Cannabidiol alleviates carbon tetrachloride-induced liver fibrosis in mice by regulating NF-κB and PPAR-α pathways.

Liver fibrosis has become a serious public health problem that can develop into liver cirrhosis and hepatocellular carcinoma and even lead to death. Cannabidiol (CBD), which is an abundant nonpsychoactive component in the cannabis plant, exerts cytoprotective effects in many diseases and under pathological conditions. In our previous studies, CBD significantly attenuated liver injury induced by chronic and binge alcohol in a mouse model and oxidative bursts in human neutrophils. However, the effects of CBD on liver fibrosis and the underlying mechanisms still need to be further explored. A mouse liver fibrosis model was induced by carbon tetrachloride (CCl4) for 10 weeks and used to explore the protective properties of CBD and related molecular mechanisms. After the injection protocol, serum samples and livers were used for molecular biology, biochemical and pathological analyses. The results showed that CBD could effectively improve liver function and reduce liver damage and liver fibrosis progression in mice; the expression levels of transaminase and fibrotic markers were reduced, and histopathological characteristics were improved. Moreover, CBD inhibited the levels of inflammatory cytokines and reduced the protein expression levels of p-NF-κB, NF-κB, p-IκBα, p-p38 MAPK, and COX-2 but increased the expression level of PPAR-α. We found that CBD-mediated protection involves inhibiting NF-κB and activating PPAR-α. In conclusion, these results suggest that the hepatoprotective effects of CBD may be due to suppressing the inflammatory response in CCl4-induced mice and that the NF-κB and PPAR-α signaling pathways might be involved in this process.

Appendiceal intussusception complicated by adenocarcinoma of the cecum: A case report.

BACKGROUND: Appendiceal intussusception is a pathological condition in which the appendix is inverted into the cecum, which may cause symptoms that resemble those of other gastrointestinal disorders and may induce intestinal obstruction. The rarity of this case presentation is the co-occurrence of appendiceal intussusception and cecal adenocarcinoma, a combination that to our knowledge has not previously been reported in the medical literature. This case provides new insights into the complexities of diagnosing and managing overlapping pathologies. CASE SUMMARY: A 25-year-old woman presented with persistent periumbilical pain and bloody stools. An initial biopsy showed cecal cancer; however, subsequent colonoscopy and computed tomography findings raised the suspicion of appendiceal intussusception, which was later confirmed postoperatively. This unique case was characterized by a combination of intussusception and adenocarcinoma of the cecum. The intervention included a laparoscopic right hemicolectomy, which led to the histopathological diagnosis of mucinous adenocarcinoma with appendiceal intussusception. The patient recovered well postoperatively and was advised to initiate adjuvant chemotherapy. This case highlights not only the importance of considering appendiceal intussusception in the differential diagnosis, but also the possibility of appendicitis and the atypical presentation of neoplastic lesions. CONCLUSIONS: Physicians should consider the possibility of appendiceal intussusception in cases of atypical appendicitis, particularly when associated with neoplastic presentation.

Neoadjuvant immunotherapy in a locally advanced colon cancer patient with MSI-H and suspected Lynch syndrome: A case report.

Carrilizumab, a PD-1 inhibitor, has shown therapeutic effectiveness in patients with late-stage or metastatic solid tumors exhibiting DNA mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H). dMMR/MSI-H cancer patients are known to be responsive to PD-1 inhibitors. However, the use of carrilizumab for preoperative immunotherapy in early, unresectable MSI-H/dMMR primary colon cancer lesions is relatively underexplored. We present the case of a 46-year-old male who sought medical attention at our institution due to a history of hematochezia for two weeks, right-sided abdominal pain for one week, and loose stools. Imaging indicated duodenal involvement, and a biopsy confirmed ascending colon adenocarcinoma with MSI-H status. Given that the patient's family exhibited a history of more than three confirmed cases of colorectal cancer spanning two generations, Lynch syndrome was considered. After four cycles of PD-1 antagonist immunotherapy with carrilizumab, the patient's symptoms resolved, and physical examination revealed no abdominal tenderness or palpable masses. Following radical colectomy, the primary tumor exhibited a pathological complete response. This case highlights the potential of preoperative neoadjuvant immunotherapy to improve staging accuracy and increase surgical resection rates in T4b MSI-H colon cancer patients without distant metastasis, suggesting a need for reconsideration of the treatment approach.

