advanced resuscitation effect, the initial P_ETCO₂ of the patients in the observation group was significantly higher than that of the patients in the control group [mmHg (1 mmHg ≈ 0.133 kPa): 15.00 (13.25, 16.00) vs. 12.00 (11.00, 13.00), P < 0.01], the time of ROSC was significantly shorter than that in the control group (minutes: 11.00±3.25 vs. 16.64±2.54, P < 0.01), and the rate of ROSC was slightly higher than that in the control group (31.58% vs. 23.91%, P > 0.05). It indicated that continuous mechanical compression during pre-hospital transfer helped to ensure continuous high-quality CPR. CONCLUSIONS Mechanical chest compression can improve the quality of continuous CPR during the pre-hospital transfer of patients with OHCA, and improve the initial resuscitation outcome of patients.
Humans ; Cohort Studies ; Carbon Dioxide ; Retrospective Studies ; Hospitals ; Out-of-Hospital Cardiac Arrest ; Cardiopulmonary Resuscitation

Objective:To analyze effect on the CD154-CD40 signaling pathway and Th1/Th2 polariza-tion by deficient inducible co-stimulator ( ICOS)-ICOS ligand ( ICOSL) signaling in mice infected with Schistosoma japonicum. Methods:ICOSL knockout ( ICOSL-KO) mice and wild-type C57BL/6J mice were used as experimental Schistosomiasis model infected with Schistosoma japonicum. The expressions of CD154 and CD40 on splenocytes and on inflammatory cells around granulomatous infiltration of liver in mice infected with Schistosoma japonicum were analyzed by flow cytometry,immunohistochemical staining, respectively, on the day before infection (0 week) and at the end of 4, 7, 12, 16 and 20 weeks post-infection. The splenocytes of the mice were stimulated with soluble egg antigen( SEA) for 72 hours, then the concentrations of interferon gamma(IFN-γ) and interleukin-4 (IL-4) in the culture supernatants were measured by sandwich enzyme-linked immunosorbent assay ( ELISA) kits. The levels of SEA-specific an-tibodies of IgG and IgG1 and IgG2a were measured in the mice sera by ELISA. The granulomatous pa-thology in the mice liver was dynamically observed by hematoxylin and eosin ( HE ) staining. Results:Compared with the wild-type C57BL/6J mice, the expressions of CD154 on CD4 + T splenocytes [(18. 62 ± 4. 76)% vs. (27. 91 ± 3. 94)%, (22. 44 ± 4. 67)% vs. (40. 86 ± 5. 21)%, (25. 50 ± 6. 81)% vs. (43. 81 ± 8. 41)%, (20. 22 ± 5. 28)% vs. (40. 95 ± 7. 34)%, (17. 87 ± 4. 59)% vs. (33. 16 ± 6. 31)%, all P <0. 01] and of CD40 on CD19 + B splenocytes [(19. 43 ± 3. 26)% vs. (24.37 ±3.59)%, (23. 00 ± 4. 47)% vs. (31. 80 ± 5. 86)%, (24. 46 ± 5. 01)% vs. (35. 85 ± 5. 32)%, (23. 42 ± 4. 69)% vs. (33. 30 ± 6. 14)%, (22. 85 ± 3. 78)% vs. (30. 88 ± 5. 94)%, all P<0 . 05 ] in the ICOSL-KO mice significantly decreased at the end of 4 , 7 , 12 , 16 and 20 weeks post-infection. Moreover, the expressions of CD154[(0. 319 ± 0. 066) vs. (0. 488 ± 0. 086), (0. 389 ± 0. 067) vs.(0.596±0.082),(0.378±0.064) vs.(0.543±0.072),(0.348±0.069) vs.(0.523±0.076), all P<0. 01] and CD40[ (0. 398 ± 0. 066) vs. (0. 546 ± 0. 079), (0. 461 ± 0. 085) vs. (0. 618 ± 0. 076), (0. 453 ± 0. 087) vs. (0. 587 ± 0. 074), (0. 449 ± 0. 065) vs. (0. 565 ± 0. 082), all P <0 . 05 ] on inflammatory cells around granulomatous infiltration in liver from the ICOSL-KO mice were sig-nificantly lower than those of the wild-type C57 BL/6 J mice at the end of 7 , 12 , 16 and 20 weeks post-in-fection. The levels of IFN-γ of the ICOSL-KO mice were significantly higher than those of the wild-type C57BL/6J mice at the end of 4, 7, 12, 16 and 20 weeks post-infection (P <0. 05). However, the levels of IL-4 of the ICOSL-KO mice were significantly lower than those of the wild-type mice ( P <0. 05). Compared with the wild-type C57BL/6J mice, the levels of SEA-specific antibodies of IgG and IgG1 and IgG2a in the sera of the ICOSL-KO mice significantly decreased (P<0. 01). Moreover, The Th2 differentiation index of the ICOSL-KO mice was significantly lower than that of the wild-type mice in post-infection (P<0. 01). Also, the ratio of IgG1/IgG2a of the ICOSL-KO mice were significantly lower than that of the wild-type mice at the end of 7 , 12 and 16 weeks post-infection ( P<0 . 05 ) . And the vo-lume of liver egg granulomas of the ICOSL-KO mice was significantly smaller than that of the wild-type mice ( P <0 . 01 ) . Conclusion: These findings suggest that there is obvious down-regulation in the expressions of CD154 and CD40 and impairment of Th2 immune response in the ICOSL-KO mice infected with Schistosoma japonicum, accompanying with notedly reduced hepatic granulomatous pathology. The ICOS-ICOSL signaling has a regulatory effect on CD154-CD40 signaling pathway, and may play an impor-tant role in the hepatic egg granuloma formation of Schistosomiasis.

