To determine the prevalence of feeding intolerance and identify associated risk factors among older patients receiving nasogastric tube feeding. We conducted a comprehensive literature search in PubMed, Embase, Cochrane, and Web of Science databases from inception to October 23, 2023. Clinical studies involving participants aged ≥ 60 years who received nasogastric tube feeding and reported the prevalence or incidence of feeding intolerance were included. Of 2187 records identified, four trials including 317 older adults were eligible for inclusion. The pooled proportion of diarrhea was 24

Immune dysregulation is involved in Parkinson's disease (PD), but the roles of C-X-C motif chemokine receptor 3 (CXCR3)/chemokine receptor 6 (CXCR6) on T cells and their correlation with peripheral inflammation remain unclear. This study investigated their expression on peripheral blood T cells and correlation with inflammation in PD. A total of 36 PD patients and 26 healthy controls were enrolled; their clinical information and laboratory test results (including the systemic immunoinflammatory index [SII], neutrophil-to-lymphocyte ratio [NLR], monocyte-to-lymphocyte ratio [MLR], platelet-to-lymphocyte ratio [PLR], monocyte-to-high-density lipoprotein ratio [MHR], and erythrocyte distribution width over platelets ratio [RPR]) were recorded. Meanwhile, a multicolour flow cytometry protocol using six cell surface antibodies (CD3, CD4, CD8, CD45RO, CXCR3, and CXCR6) was applied. The results showed that CD8+ T cells were significantly reduced in the PD group compared with healthy controls (p < 0.001), and CXCR3 expression was significantly increased on peripheral blood CD4+ effector T cells and CD8+ T cells of PD patients (p < 0.001). Additionally, CXCR6 expression was significantly elevated on cytotoxic T lymphocytes (CTLs) (p < 0.0001) but showed no significant difference on CD4+ T cells between PD patients and controls (p > 0.05). Compared with healthy controls, PD patients had significantly increased peripheral blood C-reactive protein (CRP) levels (p < 0.001) but remarkably decreased monocytes, lymphocytes, and MHR (p < 0.01). Collectively, the upregulated expression of CXCR3 and CXCR6 predominantly on CD8+ T lymphocytes may contribute to PD pathogenesis, though no significant correlation between the expression of these receptors and peripheral inflammation was observed.

IntroductionFatty acid synthase (FASN) is a key regulator of lipid metabolism, but its role in colorectal cancer (CRC) stemness and ferroptosis remains unclear.MethodsFASN expression in CRC was analyzed using TCGA data and validated in CRC cell lines (CACO-2, HCT116, SW480) and normal HIEC-6 cells via qRT-PCR and Western blot. HCT116 cells (highest FASN expression) were used for experiments. FASN silencing (shRNA) effects on CSCs were assessed via 3D spheroid formation and CD133+CD44+ flow cytometry. In vivo tumor growth was tested in BALB/c nude mice. Mechanistic assays included cholesterol detection, SREBP2 Western blot, fatostatin rescue experiments, ferroptosis markers (ferrous ions, ROS, MDA, 4-HNE, mitochondrial function), and FASN-SREBP2 co-immunoprecipitation.ResultsFASN was overexpressed in CRC tissues (TCGA) and cell lines, with highest levels in HCT116. It was upregulated in 3D spheroids and CD133+CD44+ CSCs. FASN silencing reduced spheroid formation, in vivo tumor growth, and CD133+CD44+ cells. Mechanistically, FASN knockdown decreased cholesterol, activated SREBP2, and induced ferroptosis (elevated ferrous ions, ROS, lipid peroxidation, mitochondrial dysfunction); these effects were reversed by fatostatin. Co-IP confirmed FASN-SREBP2 interaction.DiscussionFASN promotes CRC progression by enhancing CSC stemness and suppressing ferroptosis through SREBP2 inhibition, highlighting its potential as a therapeutic target.

