Evaluation of Clinical Outcomes of ses Stent in Patients with Coronary Artery Disease After Intracoronary Stenting in Small Vessels

Background:Limited data are available for sirolimus-eluting stent(SES,Cypher)implantation in patients with coronary artery disease in small vessels.The clinical longtermoutcomes of SES in patients with coronary artery disease after intracoronary stenting in small vessels has not been yet evaluated.

Evaluation of the Sensitivity and Specificity of the New Clinical Diagnostic and Classification Criteria for Kashin-Beck Disease,an Endemic Osteoarthritis,in China

This study aimed to evaluate the sensitivity and specificity of the new clinical diagnostic and classification criteria for Kashin-Beck disease （KBD） using six clinical markers： flexion of the distal part of fingers, deformed fingers, enlarged finger joints, shortened fingers, squat down, and dwarfism. One-third of the total population in Linyou County was sampled by stratified random sampling.

Clinical,serological and genetic predictors of inflammatory bowel disease course

Patients with extensive or complicated Crohn's disease(CD) at diagnosis should be treated straightaway with immunosuppressive therapy according to the most recent guidelines.In patients with localized and uncomplicated CD at diagnosis,early use of immunosuppressive therapy is debated for preventing disease progression and limiting the disabling clinical impact.In this context,there is a need for predictors of benign or unfavourable subsequent clinical course,in order to avoid over-treating with risky drugs those patients who would have experienced spontaneous mid-term asymptomatic disease without progression towards irreversible intestinal lesions.At diagnosis,an age below 40 years,the presence of perianal lesions and the need for treating the first flare with steroids have been consistently associated with an unfavourable subsequent 5-year or 10-year clinical course.The positive predictive value of unfavourable course in patients with 2 or 3 predictors ranges between 0.75 and 0.95 in population-based and referral centre cohorts.Consequently,the use of these predictors can be integrated into the elements that influence individual decisions.In the CD postoperative context,keeping smoking and history of prior resection are the stron-gest predictors of disease symptomatic recurrence.However,these clinical predictors alone are not as reliable as severity of early postoperative endoscopic recurrence in clinical practice.In ulcerative colitis(UC),extensive colitis at diagnosis is associated with unfavourable clinical course in the first 5 to 10 years of the disease,and also with long-term colectomy and colorectal inflammation-associated colorectal cancer.In patients with extensive UC at diagnosis,a rapid step-up strategy aiming to achieve sustained deep remission should therefore be considered.At the moment,no reliable serological or genetic predictor of inflammatory bowel disease clinical course has been identified.

THE ROLE OF PSYCHOSOCIAL STRESSORS,PERSONALITY AND COPING IN THE MULTIFACTORIAL ORIGIN,INITIATION AND CLINICAL COURSE OF NEOPLASTIC DISEASE AND IN HOST-DEFENSE

Summary: Retrospective and prospective bio-behavioral cancer studies have revealed that psycho social stressors may play a pivotal role in the initiation and progression of malignant neoplasia. In recent research, a pattern has emerged, which in analogy to the coronary prone pattern (type A) has been labelled type C, encompassing suppression of emotional responses, such as anger and hostility, rationality and antiemotionality, as well as high social conformity and a lack of self-assertiveness. There is growing evidence in both infrahuman and human research that specific coping styles (repressive coping) with stress may be associated with specific biologic responses, including neuroendocrine, immunologic and other bodily functions. The application of this model appears to be of importance for further research, as well as for the detection of high risk individuals, but also in regard to therapy, rehabilitation, early detection and possibly also prevention of malignant disease. This concept suggests also new directions and modifications of stress research, as stressors are to be viewed not necessarily as pathological, but in some instances as quite possibly salutary, depending on the nature of the stres-sor, the psychophysiologic state of the individual and his or her ability to cope with adverse life situations. Quite naturally, the development of this concept is still in its initial stages, there remain anumber of open questions, and it needs hardly to be pointed out in this connection that further and painstaking clinical and laboratory work is warranted in order to clarify the role of stressors, life and coping styles and its biological concomitants in neo-plastic disease.

