Mitochondrial biogenesis in white adipose tissue mediated by JMJD1A-PGC-1 axis limits age-related metabolic disease.

Mitochondria play a vital role in non-shivering thermogenesis in both brown and subcutaneous white adipose tissues (BAT and scWAT, respectively). However, specific regulatory mechanisms driving mitochondrial function in these tissues have been unclear. Here we demonstrate that prolonged activation of ß-adrenergic signaling induces epigenetic modifications in scWAT, specifically targeting the enhancers for the mitochondria master regulator genes Pgc1a/b. This is mediated at least partially through JMJD1A, a histone demethylase that in response to ß-adrenergic signals, facilitates H3K9 demethylation of the Pgc1a/b enhancers, promoting mitochondrial biogenesis and the formation of beige adipocytes. Disruption of demethylation activity of JMJD1A in mice impairs activation of Pgc1a/b driven mitochondrial biogenesis and limits scWAT beiging, contributing to reduced energy expenditure, obesity, insulin resistance, and metabolic disorders. Notably, JMJD1A demethylase activity is not required for Pgc1a/b dependent thermogenic capacity of BAT especially during acute cold stress, emphasizing the importance of scWAT thermogenesis in overall energy metabolism.

The analysis of fecal calprotectin as a diagnostic marker for anastomotic leakage after rectal cancer surgery: a pilot study.

A prospective pilot study was conducted on 11 patients with rectal cancer to investigate fecal calprotectin (FC) as a diagnostic tool for detecting anastomotic leakage (AL) after low anterior resection. Among the 11 patients, 1 patient (9.1%) experienced AL (Clavien-Dindo Grade IIIa). During the post-operative course until post-operative day (POD) 5, the white blood cell count of the patient with AL was within the normal range. The C-reactive protein level in the AL and non-AL groups showed a similar time course. On the other hand, the FC level in patient with AL dramatically increased on POD5, while the FC level of the non-AL group remained relatively stable. There was no significant correlation between the preoperative FC level and the tumor circumference rate, tumor size, depth of invasion or stage. This pilot study showed the possibility of FC as a useful diagnostic tool for the detection of AL after low anterior resection for rectal cancer.

Blood vessel remodeling in the cerebral cortex induced by binge alcohol intake in mice.

Ethanol is toxic to the brain and causes various neurological disorders. Although ethanol can directly exert toxicity on neurons, it also acts on other cell types in the central nervous system. Blood vessel endothelial cells interact with, and are affected by blood ethanol. However, the effects of ethanol on the vascular structures of the brain have not been well documented. In this study, we examined the effects of binge levels of ethanol on brain vasculature. Immunostaining analysis indicated structural alterations of blood vessels in the cerebral cortex, which became more tortuous than those in the control mice after ethanol administration. The interaction between the blood vessels and astrocytes decreased, especially in the upper layers of the cerebral cortex. Messenger RNA expression analysis revealed a unique downregulation of Vegfa mRNA encoding vascular endothelial growth factor (VEGF)-A among VEGF, angiopoietin, endothelin family angiogenic and blood vessel remodeling factors. The expression of three proteoglycan core proteins, glypican-5, neurocan, and serglycin, was also altered after ethanol administration. Thus, binge levels of ethanol affect the expression of VEGF-A and blood vessel-supporting proteoglycans, resulting in changes in the vascular structure of the cerebral cortex. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-022-00164-y.

Clinical evaluation of a surgical difficulty score for laparoscopic cholecystectomy for acute cholecystitis proposed in the Tokyo Guidelines 2018.

