目的 观察鸡血藤对α-萘异硫氰酸盐(ANIT)诱导的肝内胆汁淤积SD大鼠的治疗作用,并从调控法尼醇X受体(FXR)相关通路方面进行机制研究.方法 将40只雄性SD大鼠随机分为空白对照组(对照组)、ANIT造模组(模型组)、熊去氧胆酸60mg/kg组、鸡血藤150mg/kg组(鸡血藤低剂量组)、鸡血藤300mg/kg组(鸡血藤高剂量组)5组,每组8只.空白对照组和模型组大鼠灌胃生理盐水,其余各组灌胃相应药物,连续灌胃7d,并在第5天除对照组外灌胃ANIT诱导肝内胆汁淤积模型.给药7d后麻醉大鼠,取血清检测谷丙转氨酶(ALT),谷草转氨酶(AST),总胆红素(TBIL),总胆汁酸(TBA)的水平.并通过RT-PCR检测比较各组大鼠肝组织内FXR、小异源二聚体伴侣受体(SHP)、葡萄糖醛酸转移酶2B4(UGT2B4)、胆盐输出泵(BSEP)mRNA的表达水平.结果 与对照组比较,模型组血清中ALT、AST、TBIL、TBA水平明显升高;与模型组比较,鸡血藤高、低剂量组血清中ALT、AST、TBIL、TBA水平均有不同程度降低.与对照组比较,模型组大鼠肝小叶结构被破坏;与模型组比较,鸡血藤高、低剂量组则有不同程度改善.与对照组比较,模型组肝组织中FXR、SHP、UGT2B4、BSEP的mRNA表达均有明显降低;与模型组比较,鸡血藤高、低剂量组mRNA表达则有不同程度升高.结论 鸡血藤可改善ANIT诱导的肝内胆汁淤积SD大鼠的生存状况、肝功能和肝组织结构的病理状态,其治疗作用可能与上调FXR及其相关下游的SHP、UGT2B4、BSEP的表达,从而抑制肝内胆汁酸的合成和重吸收,促进胆汁酸的解毒和转运有关.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has become a global health emergency. The cumulative number of new confirmed cases and deaths are still increasing out of China. Independent predicted factors associated with fatal outcomes remain uncertain. RESEARCH QUESTION: The goal of the current study was to investigate the potential risk factors associated with fatal outcomes from COVID-19 through a multivariate Cox regression analysis and a nomogram model. STUDY DESIGN AND METHODS: A retrospective cohort of 1,590 hospitalized patients with COVID-19 throughout China was established. The prognostic effects of variables, including clinical features and laboratory findings, were analyzed by using Kaplan-Meier methods and a Cox proportional hazards model. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. RESULTS: In this nationwide cohort, nonsurvivors included a higher incidence of elderly people and subjects with coexisting chronic illness, dyspnea, and laboratory abnormalities on admission compared with survivors. Multivariate Cox regression analysis showed that age >= 75 years (hazard ratio [HR], 7.86; 95% CI, 2.44-25.35), age between 65 and 74 years (HR, 3.43; 95% CI, 1.24-9.5), coronary heart disease (HR, 4.28; 95% CI, 1.14-16.13), cerebrovascular disease (HR, 3.1; 95% CI, 1.07-8.94), dyspnea (HR, 3.96; 95% CI, 1.42-11), procalcitonin level > 0.5 ng/mL (HR, 8.72; 95% CI, 3.42-22.28), and aspartate aminotransferase level > 40 U/L (HR, 2.2; 95% CI, 1.1-6.73) were independent risk factors associated with fatal outcome. A nomogram was established based on the results of multivariate analysis. The internal bootstrap resampling approach suggested the nomogram has sufficient discriminatory power with a C-index of 0.91 (95% CI, 0.85-0.97). The calibration plots also showed good consistency between the prediction and the observation. INTERPRETATION: The proposed nomogram accurately predicted clinical outcomes of patients with COVID-19 based on individual characteristics. Earlier identification, more intensive surveillance, and appropriate therapy should be considered in patients at high risk.