Objective To analyze the effect of inducible costmulator (ICOS)/inducible costmulator ligand (ICOSL) signaling pathway on hepatic fibrosis in mice infected with Schistosoma japonicum.Methods Seventy-eight ICOSL knockout (ICOSL-KO) mice and 77 wild type C57BL/6J mice were used as experimental schistosomiasis model infected with Schistosoma japonicum.The sera of mice were collected on the day before infection (0 week),and at 4,7,12,16 and 20 weeks post infection.Then,the concentrations of hyaluronic acid (HA) and hydroxyproline (HYP) in mice sera were measured by sandwich enzyme linked immunosorbent assay (ELISA) kits.The expressions of transforming growth factor β1 (TGF-β1),α-smooth muscle actin (a-SMA) and Collagen-Ⅰ in livers from ICOSL-KO/wild type mice were assessed by immunohistochemical staining.The granulomatous pathology and fibrosis level in mice liver were dynamically observed by hematoxylin and eosin (HE) staining and Masson's staining,respectively.The difference between groups was detected by t test or x2 test when appropriate.Results After infection with Schistosoma japonicum,the levels of HA and HYP were gradually increased.In ICOSL-KO mice,the levels of HA at 7,12,16 and 20 weeks post infection were all significantly lower than those in wild type mice [(161.32±15.44) vs (186.01±21.24) ng/mL,t=2.528 2,P＜0.05; (166.73±18.18) vs (231.39±20.12) ng/mL,t=4.342 4,P＜0.05; (193.58±21.06) vs (252.51±25.29) ng/mL,t=4.003 9,P＜0.05; (253.98±24.53) vs (310.88±23.86) ng/mL,t=3.718 0,P＜0.05].Similarly,HYP levels in ICOSL-KO mice at 12,16 and 20 weeks post infection were all significantly lower than those in wild type mice (all P＜0.05).Immunohistochemical staining showed that TGF-β1,α-SMA and Collagen-Ⅰ expressions in liver of ICOSL-KO mice from 7 to 20 weeks post infection were all significantly lower than those of wild type mice (all P＜0.05).HE staining showed,the volume of liver egg granulomas of ICOSL-KO mice was significantly smaller than that of wild type C57BL/6J mice (P＜0.01).Furthermore,Masson's staining showed that the level of hepatic fibrosis in ICOSL-KO mice was lower than that in wild type mice and the fibrosis scores were statistically different between two groups (all P＜0.05).The mortality rate of the wilde type C57BL/6J mice was higher than that of ICOSL-KO mice.After 20 weeks of infection,the difference was statistically significant (55.84 ％ vs 37.18 ％,x2 =5.427,P＜0.05).Conclusions The degree of hepatic fibrosis and related indicators are obviously down-regulated in ICOSL-KO mice infected with Schistosoma japonicum.These findings suggest that ICOS/ICOSL signaling pathway has an important impact on the process of hepatic fibrosis caused by Schistosoma japonicum.