BACKGROUND/PURPOSE: We evaluated the difficulty score of laparoscopic cholecystectomy (LC) for acute cholecystitis (AC) proposed in the Tokyo guidelines 2018 (TG18) and analyzed the most appropriate scoring method. METHODS: We reviewed 127 patients who underwent LC for AC from January 2018 to March 2022. According to TG18, surgical difficulty was scored for five categories consisting of 25 intraoperative findings. The median, highest, and mean score of the five categories were analyzed for their association with surgical outcomes. RESULTS: The difficulty score distribution (0/1/2/3/4/5/6) was as follows: median (8/34/43/30/12/0/0), highest (1/1/32/42/36/15/0) and mean (19/49/49/10/0/0/0). In all three scoring methods, higher difficulty scores were significantly correlated with longer operative time, more blood loss, and higher occurrence of subtotal cholecystectomy in trend tests. The areas under the curve (AUCs) for prediction of prolonged operative time minutes and increased blood loss were similar in all three scoring methods. For conversion to subtotal cholecystectomy, the AUC was significantly better for the highest than median and mean score (p = .015 and p = .002, respectively). CONCLUSIONS: The difficulty score in TG18 appropriately reflects the surgical difficulty of LC for AC. The median, highest, and mean scores of the five categories are all available, and the highest scores are simple and versatile.

The Clinical Impact of Apical Lymph Node Metastasis of Colorectal Cancer After Curative Resection.

PURPOSE: The present study aimed to investigate the clinical implications of apical lymph node metastasis (ALNM) after curative resection of stage III colorectal cancer. METHODS: A retrospective study was conducted of 1403 consecutive colorectal cancer patients who underwent surgical resection at a single institution between April 2008 and January 2020. The characteristics of ALNM, the recurrence status and the relapse-free survival (RFS) were examined. RESULTS: The numbers of patients with stage ≤ I, II, III, and IV disease were 350, 437, 476, and 140 patients, respectively. Among these patients with stage III disease, ALNM was seen in 21 patients (4.4% of stage III patients). Among them, curative resection was performed in 19 patients. Recurrence was observed in 68% (13/19) of the patients with ALNM who received curative resection. The first sites of recurrence included the lymph nodes 53.8% (7/13), liver 30.8% (4/13), lung 15.4% (2/13), brain 7.7% (1/13), bone 7.7% (1/13), and peritoneum 7.7% (1/13). There was no significant difference in the RFS of patients with ALNM who were managed with or without adjuvant chemotherapy (P = 0.207). Furthermore, the RFS of the group managed without adjuvant chemotherapy and the group that received adjuvant chemotherapy with/without oxaliplatin did not differ to a statistically significant extent (P = 0.318). In stage III colorectal cancer patients with ALNM, recurrence was observed significantly more frequently in comparison to stage III colorectal cancer patients without ALNM (P = 0.007). The first site of recurrence in patients with ALNM was most frequently seen in the distant lymph nodes (P = 0.004). CONCLUSION: Our findings suggest that ALNM is strongly associated with recurrence in the distant lymph nodes and that it may lead to the development of systemic disease. The current regimen for stage III colorectal cancer may therefore not be sufficient for patients with stage III ALNM.

Intussusception of the cecum due to the acute appendicitis: A case report.

INTRODUCTION AND IMPORTANCE: Intussusception of the cecum due to acute appendicitis is rare condition. PRESENTATION OF CASE: A 17-year-old male patient presented to our hospital with a chief complaint of right lower abdominal pain, which had lasted for two days. Computed tomography (CT) revealed a "target sign" from the cecum to the ascending colon, leading to a diagnosis of cecocolic intussusception. Colonoscopy revealed an erythematous, edematous, and internally distorted cecum in the ascending colon, which was difficult to repair with air insufflation. Laparoscopic surgery was performed to remove the bowel obstruction. Repositioning of the invaginated cecum was difficult due to the presence of a hard and edematous colic wall. Therefore, laparoscopic ileocecal resection was performed to release the obstruction. The pathological diagnosis was appendicitis and abscess within the cecum wall, with no malignant findings. DISCUSSION: In our case, intussusception was considered to have caused thickening of the intestinal wall of the cecum due to inflammation of the appendix, and the thickened area became the leading point. CONCLUSION: Considering that malignancy is a frequent leading point in adult patients with intussusception, a preoperative endoscopic examination is important for minimizing bowel resection.

Pathological complete remission of relapsed tumor by photo-activating antibody-mimetic drug conjugate treatment.

