“是动病”“所生病”与十二经脉辑要

"是动病""所生病"雏形源自《阴阳十一脉灸经》《足臂十一脉灸经》,到《灵枢·经脉篇》内容、形式完整描述,《难经·二十二难》归纳成"是动病"和"所生病"两个专用名词,后世各医家之辞,经历了由简单到复杂,由单一到多元的发展,逐渐完善其诊断、治疗学意义与病候转归,还包括利用现代文献整理统计学思想系统考察的经脉归属和病候(群)关联;古代医家多从病位和病因解释和区分,结合语境及《内经》其他篇章理解,言简意赅,虽存争议,但总归于"变化-病"分析思路,包含气血先后、经络脏腑、内因外因及阴阳相对、穴动诊病、病症主治,借十二经脉条文中某类特殊情况发挥至整体,其中气血说、经络脏腑说、阴阳说等说服力欠佳;现代医家分析更丰富,通过临床观察、试验加以验证。研究方式多样,值得进一步完善,发扬及论证。古文献流传存在易遗漏、衍文、不同时代文字完善不足等,现今概念阐释与早期学术思想真实意义之间仍存在差异,缺乏验证的客观依据,需要进一步去伪存真、传承创新。

Fulminant ulcerative colitis associated with steroid-resistant minimal change disease and psoriasis: A case report

A 43-year-old Chinese patient with a history of psoriasis developed fulminant ulcerative colitis after immunosuppressive therapy for steroid-resistant minimal change disease was stopped. Minimal change disease in association with inflammatory bowel disease is a rare condition. We here report a case showing an association between ulcerative colitis, minimal change disease, and psoriasis. The possible pathological link between 3 diseases is discussed.

Induction of Erythroid Differentiation of HumanErythroleukemia K-562 Cells by Mutactimycin

Mutactimycin,a new anthracycline antibiotic,consists of 5 components: mutac-timycin A,B,C,D and 7-deoxymutactimycinone A. Mutactimycin components differ from each other in suppressing proliferation and inducing differentiation of human erythroleukemia K-562 cells. Determined by benzidine staining, the percentage of K-562 cells with hemoglobin expression was86% by mutactimycin C. The peak percentage of benzidine positive cells appeared on day 5 or 6.The differentiated cells were partially reversed after drug removal.The induced cells lost the clonogenicity in soft-agar. The kinetics of differentiation induced by mutactimycin C, in comparison with other known anthracycline antibiotics,was similar to that by doxorubicin, epirubicin anddaunorubicin. Mutactimycin C was more active than aclarubicin A. The structure-activity relationship for mutactimycin components suggested that the substituting groups on C_3, C_11, and the saccharide on C_7 might be important for their activities.

Cutting-balloon angioplasty before drug-eluting stent implantation for the treatment of severely calcified coronary lesions