Background Cardiac injury is a common condition among hospitalized coronavirus disease 2019 (COVID-19) patients, and is associated with a higher risk of mortality. However, the mechanism of myocardial injury in COVID-19 remains unclear. In this retrospective study, we compared the clinical characteristics of COVID-19 patients with different troponin I (TnI) levels during hospitalization to provide a clinical reference for the identification of those at high-risk. Methods In total, 218 patients diagnosed with COVID-19 in Yichang Central People's Hospital and Yichang Third People's Hospital between January 23 and February 19, 2020 were initially included. Of these patients, 89 underwent TnI testing during hospitalization and were finally included in the study. The medical history, clinical signs and symptoms at the time of admission, and laboratory test results were recorded. The patients were assigned to the normal TnI group (TnI <0.01 µg/L; n=67) or the elevated TnI group (TnI >0.01 µg/L; n=22). Results The incidence of elevated TnI in our patient cohort was 24.7%. There were significant differences between the two groups in the following factors: history of coronary heart disease (CHD), age, lymphocyte count, prothrombin time (PT), activated partial thromboplastin time (APTT), and levels of interleukin (IL)-6, C-reactive protein (CRP), myoglobin (MYO), lactate dehydrogenase (LDH), and albumin (all P<0.05). Binary logistic analysis showed that a history of CHD, age, lymphocyte count, IL-6, APTT, and MYO were influencing factors of elevated serum TnI. Conclusions A history of CHD, advanced age, decreased lymphocyte count, increased IL-6, increased MYO, and prolonged APTT were independent influencing factors of elevated TnI in COVID-19 patients. COVID-19 patients with these characteristics are prone to myocardial injury.

Background During the outbreak of coronavirus disease 2019 (COVID-19), consistent and considerable differences in disease severity and mortality rate of patients treated in Hubei province compared to those in other parts of China have been observed. We sought to compare the clinical characteristics and outcomes of patients being treated inside and outside Hubei province, and explore the factors underlying these differences. Methods Collaborating with the National Health Commission, we established a retrospective cohort to study hospitalised COVID-19 cases in China. Clinical characteristics, the rate of severe events and deaths, and the time to critical illness (invasive ventilation or intensive care unit admission or death) were compared between patients within and outside Hubei. The impact of Wuhan-related exposure (a presumed key factor that drove the severe situation in Hubei, as Wuhan is the epicentre as well the administrative centre of Hubei province) and the duration between symptom onset and admission on prognosis were also determined. Results At the data cut-off (31 January 2020), 1590 cases from 575 hospitals in 31 provincial administrative regions were collected (core cohort). The overall rate of severe cases and mortality was 16.0% and 3.2%, respectively. Patients in Hubei (predominantly with Wuhan-related exposure, 597 (92.3%) out of 647) were older (mean age 49.7 versus 44.9 years), had more cases with comorbidity (32.9% versus 19.7%), higher symptomatic burden, abnormal radiologic manifestations and, especially, a longer waiting time between symptom onset and admission (5.7 versus 4.5 days) compared with patients outside Hubei. Patients in Hubei (severe event rate 23.0% versus 11.1%, death rate 7.3% versus 0.3%, HR (95% CI) for critical illness 1.59 (1.05–2.41)) have a poorer prognosis compared with patients outside Hubei after adjusting for age and comorbidity. However, among patients outside Hubei, the duration from symptom onset to hospitalisation (mean 4.4 versus 4.7 days) and prognosis (HR (95%) 0.84 (0.40–1.80)) were similar between patients with or without Wuhan-related exposure. In the overall population, the waiting time, but neither treated in Hubei nor Wuhan-related exposure, remained an independent prognostic factor (HR (95%) 1.05 (1.01–1.08)). Conclusion There were more severe cases and poorer outcomes for COVID-19 patients treated in Hubei, which might be attributed to the prolonged duration of symptom onset to hospitalisation in the epicentre. Future studies to determine the reason for delaying hospitalisation are warranted.