ABSTRACT:In the present study ,we aimed to identify differentially expressed proteins between induced worms (the infec‐ted mice were treated intragastrically with ED50 PZQ) and uninduced worms (control group) for clarifying the mechanism of PZQ .ED50 PZQ was used to administrate mice that were infected with S .japonicum via intragastric incubation for consecutive‐ly 30 days .Twenty‐one days later ,mice were sacrificed after treatment with 200 mg/kg PZQ for continuously five days ,and the male worms were obtained and some of them were subjected in DMEM medium with different concentrations of PZQ in vitro for 16 hours .Then the worms were washed twice and incubated in PZQ‐free medium for 72 hours .Compared with control group ,the induced worms had lesser sensitivity to PZQ .The survival rate of induced worms was 75 .6% in vitro when the con‐centration of PZQ was 112 mol/L (the concentration was 8 times of uninduced worms Lethal Concentration ) ,significantly higher than that in the uninduced worms (11 .1% ,P<0 .05) ,showing obviously tolerance .The other induced and uninduced worms were acquired and collected for 2D‐DIGE and MALDI‐TOF‐MS ,and combined with bioinformatics to analyse the func‐tion of the identified protein .Thirty differential expression proteins were confirmed between induced and uninduced worms ,in‐cluding 12 proteins up‐regulated and 18 proteins down‐regulated .These proteins respectively ascribed to cytoskeleton‐associat‐ed protein ,glucose and energy metabolism enzymes ,stress proteins ,thioredoxin peroxidase enzymes ,and other protease .Up‐or down‐regulation of these differential proteins indicated that PZQ promote or inhibit the expression of some specific genes . These findings may help to clarify the mechanism of PZQ ,simultaneously ,providing a scientific basis for exploring new vaccine candidate antigens and targets for drug therapy .

To determine immune responses and immunopathology in ICOSL knockout (ICOSL KO) mice infected with Schistosoma japonicum,ICOSL- KO mice and wild-type C57BL/6J mice were used as experimental models for Schistosoma japonicum infection.The splenic lymphocytes were isolated from the mice the day before infection (0 week) as well as 4,7,12,16 and 20 weeks post infection,and stimulated with SEA for 72 hours in culture.The concentrations of Th1 cytokines (IFN-γand IL- 12) and Th2 cytokines (IL- 4,IL-10 and IL-13) in the culture supernatants were measured by sandwich ELISA.The levels of SEA-specific IgG antibody and its subtypes (IgG1 and IgG2a) were measured in mouse sera by ELISA.Pathological changes of hepatic granuloma in mice were determined by hematoxylin and eosin (H&E) staining.After the infection,the levels of Th1 cytokines,IFN- γ and IL 12,in ICOSL- KO mice were higher than those in wild-type C57BL/6J mice.However,the levels of Th2 cytokines (IL- 4,IL- 10 and IL- 13) were significantly decreased in ICOSL-KO mice compared to those in wild-type C57BL/6J mice.The levels of SEA-specific IgG antibody and its subtypes (IgG1 and IgG2a) in the sera of ICOSL- KO mice were also significantly lower than those of wild -type C57BL/6J mice.Moreover,the Th2 differentiation index was lower in ICOSL- KO mice than in wild-type C57BL/6J mice at 4,7,12,16 and 20 weeks post-infection.Similarly,the ratio of IgG1/IgG2a in ICOSL-KO mice was significantly lower than that in wild- type C57BL/6J mice at 7,12 and 16 weeks post- infection.Furthermore,throughout the course of disease progression,the volume of hepatic egg granuloma in ICOSL- KO mice was significantly smaller than that in wild-type C57BL/6J mice.In conclusions,there is a substantially down-regulated Th2 immune response in ICOSL- KO mice infected with Schistosoma japonicum,thus results in an attenuated hepatic lesion caused by egg granulomas.The findings indicate that the ICOS ICOSL co-stimulatory pathway plays an important role in the hepatic egg granuloma formation of schistosomiasis.