Factors contributing to clinical picture and progression of Huntington's disease

Huntington’s disease（HD）is an autosomal dominant,monogenic,progressive,neurodegenerative and rare disease with a frequency of10 per 100,000 in the Caucasian population and occurring more rarely in other races（Squitieri et al.,1994）.HD is,nevertheless,one of the most frequently and extensively studied diseases of those caused by a dynamic mutation.The HD mutation is located on the short arm of the 4th chromosome within the HTT gene.

Clinical Observation on 100 Cases of Postoperative Pain of Anal-Intestinal Diseases Treated with Vitamine K Blocking at Changqiang Point

Since the latter half of 1996, we have used vitamine K blocking at Changqiang (GV 1) for relieving the postoperative pain of anal fissure with satisfactory results. A report follows.……

Clinical analysis of 100 cases of lung transplantation for end-stage palmonary disease

Objective To estimate the indications,operative technique,perioperative treatment,postoperative complications and the outcome of lung transplantation ( LTx) for end - stage pulmonary diseases. Methods The clinical data of 100 patients with end - stage lung diseases receiving LTx in our hospital were retrospectively ana-

Crucial steps in the natural history of inflammatory bowel disease

Inflammatory bowel diseases(IBD),including ulcerative colitis(UC) and Crohn's disease(CD),are chronic,progressive and disabling disorders.Over the last few decades,new therapeutic approaches have been introduced which have led not only to a reduction in the mortality rate but also offered the possibility of a favorable modification in the natural history of IBD.The identification of clinical,genetic and serological prognostic factors has permitted a better stratification of the disease,thus allowing the opportunity to indicate the most appropriate therapy.Early treatment with immunosuppressive drugs and biologics has offered the opportunity to change,at least in the short term,the course of the disease by reducing,in a subset of patients with IBD,hospitalization and the need for surgery.In this review,the crucial steps in the natural history of both UC and CD will be discussed,as well as the factors that may change their clinical course.The methodological requirements for high quality studies on the course and prognosis of IBD,the true impact of environmental and dietary factors on the clinical course of IBD,the clinical,serological and genetic predictors of the IBD course(in particular,which of these are rel-evant and appropriate for use in clinical practice),the impact of the various forms of medical treatment on the IBD complication rate,the role of surgery for IBD in the biologic era,the true magnitude of risk of colorectal cancer associated with IBD,as well as the mortality rate related to IBD will be stressed;all topics that are extensively discussed in separate reviews included in this issue of World Journal of Gastroenterology.

Immune checkpoint inhibitor-associated arthritis in advanced pulmonary adenocarcinoma:A case report

BACKGROUND With the wide application of immune checkpoint inhibitors(ICIs)in cancer treatment,immune-related adverse events occur frequently,involving almost all organs and systems.The incidence of ICI-associated arthritis(IA)is unknown.In most cases,IA is not serious and non-lethal.Higher checkpoint inhibitor arthritis disease activity may be associated with cancer progression.Here,we report a severe case of IA with high arthritis disease activity in advanced pulmonary adenocarcinoma,causing permanent withdrawal of pembrolizumab,but the patient remained in complete remission(CR)20 mo after the development of IA.CASE SUMMARY An 81-year-old smoking man was admitted to our hospital because of left chest pain for 9 mo.He was finally diagnosed with advanced pulmonary adenocarcinoma,with programmed cell death 1 ligand 1 expression of 70%.The patient responded to pembrolizumab treatment and achieved CR,but IA occurred after the 5th cycle of pembrolizumab administration.Although non-steroidal antiinflammatory drugs and disease-modifying anti-rheumatic drugs were prescribed,arthralgia and joint swelling occurred.The symptoms of arthritis were further aggravated when immunotherapy was given again after short-term withdrawal.Clinical Disease Activity Index(CDAI)score,a traditional measure of arthritis activity,was 43.Intravenous methylprednisolone was prescribed at 20 mg/d and then tapered over the subsequent 4 wk.The symptoms of arthritis steadily improved and completely resolved 4 mo after withdrawal of pembrolizumab.A recent follow-up in June 2022 revealed satisfactory clinical recovery of arthritis and the patient remained in CR.CONCLUSION This case report highlights that early recognition of IA and appropriate treatment are critical to improving the outcome of both ICI-arthritis and lung cancer.

