Comparative analysis of the clinical effect and safety of Laparoscopic Radical Cystectomy + Orthotopic Ileal Neobladder and Open Surgery.

OBJECTIVES: To explore the clinical effect and safety of laparoscopic radical cystectomy + orthotopic ileal neobladder and open surgery. METHODS: The study was conducted at Jingzhou First People's Hospital from January 2017 to July 2018. In this study 87 patients undergoing radical cystectomy + orthotopic ileal neobladder were chosen and classified into an observation group (48 cases) and a control group (39 cases) according to the surgical methods. The observation group underwent laparoscopic surgery, while the control group underwent open surgery. Perioperative period and prognostic conditions were compared in both groups. RESULTS: The intraoperative bleeding amount obviously decreased. The recovery time of gastroenteric function and postoperative hospitalization time were significantly shortened. Postoperative pain was significantly alleviated. Compared with the control group, the observation group showed significant differences (P<0.05). The time, amount and difference in pelvic lymph node dissection in both groups were not significantly different (P>0.05). The differences in both groups in terms of the daytime/nighttime urinary continence rate, maximum urinary flow rate, internal bladder pressure, maximum bladder pressure during urination, internal urethral pressure, bladder capacity, and residual urine volume six months after the operation were not statistically significant (P>0.05). There was no significant difference in postoperative complications, including urinary fistula, bleeding, urinary tract infection, pulmonary infection, dysuria, lymphatic leakage, ureterostenosis, or relapse (P>0.05). The ileus incidence rate in the observation group was obviously lower than that in the control group, and the difference was statistically significant (P<0.05). CONCLUSION: Laparoscopic radical cystectomy + orthotopic ileal neobladder has the characteristics of limited trauma, a minimal amount of bleeding and a fast recovery. The functions of orthotopic neobladders are good, and the occurrence rate of postoperative complications is low. In addition, body immunity is protected. Hence, this procedure deserves to be promoted clinically.

Comparative study on the curative effect of laparoscopic nephron sparing surgery and renal functions under selective segmental renal artery clamping and main renal artery clamping.

OBJECTIVE: To discuss the clinical effect and safety evaluation of laparoscopic nephron sparing surgery (LNSS) under selective segmental renal artery clamping (SSRAC) and main renal artery clamping (MRAC). METHODS: Eighty-four patients with T1 localized renal tumors who were admitted and treated from October 2017 to October 2018 were retrospectively analyzed, and they were classified into the S group (42 patients) and M group (42 patients). The patients in the S group received LNSS under SSRAC, while the patients in the M group received LNSS under MRAC. The duration of the operation, amount of intraoperative blood loss, intraoperative warm ischemia time, duration of postoperative hospital stay and positive rate of incisal edge; the serum creatinine and blood urea nitrogen values before and after the operation; and the occurrence rates of intraoperative and postoperative complications were compared. RESULTS: All operations were completed smoothly. No patients had a positive incisal edge, and no patients were converted to MRAC during the operation. The duration of the operation and the amount of intraoperative blood loss increased in the S group compared with the M group. The differences were statistically significant (P <0.05). The differences in the intraoperative warm ischemia time, postoperative drainage and duration of postoperative hospital stay in both groups had no statistical significance (P >0.05). The differences in serum creatinine (SCr) and blood urea nitrogen (BUN) in both groups before the operation had no statistical significance (P >0.05). The SCr and BUN levels significantly increased 1 d and 1 m after the operation. The SCr and BUN levels 1 d and 1 m after the operation were significantly lower in the S group than in the M group, and the differences were statistically significant (P <0.05). The differences in the occurrence rates of intraoperative and postoperative complications in both groups had no statistical significance (P >0.05). CONCLUSION: SSRAC is a new renal artery clamping technology, and its curative effect on LNSS patients is significant. In addition, SSRAC has high safety and little influence on renal functions.

Endovascular recanalization for symptomatic subacute and chronic intracranial large artery occlusion of the anterior circulation: initial experience and technical considerations.

