Predictors of survival in autoimmune liver disease overlap syndromes

BACKGROUND Survival in patients with autoimmune liver disease overlap syndromes(AILDOS)compared to those with single autoimmune liver disease is unclear.AIM To investigate the survival of patients with AILDOS and assess the accuracy of non-invasive serum models for predicting liver-related death.METHODS Patients with AILDOS were defined as either autoimmune hepatitis and primary biliary cholangitis overlap(AIH-PBC)or autoimmune hepatitis and primary sclerosing cholangitis overlap(AIH-PSC)and were identified from three tertiary centres for this cohort study.Liver-related death or transplantation(liver-related mortality)was determined using a population-based data linkage system.Prognostic scores for liver-related death were compared for accuracy[including liver outcome score(LOS),Hepascore,Mayo Score,model for end-stage liver disease(MELD)score and MELD incorporated with serum sodium(MELD-Na)score].RESULTS Twenty-two AILDOS patients were followed for a median of 3.1 years(range,0.35-7.7).Fourteen were female,the median age was 46.7 years(range,17.8 to 82.1)and median Hepascore was 1(range,0.07-1).At five years post enrolment,57%of patients remained free from liver-related mortality(74%AIH-PBC,27%AIH-PSC).There was no significant difference in survival between AIH-PBC and AIH-PSC.LOS was a significant predictor of liver-related mortality(P<0.05)in patients with AIH-PBC(n=14)but not AIH-PSC(n=8).A LOS cut-point of 6 discriminated liver-related mortality in AIH-PBC patients(P=0.012,log-rank test,100%sensitivity,77.8%specificity)(Harrell's C-statistic 0.867).The MELD score,MELD-Na score and Mayo Score were not predictive of liver-related mortality in any group.CONCLUSION Survival in the rare,AILDOS is unclear.The current study supports the LOS as a predictor of liver-related mortality in AIH-PBC patients.Further trials investigating predictors of survival in AILDOS are required.

Posttreatment Lyme disease syndrome and myalgic encephalomyelitis/chronic fatigue syndrome:A systematic review and comparison of pathogenesis

Lyme disease is the most common vector-borne illness in the United States and has been causing significant morbidity since its discovery in 1977.It is well-documented that about 10%of patients properly treated with antibiotics never fully recover,but instead go on to develop a chronic illness dubbed,posttreatment Lyme disease syndrome(PTLDS)characterized by severe fatigue,cognitive slowing,chronic pain,and sleep difficulties.This review includes 18 studies that detail the symptoms of patients with PTLDS and uses qualitative analysis to compare them to myalgic encephalitis/chronic fatigue syndrome(ME/CFS),a strikingly similar syndrome.In the majority of the PTLDS studies,at least four of the six major symptoms of ME/CFS were also noted,including substantial impairment in activity level and fatigue for more than 6 months,post-exertional malaise,and unrefreshing sleep.In one of the included PTLDS articles,26 of the 29 ME/CFS symptoms were noted.This study adds to the expanding literature on the post-active phase of infection syndromes,which suggests that chronic illnesses such as PTLDS and ME/CFS have similar pathogenesis despite different infectious origins.

The conflict on posttreatment Lyme disease syndrome: a clinical mini review

Is Borrelia burgdorferi responsible for the persistence of symptoms after the standard successful course of antibiotics in Lyme disease patients?This highly controversial issue,concerning the underlying mechanism of posttreatment Lyme disease syndrome(PTLDS),still seems to be a matter of intense conflict of opinion.PTLDS is the manifestation of nonspecific symptoms including fatigue,musculoskeletal pain,dysesthesias,and neurocognitive deterioration after the standard antimicrobial therapy administered to patients suffering from Lyme disease.In this article,we review the conflicting views and published highlights of recent human studies regarding PTLDS.

