高月求教授“自免方”组方思路及其应用

探讨高月求教授运用"自免方"治疗原发性胆汁性胆管炎的临床经验。"自免方"在滋阴柔肝经典方——一贯煎的基础上用佛手取代川楝子,并增加炒白术健脾益气,蛇舌草、豨莶草清热利湿,全方共奏滋补肝肾、疏肝理气、补血益气、清热利湿之效,主治肝肾阴虚之证。

自免方联合熊去氧胆酸治疗肝肾阴虚证原发性胆汁性胆管炎随机对照研究

目的观察自免方联合熊去氧胆酸(UDCA)治疗肝肾阴虚证原发性胆汁性胆管炎(PBC)患者的临床疗效和安全性。方法73例符合纳入标准的肝肾阴虚证PBC患者,按照随机数字表法分为对照组37例和治疗组36例,对照组口服UDCA治疗,治疗组口服自免方联合UDCA治疗。比较两组治疗前、治疗后3、6个月的中医证候积分、中医证候疗效、碱性磷酸酶(ALP)、γ-谷氨酰转移酶(GGT)、总胆红素(TBIL)、总胆汁酸(TBA)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、凝血酶原时间(PT)、AST与血小板(PLT)比值指数(APRI)/基于4项因子的肝纤维化指数(FIB-4)、血常规、肌酐(Cr)、尿素氮(BUN)的变化,并观察不良反应。结果73例患者治疗过程中脱落8例,最终纳入分析65例,对照组32例,治疗组33例。对照组有效率为56.25%(18/32),治疗组有效率为96.97%(32/33),治疗组临床疗效优于对照组(χ2=27.375,P<0.05)。治疗3个月后,两组患者中医证候积分、ALP、GGT较治疗前明显下降(P<0.05),且治疗组优于对照组(P<0.05)。治疗6个月后,两组患者中医证候积分、ALP、GGT、TBA较治疗前明显下降(P<0.05),与对照组同期比较,治疗组ALP、GGT下降更显著(P<0.05)。治疗6个月后,ALT、AST、PT、APRI评分、FIB-4评分均较治疗前明显下降(P<0.05),但两组比较,差异无统计学意义(P>0.05)。治疗期间两组均未见明显不良反应。结论自免方联合UDCA能明显改善肝肾阴虚证PBC患者的中医证候积分、ALP、GGT,疗效优于单用UDCA治疗,且安全性良好。

Acute recurrent pancreatitis:An autoimmune disease?

In this review article, we will briefly describe the main characteristics of autoimmune pancreatitis and then we will concentrate on our aim, namely, evaluating the clinical characteristics of patients having recurrence of pain from the disease. In fact, the open question is to evaluate the possible presence of autoimmune pancreatitis in patients with an undefined etiology of acute pancreatitis and for this reason we carried out a search in the literature in order to explore this issue. In cases of recurrent attacks of pain in patients with "idiopathic" pancreatitis, we need to keep in mind the possibility that our patients may have autoimmune pancreatitis. Even though the frequency of this disease seems to be quite low, we believe that in the future, by increasing our knowledge on the subject, we will be able to diagnose an ever-increasing number of patients having acute recurrence of pain from autoimmune pancreatitis.

Usefulness of liver infiltrating CD86-positive mononuclear cells for diagnosis of autoimmune hepatitis