PURPOSE: This study aimed to report the clinical findings and initial clinical experience of endovascular recanalization for symptomatic subacute/chronic intracranial large artery occlusion (ILAO) of the anterior circulation. METHODS: From October 2015 to December 2017, 13 patients with symptomatic subacute/chronic ILAO of the anterior circulation were enrolled in this study and underwent endovascular recanalization. We collected the initial procedural results, including the rate of successful recanalization and periprocedural complications, and data pertaining to angiographic and clinical follow-up. RESULTS: Recanalization was successful in 11 of 13 patients (84.6%). Intraoperative complications occurred in four cases, including symptomatic distal embolism in three cases; one of which was simultaneously complicated with artery dissection. Intracerebral hemorrhage occurred in one case. Eleven patients underwent angiographic follow-up, and 12 patients underwent clinical follow-up. The results of the angiography follow-up (mean 6 ± 3.29 months) showed that in-stent restenosis occurred in one of the 11 successfully recanalized patients. However, the artery was occluded again in the patient who achieved thrombolysis in cerebral infarction (TICI) grade of 2a after treatment. Clinical follow-up (mean 5.8 ± 2.25 months) showed no recurrence of transient ischemic attack (TIA) or stroke in ten successfully recanalized cases. However, the patient who developed in-stent stenosis suffered TIA. CONCLUSIONS: Endovascular recanalization for symptomatic subacute/chronic ILAO of anterior circulation is feasible, relatively safe, and efficacious in highly selected cases, improving patients' symptoms in the short-term. However, further larger scale pilot studies are needed to determine the efficacy and long-term outcome associated with this treatment.

Visual and Electrochemical Detection of let-7a: A Tumor Suppressor and Biomarker.

Let-7a, a type of low-expressed microRNAs in cancer cells, has been investigated as a promising biomarker and therapeutic target for tumor suppression. Developing simple and sensitive detection methods for let-7a is important for cancer diagnosis and treatment. In this work, the hybridization chain reaction (HCR) was initiated by let-7a via two hairpin primers (H1 and H2). After the HCR, the remaining hairpin H1 was further detected by lateral flow assay (LFA) and electrochemical impedance spectroscopy. For LFA, biotin-modified H1(bio-H1) and free H2 were used for HCR. With the decrease of let-7a concentration, the color of T line gradually increased. As for electrochemical methods, the H1'-AuNP-modified electrode was used for detection of bio-H1 based on the difference of impedance (ΔRct) detected without and with different concentrations of let-7a participating in the HCR. This method could detect let-7a in the range of 10.0 fM and 1.0 nM with detection limits of 4.2 fM.

Case Report: Niraparib-Related Pulmonary Embolism During the Treatment of BRCA Mutant Advanced Ovarian Cancer.

Niraparib, an oral, potent, highly selective poly (ADP-ribose) polymerase (PARP) inhibitor, has promising clinical benefit for maintenance treatment of patients with ovarian cancer in partial response to platinum-based chemotherapy, especially in patients with BRCA mutation. In publicly available niraparib treatment-related adverse events, gastrointestinal disorders and hematological toxicities were most commonly reported with manageable safety profile. Herein, we first describe a severe and never-reported pulmonary embolism (PE) associated with the use of niraparib in a patient with BRCA mutation advanced high-grade serous ovarian cancer and received anticoagulant therapy after PE. There have been no reports of PE caused by the use of niraparib in patients with advanced high-grade serous ovarian cancer; knowledge of the occurrence of PE after the use of niraparib may assist other clinicians in managing this rare but potentially serious toxic effect.

Xpert MTB/RIF Assay for the Diagnosis of Lymph Node Tuberculosis in Children: A Systematic Review and Meta-Analysis.

Background: Lymph node tuberculosis (LNTB) is the leading type of extrapulmonary tuberculosis (EPTB) causing death in children. The Xpert MTB/RIF assay is a novel rapid test for the diagnosis of LNTB. Although previous evidence suggests that Xpert is reliably accurate in diagnosing EPTB in children, information is lacking for the specific type of LNTB in children. The aim of this study was to systematically assess the accuracy and reliability of Xpert for the diagnosis of LNTB in children. Methods: We systematically searched four databases, Embase, Cochrane Library, PubMed, and Web of Science, which extracted relevant data according to predefined inclusion and exclusion criteria. The data were analyzed by meta-Disc 1.4 and Stata 12.0 software to determine sensitivity, specificity, diagnostic odds ratio (DOR), etc. Results: A total of 646 samples from 8 studies were included in the analysis. The pooled sensitivity, specificity, negative likelihood ratio (NLR), positive likelihood ratio (PLR,) and combined diagnostic odds ratio (DOR) of Xpert for all samples were 0.79 (95% CI 0.70, 0.87), 0.90 (95% CI 0.86, 0.92), 0.29 (95% CI 0.19, 0.43), 7.20 (95% CI 3.32, 15.60), and 37.56 (95% CI 13.04, 108.15), respectively. The area under the curve (AUC) of the summary receiver operating characteristic (sROC) curve was 0.9050. Conclusion: Overall, Xpert showed moderate sensitivity and high specificity compared with culture in the diagnosis of LNTB in children. In addition, after analyzing the combined diagnostic odds ratio and positive LR, our study showed that Xpert has excellent diagnostic accuracy.