Cannabidiol regulates the activation of hepatic stellate cells by modulating the NOX4 and NF-κB pathways.

Cannabidiol (CBD) is an extract of natural cannabinoids that has therapeutic implications for a variety of ailments, such as neurological diseases, cardiomyopathy, and diabetes, due to its strong anti-inflammatory and oxidative stress properties. Our purpose was to reveal the possible underlying mechanisms and effect of CBD on the glucose oxidase (GO)-induced activation of HSC-T6 and LX-2 cells. The results showed that CBD effectively inhibited the proliferation and activation of HSC-T6 and LX-2 cells, and reduced the production of profibrotic factors to different degrees. CBD disrupted the NOX4 signalling pathway in activated HSC-T6 and LX-2 cells, reduced ROS and MDA levels, and increased SOD and GSH levels, thereby stabilizing the oxidative imbalance. CBD significantly inhibited the phosphorylation and degradation of NF-κB and IκBα, and decreased the release of TNF-α, IL-1ß and IL-6. Moreover, CBD and an NF-κB-specific inhibitor (CAPE) effectively inhibited the expression of α-SMA, COL I, TNF-α and IL-1ß to promote collagen metabolism and inhibit the inflammatory response. Overall, CBD inhibited HSCs activation through a and the mechanism involving the inhibition of NOX4 and NF-κB-dependent ROS regulation, thereby reducing inflammation and ameliorating oxidative imbalances.

Synchronous Double Primary Malignant Tumors and their Possible Shared Genes: A Rare Clinical Entity.

Objective: This study sought to analyze the 18F-FDG PET/CT and contrast-enhanced computed tomography (CT) images of synchronous colorectal cancer (CRC) and renal clear cell carcinoma (ccRCC) and identify the shared genes between these two types of cancer through bioinformatic analysis. Methods: A retrospective analysis was conducted on a patient with synchronous CRC and ccRCC who underwent 18F-FDG PET/CT and contrast-enhanced CT before treatment. Databases were analyzed to identify differentially expressed genes between CRC and ccRCC, and co-expression genes were extracted for RCC and CRC. Results: 18F-FDG PET/CT revealed intense metabolic activity in the primary colorectal lesion (SUVmax 13.2), while a left renal mass (diameter = 35 mm) was observed with no significant uptake. Contrast-enhanced CT during the arterial phase showed heterogeneous intense enhancement of the renal lesion, and the lesion washed out earlier than in the renal cortex in the nephrographic and excretory phases, indicating ccRCC. The histopathological results confirmed synchronous double primary malignant tumors. Our bioinformatic analysis results showed that synchronous occurrence of CRC and ccRCC may correlate with simultaneous expression of Carbonic Anhydrase 9 (CA9), integrin-binding sialoprotein (IBSP), and Fibrinogen γ chain (FGG). Conclusion: 18F-FDG PET/CT combined with contrast-enhanced CT is an effective diagnostic tool in evaluating synchronous CRC and RCC. By analyzing this clinical case and conducting bioinformatic analysis, we improved our current understanding of the mechanisms underlying synchronous tumors.

Gastric Syphilis Mimicking Lymphoma: A Case Report.