Antibody-mimetic drug conjugate is a novel noncovalent conjugate consisting of an antibody-mimetic recognizing a target molecule on the cancer cell surface and low-molecular-weight payloads that kill the cancer cells. In this study, the efficacy of a photo-activating antibody-mimetic drug conjugate targeting HER2-expressing tumors was evaluated in mice, by using the affibody that recognize HER2 (ZHER2:342 ) as a target molecule and an axially substituted silicon phthalocyanine (a novel potent photo-activating compound) as a payload. The first treatment with the photo-activating antibody-mimetic drug conjugates reduced the size of all HER2-expressing KPL-4 xenograft tumors macroscopically. However, during the observation period, relapsed tumors gradually appeared in approximately 50% of the animals. To evaluate the efficacy of repeated antibody-mimetic drug conjugate treatment, animals with relapsed tumors were treated again with the same regimen. After the second observation period, the mouse tissues were examined histopathologically. Unexpectedly, all relapsed tumors were eradicated, and all animals were diagnosed with pathological complete remission. After the second treatment, skin wounds healed rapidly, and no significant side effects were observed in other organs, except for occasional microscopic granulomatous tissues beneath the serosa of the liver in a few mice. Repeated treatments seemed to be well tolerated. These results indicate the promising efficacy of the repeated photo-activating antibody-mimetic drug conjugate treatment against HER2-expressing tumors.

MYPT1-PP1ß phosphatase negatively regulates both chromatin landscape and co-activator recruitment for beige adipogenesis.

Protein kinase A promotes beige adipogenesis downstream from ß-adrenergic receptor signaling by phosphorylating proteins, including histone H3 lysine 9 (H3K9) demethylase JMJD1A. To ensure homeostasis, this process needs to be reversible however, this step is not well understood. We show that myosin phosphatase target subunit 1- protein phosphatase 1ß (MYPT1-PP1ß) phosphatase activity is inhibited via PKA-dependent phosphorylation, which increases phosphorylated JMJD1A and beige adipogenesis. Mechanistically, MYPT1-PP1ß depletion results in JMJD1A-mediated H3K9 demethylation and activation of the Ucp1 enhancer/promoter regions. Interestingly, MYPT1-PP1ß also dephosphorylates myosin light chain which regulates actomyosin tension-mediated activation of YAP/TAZ which directly stimulates Ucp1 gene expression. Pre-adipocyte specific Mypt1 deficiency increases cold tolerance with higher Ucp1 levels in subcutaneous white adipose tissues compared to control mice, confirming this regulatory mechanism in vivo. Thus, we have uncovered regulatory cross-talk involved in beige adipogenesis that coordinates epigenetic regulation with direct activation of the mechano-sensitive YAP/TAZ transcriptional co-activators.

A clinical risk analysis of postoperative nausea and vomiting after colorectal cancer surgery

Objective: Postoperative nausea and vomiting (PONV) is a frequent complication following colorectal surgery. The present study investigated the risk factors for PONV after colorectal cancer surgery. Methods: A retrospective study of 204 patients who underwent surgery for colorectal cancer was conducted. Univariate and multivariate analyses were performed to determine the clinicopathological factors associated with PONV. Results: The overall incidence of postoperative nausea (PON) and postoperative vomit (POV) was 26.5% (54/204), and 12.3% (25/204), respectively. The univariate analysis showed that female gender (p < 0.001), no current alcohol drinking habit (p = 0.003), and no stoma creation (p = 0.023) were associated with PON. Postoperative vomit was significantly correlated with female gender (p = 0.009), high body mass index (p = 0.017), and right-sided colon cancer (p = 0.001). The multivariate logistic regression analysis revealed that female gender (odds ratio [OR]: 4.225; 95% confidence interval [CI]: 2.170-8.226; p < 0.001) was an independent risk factor for PON. A high body mass index (OR: 1.148; 95%CI: 1.018-1.295; p = 0.025), and right-sided colon cancer (OR: 3.337; 95%CI: 1.287-8.652; p = 0.013) were independent risk factors for POV. Conclusion: Our findings suggest that female gender for PON and a high body mass index and right-sided colon cancer for POV are risk factors after colorectal cancer surgery. An assessment using these factors might be helpful for predicting PONV. (AU)

Risk factors of incisional hernia at the umbilical specimen extraction site in patients with laparoscopic colorectal cancer surgery.