Background Severely calcified coronary lesions respond poorly to balloon angioplasty, resulting in incomplete and asymmetrical stent expansion. Therefore, adequate plaque modification prior to drug-eluting stent （DES） implantation is the key for calcified lesion treat- ment. This study was to evaluate the safety and efficacy of cutting balloon angioplasty for severely calcified coronary lesions. Methods Ninety-two consecutive patients with severely calcified lesions （defined as calcium arc 〉 180% calcium length ratio 〉 0.5） treated with bal- loon dilatation before DES implantation were randomly divided into two groups based on the balloon type： 45 patients in the conventional balloon angioplasty （BA） group and 47 patients in the cutting balloon angioplasty （CB） group. Seven cases in BA group did not satisfactorily achieve dilatation and were transferred into the CB group. Intravascular ultrasound （IVUS） was performed before balloon dilatation and after stent implantation to obtain qualitative and quantitative lesion characteristics and evaluate the stent, including minimum lumen cross-sectional area （CSA）, calcified arc and length, minimum stent CSA, stent apposition, stent symmetry, stent expansion, vessel dissection, and branch vessel jail. In-hospital, 1-month, and 6-month major adverse cardiac events （MACE） were reported. Results There were no statistical differences in clinical characteristics between the two groups, including calcium arc （222.2° ± 22.2° vs. 235.0° ± 22.1 °, p=0.570）, calcium length ratio （0.67 ± 0.06 vs. 0.77± 0.05, P = 0.130）, and minimum lumen CSA before PCI （2.59 ±0.08 mm2 vs. 2.52 ± 0.08 mm2, P = 0.550）. After stent implantation, the final minimum stent CSA （6.26 ± 0.40 mm2 vs. 5.03 ± 0.33 mm2; P = 0.031） and acute lumen gain （3.74 ±0.38 mm2 w. 2.44 ± 0.29 mm2, P = 0.015） were significantly larger ila the CB group than that of the BA group. There were not statis tically differences in stent expansion, stent symmetry, incomplete stent apposition, vessel dissection and branch vessel jail between two groups. The 30-day and 6-month MACE rates were also not different. Conclusions Cutting balloon angioplasty before DES implantation in severely calcified lesions appears to be more efficacies including significantly larger final stent CSA and larger acute lumen gain, without increasing complications during operations and the MACE rate in 6-month.

SEQUENCE VARIABILITY OF HUMAN CYTOMEGALOVIRUS UL144 OPEN READING FRAME IN LOW-PASSAGE CLINICAL ISOLATES

Objective To explore the relationship between human cytomegalovirus (HCMV) UL144 sequence variability and clinical disease. Methods HCMV UL144 open reading frame (ORF) was amplified by PCR assay in 72 lowpassage isolates [65 con-genitally infective children and 7 healthy children who were HCMV-DNA positive by quantitative PCR (qPCR)]. All positive PCR products were analyzed by heteroduplex mobility assay and single-stranded conformation polymorphism (HMA-SSCP) and 32 of them were sequenced. Results Fifty-five patient isolates and five healthy children isolates were HCMV-UL144 positive by PCR. Sequencing and HMA-SSCP analysis showed that significant strain-specific variability was present in the UL144 ORF. Phylogenetic analysis indicated that the nucleotide sequences could be separated into 3 major genotypes. Comparing between UL144 se-quences and the corresponding symptoms showed that genotype 2 did not exist in megacolon isolates. And genotype 1 and 3 were the major types among microcephaly and jaundice isolates respectively. Conclusions HCMV-UL144 existed in most of low passage isolates and sequences were hypervariable. The UL144 ORF and its predicted product with the high level of sequence variability in different kinds of isolates suggest that UL144 ORF might play a role in HCMV infectivity and subsequent diseases.

Sampling variability of computer-aided fractal-corrected measures of liver fibrosis in needle biopsy specimens

AIM： TO assess the sampling variability of computeraided, fractal-corrected measures of fibrosis in liver biopsies. METHODS： Samples were derived from six to eight different parts of livers removed from 12 patients with clinically and histologically proven cirrhosis undergoing orthotopic liver transplantation. Sirius red-stained sections with a thickness of 2 μm were digitized using a computer-aided image analysis system that automatically measures the surface of fibrosis, as well as its outline perimeter, fractal surface and outline dimensions, wrinldedness, and Hurst coefficient. RESULTS： We found a high degree of inter-sample variability in the measurements of the surface [coefficient of variation （CV） = 43% ± 13%] and wrinkledness （CV = 28% ± 9%） of fibrosis, but the inter-sample variability of Hurst＇s exponent was low （CV = 14% ± 2%）. CONCLUSION： This study suggests that Hurst＇s exponent might be used in clinical practice as the best histological estimate of fibrosis in the whole organ, and evidences the fact that biopsy sections, which are fundamental for the qualitative diagnosis of chronic hepatitis, play a key role in the quantitative estimate of architectural changes in liver tissue.

