Ulcerative colitis (UC) is a chronic inflammatory disease that damages colonic and rectal mucosa, and pharmacotherapy is the primary measure. However, the UC drug presents several notable problems, including low therapeutic efficacy, side effects, and high cost. Sophora moorcroftiana (S. moorcroftiana) is a plant native to the Tibetan Plateau. It is recorded that the aqueous extract of the seeds is used for treating digestive tract diseases, and the main alkaloids possess anti-inflammatory properties. Therefore, it is suggested that the water-soluble alkaloid (E2) from S. moorcroftiana may be a potential therapeutic agent against UC. The main alkaloids of the extract (E2, E2-a, and E2-b) were detected and identified by liquid chromatography-mass spectrometry (LC-MS). UC mice were induced with dextran sulfate sodium (DSS), followed by treatment with extract from S. moorcroftiana seeds. Disease activity index (DAI) scores and H&E staining were used to determine which extract has a therapeutic effect. The proportion of Tregs/Th17 cells was detected by flow cytometry, the levels of IL-6, TNF-α, IL-1β, and IL-28B in colon tissue were measured by ELISA, and the expression of p-STAT3, p-p65, p-IκBα, and p-p38 was detected with western blot. The main alkaloids of the extract were identified; there are 7 distinct alkaloids in E2, with E2-a and E2-b each containing 4, and piperine is present only in E2. Compared with the DSS group, mice treated with E2-b or E2 exhibited less severe damage, based on the milder DAI scores, longer colon length, and less pathological injury. In contrast, E2-a failed to alleviate the progression of UC. Further research revealed that both E2-b and E2 reduced the population of IL-17 A+ cells, while E2 upregulated the population of Tregs. In addition, all extracts induced a low level of IL-6, and E2 decreased the level of IL-1β. Moreover, the protein expression of p-STAT3 was significantly inhibited by E2. In the extracts of S. moorcroftiana seeds, the water-soluble alkaloid (E2) exhibits the best therapeutic efficacy in UC mice, suggesting that the compounds present in the extract is a potential therapeutic agent in UC.

Prostate cancer morbidity and mortality are increasing globally and in China, and the rate of metastasis is also rising, limiting the therapeutic effect and clinical prognosis of prostate cancer. CD151 is considered to be the first promoter of tumor metastasis in the tetraspanin superfamily. Previous research has linked CD151 to the progression of a number of malignancies, including prostate cancer. However, a recent study found that CD151 can inhibit the progression of prostate cancer. As a result, this paper examines existing research on CD151 and prostate cancer progression in order to clarify the relationship and provide a possible reference for future studies.

IL-28B, belonging to type III interferons (IFN-λs), exhibits a potent antitumor activity with reduced regulated T cells (Tregs) population, yet the effect of IL-28B on the tumor microenvironment (TME) and if IL-28B can downregulate Tregs directly in vitro are still unknown. In this study, we investigated the effects of IL-28B on Tregs in the spleen and TME in H22 tumor-bearing mice and verified the downregulation of IL-28B on Tregs in vitro. We found that rAd-mIL-28B significantly inhibited tumor growth and reduced the frequency of splenic CD4+Foxp3+ T cells. The levels of CXCL13, ICAM-1, MCP-5, and IL-7 in the serum, and the levels of IL-15 and sFasL in the tumor tissue decreased significantly after rAd-mIL-28B treatment relative to rAd-EGFP. Furthermore, the percentage of CD8+ cells in the TME was significantly increased in the rAd-mIL-28B group compared with the untreated group. In vitro, splenocytes were stimulated with anti-CD3/CD28 and IL-2 in the presence of TGF-β with or without IL-28B for three days and followed by flow cytometric, RT-PCR, and IL-10 production analysis. The results showed that IL-28B significantly reduced the proportion of induced Foxp3+ cells. It demonstrated that IL-28B may be used as a promising immunotherapy strategy against cancer.