Gastric syphilis is a rare manifestation of syphilis that occurs in about 1% of cases and is often overlooked due to its non-specific signs and symptoms. We report a case of a 28-year-old Chinese woman who presented with epigastric pain, nausea, vomiting, hematemesis, alopecia, and weight loss. She tested positive for Helicobacter pylori (H. pylori), with rapid plasma reagin (RPR) and Treponema pallidum particle assay (TPPA) tests showing titers of 1:128 and 1:320, respectively. CT imaging revealed thickening of the gastric wall, exudation around the antrum, and multiple lymphadenopathies. Gastroscopy showed multiple irregular ulcers, which resembled lymphoma. However, biopsy results did not support the presence of lymphoma, but immunohistochemistry showed an abundance of syphilis spirochetes in the mucosal lamina propria and glands. This led to a diagnosis of gastric syphilis. The patient received standard treatment for syphilis as well as anti-H. pylori therapy, and her symptoms and endoscopic findings gradually improved and eventually resolved. We hope that this case report can provide valuable insights into the diagnosis and management of gastric syphilis, which can mimic other diseases like lymphoma.

Diagnostic efficiency on ultrasound shear wave elastography in evaluation of steatosis severity for non-alcoholic fatty liver disease: a rat model.

BACKGROUND: The pathological feature of steatosis affects the elasticity values measured by shear wave elastography (SWE) is still controversial in non-alcoholic fatty liver disease (NAFLD). The aim of this study is to demonstrate the influence of steatosis on liver stiffness measured by SWE on a rat model with NAFLD and analyze feasibility of SWE for grading steatosis in absence of fibrosis. METHODS: Sixty-six rats were fed with methionine choline deficient diet or standard diet to produce various stages of steatosis; 48 rats were available for final analysis. Rats underwent abdominal ultrasound SWE examination and pathological assessment. Liver histopathology was analyzed to assess the degree of steatosis, inflammation, ballooning, and fibrosis according to the non-alcoholic fatty liver disease activity score. The diagnostic performance of SWE for differentiating steatosis stages was estimated according to the receiver operating characteristic (ROC) curve. Decision curve analysis (DCA) was conducted to determine clinical usefulness and the areas under DCA (AUDCAs) calculated. RESULTS: In multivariate analysis, steatosis was an independent factor affecting the mean elastic modules (B = 1.558, P < 0.001), but not inflammation (B = - 0.031, P = 0.920) and ballooning (B = 0.216, P = 0.458). After adjusting for inflammation and ballooning, the AUROC of the mean elasticity for identifying S ≥ S1 was 0.956 (95%CI: 0.872-0.998) and the AUDCA, 0.621. The AUROC for distinguishing S ≥ S2 and S = S3 was 0.987 (95%CI: 0.951-1.000) and 0.920 (95%CI: 0.816-0.986) and the AUDCA was 0.506 and 0.256, respectively. CONCLUSIONS: Steatosis is associated with liver stiffness and SWE may have the feasibility to be introduced as an assistive technology in grading steatosis for patients with NAFLD in absence of fibrosis.

Recent and current advances in PET/CT imaging in the field of predicting epidermal growth factor receptor mutations in non-small cell lung cancer.

Tyrosine kinase inhibitors (TKIs) are a significant treatment strategy for the management of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation status. Currently, EGFR mutation status is established based on tumor tissue acquired by biopsy or resection, so there is a compelling need to develop non-invasive, rapid, and accurate gene mutation detection methods. Non-invasive molecular imaging, such as positron emission tomography/computed tomography (PET/CT), has been widely applied to obtain the tumor molecular and genomic features for NSCLC treatment. Recent studies have shown that PET/CT can precisely quantify EGFR mutation status in NSCLC patients for precision therapy. This review article discusses PET/CT advances in predicting EGFR mutation status in NSCLC and their clinical usefulness.

Comparison of characteristics between true rectal neuroendocrine tumors and rectal hyperplastic polyps among patients with endoscope-diagnosed rectal neuroendocrine tumors.