Purpose: Incisional hernia (IH) is a frequent complication following laparoscopic colorectal surgery. The present study investigated the risk factors for IH after laparoscopic surgery for colorectal cancer. Methods: A retrospective study was conducted on 202 patients who underwent laparoscopic surgery for colorectal cancer. Univariate and multivariate analyses were performed to determine the clinicopathological factors associated with IH. Results: The overall incidence of IH was 25.7% (52 of 202). The univariate analysis showed that female sex (P=0.004), a high body mass index (P<0.001), non-current smoking habit (P=0.043), low level of hemoglobin (P=0.035), high subcutaneous fat area (P<0.001), high visceral fat area (P=0.006), low skeletal muscle area (P=0.001), long distance between the inner edges of the rectus abdominis muscle (P=0.001), long protrusion of the peritoneum at the umbilical site (P<0.001), and lymph node metastasis (P=0.007) were significantly more frequent in the group with IH than in the group without it. The multivariate logistic regression analysis revealed an older age (10-year increments: odds ratio [OR], 1.576; 95% confidence interval [CI], 1.027-2.419; P=0.037), lymph node metastasis (OR, 2.384; 95% CI, 1.132-5.018; P=0.022) and lengthy protrusion of the peritoneum at the umbilical site (10-mm increments: OR, 5.555; 95% CI, 3.058-10.091; P<0.001) were independent risk factors for IH. Conclusion: Our findings suggest that older age, lymph node metastasis, and lengthy protrusion of the peritoneum at the umbilical site are risk factors for IH after laparoscopic surgery for colorectal cancer. An assessment using these factors before the operation and the implementation of countermeasures might help prevent IH.

The serological diversity of serum IgG/IgA/IgM against SARS-CoV-2 nucleoprotein, spike, and receptor-binding domain and neutralizing antibodies in patients with COVID-19 in Japan.

Background: We compared the temporal changes of immunoglobulin M (IgM), IgG, and IgA antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein (N), spike 1 subunit (S1), and receptor-binding domain (RBD), and neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with coronavirus disease 2019 (COVID-19) to understand the humoral immunity in COVID-19 patients for developing drugs and vaccines for COVID-19. Methods: A total of five confirmed COVID-19 cases in Nissan Tamagawa Hospital in early August 2020 were recruited in this study. Using a fully automated chemiluminescence immunoassay analyzer, we measured the levels of IgG, IgA, and IgM against SARS-CoV-2 N, S1, and RBD and NAbs against SARS-CoV-2 in COVID-19 patients' sera acquired multiple times in individuals from 0 to 76 days after symptom onset. Results: IgG levels against SARS-CoV-2 structural proteins increased over time in all cases but IgM and IgA levels against SARS-CoV-2 showed different increasing trends among individuals in the early stage. In particular, we observed IgA increasing before IgG and IgM in some cases. The NAb levels were more than cut-off value in 4/5 COVID-19 patients some of whose antibodies against RBD did not exceed the cut-off value in the early stage. Furthermore, NAb levels against SARS-CoV-2 increased and kept above cut-off value more than around 70 days after symptom onset in all cases. Conclusion: Our findings indicate COVID-19 patients should be examined for IgG, IgA, and IgM against SARS-CoV-2 structural proteins and NAbs against SARS-CoV-2 to analyze the diversity of patients' immune mechanisms.

Comprehensive genomics in androgen receptor-dependent castration-resistant prostate cancer identifies an adaptation pathway mediated by opioid receptor kappa 1.