Type 2 diabetes (T2D) is a metabolic disease, in which inflammation is a key factor. It has been well established that T cells play important role in antigen-driven immune disorders or immune defense, but were less discussed in inflammatory metabolic diseases. However, accumulating evidences suggest that CD186 (also known as CXCR6)-positive tissue infiltrating T cells might play a key role in inflammatory metabolic diseases. Here, as a preliminary and exploratory study, we detected the expression levels of CXCR6 on peripheral blood T-lymphocytes of human subjects of T2D. Additionally, the expression levels of CXCR6 in BSK-db/db mice, a murine T2D model, were also detected. Results showed that, compared with the healthy control group, T2D group had significantly reduced levels of CD4+CD45RO-CD186+CD183- T lymphocytes (Z = -3.988, P < 0.001) and CD8+CD45RO+CD186+CD183- T lymphocytes (Z = -2.428, P = 0.035). CD4+CD45RO-CD186+CD183- T lymphocytes had an AUC area of 0.978 (0.93, 1.00), 88.9 % sensitivity, and 100.0 % specificity. Additionally, the sensitivity of CD8+CD45RO+CD186+CD183- was 55.6 %, and the specificity was 100.0 %, with an AUC area of 0.747 (0.522, 0.972). The levels of CD8+CD186+ (t = -3.198, P = 0.015), CD8+CD44+CD186+ (t = -2.706, P = 0.030), and CD8+CD44-CD186+ (t = -2.915, P = 0.022) in BSK-db/db mice were significantly lower than in BSK-db/db homologous control mice. Taken together, CXCR6+T cells might play a role in T2D, and has the potential to become a biomarker for T2D patients.

As the immune response product to food antigens, food-specific serum immunoglobulin G reactivity (FSsIgGR) has been reported the clinical relevance to metabolic disorders, but its connections to metabolic dysfunction-associated fatty liver disease (MAFLD) remain underexplored, particularly within Chinese populations. Understanding this association could facilitate personal diet modification for MAFLD treatment. We investigated the association between FSsIgGR and MAFLD and the mediating roles of plasma glucose markers, specifically fasting blood glucose (FPG) and hemoglobin A1c (HbA1c). This study utilized data from the Second Medical Center of the Chinese PLA General Hospital from 2017 to 2021, to analyze the relationships between FSsIgGR and MAFLD in 25,928 participants. Using a robust sampling method and adjusting for various covariates, we explored both linear and nonlinear associations using linear regression models, restricted cubic splines (RCS), subgroup analysis, and sensitivity analysis. Furthermore, mediation analyses were conducted to evaluate the role of plasma glucose markers, such as FPG and HbA1c, in these relationships. The overall prevalence of FSsIgGR-positive and MAFLD was 60.8

Gastric cancer (GC) is one of the leading causes of cancer-related mortality worldwide. Despite significant efforts and recent advances in GC treatment, therapeutic efficacy remains suboptimal. In recent years, emerging nanomaterials have demonstrated considerable potential for cancer therapy, primarily due to their ability to function as drug carriers that enable targeted and precise delivery of therapeutic agents to tumour tissues. This not only increases therapeutic efficacy but also reduces side effects. Herein, we present a comprehensive review of the major types of nanoformulations, including liposomes, albumin-based nanoparticles (NPs), polymer-based NPs, inorganic NPs, and cell-derived nanomaterials. We also examine recently reported nanoformulations for various GC treatment strategies, such as chemotherapy, radiotherapy, immunotherapy, gene therapy, phototherapy, and combined therapy. We highlight the design concepts and principles underlying these nanoformulations employed in GC treatment. Additionally, we discuss the challenges associated with nanoformulation-based treatments for GC as well as future prospects in this rapidly evolving field.

Background:There is a notable difference in prognosis between single and multiple metastases from hepatocellular carcinoma (HCC). We aimed to identify the prognostic differences among HCC patients with single metastasis to different sites. Methods:The study focused on patients with single metastasis to different organs from HCC from the Surveillance, Epidemiology, and End Results database between 2010 and 2015. We used the Kaplan-Meier method to determine overall survival (OS) and disease-specific survival (DSS). Univariate and multivariate Cox regression analysis, as well as floating absolute risk (FAR), were introduced to compare prognostic differences among the single metastasis. We applied the conditional survival (CS) to calculate the time-varying survival probability. Results:The study included 2,197 individuals. In multivariate Cox analysis, single lung metastasis [hazard ratio (HR) =1.293, 95% confidence interval (CI): 1.053-1.587, P=0.01] was linked to worse OS than single intrahepatic metastasis, while single lung metastasis (HR =1.395, 95% CI: 1.103-1.764, P=0.005) and single bone metastasis (HR =1.306, 95% CI: 1.021-1.67, P=0.03) possessed shorter DSS than single liver metastasis. FAR revealed that OS and DSS for single pulmonary metastasis were inferior to those of bone metastasis. In the subgroup analysis, chemotherapy played an interactive role in the comparison of DSS in single bone metastasis vs. liver metastasis group, as well as single lung metastasis vs. liver metastasis group, suggesting that chemotherapy may improve the survival. CS analyses showed a marked improvement in patients with single metastasis over time. Conclusions:The prognosis of single pulmonary metastasis was worse than that of single bone metastasis and single intrahepatic metastasis. The prognosis of single brain metastasis could not be determined temporarily due to data limitations.