Echinococcus multilocularis , the causative agent of alveolar echinococcosis (AE), severely threats human health and livestock farming. The first line of chemotherapeutic drug for AE is albendazole, which limits rapid extension of E. multilocularis metacestodes, but is rarely curative for AE, with severe side effects in long-term use, thus development of new anti-echinococcal drugs is mandated. Pseudolaric acid B (PAB) has long been used to treat fungal-infected dermatosis, and exerted anti-tumor, -fertility, -angiogenesis, -tubulin and antiparasitic activity. However, the effect of PAB against Echinococcus spp. remains unclear. The present study is to understand the effect of PAB against E. multilocularis in vitro and in vivo , and identify potential anti-echinococcal mechanism, as well as its toxicity. After exposure to PAB at 20 μg/ml, significant reduction of the survival rate and substantial ultrastructural destructions in E. multilocularis protoscoleces were observed in vitro . Furthermore, the wet weight of E. multilocularis cysts in the infected mice was significantly decreased after treatment with PAB (40, 20 or 10 mg/kg) for 12 weeks. Meanwhile, significant increase of both protein and mRNA expression of transforming growth factor beta 1 (TGF-β1) was detected in the serum and liver of the infected mice, whereas PAB administration lowered its expression significantly. The toxicity tests demonstrated that PAB displayed lower cytotoxicity to human liver and kidney cells (HL-7702 and HK-2 cell) with IC 50 = 25.29 and 42.94 μg/ml than albendazole with IC 50 = 3.71 and 21.22 μg/ml in vitro , and caused lower hepatoxicity and nephrotoxicity in mice than ABZ. Our findings indicated that PAB possesses potent anti-echinococcal effect, with lower toxicity than albendazole, implying a potential chemotherapeutic agent for AE. Additionally, the present study demonstrated that the suppressive effect of PAB on the parasite may involve down-regulation of TGF-β1 signaling.

Background Liver cancer, particularly hepatocellular carcinoma (HCC), is the fourth leading cause of cancer-related death worldwide. Sorafenib is a crucial drug for the treatment of advanced HCC, but it is difficult to meet the challenge of increasing clinical demands due to its severe side effects and drug resistance. Hence, development of novel antitumor drugs is urged. Previous studies showed that pseudolaric acid B (PAB) could reduce the expression of protein kinase B (PKB/Akt), a downstream effector of Notch signaling, facilitating cell apoptosis in HCC. The disruption of Notch signaling was verified to exacerbate malignant progression and drug resistance, however, the antitumor effect of PAB on Notch signaling in HCC remains unclear. Thus, this study aims to investigate the anti-HCC effect of PAB in association with the regulation of Notch1/Akt signaling. Methods CCK-8 assay and transwell assay were used to examine the cell proliferation and invasion in Huh7 cells after treatment with PAB and a Notch inhibitor DAPT. Moreover, the cell cycle of Huh7 cells after treatment with PAB was analyzed using flow cytometry. Finally, the changes of Notch1, Jagged1, Hes1, and Akt expression at the protein and mRNA level in Notch1/Akt signaling in Huh7 cells after treatment with PAB and DAPT were analyzed using immunofluorescence assay and real-time qPCR. Results The proliferation rate of Huh7 cells exposed to PAB of 0.5, 1, 2, 4, 8, 10, 20, 40, 80, 100, and 200 μmol/L revealed a time-and dose-dependent decrease in vitro, showing cell cycle arrest at G2/M phase (P < 0.05). Furthermore, compared with the untreated group, at the concentration of 40 μmol/L, the proliferation rate and invasion rate of Huh7 cells in PAB, DAPT, and PAB-DAPT combination (PAB + DAPT) group were significantly decreased (P < 0.05), but the PAB + DAPT showed no synergistic antiproliferation and anti-invasion effect in comparison with PAB treatment alone (P > 0.05). In addition, compared with the untreated group, PAB and DAPT alone significantly downregulated the expression of Notch1, Jagged1, Hes1, Akt mRNA, or/and protein in Huh7 cells (P < 0.05), but there was no significant difference in synergistic downregulated effect between the PAB + DAPT group and the PAB group (P > 0.05). Conclusion PAB can suppress proliferation and invasion of HCC cells through downregulating the expression of Notch1/Akt signaling protein and mRNA, and may be a potential novel antitumor drug candidate for the clinical treatment of HCC in the future.