Castration resistance is a lethal form of treatment failure of prostate cancer (PCa) and is associated with ligand-independent activation of the androgen receptor (AR). It is only partially understood how the AR mediates survival and castration-resistant growth of PCa upon androgen deprivation. We investigated integrative genomics using a patient-derived xenograft model recapitulating acquired, AR-dependent castration-resistant PCa (CRPC). Sequencing of chromatin immunoprecipitation using an anti-AR antibody (AR-ChIP seq) revealed distinct profiles of AR binding site (ARBS) in androgen-dependent and castration-resistant xenograft tumors compared with those previously reported based on human PCa cells or tumor tissues. An integrative genetic analysis identified several AR-target genes associated with CRPC progression including OPRK1, which harbors ARBS and was upregulated upon androgen deprivation. Loss of function of OPRK1 retarded the acquisition of castration resistance and inhibited castration-resistant growth of PCa both in vitro and in vivo. Immunohistochemical analysis showed that expression of OPRK1, a G protein-coupled receptor, was upregulated in human prostate cancer tissues after preoperative androgen derivation or CRPC progression. These data suggest that OPRK1 is involved in post-castration survival and cellular adaptation process toward castration-resistant progression of PCa, accelerating the clinical implementation of ORPK1-targeting therapy in the management of this lethal disease.

Selective PPARα Modulator Pemafibrate and Sodium-Glucose Cotransporter 2 Inhibitor Tofogliflozin Combination Treatment Improved Histopathology in Experimental Mice Model of Non-Alcoholic Steatohepatitis.

Ballooning degeneration of hepatocytes is a major distinguishing histological feature of non-alcoholic steatosis (NASH) progression that can lead to cirrhosis and hepatocellular carcinoma (HCC). In this study, we evaluated the effect of the selective PPARα modulator (SPPARMα) pemafibrate (Pema) and sodium-glucose cotransporter 2 (SGLT2) inhibitor tofogliflozin (Tofo) combination treatment on pathological progression in the liver of a mouse model of NASH (STAM) at two time points (onset of NASH progression and HCC survival). At both time points, the Pema and Tofo combination treatment significantly alleviated hyperglycemia and hypertriglyceridemia. The combination treatment significantly reduced ballooning degeneration of hepatocytes. RNA-seq analysis suggested that Pema and Tofo combination treatment resulted in an increase in glyceroneogenesis, triglyceride (TG) uptake, lipolysis and liberated fatty acids re-esterification into TG, lipid droplet (LD) formation, and Cidea/Cidec ratio along with an increased number and reduced size and area of LDs. In addition, combination treatment reduced expression levels of endoplasmic reticulum stress-related genes (Ire1a, Grp78, Xbp1, and Phlda3). Pema and Tofo treatment significantly improved survival rates and reduced the number of tumors in the liver compared to the NASH control group. These results suggest that SPPARMα and SGLT2 inhibitor combination therapy has therapeutic potential to prevent NASH-HCC progression.

Spatiotemporal dynamics of SETD5-containing NCoR-HDAC3 complex determines enhancer activation for adipogenesis.

Enhancer activation is essential for cell-type specific gene expression during cellular differentiation, however, how enhancers transition from a hypoacetylated "primed" state to a hyperacetylated-active state is incompletely understood. Here, we show SET domain-containing 5 (SETD5) forms a complex with NCoR-HDAC3 co-repressor that prevents histone acetylation of enhancers for two master adipogenic regulatory genes Cebpa and Pparg early during adipogenesis. The loss of SETD5 from the complex is followed by enhancer hyperacetylation. SETD5 protein levels were transiently increased and rapidly degraded prior to enhancer activation providing a mechanism for the loss of SETD5 during the transition. We show that induction of the CDC20 co-activator of the ubiquitin ligase leads to APC/C mediated degradation of SETD5 during the transition and this operates as a molecular switch that facilitates adipogenesis.

Immunohistochemical detection of hepatocyte nuclear factor-4α in vertebrates.