Research Survey of Animal Model of Hepatic Fibro-sis Integrated with Western Medicine Diseases and Traditional Chinese Medicine^TCM~)Syndrome

Although the animal models of hepatic fibrosis developed by former researchers have pathological changes of hepatic fibrosis, they do not include charac- teristics of important TCM syndromes such as stagnation of qi, deficiency of qi, liver depression, phlegm-dampness and blood stasis because of single-factor model- ing. Animal models of hepatic fibrosis and animal models integrated disease and syndrome were reviewed, and several new types of integrated disease and syndrome animal models constructed by multiple-factor modeling method were evaluated, under the guidance of etiological theory of TCM. This kind of hepatic fibrosis model animals has dual characteristics of disease and syndrome. It is consistent with pathological characteristics of hepatic fibrosis in western medicine when replicating the basic characteristics accorded with TCM syndrome. Thus, the pathogenesis and pathogenic process of clinical disease and syndrome formation is simulated more ac- curately, providing a new platform and pathway for studying hepatic fibrosis disease with integrated traditional Chinese and western medicine.

Hutchinson-Gilford Progeria Syndrome and its Relevance to Cardiovascular Diseases and Normal Aging

Hutchinson-Gilford progeria syndrome(HGPS,OMIM176670)is an extremely rare,sporadic genetic syndrome with a reported prevalence of one in4-8million children worldwide.At April2012,the total number of known living children with HGPS was89worldwide,according to data from the Progeria Research Foundation.

Protocol to study the effects of AMPK-mTOR/PINK-Parkin dual signaling pathways on the formation of coronary heart disease showing blood stasis symptom pattern based on traditional Chinese medicine theory of“heart governing blood and vessels”

In this study,we aim to combine gene transfection techniques with the modeling methods previously employed by the research group to deeply investigate the corresponding theories of traditional Chinese medicine regarding“myocardial energy metabolism”and“aortic thrombosis”.Our goal is to elucidate the biological mechanism underlying the occurrence and development of coronary heart disease with blood stasis syndrome from the perspectives of“heart and vessels”and“Qi(in traditional Chinese medicine,it refers to the most fundamental and subtle substances that constitute the human body and maintain life activities.At the same time,it also has the meaning of physiological function.In terms of traditional Chinese medicine,Qi and different words are used together to express different meanings)and blood”.The research content is divided into four modules as follows:1.establishment of an animal model of coronary heart disease with blood stasis syndrome through fibrinogen overexpression.2.Investigation of the mitochondrial quality control system in coronary heart disease with blood stasis syndrome under fibrinogen overexpression.3.Study of platelet autophagy in coronary heart disease with blood stasis syndrome under fibrinogen overexpression.4.Examination of the relationship between the AMPK-mTOR pathway and metabolism in platelet autophagy of coronary heart disease with blood stasis syndrome under fibrinogen overexpression.Ninety-six Sprague Dawley rats will be randomly assigned to the following groups:control group,model group,fibrinogen group and adeno-associated virus group.All rats will undergo a 14-week model construction process,and modern molecular biology methods will be employed to evaluate the model and examine relevant research indicators.The obtained data will be analyzed according to a predefined statistical analysis plan.

Association between autoimmune pancreatitis and systemic autoimmune diseases

AIM: To investigate the association between autoimmune pancreatitis (AIP) and systemic autoimmune diseases (SAIDs) by measurement of serum immunoglobulin G4 (IgG4). METHODS: The serum level of IgG4 was measured in 61 patients with SAIDs of different types who had not yet participated in glucocorticosteroid treatment. Patients with an elevated IgG4 level were examined by abdominal ultrasonography (US) and, in some cases, by computer tomography (CT). RESULTS: Elevated serum IgG4 levels (919 ± 996 mg/L) were detected in 17 (28%) of the 61 SAID patients. 10 patients had Sj gren's syndrome (SS) (IgG4: 590 ± 232 mg/L), 2 of them in association with Hashimoto's thyroiditis, and 7 patients (IgG4: 1388 ± 985.5 mg/L) had systemic lupus erythematosus (SLE). The IgG4 level in the SLE patients and that in patients with SS were not significantly different from that in AIP patients (783 ± 522 mg/L). Abdominal US and CT did not reveal any characteristic features of AIP among the SAID patients with an elevated IgG4 level. CONCLUSION: The serum IgG4 level may be elevated in SAIDs without the presence of AIP. The determination of serum IgG4 does not seem to be suitable for the differentiation between IgG4-related diseases and SAIDs.