Background: To explore the white light endoscopy and endoscopic ultrasonography (EUS) features of rectal hyperplastic polyps (rHP) misdiagnosed as rectal neuroendocrine neoplasms (rNENs). In rNENs with a diameter of 5-10 mm, the endoscopic findings are not typical and some of them are similar to rHP, so it is not uncommon to misdiagnose rNENs as rHP. However, misdiagnosis of rHP as rNENs has not been reported in the literature, which can alert clinicians to the existence of this possibility and avoid over-treatment. Methods: We collected 245 cases of rectal submucosal tumor (SMT) diagnosed by endoscopy in our hospital from January 2015 to December 2020 and 103 patients with suspected rNENs identified through endoscopy. A retrospective analysis was conducted of the shape, color, vascular dilatation, and boundary on the surface of the lesion under white light endoscope, and the source, boundary, and echo characteristics of EUS. We also analyzed the endoscopic features of rHP misdiagnosed as rNENs. Endoscopic diagnosis and pathological diagnosis were reviewed by a senior endoscopic expert and pathologist respectively. The counting data were tested and analyzed by χ2 test and Fisher exact probability method. Results: A total of 103 cases of rNENs were diagnosed by endoscope, among whom 75 cases were confirmed as rNENs (72.8%) and 8 cases as rHP (7.8%) by histopathology. There was no significant difference between rNENs and rHP in terms of gender, age, clinical manifestation, shape and color of lesions, dilatation of blood vessels on the surface, and location of lesions. Meanwhile, there were significant differences in whether the boundary of the lesion was clear under white light endoscopy, and the source, echo, and boundary of the lesion under EUS. Conclusions: The morphology of some rHP is similar to rNENs under endoscopy. The boundary is clear under white light endoscopy and the source, echo, and boundary under EUS are helpful for the diagnosis of rNENs and rHP.

Interplay of Helicobacter pylori, fibroblasts, and cancer cells induces fibroblast activation and serpin E1 expression by cancer cells to promote gastric tumorigenesis.

BACKGROUND: Helicobacter pylori (H. pylori) can disrupt the tight junctions between gastric epithelial cells and penetrate the intercellular spaces acting on epithelial cells, normal fibroblasts (NFs), and cancer-associated fibroblasts (CAFs), but their interaction in gastric cancer tumorigenesis and progression remains unclear. METHODS: Primary CAFs and NFs were isolated from paired gastric cancer tissues and adjacent normal tissues and identified by immunofluorescence staining and western blot analysis for FSP-1, α-SMA, FAP, and vimentin expression. RNA-sequencing was used to compare the transcriptomes between CAFs and NFs. The expressions of FAP, lumican, and α-SMA, human cytokine array, and Transwell assay were used to assess the transformation of NFs to CAFs. CCK-8 assay, colony formation, flow cytometry, Transwell assay, and nude mouse xenograft model were used to determine the effects of Serpin E1 on cell proliferation and metastasis in vitro and in vivo. Finally, Serpin E1 and/or FAP expression was measured in H. pylori-infected gerbil gastric mucosa and human gastric cancer tissues. RESULTS: Gastric CAFs are inflammatory CAFs with α-SMAlowFAPhighlumicanhigh. The interplay of H. pylori, fibroblasts, and cancer cells promotes the transition of NFs to CAFs by inducing cytokine release, especially Serpin E1. Long-term H. pylori infection and CAFs induce Serpin E1 expression in gerbil gastric tissues and human gastric cancer cells. Serpin E1 overexpression enhances the growth, migration, invasion of gastric cancer cells in vitro, and xenograft tumor growth in nude mice via inducing angiogenesis. Serpin E1 and FAP were highly expressed in cancer cells and CAFs of gastric cancer tissues, respectively, and a good correlation was observed between their expression. Higher Serpin E1 expression is negatively associated with the overall survival of patients with gastric cancer. CONCLUSIONS: The interplay of H. pylori, fibroblasts, and cancer cells induced Serpin E1 expression to promote the activation of NFs to CAFs and gastric carcinogenesis. Targeting Serpin E1 will provide a promising therapeutic strategy for gastric cancer by disrupting the interaction between H. pylori, CAFs, and gastric cancer cells.

Dickkopf-related protein 1/cytoskeleton-associated protein 4 signaling activation by Helicobacter pylori-induced activator protein-1 promotes gastric tumorigenesis via the PI3K/AKT/mTOR pathway.