AIM： Although the pathogenic mechanism underlying autoimmune hepatitis （AIH） remains unclear, the immune system is thought to be critical for the progression of the disease. Cellular immune responses may be linked to the hepatocellular damage in AIH. Recently, much attention has been focused on the critical functions of costimulatory molecules expressed on mononuclear cells in the generation of effective T cell-mediated immune responses. Analysis of costimulatory molecule expressed on mononuclear cells from the patients with AIH may give us insight into the pathogenic mechanism of hepatocellular damage in AIH. METHODS： Peripheral blood mononuclear cells （PBMC） were taken from the patients with AIH （34 cases） and healthy controls （25 cases）. Uver infiltrating mononuclear cells （LIMCs） were taken from the patients with AIH （18 cases）, the patient with chronic hepatitis C （CH-C） （13 cases） and the patients with fatty liver （2 cases）. Using flow cytometry, the cells were analyzed for the expression of costimulatory molecules, such as CD80, CD86, and CD152 （CTLA-4）. The results were compared with clinical data such as the level of gammaglobulin, histological grade, presence or absence of corticosteroids administration and the response to corticosteroids. RESULTS： The levels of CD80＋, CD86＋ and CD152＋ PBMC were significantly reduced in the patients with AIH as compared with healthy controls. By contrast, those cells were significantly higher in LIMC than in PBMC of the patients with AIH. Especially, the level of CD86＋ LIMC showed a marked increase irrespective of the degree of disease activity in the patients with AIH,although CD86＋ cells were rarely present in PBMC. The levels of CD86＋ cells were present in significantly higher frequency in patients with AIH than in the patients with CH-C. Furthermore, the patients with AIH with high levels of CD86＋ LIMC showed good responses to corticosteroids, whereas 2 cases of AIH with low levels of CD86＋ LIMC did not respond well. CONCLUSION： These results suggest that LIMC overexpressing costimulatory molecules such as CD80 and CD86 appears to play a role in the pathogenesis of AIH. Especially, CD86 molecule expressed on the LIMC may be useful for the diagnosis of AIH and for the prediction of the therapeutic effects of corticosteroids on AIH.

Cure of alopecia areata after eradication of Helicobacter pylori:A new association?

Alopecia areata is a disease of the hair follicles, with strong evidence supporting autoimmune etiology. Alopecia areata is frequently associated with immune-medi- ated diseases with skin manifestations such as psoriasis and lichen planus, or without skin manifestations such as autoimmune thyroiditis and idiopathic thrombocytopenic purpura. Helicobacter py/ori （H. pylorl） infection is present in around 50% of the world＇s population and has been associated with a variety of immune-mediated extra-digestive disorders including autoimmune thyroid- itis, idiopathic thrombocytopenic purpura, and psoriasis. A case of a 43-year old man with an 8-too history of alopecia areata of the scalp and beard is presented. The patient was being treated by a dermatologist and had psychiatric support, without any improvement. He had a history of dyspepsia and the urea breath test confirmed H. pylori infection. The patient went into remission from alopecia areata after H. pylori eradication. If such an association is confirmed by epidemiological studies designed for this purpose, new therapeutic options could be available for these patients, especially in areas where infection with H, pylori is highly prevalent.

Ages of celiac disease: From changing environment to improved diagnostics

From the time of Gee's landmark writings, the recent history of celiac disease (CD) can be divided into many ages, each driven by a diagnostic advance and a deeper knowledge of disease pathogenesis. At the same time, these advances were paralleled by the identification of new clinical patterns associated with CD and by a continuous redefinition of the prevalence of the disease in population. In the beginning, CD was considered a chronic indigestion, even if the causative food was not known; later, the disease was proven to depend on an intolerance to wheat gliadin, leading to typical mucosal changes in the gut and to a malabsorption syndrome. This knowledge led to curing the disease with a gluten-free diet. After the identification of antibodies to gluten (AGA) in the serum of patients and the identification of gluten-specific lymphocytes in the mucosa, CD was described as an immune disorder, resembling a chronic "gluten infection". The use of serological testing for AGA allowed identification of the higher prevalence of this disorder, revealing atypical patterns of presentation. More recently, the characterization of autoantibodies to endomysium and to transglutaminase shifted the attention to a complex autoimmune pathogenesis and to the increased risk of developing autoimmune disorders in untreated CD. New diagnostic assays, based on molecular technologies, will introduce new changes, with the promise of better defining the spectrum of gluten reactivity and the real burden of gluten related-disorders in the population. Herein, we describe the different periods of CD experience, and further developments for the next celiac age will be proposed.