Alteration of the gut microbiota (GM) is associated with various diseases, including colorectal cancer (CRC). With the development of next-generation sequencing techniques, metagenomic sequencing, along with metabolic function and antibiotic-resistant gene analyses, has been used to investigate differences in GM between CRC patients and healthy controls. Fecal samples were obtained from seven CRC patients and six healthy subjects, and the sequencing data were analyzed for similarity, a-diversity, principal component analysis (PCA), and linear discriminant analyses (LDA). Regarding Actinobacteria, 3 orders, 5 families, 9 genera, and 19 species were identified with no differences between the CRC and control groups, while the levels of Bifidobacterium bifidum and Bifidobacterium dentium were higher, and the level of Bifidobacterium breve was lower in the CRC group compared to the healthy controls (p = 0.053). Otherwise, 2 genera (Leuco-nostoc and Salmonella) and 7 species of bacteria (Parabacteroides merdae, Alistipes shahii, Alistipes finegoldii, Clostridium nexile, Salmonella enterica, unclassified Salmonella, Enterobacter cloacae) were found to be significantly differently distributed between CRC patients and healthy controls. PCA-LDA successfully classified these 2 groups with satisfactory accuracy (84.52% for metabolic function and 77.38% for resistant genes). These findings underscore the potential of GM as a diagnostic tool for CRC, offering a promising avenue for non-invasive screening and risk assessment. The identification of specific microbial signatures, particularly those linked to metabolic functions and resistance traits, could open new doors for understanding the role of the microbiome in CRC progression and treatment resistance.

Both Multiple system atrophy (MSA) and Parkinson's disease (PD) are neurodegenerative diseases in which the function or structure of the central nervous system is progressively impaired. Recent studies have shown that neuroinflammation is another important pathological mechanism driving the occurrence and development of neurodegenerative diseases. CXCL16-CXCR6 chemotaxis axis is an important mechanism that mediates T cells to break through the blood-brain barrier and to trigger the neuroinflammation. Currently, the correlation between CXCR6-positive T cells and the occurrence and development of MSA and PD diseases is still elusive. In this study, peripheral blood of PD patients with MSA and healthy control group were collected, and flow cytometry was performed to analyze the correlation between CXCR6-positive T cells and MSA, PD and healthy people. The results showed that there were significant differences in the proportion of CXCR6+ CD4 and CXCR6+ CD8 T cell subsets between MSA patients and healthy controls and between PD patients and healthy controls, suggesting that CXCR6-positive T cells may be potential biomarkers of MSA and PD.

高龄老年人由于共病多,胆管炎的治疗选择趋向于微创化,但是临床疗效不是很理想. 本文报道 8 例高龄老年人复发性胆管炎的治疗和随访病例,为高龄老年人复发性胆管炎的治疗策略选择提供参考.

Objective:To analyze the incidence, occurrence time and risk factors of cholestasis in the elderly patients after long-term jejunal feeding, and to construct a risk prediction model for cholestasis in the elderly patients after long-term jejunal feeding.Methods:Clinical data of 84 the elderly patients over 65 years of age who were hospitalized in the Second Medical Center of PLA General Hospital from July 2019 to July 2022 and underwent jejunal nutrition tube insertion more than 2 weeks after surgery were retrospectively collected. The patients were divided into two groups according to whether cholestasis occurred. The incidence of cholestasis was analyzed. In addition, univariate and multivariate analysis of related risk factors was carried out to construct the corresponding risk prediction model, and the prediction performance and clinical applicability of the model were further evaluated.Results:A total of 84 patients were included in the study, of which 38 patients developed cholestasis, with an incidence rate of 45.2%. The median time of tube feeding was 556.5 days. Multivariate analysis showed that: Uric acid, endotracheal intubation, history of heart failure, history of Alzheimer′s disease and history of diabetes were independent risk factors for cholestasis in the elderly patients after long-term feeding in jejunal tubes. The concordance index of COX risk prediction model established based on the above risk factors was 0.78. The Calibration curve and decision curve analysis showed that the model had good predictive performance and clinical applicability.Conclusion:The elderly patients are prone to cholestasis after jejunal tube feeding for a long time. Uric acid, tracheal intubation, history of heart failure, history of Alzheimer′s disease and history of diabetes are independent risk factors for cholestasis after jejunal tube feeding for a long time.