BACKGROUND: Gastric cancer (GC) is a common malignant tumor with high incidence and mortality rates globally, especially in East Asian countries. Helicobacter pylori (H. pylori) infection is a significant and independent risk factor for GC. However, its underlying mechanism of action is not fully understood. Dickkopf-related protein (DKK) 1 is a Wnt signaling antagonist, and cytoskeleton-associated protein (CKAP) 4 is a newly identified DKK1 receptor. Recent studies found that the binding of DKK1 to CAKP4 mediated the procancer signaling of DKK1 inde-pendent of Wnt signaling. We hypothesize that H. pylori-induced activation of DKK1/CKAP4 signaling contributes to the initiation and progression of GC. AIM: To investigate the interaction of H. pylori infection, DKK1 and CAKP4 in GC, as well as the underlying molecular mechanisms. METHODS: RNA sequencing was used to identify differentially expressed genes (DEGs) between H. pylori-infected and uninfected primary GC cells. Gain- and loss-of-function experiments were performed to verify the H. pylori-induced upregulation of activator protein-1 (AP-1) in GC cells. A dual-luciferase reporter assay and co-immunoprecipitation were used to determine the binding of AP-1 to the DKK1 promoter and DKK1 to CKAP4. Western blotting and immunohistochemistry detected the expression of DKK1, CKAP4, and phos-phatidylinositol 3-kinase (PI3K) pathway-related proteins in GC cells and tissues. Functional experiments and tumorigenicity in nude mice detected malignant behavior of GC cells in vitro and in vivo. RESULTS: We identified 32 DEGs between primary GC cells with and without H. pylori infection, including JUN, fos-like antigen-1 (FOSL1), and DKK1, and confirmed that the three proteins and CKAP4 were highly expressed in H. pylori-infected GC cells, H. pylori-infected gerbil gastric tissues, and human GC tissues. JUN and FOSL1 form AP-1 to transcriptionally activate DKK1 expression by binding to the DKK1 promoter. Activated DKK1 bound to CKAP4, but not the most common Wnt coreceptor low-density lipoprotein receptor-related protein 5/6, to promote GC cell growth, colony formation, migration, invasion, and xenograft tumor growth in nude mice. All these effects were driven by activation of the PI3K/AKT/mammalian target of rapamycin (mTOR) pathway. Targeting the PI3K signaling pathway by LY294002 inhibited DKK1-mediated CKAP4/PI3K signaling activity and the malignant behavior of GC cells. CONCLUSION: H. pylori induces JUN and FOSL1 expression to form AP-1, which transcriptionally activates DKK1. Binding of DKK1 to KAKP4 contributes to gastric tumorigenesis via the PI3K/AKT/mTOR pathway.

The protective effect of cannabinoid type II receptor agonist AM1241 on ConA-induced liver injury in mice via mitogen-activated protein kinase signalling pathway.

INTRODUCTION: The endocannabinoid system plays an important role in regulating the immune responses in inflammation. At present, there are no good clinical drugs for many immune liver diseases. METHODS: We explored the protective effect of the cannabinoid type II (CB2) receptor agonist AM1241 on the liver of mice with acute liver injury caused by concanavalin from the perspective of inflammation and immunity. Pathological evaluation in hepatic tissue was examined by haematoxylin and eosin (HE) staining and the levels of biochemical parameters in the serum were measured by automatic biochemical analysis. The content of inflammatory factors was measured by enzyme-linked immunosorbent assay and real-time quantitative reverse transcription polymerase chain reaction (real-time PCR). The liver apoptosis-related proteins were observed by immunohistochemistry. The expression of liver injury-related proteins was analysed by Western blot. Immune cells were isolated from the liver of mice and studied in vitro. RESULTS: Reduced levels of alanine transaminase and aspartate transaminase were observed in ConA-induced liver injury mice treated with AM1241, together with attenuated liver damage evidenced by H&E staining. Moreover, AM1241 inhibited the protein and gene expression levels of TNF-α, IL-6 and IFN-γ in the livers of mice. The phosphorylation levels of p38, JNK, ERK1/2, P65 and cAMP response element-binding protein (CREB) in the mouse were significantly reduced in AM1241 pretreatment, while the level of p-JNK increased. In addition, the P/T-P65 and P/T-CREB of the AM1241 pretreatment group were significantly reduced. The results of immunohistochemistry measurement are consistent with those of Western blotting. The CB2-mediated effect is through macrophage-like Kupffer cells. CONCLUSION: Our study suggests that the ConA-induced liver injury model in mice is protected by CB2 agonist AM1241 by modulation of CB2 receptor-rich immune cells, for example, Kupffer cells. Reduced inflammatory responses regulate apoptosis/cell death in the liver particularly hepatocytes and other parenchymal cells.