OUTCOMES OF INVASIVE STRATEGY TO PATIENTS WITH NON-ST-ELEVATION ACUTE CORONARY SYNDROMES

Objective To compare the outcomes of an invasive with a conservative strategy in the manage-ment of patients with non-ST-elevation acute coronary syndromes. Methods From January 2000 to June 2001, 505 patients presenting with unstable angina or non-Q wave myocardial infarction were divided into two groups (conservative vs. invasive) according to management strategy. Patients assigned to an early invasive strategy underwent coronary angiography within 7d of enrollment after intensive antiplatelet, antithrombotic and antiangina therapy and revascularization as appropriate. All patients were followed up at least 6 months. The primary endpoints were cardiac death and acute myocardial infarction. Recurrence angina and readmission were the secondary end-point. Results There were 194 patients in conservative group and311 patients in invasive group. Overall, coronary angiography was performed in 100% and 56% , and revascularization in 93% and 52% in the invasive and conservative groups, respectively. During a mean of 11±5.7 months (range 6 ~ 24 months) of follow-up, the occurrence of primary endpoint was significantly lower in the invasive group than that in the conservative group (3.9% vs 8. 2% , P =0. 036). The rate of recurrent angina (48% vs 17% , P =0. 001) , readmission (41% vs 13% , P = 0. 001) and revascularization (12% vs 35% , P =0. 001) was also significantly lower in patients assigned to invasive strategy. Conclusion The study indicates that the early invasive approach may be the preferred strategy in patients with unstable angina or non-Q wave myocardial infarction.

Chronic kidney disease prediction is an inexact science: The concept of “progressors” and “nonprogressors”

In 2002,the National Kidney Foundation Kidney Disease Outcomes Quality Initiative(NKF KDOQI)instituted new guidelines that established a novel chronic kidney disease(CKD)staging paradigm.This set of guidelines,since updated,is now very widely accepted around the world.Nevertheless,the authoritative United States Preventative Task Force had in August 2012acknowledged that we know surprisingly little about whether screening adults with no signs or symptoms of CKD improve health outcomes and that we deserve better information on CKD.More recently,the American Society of Nephrology and the American College of Physicians,two very well respected United States professional physician organizations were strongly at odds coming out with exactly opposite recommendations regarding the need or otherwise for"CKD screening"among the asymptomatic population.In this review,we revisit the various angles and perspectives of these conflicting arguments,raise unanswered questionsregarding the validity and veracity of the NKF KDOQI CKD staging model,and raise even more questions about the soundness of its evidence-base.We show clinical evidence,from a Mayo Clinic Health System Renal Unit in Northwestern Wisconsin,United States,of the pitfalls of the current CKD staging model,show the inexactitude and unpredictable vagaries of current CKD prediction models and call for a more cautious and guarded application of CKD staging paradigms in clinical practice.The impacts of acute kidney injury on CKD initiation and CKD propagation and progression,the effects of such phenomenon as the syndrome of late onset renal failure from angiotensin blockade and the syndrome of rapid onset end stage renal disease on CKD initiation,CKD propagation and CKD progression to end stage renal disease all demand further study and analysis.Yet more research on CKD staging,CKD prognostication and CKD predictions are warranted.Finally and most importantly,cognizant of the very serious limitations and drawbacks of the NKF K/DOQI CKD staging model,the need to individualize CKD care,both in terms of patient care and prognostication,cannot be overemphasized.

Study on Correspondence between Prescription and Syndrome and the Essence of Phlegm and Blood Stasis Syndrome in Coronary Heart Disease Based on Metabonomics

Studying the essence of a syndrome has been a key challenge in the field of Chinese medicine.Until now,due to limitations of the methods available,the progress towards understanding such complicated systems has been slow.Metabonomics encompasses the dynamics,composition and analysis of metabolites,enabling the observation of changes in the metabolic network of the human body associated with disease.Being from the point of view of the whole organism,metabonomics provides an opportunity to study the essence of a syndrome to an unprecedented level.Phlegm and blood stasis syndrome is the main syndrome associated with coronary heart disease（CHD）,which bring difficulties in clinical treatment due to difficulties associated with differentiation of symptoms and signs.The fundamental differences of material between the two also need to be interpreted.The authors consider that we can use the method of combining a disease（in this case CHD）with associated syndromes（phlegm and blood stasis syndrome）to select patients with phlegm and blood stasis syndrome of CHD,and utilize metabonomics to explore the essence of the syndrome by difference analysis of metabolite spectra.Meanwhile,we can study the syndrome in CM,observe the change regularity of metabolism spectra after the treatment of corresponding and non-corresponding prescription and syndrome,in order to validate the material fundament in the progress of syndrome formation and their differences.This will not only have great significance in enhancing the ability to identify syndrome of phlegm and blood stasis in CHD and to establish the clinical curative criteria,but will also offer a new approach of studying the essence for a syndrome using metabonomics.