Regulatory mechanisms,prophylaxis and treatment of vascular leakage following severe trauma and shock

Vascular leakage, or increased vascular permeability, is a common but important pathological process for various critical diseases, including severe trauma, shock, sepsis, and multiple organ dysfunction syndrome(MODS), and has become one of the most important causes of death for intensive care units(ICU) patients. Currently, although there has been some progress in knowledge of the pathogenesis of these vascular disorders, the detailed mechanisms remain unclear, and effective prophylaxis and treatment are still lacking. In this study, we aimed to provide a review of the literature regarding the regulatory mechanisms and prophylaxis as well as the treatment of vascular leakage in critical diseases such as severe trauma and shock, which could be beneficial for the overall clinical treatment of vascular leakage disorders.

Distribution,function and physiological role of melatonin in the lower gut

Melatonin is a hormone with endocrine, paracrine andautocrine actions. It is involved in the regulation of multiple functions, including the control of the gastroin-testinal (GI) system under physiological and pathophys-iological conditions. Since the gut contains at least 400times more melatonin than the pineal gland, a reviewof the functional importance of melatonin in the gutseems useful, especially in the context of recent clinicaltrials. Melatonin exerts its physiological effects throughspecific membrane receptors, named melatonin-1 re-ceptor (MT1), MT2 and MT3. These receptors can befound in the gut and their involvement in the regulationof GI motility, inflammation and pain has been reportedin numerous basic and clinical studies. Stable levels ofmelatonin in the lower gut that are unchanged follow-ing a pinealectomy suggest local synthesis and, further more, implicate physiological importance of endogenous melatonin in the GI tract. Presently, only a small number of human studies report possible beneficial and also possible harmful effects of melatonin in case reports and clinical trials. These human studies include patients with lower GI diseases, especially patients with irritable bowel syndrome, inflammatory bowel disease and colorectal cancer. In this review, we summarize the presently available information on melatonin effects in the lower gut and discuss available in vitro and in vivo data. We furthermore aim to evaluate whether melatonin may be useful in future treatment of symptoms or diseases involving the lower gut.

Retinal tissue hypoperfusion in patients with clinical Alzheimer’s disease

Background:It remains unknow whether retinal tissue perfusion occurs in patients with Alzheimer’s disease.The goal was to determine retinal tissue perfusion in patients with clinical Alzheimer’s disease(CAD).Methods:Twenty-four CAD patients and 19 cognitively normal(CN)age-matched controls were recruited.A retinal function imager(RFI,Optical Imaging Ltd.,Rehovot,Israel)was used to measure the retinal blood flow supplying the macular area of a diameter of 2.5 mm centered on the fovea.Blood flow volumes of arterioles(entering the macular region)and venules(exiting the macular region)of the supplied area were calculated.Macular blood flow was calculated as the average of arteriolar and venular flow volumes.Custom ultra-high-resolution optical coherence tomography(UHR–OCT)was used to calculate macular tissue volume.Automated segmentation software(Orion,Voxeleron LLC,Pleasanton,CA)was used to segment six intra-retinal layers in the 2.5 mm(diameter)area centered on the fovea.The inner retina(containing vessel network),including retinal nerve fiber layer(RNFL),ganglion cell-inner plexiform layer(GCIPL),inner nuclear layer(INL)and outer plexiform layer(OPL),was segmented and tissue volume was calculated.Perfusion was calculated as the flow divided by the tissue volume.Results:The tissue perfusion in CAD patients was 2.58±0.79 nl/s/mm^(3)(mean±standard deviation)and was significantly lower than in CN subjects(3.62±0.44 nl/s/mm^(3),P<0.01),reflecting a decrease of 29%.The flow volume was 2.82±0.92 nl/s in CAD patients,which was 31%lower than in CN subjects(4.09±0.46 nl/s,P<0.01).GCIPL tissue volume was 0.47±0.04 mm^(3) in CAD patients and 6%lower than CN subjects(0.50±0.05 mm^(3),P<0.05).No other significant alterations were found in the intra-retinal layers between CAD and CN participants.Conclusions:This study is the first to show decreased retinal tissue perfusion that may be indicative of diminished tissue metabolic activity in patients with clinical Alzheimer’s disease.