Genomic and Transcriptomic Characterization of Natural Killer T Cell Lymphoma.

Natural killer/T cell lymphoma (NKTCL) is an aggressive and heterogeneous entity of non-Hodgkin lymphoma, strongly associated with Epstein-Barr virus (EBV) infection. To identify molecular subtypes of NKTCL based on genomic structural alterations and EBV sequences, we performed multi-omics study on 128 biopsy samples of newly diagnosed NKTCL and defined three prominent subtypes, which differ significantly in cell of origin, EBV gene expression, transcriptional signatures, and responses to asparaginase-based regimens and targeted therapy. Our findings thus identify molecular networks of EBV-associated pathogenesis and suggest potential clinical strategies on NKTCL.

Retraction Note: ß2-adrenoreceptor Inverse Agonist Down-regulates Muscarine Cholinergic Subtype-3 Receptor and Its Downstream Signal Pathways in Airway Smooth Muscle Cells in vitro.

This paper has been retracted at the request of the authors.

Combined effects of histone deacetylase inhibitor and rituximab on non-Hodgkin's B-lymphoma cells apoptosis.

OBJECTIVE: The anti-CD20 monoclonal antibody rituximab has shown promising results in the clinical treatment of patients with B-cell non-Hodgkin's lymphoma (B-NHL). However, its therapeutic effect could still be improved. METHODS: This study examined the anti-tumor activity of rituximab combined with histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in CD20-positive B-NHL cell lines, as well as in primary B-NHL cells and a murine B-NHL model. RESULTS: The combination treatment sensitized B-NHL cells to apoptosis in a synergistic manner, concomitant with mitochondrial instability and Bcl-2/Bcl-XL downregulation. Particularly in Daudi cells relatively resistant to rituximab, these events were associated with nuclear factor-kappaB (NF-kappaB) inactivation and c-Myc degradation. SAHA presented functional complementation with rituximab, through decreasing IKKalpha/beta and IkappaBalpha phosphorylation, thus preventing NF-kappaB nuclear translocation. In addition, SAHA induced IkappaBalpha cleavage to a stable inhibitory form and caused NF-kappaB degradation in response to caspase-3 activation. More importantly, rituximab-SAHA combination significantly promoted primary B-NHL cells apoptosis and improved survival time of a severe combined immunodeficient mouse lymphoma model established with intravenous injection of Daudi cells. CONCLUSION: These findings emphasized the value of targeting apoptosis signaling pathway in lymphoma therapy. Rituximab in conjunction with histone deacetylase inhibitor may represent a novel strategy in treating patients with B-NHL.

Overexpression of miR-1290 contributes to cell proliferation and invasion of non small cell lung cancer by targeting interferon regulatory factor 2.

MicroRNAs are small endogenous non-coding RNAs, which can frequently emerge as regulators in many cancer types. MiR-1290 was found to be abnormally elevated in non small cell lung cancer (NSCLC). However, the underlying molecular mechanism still needs to be investigated. Here, we demonstrated that miR-1290 expression levels were remarkably upregulated in NSCLC tissues compared to adjacent normal tissues. Higher miR-1290 expression levels positively associated with lymph node metastasis and advanced tumor stage. Functional assays showed that upregulated miR-1290 expression in NSCLC cells enhanced cell proliferation, cell colony formation and invasion capacities in vitro. Furthermore, we found that miR-1290 promoted cell proliferation related protein CDK2 and CDK4 expression and enhanced Epithelial-Mesenchymal Transition (EMT) process by downregulating E-cadherin expression and upregulating N-cadherin expression. Bioinformatics analysis and luciferase reporter gene assays revealed that Interferon regulatory factor 2 (IRF2) was a direct target of miR-1290. Overexpression of miR-1290 can degrade IRF2 mRNA and downregulated IRF2 protein expression in NSCLC cells. Upregulated IRF2 could partly rescue the promoting effects induced by miR-1290 overexpression on cell proliferation and invasion of NSCLC. Additionally, we confirmed that reduced miR-1290 expression could suppress tumor growth using a tumor xenograft model in vivo. Thus, we concluded that miR-1290 may serve as a potential target of NSCLC treatment.