Background Since December 2019, acute respiratory disease (ARD) due to 2019 novel coronavirus (2019-nCoV) emerged in Wuhan city and rapidly spread throughout China. We sought to delineate the clinical characteristics of these cases. Methods We extracted the data on 1,099 patients with laboratory-confirmed 2019-nCoV ARD from 552 hospitals in 31 provinces/provincial municipalities through January 29 th , 2020. Results The median age was 47.0 years, and 41.90% were females. Only 1.18% of patients had a direct contact with wildlife, whereas 31.30% had been to Wuhan and 71.80% had contacted with people from Wuhan. Fever (87.9%) and cough (67.7%) were the most common symptoms. Diarrhea is uncommon. The median incubation period was 3.0 days (range, 0 to 24.0 days). On admission, ground-glass opacity was the typical radiological finding on chest computed tomography (50.00%). Significantly more severe cases were diagnosed by symptoms plus reverse-transcriptase polymerase-chain-reaction without abnormal radiological findings than non-severe cases (23.87% vs. 5.20%, P <0.001). Lymphopenia was observed in 82.1% of patients. 55 patients (5.00%) were admitted to intensive care unit and 15 (1.36%) succumbed. Severe pneumonia was independently associated with either the admission to intensive care unit, mechanical ventilation, or death in multivariate competing-risk model (sub-distribution hazards ratio, 9.80; 95% confidence interval, 4.06 to 23.67). Conclusions The 2019-nCoV epidemic spreads rapidly by human-to-human transmission. Normal radiologic findings are present among some patients with 2019-nCoV infection. The disease severity (including oxygen saturation, respiratory rate, blood leukocyte/lymphocyte count and chest X-ray/CT manifestations) predict poor clinical outcomes.

AbstractObjectiveTo evaluate the spectrum of comorbidities and its impact on the clinical outcome in patients with coronavirus disease 2019 (COVID-19).DesignRetrospective case studiesSetting575 hospitals in 31 province/autonomous regions/provincial municipalities across ChinaParticipants1,590 laboratory-confirmed hospitalized patients. Data were collected from November 21st, 2019 to January 31st, 2020.Main outcomes and measuresEpidemiological and clinical variables (in particular, comorbidities) were extracted from medical charts. The disease severity was categorized based on the American Thoracic Society guidelines for community-acquired pneumonia. The primary endpoint was the composite endpoints, which consisted of the admission to intensive care unit (ICU), or invasive ventilation, or death. The risk of reaching to the composite endpoints was compared among patients with COVID-19 according to the presence and number of comorbidities.ResultsOf the 1,590 cases, the mean age was 48.9 years. 686 patients (42.7%) were females. 647 (40.7%) patients were managed inside Hubei province, and 1,334 (83.9%) patients had a contact history of Wuhan city. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached to the composite endpoints. 399 (25.1%) reported having at least one comorbidity. 269 (16.9%), 59 (3.7%), 30 (1.9%), 130 (8.2%), 28 (1.8%), 24 (1.5%), 21 (1.3%), 18 (1.1%) and 3 (0.2%) patients reported having hypertension, cardiovascular diseases, cerebrovascular diseases, diabetes, hepatitis B infections, chronic obstructive pulmonary disease, chronic kidney diseases, malignancy and immunodeficiency, respectively. 130 (8.2%) patients reported having two or more comorbidities. Patients with two or more comorbidities had significantly escalated risks of reaching to the composite endpoint compared with those who had a single comorbidity, and even more so as compared with those without (all P<0.05). After adjusting for age and smoking status, patients with COPD (HR 2.681, 95%CI 1.424-5.048), diabetes (HR 1.59, 95%CI 1.03-2.45), hypertension (HR 1.58, 95%CI 1.07-2.32) and malignancy (HR 3.50, 95%CI 1.60-7.64) were more likely to reach to the composite endpoints than those without. As compared with patients without comorbidity, the HR (95%CI) was 1.79 (95%CI 1.16-2.77) among patients with at least one comorbidity and 2.59 (95%CI 1.61-4.17) among patients with two or more comorbidities.ConclusionComorbidities are present in around one fourth of patients with COVID-19 in China, and predispose to poorer clinical outcomes.HighlightsWhat is already known on this topic-Since November 2019, the rapid outbreak of coronavirus disease 2019 (COVID-19) has recently become a public health emergency of international concern. There have been 79,331 laboratory-confirmed cases and 2,595 deaths globally as of February 25th, 2020-Previous studies have demonstrated the association between comorbidities and other severe acute respiratory diseases including SARS and MERS.-No study with a nationwide representative cohort has demonstrated the spectrum of comorbidities and the impact of comorbidities on the clinical outcomes in patients with COVID-19.What this study adds-In this nationwide study with 1,590 patients with COVID-19, comorbidities were identified in 399 patients. Comorbidities of COVID-19 mainly included hypertension, cardiovascular diseases, cerebrovascular diseases, diabetes, hepatitis B infections, chronic obstructive pulmonary disease, chronic kidney diseases, malignancy and immunodeficiency.-The presence of as well as the number of comorbidities predicted the poor clinical outcomes (admission to intensive care unit, invasive ventilation, or death) of COVID-19.-Comorbidities should be taken into account when estimating the clinical outcomes of patients with COVID-19 on hospital admission.

