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.

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.

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.

Androgens and male aging：current evidence of safety and efficacy

Many signs of aging,such as sexual dysfunction,visceral obesity,impaired bone and muscle strength,bear a close resemblance to features of hypogonadism in younger men. The statistical decline of serum testosterone in aging men is solidly documented. It has been presumed that the above features of aging are related to the concurrent decline of androgens,and that correction of the lower-than-normal circulating levels of testosterone will lead to improvement of symptoms of aging. But in essence,the pivotal question whether the age-related decline of testosterone must be viewed as hypogonadism,in the best case reversed by testosterone treatment,has not been definitively resolved. Studies in elderly men with lower-than-normal testosterone report improvement of features of the metabolic syndrome,bone mineral density,of mood and of sexual functioning. But as yet there is no definitive proof of the beneficial effects of restoring testosterone levels to normal in elderly men on clinical parameters. Few of these studies meet as yet rigorous standards of scientific enquiry：double-blind,placebo-controlled design of the study. The above applies also to the assessment of safety of testosterone administration to elderly men. There is so far no convincing evidence that testosterone is a main factor in the development of prostate cancer in elderly men and guidelines for monitoring the development of prostate disease have been developed. It is of note that there are presently no long-term safety data with regard to the prostate. Polycythemia is another potential complication of testosterone treatment. It is dose dependent and can be managed with dose adjustment.

Pathological study on severe acute respiratory syndrome

Objective To study the pathological characteristics of severe acute respiratory syndrome (SARS) and its relationship to clinical manifestation Methods Tissue specimens from 3 autopsies of probable SARS cases were studied by microscope, and the clinical data was reviewed Results The typical pathological changes of lungs were diffuse hemorrhaging on the surface A combination of serous, fibrinous and hemorrhagic inflammation was seen in most of the pulmonary alveoli with the engorgement of capillaries and detection of micro thrombosis in some of these capillaries Pulmonary alveoli thickened with interstitial mononuclear inflammatory infiltrates, suffered diffuse alveolar damage, experienced desquamation of pneumocytes and had hyaline membrane formation, fibrinoid materials, and erythrocytes in alveolar spaces There were thromboembolisms in some bronchial arteries Furthermore, hemorrhagic necrosis was also evident in lymph nodes and spleen with the attenuation of lymphocytes Other atypical pathological changes, such as hydropic degeneration, fatty degeneration, interstitial cell proliferation and lesions having existed before hospitalization were observed in the liver, heart, kidney and pancreas Conclusion Severe damage to the pulmonary and immunological systems is responsible for the clinical features of SARS and may lead to the death of patients

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.

Validation of diagnostic algorithms for syndromic management of sexually transmitted diseases

s To validate our revised syndromic algorithms of the management of sexually trans mitted diseases and determine their sensitivity, specificity, positive predictiv e value and cost effectiveness Methods Patients with either urethral discharge, vaginal discharge or genital ulcer, wer e selected during their first visits to three urban sexually transmitted disease clinics in Fujian Province, China They were managed syndromically according t o our revised flowcharts The etiology of the syndromes was detected by laborat ory testing The data were analyzed using EPI INFO V6 0 software Results A total of 736 patients were enrolled into the study In male patients with ur ethral discharge, the sensitivities for gonococcal and chlamydial infections wer e 96 7% and 100%, respectively, using the syndromic approach The total positi ve predictive value was 73% In female patients with vaginal discharge, the sen sitivity was 90 8%, specificity 46 9%, positive predictive value 50 9%, and n egative predictive value 89 3% for the diagnosis of gonorrhea and/or chlamydial infection by syndromic approach In patients with genital ulcer, the sensitivi ties were 78 3% and 75 8%, specificities of 83 6% and 42 9%, and positive pr edictive values of 60 0% and 41 0% for the diagnosis of syphilis and genital h erpes, respectively, using the syndromic approach Cost effectiveness analysi s indicated that the average cost of treatment for a patient with urethral disch arge was RMB 46 03 yuan using syndromic management, in comparison with RMB 149 19 yuan by etiological management Conclusions The syndromic management of urethral discharge was relatively effective and suit ed clinical application The specificity and positive predictive value for sy ndromic management of vaginal discharge are not satisfactory The revised flowc hart of genital ulcer syndrome could be suitable for use in clinical settings Further validation and revision are needed for syndromic approaches of vaginal d ischarge and genital ulcer