A population balance model describing the cell cycle dynamics of myeloma cell cultivation.

A multi-staged population balance model is proposed to describe the cell cycle dynamics of myeloma cell cultivation. In this model, the cell cycle is divided into three stages, i.e., G1, S, and G2M phases. Both DNA content and cell volume are used to differentiate each cell from other cells of the population. The probabilities of transition from G1 to S and division of G2M are assumed to be dependent on cell volume, and transition probability from S to G2M is determined by DNA content. The model can be used to simulate the dynamics of DNA content and cell volume distributions, phase fractions, and substrate and byproduct concentrations, as well as cell densities. Measurements from myeloma cell cultivations, especially the FACS data with respect to DNA distribution and cell fractions in different stages, are employed for model validation.

[Expression of tumor suppressor gene PRDM1 in lung cancers].

OBJECTIVE: To determine the expression of tumor suppressor gene PRDM1 in lung cancers. METHODS: Forty-five cases were enrolled in this study, including squamous cell carcinoma (20 cases), adenocarcinoma (15 cases), and small cell cancer (10 cases). PRDM1 protein was detected in paraffin-embedded tissue by immunohistochemistry. Tumor cells in lung cancers were further selected by laser microdissection for RT-PCR analysis. PRDM1 protein in frozen tissue was also detected by Western blot. RESULTS: (1) PRDM1 protein was found in paraffin-embedded tissues in 90.0% (18/20) of squamous cell carcinoma, 13.3% (2/15) of adenocarcinoma, and 0 (0/10) small cell lung cancer. Squamous cell carcinoma predominantly expressed PRDM1 protein ( P < 0.01). (2) Gene product of PRDM1 DNA binding region was not found in microdissected tumor cells, but an abnormal PRDM1 protein about 70 KD was detected simultaneously in whole tumor tissue. CONCLUSION: PRDM1 may be considered as a specific biomarker in pulmonary squamous cell carcinoma. The abnormal PRDM1 expression both at transcriptional and protein levels indicated that this tumor suppressor gene lost its function, which may become a new target in the strategy of treatment for lung cancers.

ß2-adrenoreceptor Inverse Agonist Down-regulates Muscarine Cholinergic Subtype-3 Receptor and Its Downstream Signal Pathways in Airway Smooth Muscle Cells in vitro.

Mechanisms underlying ß2-adrenoreceptor (ß2AR) inverse agonist mediated bronchoprotectiveness remain unknown. We incubated ICI118,551, formoterol, budesonide, and formoterol plus budesonide, as well as ICI118,551 or pindolol plus formoterol, ICI118,551 plus forskolin, SQ22,536 or H89 plus formoterol in ASMCs to detect expressions of M3R, PLCß1 and IP3. The level of M3R in the presence of 10-5 mmol/L ICI118,551 were significantly decreased at 12 h, 24 h and 48 h (P < 0.05), and at 24 h were significantly reduced in ICI118,551 with concentration of 10-5 mmol/L, 10-6 mmol/L, 10-7 mmol/L, and 10-8 mmol/L (P < 0.05). The level of IP3 in 10-5 mmol/L ICI118,551 was significantly diminished at 24 h (P < 0.01), except for that at 1 h, neither was in the level of PLCß1. A concentration of 10-5 mmol/L ICI118,551 at 24 h showed a significant reduction of M3R level compared to formoterol (P < 0.01), budesonide (P < 0.01), and formoterol + budesonide (P < 0.05), but significant reduction of PLCß1 and IP3 was only found between 10-5 mmol/L ICI118,551 and formoterol at 24 h, but not in the comparison of budesonide or formoterol + budesonide. Pindolol and H89 could not inhibit the formoterol-induced expression of M3R (P > 0.05), but SQ22,536 significantly antagonized the formoterol-induced M3R expression (P < 0.05). In conclusions, ß2AR inverse agonist, ICI118,551, exerts similar bronchoprotective effects to corticosteroids via decreasing the expression of M3R and inhibiting the production of IP3.