Background: Crucial roles of hematologic and immunologic responses in progression of coronavirus disease 2019 (COVID-19) remain largely unclear. Objective: We sought to address the dynamic changes in hematologic and immunologic biomarkers and their associations with severity and outcomes of COVID-19. Methods: A retrospective study including 548 patients with COVID-19 with clarified outcome (discharged or deceased) from a national cohort in China was performed. Cross-sectional and longitudinal variations were compared and the associations with different severity and outcomes were analyzed. Results: On admission, the counts of lymphocytes, T-cell subsets, eosinophils, and platelets decreased markedly, especially in severe/critical and fatal patients. Increased neutrophil count and neutrophils-to-lymphocytes ratio were predominant in severe/critical cases or nonsurvivors. During hospitalization, eosinophils, lymphocytes, and platelets showed an increasing trend in survivors, but maintained lower levels or dropped significantly afterwards in nonsurvivors. Nonsurvivors kept a high level or showed an upward trend for neutrophils, IL-6, procalcitonin, D-dimer, amyloid A protein, and C-reactive protein, which were kept stable or showed a downward trend in survivors. Positive correlation between CD8(+) T-cell and lymphocytes count was found in survivors but not in nonsurvivors. A multivariate Cox regression model suggested that restored levels of lymphocytes, eosinophils, and platelets could serve as predictors for recovery, whereas progressive increases in neutrophils, basophils, and IL-6 were associated with fatal outcome. Conclusions: Hematologic and immunologic impairment showed a significantly different profile between survivors and nonsurvivors in patients with COVID-19 with different severity. The longitudinal variations in these biomarkers could serve to predict recovery or fatal outcome.

目的 探讨苦参碱对硫代乙酰胺诱导的肝纤维化大鼠的影响.方法 将50只雄性SD大鼠随机分为空白组、模型组及苦参碱低、中、高剂量组(40、80、160 mg/kg),除空白组外其余组皮下注射硫代乙酰胺诱导肝纤维化模型,2次/周,共注射10周;第5周各组灌胃给药,1次/d.10周后,全自动生化分析仪检测大鼠血清ALT、AST水平及HA、CIV、IPCⅢ水平,HE染色观察肝组织病理状况,免疫组化检测α-SMA蛋白表达,qRT-PCR检测肝组织中CTGF、α-SMA、TIMP-1 mRNA表达.结果 与模型组比较,苦参碱组降低了大鼠血清中ALT、AST、HA、CIV、PCⅢ水平(P＜0.05,P＜0.01),促进CTGF、α-SMA和TIMP-1 mRNA表达(P＜0.01),抑制α-SMA蛋白表达,改善肝组织纤维化程度.结论 苦参碱可抑制硫代乙酰胺诱导的大鼠肝纤维化,改善其肝功能,其作用可能与抑制CTGF、α-SMA和TIMP-1表达有关.

BackgroundThe coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide.ObjectiveTo evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status.MethodsWe analysed data from 1590 laboratory confirmed hospitalised patients from 575 hospitals in 31 provinces/autonomous regions/provincial municipalities across mainland China between 11 December 2019 and 31 January 2020. We analysed the composite end-points, which consisted of admission to an intensive care unit, invasive ventilation or death. The risk of reaching the composite end-points was compared according to the presence and number of comorbidities.ResultsThe mean age was 48.9 years and 686 (42.7%) patients were female. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached the composite end-points. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD (HR (95% CI) 2.681 (1.424–5.048)), diabetes (1.59 (1.03–2.45)), hypertension (1.58 (1.07–2.32)) and malignancy (3.50 (1.60–7.64)) were risk factors of reaching the composite end-points. The hazard ratio (95% CI) was 1.79 (1.16–2.77) among patients with at least one comorbidity and 2.59 (1.61–4.17) among patients with two or more comorbidities.ConclusionAmong laboratory confirmed cases of COVID-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.