Response of the South China Sea summer monsoon onset to air-sea heat fluxes over the Indian Ocean

We objectively define the onset date of the South China Sea (SCS) summer monsoon, after having evaluated previous studies and considered various factors. Then, interannual and interdecadal characteristics of the SCS summer monsoon onset are analyzed. In addition, we calculate air-sea heat fluxes over the Indian Ocean using the advanced method of CORARE3.0, based on satellite remote sensing data. The onset variation cycle has remarkable interdecadal variability with cycles of 16 a and 28 a. Correlation analysis between air-sea heat fluxes in the Indian Ocean and the SCS summer monsoon indicates that there is a remarkable lag correlation between them. This result has important implications for prediction of the SCS summer monsoon, and provides a scientific basis for further study of the onset process of this monsoon and its prediction. Based on these results, a linear regression equation is obtained to predict the onset date of the monsoon in 2011 and 2012. The forecast is that the onset date of 2011 will be normal or 1 pentad earlier than the normal year, while the onset date in 2012 will be 1-2 pentads later.

Involvement of interleukin-15 and interleukin-21, two γ-chain-related cytokines, in celiac disease

Celiac disease (CD), an enteropathy caused by dietary gluten in genetically susceptible individuals, is histologically characterized by villous atrophy, crypt cell hyperplasia, and increased number of intra-epithelial lymphocytes. The nature of CD pathogenesis remains unclear, but recent evidence indicates that both innate and adaptive immune responses are necessary for the phenotypic expression and pathologic changes characteristic of CD. Extensive studies of molecules produced by immune cells in the gut of CD patients have led to identification of two cytokines, namely interleukin (IL)-15 and IL-21, which are thought to play a major role in orchestrating the mucosal inflammatory response in CD. Here we review the current knowledge of the expression and function of IL-15 and IL-21 in CD.

Protective Effect of Emodin against Lipopolysaccharides-induced Corneal Injury in Rats

Objective To investigate the effect of emodin on lipopolysaccharides （LPS）-induced corneal injury in rats. Methods Three parallel incisions on the central surface of corneal epithelium were made and LPS was applied on them to induce corneal injury in Wistar rats. All rats were randomly divided into emodin group （n=40） and keratitis group （n=40）. Rats in the emodin group received subconjunctival injection of emodin and rats in the keratitis group received its vehicle 30 minutes before LPS exposure. At different time points-1 3, 6, 12, and 24 hours after LPS exposure, the symptoms of all rats were observed and the severity of their ocular inflammation was examined with a slit lamp microscope, then 8 rats in each group were killed through cervical dislocation and their eyes were enucleated and prepared to observe pathological changes of corneal tissue under a light microscope. The activation of nuclear factor-loB （NF-κB） under different condi- tions was determined by Western blot. Immunocytochemistry staining with an antibody against intercellular adhesion molecule-1 （ICAM-1） was performed to identify positive cells in corneal tissues. Results The model of acute keratitis was successfully established in Wistar rats. LPS could induce a typical corneal inflammatory response, such as hyperemia, corneal edema and opacity, which were observed in model rats. Compared with keratitis group, both ocular behaviors and damages of the corneal structure were improved in emodin group. Furthermore, the activation of NF-κB and the expression of ICAM-1 induced by LPS were markedly inhibited in emodin group. Conclusion Emodin can inhibit the activation of NF-κB and the expression of ICAM-I induced by LPS in corneas, protect against acute corneal injury, and improve symptoms in rats.

Comparison of the Immunogenicities of HIV-1 Mutants Based on Structural Modification of env

Eleven env mutants were designed and generated by site-directed mutagenesis of the regions around NAb epitopes and deletions of variable regions in env. The immunogenicities of the generated mutants were evaluated using single-cycle infection neutralization assays with two pseudoviruses and IFN-γ ELISPOT. Overall, five mutants (dWt, M2, M5-2, M5-1 and dM7) induced higher neutralization activities for both pseudoviruses than plasmid Wt, while only two of the mutants (dWt and M5-2) showed significant differences (P<0.05). Two mutants (M2 and dM2) induced more Env-specific T cells than plasmid Wt. Statistically however, significance was only reached for mutant M2. Thus, properly modified HIV-1 Env may have the potential to induce potent cellular and humoral immune responses.