Metformin is associated with survival benefit in pancreatic cancer patients with diabetes: a systematic review and meta-analysis.

BACKGROUND: Pancreatic cancer is a highly lethal disease with a poor prognosis while metformin has been associated with a decreased risk of pancreatic cancer. Although the benefit of metformin was observed for pancreatic cancer prevention, it is not clear whether it can also affect the survival of pancreatic cancer patients with type 2 diabetes mellitus. A systematic review and meta-analysis was conducted to assess the effect of metformin on the survival of pancreatic cancer patients with type 2 diabetes mellitus. METHODS: Two independent authors searched PubMed and Web of science up to 08/07/2016. We assessed studies for eligibility, extracted data, and examined their quality, with the primary outcome as overall survival. We used published hazard ratio (HR) available or estimated based on other survival data. We pooled the data and used a random-effect model to combine direct comparisons from included articles. We also investigated treatment effects by different countries, quality and the time of metformin initiation. RESULTS: We found that there was a relative survival benefit associated with metformin treatment compared with non-metformin treatment in both overall survival (OS) ([HR] 0.84; 95% confidence interval [CI]: 0.73 - 0.96). These associations were also observed in subgroups of Asian countries and high quality articles. CONCLUSIONS: Our results support the notion that metformin maybe the best anti-diabetic medicine of choice in patients with pancreatic cancer and concurrent type 2 diabetes mellitus. The perspectives of enhancing survival of pancreatic cancer patients with diabetes mellitus by the use of metformin deserve more attention in future research and clinical practice.

The preventive effects of hyperoside on lung cancer in vitro by inducing apoptosis and inhibiting proliferation through Caspase-3 and P53 signaling pathway.

Though advanced surgical operation and chemotherapy have been under taken, lung cancer remains one of the most aggressive and fatal human malignancies with a low survival rate. Thus, novel therapeutic strategies for prevention and remedy are urgently needed in lung cancer. Hyperoside, known as quercetin-3-O-ß-d-galactopyranoside, is a natural flavonol glycoside discovered in plants of genera Hypericum, displaying anti-oxidant, anticancer, and anti-inflammatory properties. In the study, we attempted to investigate whether hyperoside could inhibit lung cancer progression via Caspase-3- and P53-regulated cell death. In in vitro and in vivo experiments, we explored hyperoside at three different dosages on cell apoptosis, cell proliferation, cell migration, cell invasion, cell cycle distribution, the related signalling pathways, as well as xenograft tumor growth. Our data suggested that hyperoside exerted inhibitory role in lung cancer development. Inhibition of NF-κB transcriptional activity, Caspase-9/Caspase-3 activation, the cell cycle arrest, and suppression of cell proliferation-related signaling pathway led to the lung cancer inhibition. Further, via mice xenograft model in vivo, we indicated that hyperoside completely impeded tumor growth through angiogenesis inhibition. Our study illustrated that hyperoside might provide a synergistic anticancer effects that warrant further study and investigation due to its potential role in clinical applications.

MicroRNA-524-5p suppresses the growth and invasive abilities of gastric cancer cells.

Previous studies have demonstrated that microRNAs (miRNAs) are associated with tumor development and progression. miRNA-524-5p (miR-524-5p) has been reported to be involved in the development and progression of several types of cancer, but its role in gastric cancer has not been fully elucidated to date. Therefore, the aim of the present study was to investigate the expression levels and function of miR-524-5p in human gastric cancer. The expression levels of miR-524-5p were assessed in gastric cancer specimens and cell lines, including MKN-45, SGC-7901 and MGC-803 cell lines and gastric epithelial mucosa GES-1 cells, using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell proliferation and cell apoptosis assays and invasion analysis in gastric cancer cell lines were performed to evaluate the effects of miR-524-5p on gastric cancer cells in vitro. The expression levels of matrix metallopeptidase (MMP)-2 and MMP-9 were determined by RT-qPCR and western blot analysis. The expression of miR-524-5p was significantly decreased in gastric cancer tissues and cell lines. Additionally, the results of the in vitro experiments demonstrated that overexpression of miR-524-5p inhibited cell proliferation and invasion, and promoted cell apoptosis in gastric cancer cells. Human gastric cancer SGC-7901 and MGC-803 cell lines transfected with miR-524-5p exhibited reduced expression levels of MMP-2 and MMP-9. Taken together, the results of the present study indicated that miR-524-5p may function as a novel tumor suppressor gene in gastric cancer, and may serve as a biomarker and therapeutic target for the treatment of gastric cancer.