Effect of Metabolic Syndrome Score, Metabolic Syndrome, and Its Individual Components on the Prevalence and Severity of Angiographic Coronary Artery Disease

Background： The clinical significance of metabolic syndrome （MS） score, MS, and its individual components with respect to risk prediction of coronary artery disease （CAD） remains unclear. The objective of this study was to investigate whether and to what extent MS score, MS, and its individual components were related to the risk of CAD. Methods： Among 1191 participants who underwent coronary angiography for the confirmation of suspected myocardial ischemia, 858 were included in this study according to the inclusion criteria from September 2010 to June 2013. MS was diagnosed with the 2005 National Cholesterol Education Program Adult Treatment Panel III criteria. The severity of coronary atherosclerosis was assessed by Gensini score. Results： The results showed that the age- and sex-adjusted odds ratios （ORs） tbr CAD were as follows： MS score, 1.327; MS, 2.013; elevated waist circumference, 1.447; reduced high-density lipoprotein cholesterol, 1.654： and elevated fasting glucose, 1.782： all P〈 0.05： whereas for elevated triglycerides, 1.324, and elevated blood pressure, 1.342, both P 〉 0.05. Alter multivariate adjustment, results showed that only MS and elevated fasting glucose were significantly associated with CAD （OR, 1.628, 95% confidence interval [CI], 1.151-2.305, P = 0.006 for elevated fasting glucose, and OR, 1.631, 95% CI, 1.208-2.203, P = 0.001 for MS）. The study showed that only MS score and elevated fasting glucose were significantly associated with Gensini score （standardized coefficient, 0.101, P = 0.031 for elevated fasting glucose and standardized coefficient, 0.103, P = 0.009 for MS score）. Conclusions： The present study demonstrated that MS score, MS, and its individual components might have different contributions to CAD prevalence and severity. MS and elevated fasting glucose were independent risk factors for the prevalence of angiographic CAD whereas MS score and elevated fasting glucose were significantly associated with the severity of CAD.

Clinical treatment of myasthenia gravis with deficiency of spleen and kidney based on combination of disease with syndrome theory

OBJECTIVE: To study the use of Jianjining in the treatment of myasthenia gravis (MG) patients with a deficiency of both spleen and kidney via the theory on the combination of disease with syndrome. METHODS: Sixty MG patients with a deficiency of both spleen and kidney were randomly divided into an treatment group (n=30) treated with Jianjining granules and Western Medicine (prednisone or pyridostigmine bromide) and a control group (n= 30) treated with Jianjining granules. The dosage of the three drugs was reduced over the course of treatment. After 3 and 6 months of treatment, the curative effect was evaluated with the muscle weakness severity scale (MWSS). RESULTS: The MWSS score after treatment declined significantly in both groups. The score in the treatment group was much lower than that in thecontrol group (P<0.05). The total effective rate was 63.33% (19/30) in the treatment group and 36.67% (11/30) in the control group after 3 months of treatment, and 80.00% (24/30) and 50.00% (15/30), respectively, after 6 months of treatment. The obvious and total effective rates in the treatment group were much higher than those in the control group (P<0.05). After 6 months of treatment, there were no obvious differences (P>0.05) in the obvious and effective rates between the 2 groups. However, the total effective rate in the treatment group was much higher than that in the control group (P<0.01). CONCLUSION: Using the theory on the combination of disease with syndrome, we found that the curative effect of Jianjining and Western Medicine on MG patients with deficiency of both spleen and kidney is worth further exploration.