Knockout of the Cannabinoid Receptor 2 Gene Promotes Inflammation and Hepatic Stellate Cell Activation by Promoting A20/Nuclear Factor-κB (NF-κB) Expression in Mice with Carbon Tetrachloride-Induced Liver Fibrosis.

BACKGROUND This study aimed to investigate the effect of deleting the cannabinoid receptor 2 (CB2) gene on the development of hepatic fibrosis induced by carbon tetrachloride (CCl4) in mice via regulating inflammation. MATERIAL AND METHODS The DNA was extracted from the tails of mice to identify whether the cannabinoid receptor 2 gene was successfully knocked out. A liver fibrosis model was established by an intraperitoneal injection of CCl4 into mice. Hepatic damage and hepatic fibrosis were evaluated by detecting serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and staining paraffin sections of liver tissue with hematoxylin-eosin (HE). The secretion and distribution of collagen in liver tissue were observed by Masson staining. Western blot analysis was performed to detect the expression of a-smooth muscle actin (alpha-SMA), transforming growth factor-ß1 (TGF-ß1), tumor necrosis factor alpha-induced protein 3 (A20), phosphorylated nuclear factor-kB p65 (p-NF-kappaB p65), tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) in liver tissue. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of IL-6 and TNF-alpha mRNA in liver tissue. RESULTS Compared with the control mice, the mice with CB2 knockout that were exposed to CCl4 exhibited increased liver damage, liver fibrosis, and upregulated alpha-SMA, TGF-ß1, A20, and p-NF-kappaB p65 protein levels. IL-6 and TNF-alpha protein levels and mRNA levels were upregulated. CONCLUSIONS The deletion of the CB2 gene promoted the activation of hepatic stellate cells in mice with liver fibrosis and aggravated liver fibrosis by up-regulating the protein expression of A20 and p-NF-kappaB p65 and inducing inflammatory response, potentially providing new insight into the treatment of liver fibrosis.

Study on the Appropriate Timing of Postoperative Adaptive Radiotherapy for High-Grade Glioma.

PURPOSE: To investigate the appropriate timing of adaptive radiotherapy (ART) for high-grade glioma. METHODS: Ten patients with high-grade gliomas were selected and underwent CT/MRI (CT1/MRI1, CT2/MRI2, CT3/MRI3, and CT4/MRI4) scans before RT and during 10-, 20- and 30-fraction RT, and the corresponding RT plans (plan1, plan2, plan3 and plan4) were made. The dose of the initial plan (plan1) was projected to CT2 and CT3 using the image registration technique to obtain the projection plans (plan1-2 and plan1-3) and by superimposing the doses to obtain the ART plans (plan10+20 and plan20+10), respectively. The dosimetric differences in the target volume and organs at risk (OARs) were compared between the projection and adaptive plans. The tumor control probability (TCP) for the planning target volume (PTV) and normal tissue complication probability (NTCP) for the OARs were compared between the two adaptive plans. RESULTS: Compared with the projection plan, the D2 to the PTV of ART decreased, the conformity index (CI) to the PTV increased, and the D2/Dmean to the brainstem, optic chiasm and pituitary, as well as the V20, V30, V40 and V50 to the normal brain decreased. The D2 to the pituitary and optic chiasm as well as the V20, V30, V40 and V50 to the normal brain in plan10+20 were lower than those in plan20+10, while the CI to the PTV was higher than that in plan20+10. The TCP of the PTV in plan10+20 was higher than that in plan20+10. CONCLUSION: ART can improve the precision of target volume irradiation and reduce the irradiation dose to the OARs in high-grade glioma. The time point after 10 fractions of RT is appropriate for ART.

