TGF-ß1/SMAD3-driven GLI2 isoform expression contributes to aggressive phenotypes of hepatocellular carcinoma.

Hedgehog signaling is activated in response to liver injury, and modulates organogenesis. However, the role of non-canonical hedgehog activation via TGF-ß1/SMAD3 in hepatic carcinogenesis is poorly understood. TGF-ß1/SMAD3-mediated non-canonical activation was found in approximately half of GLI2-positive hepatocellular carcinoma (HCC), and two new GLI2 isoforms with transactivating activity were identified. Phospho-SMAD3 interacted with active GLI2 isoforms to transactivate downstream genes in modulation of stemness, epithelial-mesenchymal transition, chemo-resistance and metastasis in poorly-differentiated hepatoma cells. Non-canonical activation of hedgehog signaling was confirmed in a transgenic HBV-associated HCC mouse model. Inhibition of TGF-ß/SMAD3 signaling reduced lung metastasis in a mouse in situ hepatic xenograft model. In another cohort of 55 HCC patients, subjects with high GLI2 expression had a shorter disease-free survival than those with low expression. Moreover, co-positivity of GLI2 with SMAD3 was observed in 87.5% of relapsed HCC patients with high GLI2 expression, indicating an increased risk of post-resection recurrence of HCC. The findings underscore that suppressing the non-canonical hedgehog signaling pathway may confer a potential strategy in the treatment of HCC.

Trends and projections of inflammatory bowel disease at the global, regional and national levels, 1990-2050: a bayesian age-period-cohort modeling study.

BACKGROUND: Inflammatory bowel disease (IBD) is a global health concern with varying levels and trends across countries and regions. Understanding these differences is crucial for effective prevention and treatment strategies. METHODS: Using data from the 2019 Global Burden of Disease study, we examine IBD incidence, mortality, and disability-adjusted life years (DALYs) rates in 198 countries from 1990 to 2019. To assess changes in the burden of IBD, estimated annual percentage changes (EAPC) were calculated, and a Bayesian age-period-cohort model was used to predict the future 30-year trends of IBD. RESULTS: In 2019, there were 405,000 new IBD cases globally (95% uncertainty interval (UI) 361,000 to 457,000), with 41,000 deaths (95% UI 35,000 to 45,000) and 1.62million DALYs (95% UI 1.36-1.92million). The global age-standardized incidence rate in 2019 was 4.97 per 100,000 person-years (95% UI 4.43 to 5.59), with a mortality rate of 0.54 (95% UI 0.46 to 0.59) and DALYs rate of 20.15 (95% UI 16.86 to 23.71). From 1990 to 2019, EAPC values for incidence, mortality, and DALYs rates were - 0.60 (95% UI - 0.73 to - 0.48), - 0.69 (95% UI - 0.81 to - 0.57), and - 1.04 (95% UI - 1.06 to - 1.01), respectively. Overall, the burden of IBD has shown a slow decline in recent years. In SDI stratification, regions with higher initial SDI (high-income North America and Central Europe) witnessed decreasing incidence and mortality rates with increasing SDI, while regions with lower initial SDI (South Asia, Oceania, and Latin America) experienced a rapid rise in incidence but a decrease in mortality with increasing SDI. Predictions using a Bayesian model showed lower new cases and deaths from 2020 to 2050 than reference values, while the slope of the predicted incidence-time curve closely paralleled that of the 2019 data. CONCLUSION: Increasing cases, deaths, and DALYs highlight the sustained burden of IBD on public health. Developed countries have stabilized or declining incidence rates but face high prevalence and societal burden. Emerging and developing countries experience rising incidence. Understanding these changes aids policymakers in effectively addressing IBD challenges in different regions and economic contexts.

Solid pseudopapillary neoplasm: Report of a case of primary ovarian origin and review of the literature.