Haoqin Qingdan Decoction(蒿芩清胆汤)and Ribavirin Therapy Downregulate CD14 and Toll-Like Receptor 4 in Febrile Disease with Dampness-Heat Syndrome in A Mouse Model

Objective： To evaluate the effect of Chinese medicine Haoqin Qingdan Decoction （蒿芩清胆汤, HQD） for febrile disease dampness-heat syndrome （FDDHS）. Methods： Forty mice were divided into four groups, including normal control, FDDHS （induced by Radix et Rhizoma Rhei recipe and influenza virus A1 FM1 model）, HQD, and the ribavirin groups （10 in each）. The normal control and FDDHS groups were administered normal saline. HQD and the ribavirin groups were administered HQD and ribavirin intragastrically once daily at a dose of 64 g/（kg.d） and 0.07 g/（kg.d）, respectively for 7 days. Lethargy, rough hair, diarrhea, tongue color and sole color were evaluated for pathological changes in morphology. The tongue and lung tissues were collected for histology. The CD14 and toll-like receptor 4 （TLR4） expression levels were measured using real-time quantitative polymerase chain reaction. Results： More than 80% of the FDDHS mice showed hypokinesia and lethargy, and pathological changes associated with rough hair, diarrhea, tongue color and sole color. With advanced treatment for 7 days, the thick greasy tongue fur of the HQD and ribavirin groups were thinner than that of the FDDHS group （P〈0.05）, and it was the thinnest in the ribavirin group as compared with that in other groups （P〈0.05）. The CD14 and TLR4 expression levels in the lung tissues of HQD and ribavirin groups significantly delined compared with the model group （P〈0.05 or P〈0.01）. CD14 was down-regulated more remarkably in the HQD group compared with the ribavirin group （P〈0.05）, whereas the converse was true with TLR4 （P〈0.05）. Conclusions： We established a FDDHS mouse model showing systemic clinical symptoms. Both HQD and ribavirin can inhibit the expression of CD14 and TLR4 in FDDHS mice, while the effect of ribavirin might be much more violent. The expression changes of CD14 and TLR4 consistently refers to lipopolysaccharide, the commonly and hotly inducing factor in FDDHS.

Metabolomic Profiling Reveals Distinct Patterns of Tricarboxylic Acid Disorders in Blood Stasis Syndrome Associated with Coronary Heart Disease

Objective： To investigate the underlying metabolomic profiling of coronary heart disease（CHD） with blood stasis syndrome（BSS）. Methods： CHD model was induced by a nameroid constrictor in Chinese miniature swine. Fifteen miniature swine were randomly divided into a model group（n=9） and a control group（n=6）, respectively according to arandom number table. After 4 weeks, plasma hemorheology was detected by automatic hemorheological analyzer, indices including hematocrit, plasma viscosity, blood viscosity, rigidity index and erythrocyte sedimentation rate; cardiac function was assessed by echocardiograph to detect left ventricular end-systolic diameter（LVED）, left ventricular end-diastolic diameter（LVEDd）, ejection fraction（EF）, fractional shortening（FS） and other indicators. Gas chromatography coupled with mass spectrometry（GC-MS） and bioinformatics were applied to analyze spectra of CHD plasma with BSS. Results： The results of hemorheology analysis showed significant changes in viscosity, with low shear whole blood viscosity being lower and plasma viscosity higher in the model group compared with the control group. Moreover, whole blood reduction viscosity at high shear rate and whole blood reduction viscosity at low shear rate increased significantly（P〈0.05）. The echocardiograph results demonstrated that cardiac EF and FS showed significant difference（P〈0.05）, with EF values being decreased to 50% or less. The GC-MS data showed that principal component analysis can clearly separate the animals with BSS from those in the control group. The enriched Kyoto Encyclopedia of Genes and Genomes biological pathways results suggested that the patterns involved were associated with dysfunction of energy metabolism including glucose and lipid disorders, especially in glycolysis/gluconeogenesis, galactose metabolism and adenosine-triphosphate-binding cassette transporters. Conclusion： Glucose metabolism and lipid metabolism disorders were the major contributors to the syndrome classification of CHD with BSS.