Efficacy and safety of Amla(Phyllanthus emblica L.) in non-erosive reflux disease:a double-blind,randomized,placebo-controlled clinical trial

Background： Gastroesophageal reflux disease （GERD） is one of the most common gastrointestinal com- plaints. GERD, caused by the reflux of stomach contents into the esophagus, leads to troublesome symptoms such as heartburn and regurgitation. It is classified into two types： erosive esophagitis, characterized by visible esophageal mucosa erosion in endoscopy, and non-erosive reflux disease （NERD）. GERD is a chronic and recurrent disease that impairs the quality of life and imposes socioeco- nomic and therapeutic burdens to both patients and society. Objective： Due to the failure of the conventional treatments for GERD and to the traditional use of Amla （Phyllanthus emblica L.）, in addition to beneficial effects shown in recent studies, we evaluated the safety and efficacy of Amla tablet for improvement of symptoms of patients with NERD. Design, setting, participants and interventions： We designed a double-arm, randomized, double-blind, placebo-controlled clinical trial. Sixty-eight patients who had classic symptoms of GERD （heartburn, regurgitation and epigastralgia） for at least three months before the start of the trial were randomized in two parallel groups. Patients in the Amla group received two 500 mg Amla tablets twice a day, after meals, for 4 weeks. In the control group, patients received placebo tablets similar to the Amla prescription. Main outcome measures： The patients were visited at baseline, and at the end of the 2nd and 4th weeks of intervention; their symptoms were measured on a frequency and severity scale for the symptoms of NERD, according to the quality of life in reflux-associated disease questionnaire. Results： Frequencies of heartburn and regurgitation in both groups of the study were significantly reduced after intervention （P 〈 0.001）. Repeated measures logistic regression analysis showed that, in the Amla group, there was a more significant reduction in regurgitation frequency, heartburn frequency, regurgita- tion severity and heartburn severity during the study period, compared with the placebo group （P 〈 0.001 ）. Conclusion： This randomized double-blind, placebo-controlled clinical trial demonstrated that Amla could reduce frequencies of heartburn and regurgitation and improve heartburn and regurgitation severity in patients with NERD.

The clinical and genetic characteristics in children with mitochondrial disease in China

Mitochondrial disease was a clinically and genetically heterogeneous group of diseases, thus the diagnosis was very difficult to clinicians. Our objective was to analyze clinical and genetic characteristics of children with mitochondrial disease in China. We tested 141 candidate patients who have been suspected of mitochondrial disorders by using targeted next-generation sequencing(NGS), and summarized the clinical and genetic data of gene confirmed cases from Neurology Department, Beijing Children's Hospital, Capital Medical University from October 2012 to January 2015. In our study, 40 cases of gene confirmed mitochondrial disease including eight kinds of mitochondrial disease, among which Leigh syndrome was identified to be the most common type, followed by mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes(MELAS). The age-of-onset varies among mitochondrial disease, but early onset was common. All of 40 cases were gene confirmed, among which 25 cases(62.5%)with mitochondrial DNA(mtDNA) mutation, and 15 cases(37.5%) with nuclear DNA(nDNA) mutation. M.3243A>G(n=7)accounts for a large proportion of mtDNA mutation. The nDNA mutations include SURF1(n=7),PDHA1(n=2),and NDUFV1,NDUFAF6, SUCLA2, SUCLG1, RRM2 B, and C12orf65, respectively.

AN INVESTIGATION OF PEDIGREES OF 110 PATIENTS WITH GRAVES' DISEASE AND THE CLINICAL SIGNIFICANCE OF DETERMINATIONS OF ANTITHYROID ANTIBODIES OF THEIR FIRST-DEGREE RELATIVES

Eight hundred and ten pedigree members of 110 patients with Graves' disease were studied. In 700 first-egree relatives, inquiry of medical history, physical examination (including eyes, thyroid, heart rate, etc), thyroid function tests (serum T3, T4 and TSH levels), determinations of thyroglobulin antibodies (TgAb) and thyroid microsomal antibodies (TmAb) were performed. For male (female) probands, the incidence of Graves' disease in male (female) first-degree relatives were investigated and their serum TgAb and TmAb were analysed. The incidence of these two kinds of autoantibodies in the male (female) first-egree relatives of familial and nonfamilial Graves' disease were analysed. Eighteen persons with positive TgAb and TmAb from 5 pedigrees had been followed up one year after initial determinations. Our results suggest that the positive rates of TgAb and TmAb in the first-egree relatives of Graves' disease were coincident with the incidence of Graves' disease, and the positive results of TgAb and TmAb in the first-egree relatives of Graves' disease may be an indicator of pre-raves' disease or pre-utoimmune thyroid diseases.