OBJECTIVE:To evaluate the effects of hepatitis B virus (HBV) on helper T lymphocytes 17 (Th17), regulatory T lymphocyte (Treg) and Th17/Treg ratio in chronic hepatitis B patients in different alanine aminetransferase (ALT) stages.METHODS:In the study, 336 chronic hepatitis B patients in the first hospital of Lanzhou University were analyzed. The hepatitis B antigen antibody parameters were measured by chemiluminescence immunoassay analyzer, the liver function parameters were measured by automatic biochemical analyzer, the HBV loads were measured by quantitative PCR, Th17, Treg and Th17/Treg ratios were detected by flow cytometry. Among them, 111 cases (ALT < 40 U/L) of ALT were normal hepatitis B, 108 cases of chronic hepatitis B with ALT above normal upper limit and < 2 times higher (40 U/L≤ALT < 80 U/L), and 117 cases of chronic hepatitis B with ALT above 2 times normal upper limit (80 U/L≤ALT). According to the viral load, they were divided into low replication group with HBV DNA < 4.0 lg copies/mL, medium replication group with 4.0 lg copies/mL≤HBV DNA < 6.0 lg copies/mL and high replication group with HBV DNA ≥ 6.0 lg copies / mL. Dunnett T3 variance analysis were used to analyze the effects of HBV on Th17, Treg and Th17/Treg ratio in the chronic hepatitis B patients in different ALT stages. The changes of virological and immunological indexes before and after treatment were observed for 24 weeks of antiviral therapy in the hepatitis B patients with ALT≥double upper limit of normal group.RESULTS:In the ALT normal group, different virus load HBV had minor effects on Th17, Treg and Th17/Treg ratio. In the ALT≥2 times upper limit of normal group, with the virus load increased, Th17 (3.18%±0.79% in low replication group, 3.78%±0.92% in medium replication group and 4.57%±1.15% in high replication group), Treg cells (5.52%±1.58% in low replication group, 5.89%±1.84% in medium replication group and 6.37%±2.35% in high replication group) and their ratio Th17/Treg (0.57±0.25 in low replication group, 0.65±0.29 in medium replication group and 0.73±0.36 in high replication group) were significantly increased (P < 0.05). After entecavir treatment 24 weeks, the patient' s HBV-DNA decreased significantly, Th17 (3.89%±1.02% vs. 2.06%±0.46%), Treg (6.02%±2.03% vs. 5.06%±1.25%), Th17/Treg ratio (0.65±0.28 vs. 0.41±0.14) decreased significantly (P < 0.05).CONCLUSION:Investigation on the effects of HBV on Th17 and Treg cells and their ratios in different ALT states can clarify the effects of HBV on the body from the immunological perspective and can further understand the ALT grouping for antiviral treatment theoretical significance, which is helpful for clinical treatment.

Chronic inflammation plays a positive role in the development and progression of colitis-associated colorectal cancer (CAC). Medicinal plants and their extracts with anti-inflammatory and immunoregulatory properties may be an effective treatment and prevention strategy for CAC. This research aimed to explore the potential chemoprevention of paeoniflorin (PF) for CAC by network pharmacology, molecular docking technology, and in vivo experiments. The results showed that interleukin-6 (IL-6) is a key target of PF against CAC. In the CAC mouse model, PF increased the survival rate of mice and decreased the number and size of colon tumors. Moreover, reduced histological score of colitis and expression of Ki-67 and PCNA were observed in PF-treated mice. In addition, the chemoprevention mechanisms of PF in CAC may be associated with suppression of the IL-6/STAT3 signaling pathway and the IL-17 level. This research provides experimental evidence of potential chemoprevention strategies for CAC treatment.

Echinococcosis, which is caused by the larvae of cestodes of the genus Echinococcus, is a parasitic zoonosis that poses a serious threat to the health of humans and animals globally. Albendazole is the drug of choice for the treatment of echinococcosis, but it is difficult to meet clinical goals with this chemotherapy due to its low cure rate and associated side effects after its long-term use. Hence, novel anti-parasitic targets and effective treatment alternatives are urgently needed. A previous study showed that verapamil (Vepm) can suppress the growth of Echinococcus granulosus larvae; however, the mechanism of this effect remains unclear. The aim of the present study was to gain insight into the anti-echinococcal effect of Vepm on Echinococcus with a particular focus on the regulatory effect of Vepm on calcium/calmodulin-dependent protein kinase II (Ca2+/CaM-CaMKII) in infected mice. The anti-echinococcal effects of Vepm on Echinococcus granulosus protoscoleces (PSC) in vitro and Echinococcus multilocularis metacestodes in infected mice were assessed. The morphological alterations in Echinococcus spp. induced by Vepm were observed by scanning electron microscopy (SEM), and the changes in calcium content in both the parasite and mouse serum and liver were measured by SEM-energy dispersive spectrometry, inductively coupled plasma mass spectrometry and alizarin red staining. Additionally, the changes in the protein and mRNA levels of CaM and CaMKII in infected mice, and in the mRNA levels of CaMKII in E. granulosus PSC, were evaluated after treatment with Vepm by immunohistochemistry and/or real-time quantitative polymerase chain reaction. In vitro, E. granulosus PSC could be killed by Vepm at a concentration of 0.5 μg/ml or higher within 8 days. Under these conditions, the ultrastructure of PSC was damaged, and this damage was accompanied by obvious calcium loss and downregulation of CaMKII mRNA expression. In vivo, the weight and the calcium content of E. multilocularis metacestodes from mice were reduced after treatment with 40 mg/kg Vepm, and an elevation of the calcium content in the sera and livers of infected mice was observed. In addition, downregulation of CaM and CaMKII protein and mRNA expression in the livers of mice infected with E. multilocularis metacestodes was found after treatment with Vepm. Vepm exerted a parasiticidal effect against Echinococcus both in vitro and in vivo through downregulating the expression of Ca2+/CaM-CaMKII, which was over-activated by parasitic infection. The results suggest that Ca2+/CaM-CaMKII may be a novel drug target, and that Vepm is a potential anti-echinococcal drug for the future control of echinococcosis.