Human Endogenous Retroviruses in Clear Cell Renal Cell Carcinoma: Biological Functions and Clinical Values.

Human endogenous retroviruses (HERVs) form an important part of the human genome, commonly losing their coding ability and exhibiting only rare expression in healthy tissues to promote the stability of the genome. However, overexpression of HERVs has been observed in various malignant tumors, including clear cell renal cell carcinoma (ccRCC), and may be closely correlated with tumorigenesis and progression. HERVs may activate the interferon (IFN) signaling pathway by a viral mimicry process to enhance antitumor immune responses. There is increasing interest in the diagnostic and prognostic value of HERVs in cancers, and they may be candidate targets for tumor immunotherapy. The review will introduce the biological functions of HERVs in ccRCC and their clinical value, especially in regard to immunotherapy.

Quantification of hepatic steatosis in histologic images by deep learning method.

OBJECTIVE: To develop and test a novel method for automatic quantification of hepatic steatosis in histologic images based on the deep learning scheme designed to predict the fat ratio directly, which aims to improve accuracy in diagnosis of non-alcoholic fatty liver disease (NAFLD) with objective assessment of the severity of hepatic steatosis instead of subjective visual estimation. MATERIALS AND METHODS: Thirty-six 8-week old New Zealand white rabbits of both sexes were fed with high-cholesterol, high-fat diet and sacrificed under deep anesthesia at various time points to obtain the pathological specimen. All rabbits were performed by multislice computed tomography for surveillance to measure density changes of liver parenchyma. A deep learning scheme using a convolutional neural network was developed to directly predict the liver fat ratio based on the pathological images. The average error value, standard deviation, and accuracy (error <5%) were evaluated and compared between the deep learning scheme and manual segmentation results. The Pearson's correlation coefficient was also calculated in this study. RESULTS: The deep learning scheme performs successfully on rabbit liver histologic data, showing a high degree of accuracy and stability. The average error value, standard deviation, and accuracy (error <5%) were 3.21%, 4.02%, and 79.10% for the cropped images, 2.22%, 1.92%, and 88.34% for the original images, respectively. The strong positive correlation was also observed for cropped images (R = 0.9227) and original images (R = 0.9255) in comparison to labeled fat ratio. CONCLUSIONS: This new deep learning scheme may aid in the quantification of steatosis in the liver and facilitate its treatment by providing an earlier clinical diagnosis.

Clinical findings and autophagic pathology in neutral lipid storage disease with myopathy.

Neutral lipid storage disease with myopathy (NLSDM) is a triglyceride metabolic disorder caused by defects of adipose triglyceride lipases (ATGL). The coexistence of lipid vacuoles and rimmed vacuoles in the myofibers is a characteristic pathological change in some NLSDM cases. However, it has not been explored whether autophagic abnormalities exist in the NLSDM myofibers with rimmed vacuole. Herein, we report that 5 patients with NLSDM initially presented with muscle weakness in the right arm related to long-term physical efforts, then developed muscle weakness of other limbs. Pathogenic mutations in the PNPLA2 gene were identified in all patients. Myopathological analysis showed a coexistence of massive lipid vacuoles and rimmed vacuoles, which was not associated with the age of onset or mutation sites, but closely related to the severity of muscle degeneration. The rimmed vacuoles showed strong immunopositivity to autophagic markers, but were negative to apoptotic markers. Significant immunoreactivity of p62 was observed in the rimmed vacuoles, while the lysosomal marker LAMP1 was severely decreased. Our study expanded the clinical and genetic spectrum of NLSDM. Loss of ATGL activity in muscle fibers with rimmed vacuoles induced a marked increase in autophagic formation, but lowered down the turnover of autolysosomes due to malfunction of lysosomes.