Acquired drug resistance is one of the main limitations in pharmacological therapy of malignancies including gastric cancer. MicroRNAs (miRNAs) are a class of small noncoding RNAs that suppress their targets by binding to the 3'UTR region of genes. In this study, we explored investigate the target gene of miR-494 and its roles in chemoresistance of gastric cancer. We found that miR-494 was significantly down-regulated in gastric cancer cells lines compared to the normal gastric epithelial cell line. Exogenous overexpression of miR-494 increased the chemosensitivity of gastric cancer cells to doxorubicin. Moreover, miR-494 expression was reduced in a doxorubicin-resistant gastric cancer cells (AGS/dox) compared with the parental cells. MTT assay showed that AGS/dox cells exhibited an elevated viability compared with the parental cells. Enforced expression of miR-494 inhibited AGS/dox cell viability and colony formation ability. In addition, we demonstrated that elevated expression of miR-494 inhibited the mRNA and protein expression of phosphodiesterases 4D (PDE4D) in gastric cancer cell. Luciferase assay showed that miR-494 directly targeted the 3'UTR region of PDE4D. Furthermore, restoration of PDE4D recovered the chemoresistance in miR-494-overexpressed gastric cancer cells. Taken together, this study demonstrated that miR-494 enhanced doxorubicin sensitivity via regulation of PDE4D expression, suggesting a novel therapeutic strategy for anti-chemoresistance in gastric cancer.

肝内胆汁淤积症的病因广泛,发病机制较复杂,目前尚缺乏特效治疗方法.肝内胆汁淤积症属中医“黄疸”范畴,传统中药对治疗黄疸有独特的作用,历代医家在治疗过程中,或多或少都运用到了“通络法”思想.黄疸以“瘀”为要点,通络法以“通”治“瘀”,二者理论核心较为契合.近来临床上有不少运用通络法思想治疗肝内胆汁淤积症的研究,取得了较好的疗效.

目的:分析婴幼儿脓毒症患者早期炎性细胞因子及血培养检测的临床意义.方法:随机选取我院2012年2月至2014年5月住院治疗的婴幼儿脓毒症患者60例为观察组,并选取同期的健康婴幼儿61例为对照组,观察两组降钙素原(PCT)、软骨糖蛋白39(YKL-40)、超敏C反应蛋白(hs-CRP)、白细胞计数(WBC)水平及血培养阳性率.结果:观察组治疗前PCT、YKL-40、hs-CRP、WBC水平及血培养阳性率与对照组差异均有统计学意义(P＜0.05),且观察组治疗前后的PCT、YKL-40、hs-CRP、WBC水平及血培养阳性率均具有统计学差异(P＜0.05);多项联合在各时期的敏感度均高于单项检测,且五项联合在各时期的敏感度均最高,12h后均为100％.结论:PCT、YKL-40、hs-CRP、WBC水平及血培养可用于婴幼儿脓毒症诊断,且五项联合的诊断敏感度最高.

目的 探讨结肠灌洗联合中药保留灌肠治疗慢性重型肝炎患者内毒素血症的临床疗效.方法 随机将120例慢性重型肝炎患者分为两组.60例治疗组患者采用结肠灌洗加中药保留灌肠配合内科药物治疗,60例对照组仅用内科药物治疗.结果 治疗组患者治疗前后血内毒素(1.1±0.3 Eu/ml对0.7±0.2 Eu/ml)、TBIL(376.5±105.6μmol/L对133.7±56.4 μmol/L)、血氨(187.8±89.8 mmo/ml对87.7±37.7 mmol/ml)和PTA(37.6±8.0%对65.7±16.6%)改善明显,并优于对照组(分别为1.1±0.3 Eulml对1.0±0.2 Eu/ml,379.3±108.2μmol/L对232.7±98.3 μmol/L,190.5±83.5 mmol/ml对92.6±51.7mmol/ml和36.2±8.9%对49.6±15.6%.治疗组患者的存活率为68.3%(41/60),与对照组46.7%(28/60)比差异有显著性意义(x2=5.88,P＜0.05).结论 结肠灌洗联合中药保留灌肠配合内科药物治疗慢性重型肝炎患者内毒素血症疗效显著,能迅速改善肝功能,改善预后,提高生存率.