目的 研究白藜芦醇(Resveratrol,RES)体外对多房棘球蚴原头节(Protoscoleces,PSCs)和微囊的作用效果,为多房棘球蚴病的临床用药提供新的依据.方法 PSCs体外经不同浓度(5、10、20、40、80、100、200和400 μmol/L)的RES作用7 d,采用台盼蓝染色观察其活力与形态变化,采用扫描电镜和透射电镜观察其超微结构变化,运用化学发光法检测上清中碱性磷酸酶(Alkaline phosphatase,ALP)活性;微囊体外经RES(40 μmol/L)作用14 d后于光镜下观察其活力和形态变化,运用化学发光法检测上清中ALP活性.结果 不同浓度的RES体外持续作用7 d,PSCs死亡率呈剂量、时间依赖性增高,并伴随大量小钩脱落.当40 μmol/LRES作用至第6 d,PSCs死亡率达到100％,且虫体小钩、吸盘和外皮等超微结构被破坏;在同条件下,阿苯达唑亚砜(Albendazole sulfoxide,ABZ-SO)处理组中PSCs死亡率为13.25％±1.41％,对照组-二甲基亚砜(Dimethyl sulfoxide,DMSO)组PSCs死亡率仅为6％±0.71％.不同浓度的RES作用至第6 d,PSCs培养上清中ALP活性呈剂量依赖性升高(F=36.94,P＜0.001),其中,RES浓度为20和40 μmol/L时,上清中ALP活性分别为(2.72±0.24)U/L和(2.95±0.10)U/L,分别与 DMSO组(1.97±0.18)U/L 间差异存在统计学意义(t=2.94,P=0.0259和 t=7.066,P=0.0004).另外,RES作用至14 d,微囊透光性降低,生发层皱缩且与角质层分离,同时上清中ALP活性(2.74±0.15)U/L高于较DMSO组(2.08±0.09)U/L(t=3.83,P=0.019),但 ABZ-SO组(2.29±0.14)U/L 与 DMSO组间差异无统计学意义(t=1.271,P=0.273).结论 白藜芦醇体外可抑制多房棘球蚴原头节和微囊的活性,有望成为治疗多房棘球蚴病的潜在候选药物.