Effects of different Chinese herbal prescriptions on cytokines in autoimmune prostatitis rats

OBJECTIVE:To observe and compare the effects of Chinese herbal prescriptions for promoting blood circulation,clearing heat,removing toxicity,and dispersing stagnated liver-Qi on cytokines in model rats with experimental autoimmune prostatitis(EAP) to provide an experimental basis for the use of Chinese herbal prescriptions in the treatment of chronic prostatitis.METHODS:One-hundred and ten male Wistar rats were randomly divided into 11 groups:blank group;model group;Huoxuehuayu(promoting blood circulation to remove blood stasis) high,middle,and low dose groups;Qingrejiedu(clearing heat and removing toxicity) high,middle,and low dose groups;and Shuganliqi(dispersing stagnated liver-Qi) high,middle,and low dose groups.Except the blank group,rats in all groups were injected subcutaneously in multiple points on days 0 and 30 with prostatic protein extractive solution(60 mg/ml_),and intraperitoneally injected with diphtheria-pertussis and tetanus vaccine(DPT vaccine) to establish the EAP model.Model rats were administrated high,middle,and low doses of Chinese herbal prescriptions and were sacrificed after 4 weeks.Pathological changes in the prostate gland were observed with HE staining and changes in serum interleukin-6(IL-6),interleukin-8(IL-8),and prostaglandin E_2(PGE_2) levels were detected with enzyme-linked immunosorbent assay.RESULTS:Compared with the blank group,serum PGE_2,IL-6,and IL-8 levels in the model group were significantly higher(P < 0.05).Compared with the model group,serum PGE_2,IL-6,and IL-8 levels in the Qingrejiedu low dose and middle dose groups were significantly lower(P < 0.05),with the lower dose having a more obvious effect.Serum PGE_2,IL-6,and IL-8 levels in the Huoxuehuayu high dose group(P < 0.05),IL-6 and IL-8 levels in the Huoxuehuayu middle dose group(P < 0.05),and the IL-8level in the Huoxuehuayu low dose group were significantly lower than those in the model group(P < 0.05).There were significant differences in PGE_2 and IL-6 levels among the different dose groups of Shuganliqi drugs(P < 0.05).Compared with the model group,serum PGE_(2/) IL-6,and IL-8levels in the Shuganliqi high dose group(P <0.05) and IL-8 level in the Shuganliqi low dose group were significantly lower(P < 0.05),while the Shuganliqi middle dose group did not change significantly(P > 0.05).CONCLUSION:Therefore,in TCM treatment of autoimmune prostatitis,different treatment methods should select different doses.For prescriptions that clear heat and remove toxicity,low doses should be used.For prescriptions that promote blood circulation to remove blood stasis and for prescriptions that disperse stagnated liver-Qi,high doses should be used.

Fractional-Order Model of the Disease Psoriasis:A Control Based Mathematical Approach

Autoimmune diseases are generated through irregular immune response of the human body. Psoriasis is one type of autoimmune chronic skin diseases that is differentiated by T-Cells mediated hyper-proliferation of epidermal Keratinocytes. Dendritic Cells and CD8＋ T-Cells have a significant role for the occurrence of this disease. In this paper, the authors have developed a mathematical model of Psoriasis involving CD4＋ T-Cells, Dendritic Ceils, CD8＋ T-Cells and Keratinocyte cell populations using the fractional differential equations with the effect of Cytokine release to observe the impact of memory on the cell-biological system. Using fractional calculus, the authors try to explore the suppressed memory, associated with the cell-biological system and to locate the position of Keratinocyte cell population as fractional derivative possess non-local property. Thus, the dynamics of Psoriasis can be predicted in a better way using fractional differential equations rather than its corresponding integer order model. Finally, the authors introduce drug into the system to obstruct the interaction between CD4＋ T-Cells and Keratinocytes to restrict the disease Psoriasis. The authors derive the Euler-Lagrange conditions for the optimality made through Matlab by developing iterative of the drug induced system. Numerical simulations are schemes.