The C-X-C motif ligand 16, or CXCL16, is a chemokine that belongs to the ELR - CXC subfamily. Its function is to bind to the chemokine receptor CXCR6, which is a G protein-coupled receptor with 7 transmembrane domains. The CXCR6/CXCL16 axis has been linked to the development of numerous autoimmune diseases and is connected to clinical parameters that reflect disease severity, activity, and prognosis in conditions such as multiple sclerosis, autoimmune hepatitis, rheumatoid arthritis, Crohn's disease, and psoriasis. CXCL16 is expressed in various immune cells, such as dendritic cells, monocytes, macrophages, and B cells. During autoimmune diseases, CXCL16 can facilitate the adhesion of immune cells like monocytes, T cells, NKT cells, and others to endothelial cells and dendritic cells. Additionally, sCXCL16 can regulate the migration of CXCR6-expressing leukocytes, which includes CD8+ T cells, CD4+ T cells, NK cells, constant natural killer T cells, plasma cells, and monocytes. Further investigation is required to comprehend the intricate interactions between chemokines and the pathogenesis of autoimmune diseases. It remains to be seen whether the CXCR6/CXCL16 axis represents a new target for the treatment of these conditions.

Objective:To study the in vitro killing of Helicobacter pylori by a novel Nisin mixture and type A Nisin and to evaluate the bactericidal efficacy of the novel Nisin mixture.Methods:(1)Three strains of Hp standard strain NCTC 11637, clinical strain C27 and clinical strain C28 were selected in the experiment.The same concentration of type A Nisin, new Nisin mixture and blank control group were applied to H. pylori for two hours, and the growth of bacteria in each experimental group and blank control group was recorded after four days of incubation; (2)The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the new nisin mixture against Hp standard strain NCTC 11637 and clinical strains were detected by critical dilution method, and the antibacterial diameter of the new nisin mixture was determined by disk diffusion method; (3)To investigate the effect of hydrochloric acid acidification on the novel Nisin mixture; (4)Antibiotic drug sensitivity testing was carried out by the E-test method.Results:(1)At the same concentration, the novel Nisin mixture group had a bactericidal effect compared with the type A Nisin group; (2)The MIC of novel Nisin mixture varied in different H. pylori strains, with values between 16 IU/ml to 32 IU/ml, and the MBC was the same at 32 IU/ml.the inhibitory diameters of novel Nisin mixture against Hp standard strain NCTC 11637, clinical strain C27 and clinical strain C28 ranged from 3.3 cm to 3.8 cm; (3)Hydrochloric acid acidification did not affect the bactericidal effect of novel Nisin mixture; (4)novel Nisin mixture has synergistic effect with tetracycline to kill HP, but the synergistic effect with metronidazole is not obvious.Conclusion:The novel Nisin mixture has good killing effect on H. pylori under the present experimental conditions and good acid resistance, and it has synergistic effect with tetracycline to kill Hp, which is expected to provide a new way for antibiotic synergistic therapy to eradicate H. pylori infection.

目的 探讨胃黏膜低级别上皮内瘤变(LGIN)的临床病理特征及预后.方法 回顾性分析2012年5月 ～2017年5月解放军总医院第二医学中心53503例胃镜检查结果,发现胃黏膜LGIN患者509例,其中260例进行了平均32个月随访.结果 胃黏膜LGIN总检出率0.95％,其中轻度异型增生0.87％,中度异型增生0.08％;60岁以上老年患者患病率最高,为1.5％;胃窦部多见,占74.1％;伴有慢性炎症者为84.5％,伴有急性炎症者为42.6％;伴有萎缩者为15.3％,伴有肠化者为67.0％,且萎缩、肠化与年龄、部位、镜下形态有关(P<0.05).随访患者轻度异型增生消失率88.8％,癌变率0.4％,并发其他部位恶性肿瘤发生率为0.8％;中度异型增生消失率68.4％,癌变率10.5％.结论 胃黏膜LGIN患病率随着年龄的增加而增加,经过内科治疗大部分LGIN可以消退,少部分患者出现癌变,在进行胃镜随访的同时要警惕别漏诊其他部位恶性肿瘤.