The metacestode stage of Echinococcus granulosus can cause cystic echinococcosis (CE), which still widely occurs around the world. Since the early 1970s, benzimidazoles have been shown to inhibit the growth of cysts and used to treat CE. However, benzimidazoles are still ineffective in 20%-40% of cases. In order to explore the new agents against CE, we have investigated the therapeutic effect of the recombinant adenoviral vector expressing mouse IL-28B (rAd-mIL-28B) on protoscoleces-infected mice. In our study, we successfully established the model mice which infected with protoscoleces intraperitoneally. At 18 weeks post-infection, the mice received rAd-mIL-28B (1×107 PFU) weekly by intramuscular injection for 6 weeks. Compared with the untreated control (13.1 ± 2.2 g), there was a significant reduction in cysts wet weight in rAd-mIL-28B group (8.3 ± 3.5 g) (P < 0.05), especially in Albendazole (ABZ) + rAd-mIL-28B group (5.8 ± 1.4 g) (P < 0.01). We also observed the severe damage of the germinal layer and the laminated layer of cysts after treatment. rAd-mIL-28B group showed a prominent increase in the level of Th1 type cytokines (such as IFN-γ, IL-2 and TNF-α). Meanwhile, the frequency of Foxp3+ T cells was decreased in the rAd-mIL-28B group (4.83 ± 0.81%) and ABZ + rAd-mIL-28B group (4.60 ± 0.51%), comparing with the untreated group (8.13 ± 2.60%) (P < 0.05). In addition, compared with the untreated control (122.14 ± 81.09 pg/ml), the level of IFN-γ significantly increased in peritoneal fluid in the rAd-mIL-28B group (628.87 ± 467.16 pg/ml) (P < 0.05) and ABZ + rAd-mIL-28B group (999.76 ± 587.60 pg/ml) (P < 0.001). Taken together, it suggested that ABZ + IL-28B may be a potential therapeutic agent against CE.

Coronavirus disease (COVID-19) causes a serious threat to human health. Virus-like particles (VLPs) constitute a promising platform in SARS-CoV-2 vaccine development. In this study, the E, M, and S genes were cloned into multiple cloning sites of a new triple expression plasmid with one p10 promoter, two pPH promoters, and three multiple cloning sites. The plasmid was transformed into DH10 BacTMEscherichia coli competent cells to obtain recombinant bacmid. Then the recombinant bacmid was transfected in ExpiSf9TM insect cells to generate recombinant baculovirus. After ExpiSf9TM cells infection with the recombinant baculovirus, the E, M, and S proteins were expressed in insect cells. Finally, SARS-CoV-2 VLPs were self-assembled in insect cells after infection. The morphology and the size of SARS-CoV-2 VLPs are similar to the native virions.

The aim of the present study was to explore the effect of hepatitis B virus on T lymphocyte and its subsets in different ALT states, and elucidate the immunological mechanism of ALT basing antiviral therapy for hepatitis B. 363 chronic hepatitis B patients were selected as the study subjects. According to ALT abnormalities, the patients were divided into three study groups. ALT normal group 131 cases, normal≦ ALT < 2 times of upper limit group 110 cases, ALT ≥ 2 times of upper limit group 122 cases. Entecavir was given to the ALT ≥ 2 times of upper limit group patients and followed up for 24 weeks. The hepatitis B antigen antibody parameters were measured by chemiluminescence immunoassay analyzer, the liver function parameters were measured by automatic biochemical analyzer, the hepatitis B virus load were measured by quantitative PCR analyzer, T lymphocytes were detected by flow cytometry, the level of IL-2, IFN-γ, IL-4 and IL-10 were detected by enzyme-linked immunosorbent assay. Detecting the influence of different hepatitis B viru loads in different groups on immunological indexes, and the virological and immunological indexes changes in before and after antiviral therapy patients. In the ALT normal group, different virus load hepatitis B virus had minor effect on T lymphocytes and their subsets (P > 0.05). In the ALT ≥ double upper limit of normal group. with the virus load increased, The total number of T lymphocytes, CD3+ CD4 + T lymphocytes decreased, (P < 0.05)CD3+ CD8 + T lymphocytes increased(P < 0.05). With the virus load increased the cytokines IL-2, IFN-γ which reflect the Th1 lymphocytes increased(P < 0.05), the cytokines IL-4、IL-10 which reflect the Th2 lymphocytes decreased(P < 0.05). Before and after 24 weeks of entecavir treatment, the patient's HBV-DNA decreased significantly(P < 0.05) and the body's immune function improved significantly. (P < 0.05)The influence of hepatitis B virus on immune function is different in different ALT states. Therefore, the scientific significance of ALT grouping in the hepatitis B treatment can be clarified from the immunological point.

基于岗位胜任力的要求,为适应现代医学特点,阐明了课程整合的必要性.以器官系统为框架梳理了"病原生物学"与"免疫学"两门课程内容,同时结合CBL教学,围绕培养目标,以问题为导向,探讨建立全新的课程模式.通过学科的整合减少了教学内容的重复,弥合了基础与临床医学分离的缺点,落实了以学生为中心、以任务为导向的现代医学教育理念,推动了基础医学拔尖人才和卓越医师培养,提升了人才培养质量.最后指出了课程整合中存在的教师教学能力有待提高、缺乏权威整合教材等问题.