Objective To investigate the clinical efficacy of Telbivudine in the treatment of chronic severe hepatitis B.Methods 60 patients with chronic severe hepatitis B were randomly divided into 2 groups. The control group(n=30) was given conventional therapy, while the treatment group treated with telbivudine,600mg daily,on the basis of routine. Before and after treatment for 2, 4, 12 weeks, the level of HBV DNA of the two groups were detected, and hepatic function and PTA measured on the forth week. The efficacy of treatment at the forth week was evaluated.Results HDV DNA negative conversion rate of 33%(after 2 weeks), 80%(after 4 weeks) and 83.3% (after 12 weeks) in treatment, that was significantly higher than those in control group (0 after 2 weeks, 3.3% after 4 weeks, and 10% after 12 weeks)(P <0.01). After treatment for 4 weeks, the improvement of TBil and PTA in treatment group were much better than those in the control group (P<0.01),The total effective rates of treatment group and control group were 67.7% and 40% (P＜0.05).Conclusion Telbivudine had an strong anti-HBV activity, and a rapid effect. It will significantly improve the hepatic function for patients with severe hepatitis B.

结核病的感染、发生、发展及转归都与机体细胞免疫反应有关,其中CD4和CD8T细胞在机体对结核杆菌的免疫应答中起重要作用,结核患者体内Th1/Th2失衡及其动态演变贯穿于结核病全程.γ-干扰素和微卡近年来已被国内、外用于结核病的免疫治疗.为了解γ-干扰素和微卡作为免疫佐剂辅助治疗肺结核的有效性及其免疫机制,我们进行了非盲随机对照临床实验,现将结果报告如下.

Objective:To investigate the clinical effectiveness of the coloclyster combined with plasma exchange in patients with severe chronic hepatitis.Methods:Two hundred and fonty-six patients with severe chronic hepatitis were divided into three groups:combined group with 86 patients,received coloclyster and plasma exchange,also traditional medical treatment;the plasma exchange group with 80 patients,received plasma exchange and traditional medical treatment;the controlled group with 80 patients just received the traditional medical treatment.To compare serum endotoxin,liver function,blood ammonia,and other biochemical markers of the three groups before and after treatment,observe the improvement in patients with clinical symptoms and signs,and its prognosis.Results:The declined range of serum endotoxin,blood ammonia,improvement of clinical symptoms,increasing of survival rate in combined group were better than that of the plasma exchange group and the controlled group.Conclusion:The coloclyster combined with plasma exchange can effectively decrease the endotoxemia,ameliorate the liver function,improve the clinical symptoms,increase the survival rate for patients with severe chronic hepatitis.

目的 探讨γ-干扰素联合微卡辅助抗结核治疗的疗效及免疫机制.方法 160例肺结核患者随机分为四组:基础用药组、γ-干扰素组、微卡组及联合组,每组40例.基础用药:所有病例均采用标准短程化疗(2HREZ/4HR),各干预组均给予相应的药物,观察各组2个月末痰菌阴转和病灶吸收情况,治疗前和2个月末用APAAP法检测患者外周血T细胞亚群CD4+、CD8+比例,同时用EKUSA 法检测患者外周血IFN-γ和IL-4含量.结果 与基础用药组比较,γ-干扰素组、微卡组、联合组痰菌阴转率明显升高(P＜0.05);与γ-干扰素组、微卡组比较,联合组痰菌阴转率差异无统计学意义(P＞0.05);与基础用药组比较,γ-干扰素组、微卡组、联合组病灶吸收显效率增加(P＜0.05);与γ-干扰素组、微卡组比较,联合组病灶吸收显效率更明显(P＜0.05).γ-干扰素组、微卡组、联合组外周血T细胞亚群CD4+比例和IFN-γ含量变化值均显著高于基础用药组(P＜0.05);与γ-干扰素组、微卡组比较,联合组变化值增高更显著(P＜0.05).γ-干扰素组、微卡组、联合组外周血T细胞亚群CD8+比例和IL-4含量变化值显著低于基础用药组(P＜0.05);与γ-干扰素组、微卡组比较,联合组变化值降低更显著(P＜0.05).结论 γ-干扰素和微卡能改善肺结核患者的细胞免疫功能,有助于痰菌转阴,促进病灶吸收,增强化疗疗效,是较好的结核病免疫治疗制剂,且两者联用具有协同作用。