目的 探索聚普瑞锌(Polaprezinc,PZ)对缺血性结肠炎(ischemic colitis,IC)大鼠结肠黏膜损伤的修复作用及可能机制.方法 40只大鼠随机分为3组:实验组(开腹+激光照射+PZ治疗)24只、对照组(开腹+激光照射)12只、空白组4只.光化学法建立IC大鼠模型,实验组造模后每天给予3000 mg/L的PZ溶液3 ml,余自由进食水.对照组造模后与空白组仅自由进食水.术后第5天处死大鼠,肉眼观察结肠黏膜大体表现,显微镜下进行结肠黏膜损伤程度评分,免疫组化方法评估结肠黏膜组织中HSP70和NF-κB p50的表达.结果 实验组大鼠肉眼可见结肠损伤显著低于对照组(16.67％vs 58.33％,P<0.05).实验组结肠黏膜糜烂、炎症及淋巴细胞浸润均较对照组轻,差异有统计学意义(P<0.05).实验组结肠损伤评分(1.125±1.262)分显著低于对照组(2.750±1.138)分(P<0.01).实验组结肠黏膜HSP70表达显著高于对照组(P<0.01),实验组NF-κB p50表达显著低于对照组(P<0.01).结论 PZ能够减轻IC模型大鼠结肠黏膜炎症及糜烂,促进黏膜损伤修复;其机制可能是通过促进HSP70表达,降低NF-κB p50表达进而抑制其活性来实现.

Objective: To analyze the clinical characteristics and explore the risk predictors on mortality in elderly patients with acute cholecystitis and cholangitis. Methods: We conducted a retrospective analysis of elderly patients hospitalized in the Second Medical Center of General Liberation Army Hospital for acute cholecystitis and cholangitis during 2000 to 2018. Clinical data and risk predictors on mortality were assessed. The patients were stratified into three groups based on age:Ⅰ (65-74 years old),Ⅱ (75-84 years old), and Ⅲ (≥85 years old). Logistic regression analysis was used to identify the predictors of mortality. Results: A total of 574 patients were finally enrolled with the mean age 87.6 years including 191 in group Ⅰ, 167 in group Ⅱ, and 216 in group Ⅲ. The main cause of acute cholecystitis and cholangitis was gallstone (76.3%),and the main symptom was abdominal pain (62.9%),followed by chills(62.5%),fever(59.8%),jaundice (47.2%) and septic shock(26.3%). Cholecystitis was the most common diagnosis in groups Ⅰ and Ⅱ,whereas it was cholangitis in group Ⅲ. Percutaneous transhepatic biliary/gallbladder drainage (PTBD/PTGD) and endoscopic retrograde cholangiopancreatography (ERCP) were administrated more frequently in groups Ⅲ. A total of 35 patients (6.1%) died during follow-up. Senior in age (OR=11.1),the Charlson comorbidity index (OR=19.5),cancers (OR=9.6),blood stream infections (OR=7.4),severity of cholecystitis and cholangitis (OR=4.2) were risk factors associated with mortality. Conclusions: Even in the elderly patients with acute cholecystitis and cholangitis,comorbidity is one of the main factors affecting clinical outcomes. Due to the poor performance, this group of population presents more severe disease and undergoes conservative treatment strategies.