2020年初,新型冠状病毒肺炎疫情加速了线上教学,教研组利用"网络教学平台+医学免疫学APP+录制视频+QQ屏幕共享直播+QQ群讨论"多个线上平台,通过"课前准备+课堂直播+讨论+课后巩固反思"等多角度混合教学方法开展疫情期间医学免疫学线上教学,促进教学效果的提升和学生学习的主动性.同时分析线上教学的利弊,为促进教学改革提供实践参考.

Cystic echinococcosis (CE), a complex and neglected zoonotic infectious disease, is mainly caused by larval tapeworm Echinococcus granulosus with a worldwide distribution. For CE, an effective drug treatment is not yet available. The present study was conducted to evaluate the efficacy of hMASP-2-based immunotherapy against hydatid cysts by using murine model. Eighteen weeks after infection with 2000 viable protoscoleces intraperitoneally, the infected mice were treated with hMASP-2 DNA nanolipoplexes (pcDNA3.1-hMASP-2) and albendazole respectively. After six weeks treatment, a significant reduction in the weight of cysts was observed both in the pcDNA3.1-hMASP-2 group and albendazole group compared with the untreated group (P  <  0.05). The hMASP-2 DNA nanolipoplexes not only inhibited the development of germinal layer, but also induced the extensive degeneration and damage of the germinal layer cells. Furthermore, compared with the untreated group, the number of CD4+T cells and CD8+T cells and the level of serum IFN-γ were significantly increased (P < 0.05). The frequency of PD-1+T-cell subpopulations including CD4+PD-1+T cells and CD8+PD-1+T cells and the level of serum IL-4 were notably decreased (P < 0.05) in the pcDNA3.1-hMASP-2 treatment group. Therefore, the hMASP-2 DNA nanolipoplexes displayed an effective treatment for echinococcosis through inhibiting the development of cysts and up-regulatory T-cell immunity. This new hMASP-2-based immunotherapeutic strategy could be a potential alternative for the treatment of CE, but further studies are recommended to evaluate the full potential of these hMASP-2 DNA nanolipoplexes in the treatment of human CE.

乙型肝炎的发生发展与机体病理性免疫损伤、特别是与以T淋巴细胞及其亚群介导的细胞免疫应答密切相关.乙型肝炎病毒在我国以B基因型和C基因型为主,B/C基因型的乙型肝炎病毒的发病机制有很大差别,但是目前很少有文献探讨在不同免疫阶段B/C基因型乙型肝炎病毒感染的人体中T淋巴细胞及其亚群表达谱的差异,本文就此进行探讨.

The alveolar echinococcosis of human is a severe helminthic disease caused by the larva of Echinococcus multilocularis tapeworms. Novel compounds or therapy strategies for the treatment of alveolar echinococcosis are urgently needed due to the limitation of the widely used albendazole. Magnetic microspheres as drug carriers in magnetically targeted therapy of tumor have gained growing interests advantaged by delivering the drug to the aimed site, achieving localized therapeutic effect effectively under the influence of an external magnetic field. In this study, we formulated magnetic microspheres loaded with E2-a (PLGA-Fe-E2-a) and identified the activity in E. multilocularis -infected mice which infected with 3,000 protoscoleces intraperitoneally. Compared with the untreated control, with the help of a magnet, there was a significant reduction in parasite burden with PLGA-Fe-E2-a treatment and similar reduction observed with albendazole. PLGA-Fe-E2-a treatment group also showed a significant increase in the IFN-γ level and impaired morphological and ultrastructural alterations. Most importantly, one-third concentrations of E2-a from PLGA-Fe-E2 based on the release profile of E2-a was equally effective in inhibiting metacestode growth as E2-a treated group, supporting efficacy and bioavailability of a drug. It will be an alternative treatment for alveolar echinococcosis using magnetic microspheres as drug carriers.