Assessment of Clinical Effect of Therapy Combining Disease with Syndrome on Rheumatoid Arthritis

Objective： To observe the effectiveness and safety of a therapy combining disease with syndrome on rheumatoid arthritis. Methods： Eighty patients with rheumatoid arthritis belonging to syndrome of damp-heat obstruction were randomly divided into a treatment group and a control group according to stratified blocked randomization method.Forty cases in the control group orally took Loxoprofen Sodium Tablet and Leifumite Tablet and the other 40 cases in the treatment group orally took a Chinese medicine for 12 weeks as a course of treatment. ACR therapeutic effect was used as the standard for evaluating the total therapeutic effect. Results： After l 2 weeks of treatment, there was a statistical difference （P〈0.01） in the improvement of VAS score, morning stiffness time, number of swelling joints, index of swelling joints, number of joints with tenderness, index of joints with tenderness, average grip strength of both hands, DSA28 score, HAQ, patient＇s assessment, physician＇s assessment, ESR, CRP and RF in both groups. The improvement of morning stiffness time, number of swelling joints, index of swelling joints, grip strength, HAQ and patient＇s assessment in the treatment group was much better than that in the control groups with statistical difference （P〈0.05）. ACR20, ACR50 and ACR70 was 27.5% （11/40）, 37.5% （15/40） and 22.5% （9/40） respectively in the treatment group and 40% （16/40）, 27.5% （11/42） and 10.0% （4/40） respectively in the control group with statistical difference （P〈0.05） in the superiority of the treatment group over the control group. The incidence of adverse reaction in the control group was higher than that in the treatment group （P〈0.05）. Conclusion： Definite therapeutic effect and high safety can be achieved in using the therapy combining disease with syndrome to treat rheumatoid arthritis belonging to syndrome of damp-heat obstruction.

Relationship between Two Blood Stasis Syndromes and Inflammatory Factors in Patients with Acute Coronary Syndrome

Objective： To investigate the relationship between inflammatory factors and two Chinese medicine（CM） syndrome types of qi stagnation and blood stasis（QSBS） and qi deficiency and blood stasis（QDBS） in patients with acute coronary syndrome（ACS）. Methods： Sixty subjects with ACS, whose pathogenesis changes belongs to qi disturbance blood stasis syndrome, were divided into 2 groups： 30 in the QSBS group and 30 in the QDBS group. The comparative analysis on them was carried out through comparing general information, coronary angiography and inflammatory factors including intracellular adhesion molecule-1（ICAM-1）, chitinase-3-like protein 1（YKL-40） and lipoprotein-associated phospholipase A2（Lp-PLA2）. Results： Compared with the QSBS group, Lp-PLA2 and YKL-40 levels in the QDBS group showed no-significant difference（P〉0.05）; ICAM-1 was significantly higher in the QDBS group than in the QSBS group in the pathological processes of qi disturbance and blood stasis syndrome of ACS（P〈0.05）. Conclusion： Inflammatory factor ICAM-1 may be an objective basis for syndrome typing of QSBS and QDBS, which provides a research direction for standardization research of CM syndrome types.

Study on Mitochondrial Ultrastructure, Traco Elementsand Their Correlative Factore in Cells ot Gastric Mucosa ot theGastropathic Patienta with Spleen Deficiency Syndrome

Atfer examining 88 gastropathic patieiits with Spleen deficiency syndrome by iJsing transmis-sion electron microscope, X-ray energy disperse analysis system, histochemical staining and radioimmunomethods, the authors found that the gastric mucosa cyclic adenosine monophosphate, superoxide dismutaselevel, quantity of mitochondria and its crista, the ratio of diameter between ventricle and cavity of mitochon-dria aiid the conteiit ot zinc (Zn) , copper (Cu) of mitochondria were decreasing to certain extent which tendsto get lower and lower with different groups in the order of health coritrol group, Spleen Qi deficiency groupaiid SPIeen deficiency with Qi stagnation group; chronic superficial gastritis group, chronic atrophic gastritisgroup and gastric cancor group , complete small intestinal metaplasia (IM) group, incomplete small iM group,complete colonic iM groiJp and incomplete colonic iM group (P< 0 . 05￣0 . 001 ) . While tlie degeiieratiori rateof mitochondria, Cu/Zn ratio, metaplasia rate of gastric mucosa, rate of incomplete colonic IM and content ofIipid peroxide were increasing in the above order (P < 0 . 05 ￣0 . 001 ) . It is suggested that tlie comprehensiveeffect ot the degeneration of mitochoridria and the quantitative changes of its correlative factors is the phys-iopathologic base for indecing SPIeen deficiency disease, gastric mucosa iM and canceration.