Ischemic colitis (IC)is one of the major causes of acute lower gastrointestinal bleeding and usually occurs in the elderly. Hypoperfusion of the mesenteric microvasculature,even induced by constipation in the elderly,is by far the approximate mechanism. The clinical manifestations of IC vary depending on the extent and duration of ischemia. The presenting symptoms include sudden cramping abdominal pain;an urgent desire to defecate;and passage within 24 hours of bright red or maroon blood or bloody diarrhea. CT scan should be the first imaging modality of choice for patients with suspected IC to assess the distribution and phase of colitis. Early colonoscopy (within 48 hours of presentation)should be performed to confirm the diagnosis if without gangrene and perforation. Nonsurgical treatment approach usually includes bowel rest,intravenous fluid,electrolyte repletion,correction of precipitating conditions and antibiotic usage,occasionally with administration of total parenteral nutrition. It has been shown that isolated right colonic ischemia (IRCI)has a worse outcome than ischemia affecting other regions of the colon. Surgical intervention should be considered in the presence of IRCI or pan-colonic ischemia and in the presence of gangrene.

Treatment and management of cancers in elderly patients require some special considerations. A better understanding of how cancers progress in those elderly patients who have not received any anticancer treatments could better help us in treating these patients and in making end-of-life decisions. Over the past years, we had encountered 57 elderly patients, aged 75 to 94 years (87.6 on average), with a cancer in the digestive system, who refused to accept anticancer treatment but who did receive the best available supportive and palliative care. Clinicopathological data of these patients were analyzed. Of these 57 cases, 49 were at an advanced or late stage, while the remaining eight were at an early stage at the time of diagnosis. The median overall survival time of all the patients was 11 months, and almost the entire cohort manifested multiple-organ impairments. The average number of malfunctioning organs per patient was 3.68. After carefully predicting, and then preventing or managing complications, only 54.4% of the patients eventually died of multiple-organ functional failure. Nearly 18% of the single organ dysfunctions were finally well-controlled. Our data provide the first statistical information on the survival time and the direct cause of death of the elderly patients with a cancer in the digestive system not treated with chemotherapy or other direct anticancer interventions, but who did receive the best available supportive and palliative cares. During their struggle with cancer, elderly patients clearly could benefit from prophylactic interventions on organ dysfunction.

众所周知,血淀粉酶和脂肪酶是检测胰腺功能的常用实验室指标,中国急性胰腺炎(AP)诊治指南也指出,符合以下3项特征中的2项,即可诊断为急性胰腺炎:(1)与AP符合的腹痛(急性、突发、持续、剧烈的上腹部疼痛,常向背部放射);(2)血清淀粉酶和(或)脂肪酶活性至少高于正常上限值3倍;(3)增强CT/MRI或腹部超声呈AP影像学改变[1].近年来血液自动生化分析仪的广泛应用,使得血淀粉酶、脂肪酶的检测越来越广泛,临床观察到血淀粉酶、脂肪酶数值升高而无腹部疼痛症状,影像学检查又无胰腺疾病证据的受检者经常能够见到. 在排除实验室检测误差的情况下,血淀粉酶、脂肪酶数值升高如何评价,成为临床医生需要明确的问题.

Smoking is a major risk factor for developing pancreatic adenocarcinoma (PDAC); however, little is known about the mechanisms involved.Here we employed a genetic animal model of early stages of PDAC that overexpresses oncogenic Kras in the pancreas to investigate the mechanisms of smoking-induced promotion of the disease in vivo. We confirmed the regulation of the interactions between the tumor microenvironment cells using in vitro cellular systems.Aerial exposure to cigarette smoke stimulated development of pancreatic intraepithelial neaoplasia (PanIN) lesions associated with a tumor microenvironment-containing features of human PDAC including fibrosis, activated stellate cells, M2-macrophages and markers of epithelial-mesenchymal transition (EMT). The pro-cancer effects of smoking were prevented by Histone Deacetylase HDAC I/II inhibitor Saha.Smoking decreased histone acetylation associated with recruitment of and phenotypic changes in macrophages; which in turn, stimulated survival and induction of EMT of the pre-cancer and cancer cells. The interaction between the cancer cells and macrophages is mediated by IL-6 produced under the regulation of HDAC3 translocation to the nucleus in the cancer cells. Pharmacological and molecular inhibitions of HDAC3 decreased IL-6 levels in cancer cells. IL-6 stimulated the macrophage phenotype change through regulation of the IL-4 receptor level of the macrophage.This study demonstrates a novel pathway of interaction between cancer cells and tumor promoting macrophages involving HDAC3 and IL-6. It further demonstrates that targeting HDAC3 prevents progression of the disease and could provide a strategy for treating the disease considering that the HDAC inhibitor we used is FDA approved for a different disease.