An analysis of clinical features of celiac disease patients in different ethnic

Objective To summarize the clinical of different racial patients with celiac disease(CD)and analyze the disease prevalence,diagnosis and treatment in Chinese population.Methods All the patients were diagnosed as CD and enrolled in Beijing United Family Hospital between January 2005 and July 2015.Clinical data including nationality,age,symptoms,endoscopic and patho-

Thiopurine methyltransferase gene polymorphisms and activity in Chinese patients with inflammatory bowel disease treated with azathioprine

Background The thiopurine drugs are well established in the treatment of inflammatory bowel disease （IBD）. However, uncertainty regarding the risk for neutropenia and hepatotoxicity deters its using. Thiopurine methyltransferase （TPMT） is the key enzyme in the metabolism of thiopurine. The aim of this study was to investigate the association of TPMT polymorphisms and activity with azathioprine （AZA）-related adverse events and clinical efficacy in Chinese Han patients with IBD. Methods Fifty-two Han IBD patients treated with AZA were assessed for TPMT＊2, ＊3A, ＊3B, and ＂3C, and for adverse events. Then, using reverse-phase high-performance liquid chromatography, TPMTactivity was measured in 13 patients to analyze its correlation with AZA-related toxicity and clinical efficacy. Results Of the 52 patients, five experienced myelotoxicity and one experienced hepatotoxicity during treatment. No TPMT＊2, ＊3A, ＊3B or ＂3C polymorphisms were detected in any of the 52 patients. In the 13 patients with TPMT activity measurement, TPMT activity ranged from 7.2 to 28.8 U/ml packed red blood cells （pRBCs）. Among the 5 patients who suffered from myelotoxicity, 3 were affected in the early stage of AZA therapy. In these 3 patients, TPMT levels were significantly lower than those in patients without myelotoxicity, which reached statistical significance （（9.3±2.1） U/ml pRBC vs. （18.0±6.2） U/ml pRBC; P=-0.046）. One patient who had higher TPMTactivity （28.8 U/ml pRBC） suffered from hepatotoxicity during AZA therapy. Patients who achieved a clinical response had lower TPMTactivity than those failed to respond （（13.7±3.5） U/ml pRBC vs. （22.0±5.5） U/ml pRBC; P=-0.009）. Conclusions TPMT variants do not completely account for the AZA-related myelotoxicity in Chinese Han IBD patients. However, measurement of TPMT activity may be helpful in reducing the risk of toxicity, and predicting the therapeutic efficacy.

Biomarkers for Parkinson's Disease:Recent Advancement

As a multi-factorial degenerative disease, Parkinson＇s disease （PD） leads to tremor, gait rigidity, and hypokinesia, thus hampering normal living. As this disease is usually detected in the later stages when neurons have degenerated completely, cure is on hold, ultimately leading to death due to the lack of early diagnostic techniques. Thus, biomarkers are required to detect the disease in the early stages when prevention is possible. Various biomarkers providing early diagnosis of the disease include those of imaging, cerebrospinal fluid, oxidative stress, neuroprotection, and inflammation. Also, biomarkers, alone or in combination, are used in the diagnosis and evolution of PD. This review encompasses various biomarkers available for PD and discusses recent advances in their development.

Induced neural stem/precursor cells for fundamental studies and potential application in neurodegenerative diseases

Recent research has shown that defined sets of exogenous factors are sufficient to convert rodent and human somatic cells directly into induced neural stem cells or neural precursor cells（iNSCs/iNPCs）.The process of transdifferentiation bypasses the step of a pluripotent state and reduces the risk of tumorigenesis and genetic instability while retaining the self-renewing capacity.This iNSC/iNPC technology has fueled much excitement in regenerative medicine,as these cells can be differentiated into target cells for replacement therapy for neurodegenerative diseases.Patients＇ somatic cell-derived iNSCs/iNPCs have also been proposed to serve as disease models with potential value in both fundamental studies and clinical applications.This review focuses on the mechanisms,techniques,and applications of iNSCs/iNPCs from a series of related studies,as well as further efforts in designing novel strategies using iNSC/iNPC technology and its potential applications in neurodegenerative diseases.