Protective effects of 2,4-dihydroxybenzophenone against acetaminophen-induced hepatotoxicity in mice

AIM:To examine the effects of 2,4-dihydroxybenzophenone(BP-1),a benzophenone derivative used as an ultraviolet light absorbent,on acetaminophen(APAP)induced hepatotoxicity in C57BL/6J mice.METHODS:Mice were administered orally with BP-1 at doses of 200,400 and 800 mg/kg body weight respectively every morning for 4 d before a hepatotoxic dose of APAP(350 mg/kg body weight) was given subcutaneously.Twenty four hours after APAP intoxication,the serum enzyme including serum alaine aminotransferase(ALT),aspartate aminotransferase(AST),lactate dehydrogenase(LDH) were measured and liver histopathologic changes were examined.RESULTS:BP-1 administration dramatically reduced serum ALT,AST and LDH levels.Liver histopathological examination showed that BP-1 administration antagonized APAP-induced liver pathological damage in a dose-dependent manner.Further tests showed that APAP-induced hepatic lipid peroxidation was reduced significantly by BP-1 pretreatment,and glutathione depletion was ameliorated obviously.CONCLUSION:BP-1 can effectively protect C57BL/6J mice from APAP-induced hepatotoxicity,and reduction of oxidative stress might be part of the protection mechanism.

Transradial versus transfemoral rotablation for heavily calcified coronary lesions in contemporary drug-eluting stent era

Background Although radial access for drug-eluting stent （DES） combined with rotational atherectomy （RA） in patients with calcified coronary lesions may be associated with a lower risk of major bleeding complications and obtain favorable clinical results compared with femoral access, the long-term outcome data of this approach were limited in contemporary DES era. Methods ＆ Results This retrospective study sought to compare in-hospital and long-term outcomes for patients undergoing RA via the transradial （TR） and transfemoral （TF） route in 126 consecutive patients （59 radial, 67 femoral） from 2009 to 2014. TR RA procedures were performed in 44/62 （71%） by the three TR operators, compared with 15/64 （23%） by the four TF operators in the present study. Significantly smaller diameter guide catheters and burrs （1.39 ± 0.16 mm vs. 1.53 ± 0.24 mm, P = 0.001） were used in the TR group. Procedural success rates were similar in both TR and TF groups. There was a significantly less major access site bleeding complications in favor of radial artery access （2% vs. 16%, P = 0.012）. The incidence of in-hospital death or myocardial infarction was low in both groups. Although a trend of lower adverse event rate was demonstrated in the TR group compared with the TF one, no statistical significance （21% vs. 27%, P = 0.135） was detected. Conclusions Radial access, a useful alternative to femoral access for RA and DES, can be safely and successfully performed on up to 71% of the patients with heavily calcified coronary lesions needing RA by experienced TR operators.

Epigenetic changes in virus-associated human cancers

Epigenetics of human cancer becomes an area of emerging research direction due to a growing understanding ofspecific epigenetic pathways and rapid development of detection technologies. Aberrant promoter hypermethylation is aprevalent phenonmena in human cancers. Tumor suppressor genes are often hypermethylated due to the increasedactivity or deregulation of DNMTs. Increasing evidence also reveals that viral genes are one of the key players inregulating DNA methylation. In this review, we will focus on hypermethylation and tumor suppressor gene silencing andthe signal pathways that are involved, particularly in cancers closely associated with the hepatitis B virus, simian virus40 (SV40), and Epstein-Barr virus. In addition, we will discuss current technologies for genome-wide detection ofepigenetically regulated targets, which allow for systematic DNA hypermethylation analysis. The study of epigeneticchanges should provide a global view of gene profile in cancer, and epigenetic markers could be used for early detection,prognosis, and therapy of cancer.