Objective To study the immunotherapeutic effects and its mechanism of IFN-γ combined with M.vaccae vaccine on mice model with tuberculosis.Methods Sixty BALB/c mice were randomly divided into 5 groups: normal group,tuberculosis model group,IFN-γ group,M.vaccae vaccine group,the IFN-γ+ M.vaccae vaccine group.Each group included 12 mice.Forty-eight mice was infected by the tail vein with 1×106 CFU of M.tuberculosis H37Rv strain,and treated intraperitoneally with the saline,IFN-γ,IFN-γ combined with M.vaccae vaccine at 10 days after infection.Six mice each group were sacrificed at 6 weeks after infection.The body weights of the mice and the weights of lungs and spleens from the mice were measured.The lungs and spleens of the mice were taken,determined the CFU,and observed histopathologic changes.The level of IFN-γ and IL-4 in the blood were detected with ELISA method.The expression of IFN-γ mRNA and IL-4 mRNA in lungs were detected by RT-PCR method.The survival times in the other 30 mice were evaluated in 60 days.Results The pathological changes of lungs in the three treatment groups were localized,while those in tuberculosis model group were extensive.All of mice died in tuberculosis model group,none of mice died in the normal group and the IFN-γ+ M.vaccae vaccine group,only one mice died in IFN-γ group and M.vaccae vaccine group.At 6 weeks after infection,compared with tuberculosis model group,the CFUs in lungs and spleens were significantly decreased in IFN-γ groups(7.12±0.51) and(6.42±0.48) and in M.vaccae vaccine groups(6.31±0.47) and(6.07±0.39),particularly in the IFN-γ+ M.vaccae vaccine group(2.67±0.36) and(2.12±0.33)(P<0.05).The level of IFN-γ in the blood and the expression of IFN-γ mRNA in lung tissue of mice in tuberculosis model group(162±46) pg/ml and(0.18±0.06) were lower than that in normal group((521±198) pg/ml and(0.98±0.13))(P<0.01),and IFN-γ groups(402±134) pg/ml and(0.66±0.08),M.vaccae vaccine groups(416±153) pg/ml and(0.68±0.09) and IFN-γ+ M.vaccae vaccine group(493±145) pg/ml,(0.81±0.11) were higher than that in tuberculosis model group(P<0.05).The level of IL-4 in the blood and the expression of IL-4 mRNA in lung tissue in tuberculosis model group((102±24.8) pg/ml and(1.46±0.25))were higher than that in normal group((56.2±14.5) pg/ml and(0.04±0.01))(P<0.01),and IFN-γ groups((73.5±15.3) pg/ml and(0.63±0.12)),M.vaccae vaccine groups(71.3±14.6) pg/ml and(0.59±0.13) and IFN-γ+ M.vaccae vaccine group(60.8±12.7) pg/ml and(0.28±0.03) were lower than that in tuberculosis model group(P<0.05).Conclusions IFN-γ combined with M.vaccae vaccine could improve host defence against the infection of Mycobacterium tuberculosis,and reduce mycobacterial growth during tuberculosis,and might be associated with a decrease in inflammation in lung and spleen tissue by activating the Th1 response,and inhibiting the Th2 response,and they have cooperative effect.

门脉高压性胃病(Portal Hypertensive Gastropathy,PHG)是指门脉高压患者内镜下胃黏膜的特殊病变.在肝硬化合并上消化道出血的病因构成中,PHG的因素已被认识和重视.为寻求有效的治疗方法,我院于2003年4月至2007年9月采用心得安联合铝碳酸镁治疗PHG201例,现报告如下.