Objective To study the expression levels of inducible costimulator (ICOS) on CD4+ T cells in peripheral blood in patients with chronic hepatitis B and its change after treated with interferon.Methods All 56 patients were divided into two groups (interferon group has 28 cases,lamivudine group has 28 cases),and interferon group treated by PEG-IFN-α 2a,lamivudine group treated by lamivudine,respectively.There were 20 healthy individuals as control group.The levels of ICOS on CD4+ T cells of patients with chronic hepatitis B were kinetically detected by flow cytometry.The copies of HBV DNA in sera were dynamically detected by real-time PCR.Results The levels of ICOS on CD4+ T cells in patients with chronic hepatitis B was higher than that of normal controls(P＜0.001 ).However,the expressions of ICOS on CD4+ T cells in patients could be deduced by PEG-IFN-α 2a and obviously decreased after treatment.There was significant difference between interferon group and lamivudine group (P＜0.05 in 24 weeks,and P＜0.01 in 48 weeks).After treatment,the change values of ICOS in interferon group was positively correlated with the change copies of HBV DNA (r =0.972,P＜0.001 ).However,the change values mentioned above that did not find correlation in lamivudine group(r=-0.101,P=0.608).Conclusion The study shows the patients with chronic hepatitis B have disordered in cellular immunity and increased with the expression of ICOS on CD4+ T cells.PEG-IFN-α 2a could decrease the expression of ICOS on CD4+ T cells in patients,and correct the Th2 type immune polarization to some extent,and that plays a positive role in antiHBV.

To explore the action target of praziquantel (PZQ) and its underlying mechanism of action, adult male worms of Schistosoma japonicum were collected from the hepatic vein of Kunming mice infected at least 6 or more weeks previously with single-sex cercariae of S.japonicum by perfusion method. These worms were subjected to the action of calcium channel blockers (CCBs) or actin depolymerizing/stabilizing agents interfering with function of the calcium channel. The adult male worms in DMEM culture medium were co-cultivated with near-lethal dose of PZQ(14 μmol/L) overnight(16 hours).Then, the parasites were washed 3 times with sterile physiologic saline next morning after cultivation, re-suspended in new and drug-free medium and then observed under stereo-microscopy during the following 5 days. The experimental results showed that majority of adult male worms of S.japonicum were killed by the action of PZQ in a dose of 14 μmol/L in vitro under normal condition; while the worms pre-incubated with the actin depolymerizing agent cyto chalasin D (CyD) were able to survive in the condition containing 14 μmol/L of PZQ with a survival rate of 100%, and the worms pre-incubted with CCBs, such as nitrendipine and nifedipineu showed a survival rate of about 50% under the same condition. The results of this study suggest that the calcium channel of Schistosomes may be involved in the action target of PZQ and its underlying mechanism.

Purpose To oberve the dynamics of liver granuloma and the relative changes of Thl/Th2cytokine levels in mice infected with Schistosoma japonicum, and investigate the role of Th1/Th2 in S.japontcum granuloma formation and regulation. Methods Liver granuloma measurement were performedby histological examination and the ELISA were used for the quantitative determination of IL-2, IFNr andIL-4 in murine serum and spleen lymphocyte culture medium at 0,4,6,8,10 and 12 wk after infection.Results At 6 wk liver granuloma formation appeared and at 8 wk liver granuloma peaked. After 12 wk livergranuhoma diminished obviously. Meanwhile, at 4 - 6 wk IL-2, IFNr and IL-4 began to rise, at 8 wk thelevels of Th1 cytokines IL-2 and IFNγ peaked and then declined, and at 8 wk the levels of Th2 cytokines IL-4 were rapidly enhanced and increased obviously with a prolongation of the infection duration.Conclusions The Th1cytokines IL-2 and IFNγ were correlated well with S. japonicum granulomaformation and vigour, and the Th2 cytokines IL-4 might play an important role in down-regulating egggranuloma reaction at chronic schistosomiasis by inhibiting the Th1cytokines.