Hepatocyte nuclear factor-4α (HNF4α) presents in multiple isoforms generated using alternative promoter (P1 and P2) and splicing. Neither conservation of tissue distribution of HNF4α isoforms, nor presence of alternative promoter usage is known. In this study, to detect the expression of HNF4α in some species of animals, we have applied monoclonal antibodies against P1 (K9218) and P2 (H6939) promoter-driven and P1/P2 promoter-driven H1415 HNF4α for immunohistochemistry and western blot analysis. Antibody K9218 was observed in the hepatocytes, proximal tubules of the kidney, and epithelial cells in the mucosa of the small intestine and colon of rats, chicken, and tortoise, whereas antibody H6939 signal were detected in the stomach, pancreas, bile duct, and pancreatic duct of human and rats. The signal for antibody K9218 was recognized in tissues of a wide range of mammals, bird, reptile, amphibian, and fish as well. Antibody H1415 displayed a positive reaction in hepatocytes and intestinal epithelial cells in chicken and tortoise, whereas the bile duct, mucosal epithelial cells in the stomach, or pancreas in these animals were negative. Western blotting showed the binding of the antibody with HNF4α protein from each animal. The sequence of human HNF4α was 100% identical to murine and rat HNF4α, 88.9% to chicken, 77.8% to Xenopus HNF4α, and 81.5% to medaka. However, the specific part of human and invertebrate Drosophila HNF4 shares only 14.8% sequence identity. This antibody is useful for detecting HNF4α isoforms in a wide range of vertebrates, and suggests many insights into animal evolution.

Ubiquitination-dependent and -independent repression of target genes by SETDB1 reveal a context-dependent role for its methyltransferase activity during adipogenesis.

The lysine methyltransferase SETDB1, an enzyme responsible for methylation of histone H3 at lysine 9, plays a key role in H3K9 tri-methylation-dependent silencing of endogenous retroviruses and developmental genes. Recent studies have shown that ubiquitination of human SETDB1 complements its catalytic activity and the silencing of endogenous retroviruses in human embryonic stem cells. However, it is not known whether SETDB1 ubiquitination is essential for its other major role in epigenetic silencing of developmental gene programs. We previously showed that SETDB1 contributes to the formation of H3K4/H3K9me3 bivalent chromatin domains that keep adipogenic Cebpa and Pparg genes in a poised state for activation and restricts the differentiation potential of pre-adipocytes. Here, we show that ubiquitin-resistant K885A mutant of SETDB1 represses adipogenic genes and inhibits pre-adipocyte differentiation similar to wild-type SETDB1. We show this was due to a compensation mechanism for H3K9me3 chromatin modifications on the Cebpa locus by other H3K9 methyltransferases Suv39H1 and Suv39H2. In contrast, the K885A mutant did not repress other SETDB1 target genes such as Tril and Gas6 suggesting SETDB1 represses its target genes by two mechanisms; one that requires its ubiquitination and another that still requires SETDB1 but not its enzyme activity.

The risk factors of acute urinary retention after laparoscopic colorectal cancer surgery in elderly patients receiving epidural analgesia.

PURPOSE: Urinary retention (UR) is a frequent complication following laparoscopic colorectal surgery. The aim of the present study was to investigate the risk factors for acute UR after laparoscopic surgery for colorectal cancer in patients receiving epidural analgesia. METHODS: A retrospective study was conducted of 201 patients who underwent laparoscopic surgery for colorectal cancer among those receiving epidural analgesia. Univariate and multivariate analyses were performed to determine the clinicopathological factors associated with acute UR. Acute UR was defined as Clavien-Dindo classification grade ≥ 1. RESULTS: The overall incidence of acute UR was 17.9% (36/201). The univariate analysis showed that male gender (P = 0.043), a history of chronic heart failure (P = 0.009), an increased level of serum creatinine (P = 0.028), an increased intraoperative fluid volume (P = 0.016), and an early postoperative date of urinary catheter removal (P = 0.003) were both associated with acute UR. The multivariate logistic regression analysis revealed an increased intraoperative fluid volume (100-ml increments; odds ratio [OR]: 1.085, 95% confidence interval [CI]: 1.034-1.138, P < 0.001), history of chronic heart failure (OR: 6.843, 95% CI: 1.893-24.739, P = 0.003), and postoperative date of urinary catheter removal (OR: 0.550, 95% CI: 0.343-0.880, P = 0.013) were independent risk factors for acute UR. CONCLUSION: Our findings suggest that an increased intraoperative fluid volume, history of chronic heart failure, and early removal of the urinary catheter are risk factors of UR after laparoscopic surgery for colorectal cancer in patients receiving epidural analgesia. An assessment using these factors might be helpful for predicting acute UR.