A long-acting ß2-adrenergic agonist increases the expression of muscarine cholinergic subtype­3 receptors by activating the ß2-adrenoceptor cyclic adenosine monophosphate signaling pathway in airway smooth muscle cells.

The persistent administration of ß2­adrenergic (ß2AR) agonists has been demonstrated to increase the risk of severe asthma, partly due to the induction of tolerance to bronchoprotection via undefined mechanisms. The present study investigated the potential effect of the long­acting ß2­adrenergic agonist, formoterol, on the expression of muscarinic M3 receptor (M3R) in rat airway smooth muscle cells (ASMCs). Primary rat ASMCs were isolated and characterized following immunostaining with anti­α­smooth muscle actin antibodies. The protein expression levels of M3R and phospholipase C­ß1 (PLCß1) were characterized by western blot analysis and the production of inositol 1,4,5­trisphosphate (IP3) was determined using an enzyme­linked immunosorbent assay. Formoterol increased the protein expression of M3R in rat ASMCs in a time­ and dose­dependent manner, which was significantly inhibited by the ß2AR antagonist, ICI118,551 and the cyclic adenosine monophosphate (cAMP) inhibitor, SQ22,536. The increased protein expression of M3R was positively correlated with increased production of PLCß1 and IP3. Furthermore, treatment with the glucocorticoid, budesonide, and the PLC inhibitor, U73,122, significantly suppressed the formoterol­induced upregulated protein expression levels of M3R and PLCß1 and production of IP3. The present study demonstrated that formoterol mediated the upregulation of M3R in the rat ASMCs by activating the ß2AR­cAMP signaling pathway, resulting in increased expression levels of PLCß1 and IP3, which are key to inducing bronchoprotection tolerance. Administration of glucocorticoids or a PLC antagonist prevented formoterol­induced bronchoprotection tolerance by suppressing the protein expression of M3R.

Exome sequencing identifies somatic mutations of DDX3X in natural killer/T-cell lymphoma.

Natural killer/T-cell lymphoma (NKTCL) is a malignant proliferation of CD56(+) and cytoCD3(+) lymphocytes with aggressive clinical course, which is prevalent in Asian and South American populations. The molecular pathogenesis of NKTCL has largely remained elusive. We identified somatic gene mutations in 25 people with NKTCL by whole-exome sequencing and confirmed them in an extended validation group of 80 people by targeted sequencing. Recurrent mutations were most frequently located in the RNA helicase gene DDX3X (21/105 subjects, 20.0%), tumor suppressors (TP53 and MGA), JAK-STAT-pathway molecules (STAT3 and STAT5B) and epigenetic modifiers (MLL2, ARID1A, EP300 and ASXL3). As compared to wild-type protein, DDX3X mutants exhibited decreased RNA-unwinding activity, loss of suppressive effects on cell-cycle progression in NK cells and transcriptional activation of NF-κB and MAPK pathways. Clinically, patients with DDX3X mutations presented a poor prognosis. Our work thus contributes to the understanding of the disease mechanism of NKTCL.

Specific tissue expression and cellular localization of human apolipoprotein M as determined by in situ hybridization.

Apolipoprotein M (apoM) is a recently discovered human apolipoprotein predominantly present in high-density lipoprotein (HDL), and in minor proportion in triglyceride-rich lipoprotein (TGRLP) and low-density lipoprotein (LDL). The gene coding for apoM has been detected in all mammal genomes. The function of apoM is unknown yet. In the present study, we demonstrated that apoM is exclusively expressed in a strong manner in adult liver and kidney, and is expressed weakly in fetal liver and kidney as detected with human multiple tissue expression array. Both immunohistochemical staining and apoM mRNA in situ hybridization demonstrated that apoM was exclusively expressed in hepatocytes in human liver and in tubular epithelial cells in human kidney. The present study helps to elucidate the pathophysiological functions of apoM in vivo.