VEGFmRNA and eNOSmRNA expression in immature rabbits with bleomycin-induced pulmonary hypertension

Objective: To investigate the evolution of pulmonary hypertension, the pathological changes of pulmonary arteries, and the expression of VEGFmRNA and eNOSmRNA of pulmonary arterial endothelial cells in immature rabbits treated with intratracheal bleomycin (BLM). Methods: Immature rabbits were divided into control and BLM group. Two and four weeks after intratracheal normal saline or BLM injection, the systolic, diastolic and mean pulmonary artery pressure (PASP, PADP, MPAP) were measured by micro-catheter; the pathological changes and the expression of VEGFmRNA and eNOSmRNA of endothelial cells in pulmonary arteries were evaluated by HE and in situ hybridization.Results: Two and four weeks after intratracheal injection of BLM, the PASP, PADP and MPAP increased 53%, 49%, 52%in 2 weeks, and 43%, 89%, 56% in 4 weeks; the wall thickness increased and the cavity in middle and small pulmonary arteries became narrow; the Thickness Index (TI) and Area Index (AI) increased 25%, 14% in 2 weeks, and 22%, 24% in 4 weeks; the level of VEGFmRNA and eNOSmRNA expression decreased 46%, 43% in 2 weeks, and 43%, 51% in 4 weeks.There was no significant difference between 2 weeks and 4 weeks BLM groups. Conclusion: The pulmonary artery pressure was elevated, the thickness of wall increased and the cavity became narrow in middle and small pulmonary arteries, and the level of VEGFmRNA and eNOSmRNA expression in pulmonary arterial endothelial cells decreased in immature rabbits after 2 weeks and 4 weeks of intratracheal 4 U/kg BLM injection.

Dietary advanced glycation end-products aggravate non-alcoholic fatty liver disease

AIM To determine if manipulation of dietary advanced glycation end product(AGE), intake affects nonalcoholic fatty liver disease(NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol(HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mR NA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content(a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, α-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/-animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD.

Is iron overload in alcohol-related cirrhosis mediated by hepcidin?

In this case report we describe the relationship between ferritin levels and hepcidin in a patient with alcohol-related spur cell anemia who underwent liver transplantation.We demonstrate a reciprocal relation-ship between serum or urinary hepcidin and serum ferritin,which indicates that inadequate hepcidin production by the diseased liver is associated with elevated serum ferritin.The ferritin level falls with increasing hepcidin production after transplantation.Neither inflammatory indices(IL6)nor erythropoietin appear to be related to hepcidin expression in this case.We suggest that inappropriately low hepcidin production by the cirrhotic liver may contribute substantially to elevated tissue iron stores in cirrhosis and speculate that hepcidin replacement in these patients may be of therapeutic benefi t in the future.

Schwannoma of the sino-nasal tract:a rare clinico-pathological entity revisited

Schwannomas are benign neoplasms arising from Schwann cells of the peripheral,cranial and autonomic nerves.We report a case of schwannoma in the sino-nasal tract,a very rare site of tumour origin with unusual pseudoangiomatous histopathological changes,which we came across in a 22 years male with progressive nasal obstruction.