Plexiform fibromyxoma of the small bowel: A case report.

BACKGROUND: Plexiform fibromyxoma is a rare, special type of mesenchymal tumor. The most common presenting symptoms are anemia, hematemesis, and hematochezia, without sex or age predilection. The reported cases have mainly occurred in the gastric antrum and pylorus region, with some cases in the duodenum. CASE SUMMARY: We report here a case of plexiform fibromyxoma in the upper segment of the jejunum, which was continuously followed up for 3 years after surgical removal. Plexiform fibromyxoma showed multinodular or plexiform growth. The cells in the tumor node were spindle-shaped but few in number and mitotic figures. Small blood vessels and mucous matrix were found among the tumor cells. Immunohistochemistry revealed that the plexiform fibromyxoma cells were positive for smooth muscle actin, focally positive for CD10, and negative for cytokeratin, CD117, DOG-1 (discovered on GIST-1) desmin, S-100, epithelial membrane antigen, and CD34. Ki-67 labeling index was < 5%. Plexiform fibromyxoma showed benign biological behavior. After 3 years of consecutive postoperative follow-up, no obvious signs of metastasis or recurrence were found by imaging examination. CONCLUSION: Plexiform fibromyxoma is a rare type of mesenchymal tumor. The diagnosis mainly depends on pathological examination, and it should be distinguished from other gastrointestinal mesenchymal tumors.

The Concept of Ecthyma Gangrenosum Illustrated by a Fusarium oxysporum Infection in an Immunocompetent Individual.

Ecthyma gangrenosum (EG) involves necrotic cutaneous lesions caused by bacteria, mainly Pseudomonas aeruginosa, and is usually seen in immunocompromised patients with septicemia. However, clinically similar infections have been published with fungi as etiologic agents. We present a case of an EG-like lesion due to Fusarium oxysporum confirmed by clinical diagnosis, culture and molecular identification and discuss the definition of EG.

The clinical and genetic features in a cohort of mainland Chinese patients with thyrotoxic periodic paralysis.

BACKGROUND: Thyrotoxic periodic paralysis (TPP) is a life-threatening channelopathy manifesting as recurrent episodes of hypokalemia and muscle weakness in the presence of hyperthyroidism. Recent findings indicate defects of inward rectifying K+ (Kir) channels are associated with some TPP patients. The associations are not only found in Caucasian population (mainly Brazilian), but also in Singaporean population. However, potential genetic risk factors for mainland Chinese patients, the largest group of TPP cases in the world, have been largely unexplored. METHODS: Samples of DNA from 127 individuals with TPP and 102 hyperthyroidism male controls self-reported as mainland Chinese were collected from 5 clinical centers from Jan 2011 to Jan 2014. The KCNJ2 gene, KCNJ18 gene, as well as loci polymorphisms (rs623011and rs312691) at 17q24.3 were directly sequenced in TPP patients and controls. Clinical data were summarized from TPP participants for genotype/phenotype correlations. RESULTS: 3.1% of TPP cases harbored KCNJ18 gene mutations in mainland Chinese patients. Patients with KCNJ18 mutation had shorter attack duration, higher prevalence of muscle soreness and weakness recurrence than patients without KCNJ18 mutation. The alleles at 17q24.3 (rs623011and rs312691) were more common in patients with TPP than in controls, and therefore were significant risk factors for TPP (odds ratio, 11.94 and 10.57; 95% CI, 5.93-24.05 and 5.48-20.40; P = 1.81 × 10(-14) and 1.07 × 10(-14) respectively). CONCLUSIONS: This study demonstrates that the KCNJ18 variants are only responsible for a small proportion of TPP patients in mainland China. There are significant clinical differences between patients with KCNJ18 mutations and patients without KCNJ18 mutations. In addition, the rs623011and rs312691 loci are significantly associated with TPP patients in mainland China, and highlight the Kir2.1 channel as a causative target in TPP.