Loss of Down syndrome critical region-1 leads to cholesterol metabolic dysfunction that exaggerates hypercholesterolemia in ApoE-null background.

Down syndrome critical region (DSCR)-1 functions as a feedback modulator for calcineurin-nuclear factor for activated T cell (NFAT) signals, which are crucial for cell proliferation and inflammation. Stable expression of DSCR-1 inhibits pathological angiogenesis and septic inflammation. DSCR-1 also plays a critical role in vascular wall remodeling associated with aneurysm development that occurs primarily in smooth muscle cells. Besides, Dscr-1 deficiency promotes the M1-to M2-like phenotypic switch in macrophages, which correlates to the reduction of denatured cholesterol uptakes. However, the distinct roles of DSCR-1 in cholesterol and lipid metabolism are not well understood. Here, we show that loss of apolipoprotein (Apo) E in mice with chronic hypercholesterolemia induced Dscr-1 expression in the liver and aortic atheroma. In Dscr-1-null mice fed a high-fat diet, oxidative- and endoplasmic reticulum (ER) stress was induced, and sterol regulatory element-binding protein (SREBP) 2 production in hepatocytes was stimulated. This exaggerated ApoE-/--mediated nonalcoholic fatty liver disease (NAFLD) and subsequent hypercholesterolemia. Genome-wide screening revealed that loss of both ApoE and Dscr-1 resulted in the induction of immune- and leukocyte activation-related genes in the liver compared with ApoE deficiency alone. However, expressions of inflammation-activated markers and levels of monocyte adhesion were suspended upon induction of the Dscr-1 null background in the aortic endothelium. Collectively, our study shows that the combined loss of Dscr-1 and ApoE causes metabolic dysfunction in the liver but reduces atherosclerotic plaques, thereby leading to a dramatic increase in serum cholesterol and the formation of sporadic vasculopathy.

A clinical risk analysis of early post-operative delirium after laparoscopic colorectal cancer surgery in elderly patients: a retrospective study.

PURPOSE: Early post-operative delirium (EPOD) is a frequent complication following colorectal surgery. The present study investigated the risk factors for EPOD after laparoscopic colorectal surgery in elderly patients. METHODS: A retrospective study was conducted among 208 patients ≥70 years old who underwent laparoscopic colorectal surgery. Univariate and multivariate analyses were performed to determine the clinicopathological factors associated with the EPOD. RESULTS: The overall incidence of EPOD was 10.1% (21/208). The univariate analysis showed that an older age (≥80 years old; P=0.002), sleeping pill medication before surgery (P=0.037), a history of dementia (P=0.030) and cerebrovascular disease (P=0.017), elevated levels of D-dimer (P=0.016), maximum intraoperative temperature ≥37 °C (P=0.036), and non-continuous usage of droperidol with analgesia (P=0.005) were associated with EPOD. The multivariate logistic regression analysis revealed an older age (≥80 years old; odds ratio [OR]: 6.26, 95% confidence interval [CI]: 1.94-20.15, P=0.002), sleeping pill medication before surgery (OR: 5.39, 95% CI: 1.36-21.28, P=0.016), history of cerebrovascular disease (OR: 3.91, 95% CI: 1.12-13.66, P=0.033), and maximum intraoperative temperature ≥37 °C (OR: 5.10, 95% CI: 1.53-16.92, P=0.008) to be independent risk factors. When the patients were divided into groups according to the number of positive risk factors, the prevalence rate was 6.5%, 16.0%, and 63.6% for patients with 1, 2, and 3 positive risk factors, respectively. CONCLUSION: Our findings suggest that an older age, sleeping pill medication before surgery, history of cerebrovascular disease, and maximum intraoperative temperature ≥37 °C are independent risk factors of EPOD after laparoscopic colorectal surgery in elderly patients.