NITRIC OXIDE AND VEGF EXPRESSION IN ISCHEMIC-HYPOXIC RETINOPATHY

Objective To evaluate nitric oxide(NO)and vascular endothelial growth factor(VEGF)in vitreous humor and blood samples in patients with proliferative diabetic retinopathy(PDR)and in patients with branch retinal vein occlusion(BRVO).Methods NO concentrations were determined by using the Greiss reaction in plasma and vitreous humor samples.VEGF levels were assayed by ELISA.The patients in the studies were divided into four groups:16 patients with PDR,5 patients with BRVO,11 patients with rhegmatogenous retinal detachment(RRD),and 10 patients with idiopathic macular hole(IMH).Results The vitreous fluid levels of NO were significantly higher in patients with PDR(15.2μmol/L,4.6-50.9μmol/L)than those in the other three groups(F=5.13,P=0.005).The concentrations of VEGF were significantly higher in patients with PDR and BRVO(1507.2 μg/mL,50.71-3722.0μg/ml;838.8μg/mL,159.6-3328.0μg/mL)than those in the other two groups(F=6.84,P=0.0008),but highest in PDR(T=3.92,P=0.001).There was no significant difference between NO and VEGF in serum in four groups.There was no correlation between concentrations of NO and VEGF in four groups whatever in vitreous or plasma(all P>0.05).Conclusion The results suggest that higher levels of NO and VEGF may be related to the angiogenesis in DR.

Therapeutic Effect of Zygophyllum cornutum on Metabolic Disturbances, Oxidative Stress in Heart Tissue and Histological Changes in Myocardium of Streptozotocin-induced Diabetic Rats

The present study depicts the therapeutic effect of Zygophyllum cornutum methanolic extract （ZCME） on metabolic disturbances, oxidative stress in heart and myocardium histological changes in streptozotocin （STZ）-induced diabetic rats. Three days after diabetes induction, ZCME was administered orally for six weeks （700 mg/kg bw/day）. Serum glucose and lipid profile were evaluated. Reduced glutathione （GSH）, catalase （CAT） and thiobarbituric acid reactive substances （TBARS） were measured in heart tissue. The results showed increased levels of blood glucose, total cholesterol （TC）, LDL cholesterol （LDL-C） and triglyceride （TG） in the diabetic rats. On the other hand, the level of HDL cholesterol （HDL-C） decreased. Compared to the control normal rats, the level of TBARS in heart tissue was markedly increased while GSH and CAT were significantly modified in the diabetic rats. Oral administration of ZCME has normalized serum glucose and lipid profile. TBARS were significantly reduced in heart while CAT and GSH were markedly normalized. Myocardium sections showed the absence of histological changes observed in the diabetic rats. The study suggests that Zygophyllum cornutum may provide a useful therapeutic option in the reversal of metabolic disturbances and oxidative stress-induced cardiac dysfunction in diabetes mellitus.

Benefit of everolimus as a monotherapy for a refractory breast cancer patient bearing multiple genetic mutations in the PI3K/AKT/mTOR signaling pathway

A postmenopausal patient with a diagnosis of estrogen receptor(ER)(+), progesterone receptor(PR)(+), and human epidermal growth factor receptor-2(HER2)(-) breast cancer was reported. The patient refused surgery and was resistant to conventional chemotherapy regimens. Computed tomography and the circulating tumor cell test indicated that the patient's tumor burden increased rapidly even after several chemotherapy sessions. Multiple genetic aberrances in the phosphatidylinositol3-kinases(PI3 K) signaling pathway were detected via next-generation sequencing(NGS)-based liquid biopsy, including a p. G1007 R missense mutation in exon 21 of PIK3 CA(33.61%), a p.L70 fs frameshift mutation in exon 3 of phosphatase and tension homolog deleted on chromosome ten(PTEN)(49.14%), and a p. D1542 Y missense mutation in exon 32 of mammalian target of rapamycin(m TOR)(1.66%). Therefore, only the m TOR inhibitor everolimus was administered to the patient. Partial remission(PR) was observed after 2 months, and sustained stable disease(SD) was observed after a year and a half. Subsequent sequencing showed that the mutation ratio of PIK3 CA decreased to 4.17%, and that the PTEN and m TOR mutations disappeared, which revealed the significant curative effect of everolimus. We report the first case of successful monotherapy treatment using everolimus in a patient with advanced breast cancer bearing mutations in genes involved in the PI3 K/ARK/m TOR signaling pathway. The success of this case highlights the invaluable clinical contribution of NGS-based liquid biopsy, as it successfully provided an optimal therapeutic target for the patient with advanced breast cancer.