目的:探讨乙型肝炎病毒(HBV)在不同丙氨酸氨基转移酶(ALT)状态下对T淋巴细胞及其亚群的影响,阐明以ALT分组抗病毒治疗乙型肝炎(乙肝)的免疫学机制.方法:选取慢性乙肝患者363例作为研究对象,根据ALT异常情况分为ALT正常组(131例)、ALT大于等于正常上限且小于2倍增高组(110例)和ALT大于等于正常上限2倍增高组(122例).对ALT大于等于正常上限2倍增高组患者给予恩替卡韦治疗,随访24周.采用化学发光免疫分析仪检测乙肝抗原抗体指标,采用全自动生化分析仪检测肝功能指标,采用全自动荧光定量PCR分析仪检测被测者的病毒载量,采用流式细胞仪检测T淋巴细胞分类,酶联免疫吸附实验(ELISA)法检测患者血清中白细胞介素12 (IL-2)、干扰素γ(IFN-γ)、白细胞介素4(IL-4)和白细胞介素10(IL-10)水平,检测不同组别中不同载量HBV对机体免疫学指标的影响及抗病毒治疗前后患者病毒学及免疫学指标的变化.结果:在ALT正常组中,不同载量HBV患者T淋巴细胞总数、Th/i淋巴细胞数、Ts/c淋巴细胞数及血清中IL-2、IFN-γ、IL-4和IL-10水平比较差异无统计学意义(P＞0.05);在ALT大于等于正常上限2倍增高组,随着病毒载量的增加,患者T淋巴细胞总数和Th/i淋巴细胞数明显下降(P＜0.05),Ts/c淋巴细胞数明显升高(P＜0.05),反映Th1细胞的细胞因子IL-2和IFN-γ水平明显升高(P＜0.05),反映Th2细胞的细胞因子IL-4和IL-10水平明显下降(P＜0.05).与治疗前比较,恩替卡韦治疗24周后,患者HBV DNA明显下降(P＜0.05),T淋巴细胞总数和Th/i淋巴细胞数明显升高(P＜0.05),Ts/c淋巴细胞数明显下降(P＜0.05),血清中IL-2和IFN-γ水平明显下降(P＜0.05),IL-4和IL-10水平明显升高(P＜0.05).结论:HBV在不同ALT状态下对机体免疫功能有不同的影响,对于ALT大于等于正常上限2倍增高的乙肝患者进行抗病毒治疗可明显改变机体的免疫状态.

Sepsis-induced myocardial dysfunction was the leading cause of morbidity and mortality in hospitalized patients and yet there were no effective therapies. With excessive released inflammatory mediators through the TLR4-trigger NF-κB signaling pathway being implicated as key players in sepsis-induced myocardial injury, we prepared astragalus polysaccharide (APS) nanoparticles as an TLR4-responsive drug for alleviating sepsis-induced myocardial injury. Firstly, treatment with APS nanoparticles in LPS-treated H9c2 cells to evaluate the direct effect demonstrated that this drug maintained the cell viability, cell morphology and exerted anti-apoptotic effects. Additionally, animal studies using cecal ligation and puncture (CLP) in C57BL/6 mice revealed that APS nanoparticles were much more efficacious in attenuating sepsis-induced myocardial injury by down-regulating the bacterial loads, inhibiting serum C-reactive protein (CRP), white blood cells (WBC) levels, alleviating myocardial histopathologic abnormalities, remarkably reducing the cardiac troponin I (cTnI). Moreover, APS nanoparticles significantly decreased the myocardial inflammatory cytokine expression and inhibited the activity of TLR4/NF-κB pathway. In conclusion, APS nanoparticles could protect the sepsis-induced cardiac dysfunction. The mechanism of the protective action of APS nanoparticles seems to involve its ability to reduce inflammatory response and to suppress TLR4/NF-κB pathway. This drug may be a potential candidate strategy for septic cardiac dysfunction treatment.

The echinococcosis of humans and animals is a chronic helminthic disease caused by the larva of genus Echinococcus tapeworms. It is a globally distributed disease which is an important socioeconomic and public health problem in many low and middle-income countries. This research aimed to firstly quantitatively analyze the publications with bibliometrics software and evaluated the hot topics and emerging trends of echinococcosis research from 1980 to 2017. A total of 7688 references on echinococcosis research were retrieved from the Web of Science Core Collection database. Then the reference was analyzed with CiteSpace software to make the knowledge network maps. The largest cluster (#0) with 83 members was cystic echinococcosis, and cystic echinococcosis, mebendazole, antibody and transmission were the four keywords with the strongest citation bursts in the echinococcosis research field. Furthermore, cystic echinococcosis, chemotherapy and immunodiagnosis, management of definitive and intermediate host are the top four research hot topics and emerging trends in the echinococcosis field. This research presents an insight into the echinococcosis field and valuable visualizing information for echinococcosis researchers to detect new viewpoints on cooperative countries/institutions, potential co-workers and research frontiers.