Background: Solid pseudopapillary neoplasms (SPNs) are uncommon tumors of low malignancy with a generally favorable prognosis, mostly originating from the pancreas. To date, 12 cases of SPNs with a primary ovarian origin (SPN-Os) have been reported globally, and their detailed characteristics have not been fully elucidated. Case description: We reported the 13th SPN-O case, which occurred in a 52-year-old woman with an 18.5 cm left ovarian mass. Four imaging methods, including ultrasound, computed tomography, magnetic resonance imaging and positron emission tomography, were utilized before surgery. An elevated level of serum cancer antigen 125 was detected and a total hysterectomy plus bilateral salpingo-oophorectomy was performed. Microscopic examination revealed a typical solid pseudopapillary structure. The tumor cells were stained focally for pan-cytokeratin, synaptophysin, CD99 and CD10, while ß-catenin, vimentin and CD56 were diffusely expressed. The Ki-67 proliferation index was 3%, and immunohistochemical (IHC) staining for chromogranin-A, inhibin-a, and E-cadherin was negative. No evidence of recurrence or metastasis was observed by clinical and imaging data during a 5-month postoperative follow-up. Conclusion: This is a report of an unusual case of a primary ovarian SPN with an up-to-date review of SPN-Os. A minimum combination of imaging methods and IHC stains was proposed for SPN-Os, which may prove beneficial in clinical practice.

Therapeutic efficacy of nutritional support by percutaneous endoscopic gastrostomy in critically ill patients: A self-control clinical trial.

BACKGROUND & OBJECTIVE: Percutaneous endoscopic gastrostomy (PEG) is a procedure to provide enteral nutrition for critically ill patients. It is commonly used in clinical practice; however, the widespread use of PEG is controversial. Our objective was to evaluate the therapeutic effect of nutritional support by PEG in these critically ill patients. METHODS: A total of 64 critically ill patients including 41 males and 23 females (aged 23-84) were identified by the Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system during September 2004 to June 2012. The nutritional status before and after PEG was mainly assessed by the tricep skinfold thickness and serum albumin level. The nutritional status and pathological condition were assessed at 4, 8 and 12 weeks before and after PEG feeding. The assessment was according to the classical method of the human nutritional status. Follow-up was performed at one month, three months and 1.5 year after gastrostomy. Statistical analysis was performed by SPSS 11.5 software. The incidence of inhalation pneumonia and gastroesophageal regurgitation was compared by chi square (χ2) test. P<0.05 were considered statistically significant. RESULTS: Among the 64 patients, 9 patients died of their former diseases or related symptoms. Postoperative follow-up showed that both nutritional status and complications were improved after PEG in 55 patients (P<0.05). The serum albumin and tricep skinfold thickness levels were significantly increased. The incidence of hypoglycemia, hypocalcemia, hypokalemia and hyponatremia were lower than pre-operation. The frequencies of complications were significantly reduced. No severe complications occurred in any patient. CONCLUSIONS: Our study confirmed that PEG was a good long-term route of nutritional supply with no serious complications for critically ill patients.

[Influence of bear bile on rat hepatocarcinoma induced by diethylnitrosamine].

To investigate the influence of bear bile on rat hepatocarcinoma induced by diethylnitrosamine (DEN), a total of 40 rats were randomly divided into 4 groups: normal control group, model group, and two bear bile treatment groups. The rat liver cancer model was induced by breeding with water containing 100 mg x L(-1) DEN for 14 weeks. The rats of the bear bile groups received bear bile powder (200 or 400 mg x kg(-1)) orally 5 times per week for 18 weeks. The general condition and the body weight of rats were examined every day. After 18 weeks the activities of serum alanine transaminase (ALT), aspartate transaminase (AST) and total bilirubin (TBIL) were detected. Meanwhile, the pathological changes of liver tissues were observed after H&E staining. The expression of proliferative cell nuclear antigen (PCNA) and a-smooth muscle actin (alpha-SMA) in liver tissue were detected by immunohistochemical method. After 4 weeks the body weights of rats in normal group were significantly more than that in other groups (P < 0.05); and that in the two bile groups was significantly more than that in the model group. Compared with normal group, the level of serum glutamic-pyruvic transaminase and total bilirubin increased significantly in other groups; compared with model group, these two indexes decreased significantly in two bile groups. Hepatocellular carcinoma occurred in all rats except for normal group; there were classic cirrhosis and cancer in model group while there were mild cirrhosis and high differentiation in two bile groups. There were almost no expressions of PCNA and alpha-SMA in normal group while there were high expressions in model group; the two bile groups had some expressions but were inferior to the model group, and alpha-SMA reduced markedly. It indicated that bear bile restrained the development of liver cancer during DEN inducing rat hepatocarcinoma, which may be related to its depressing hepatic stellate cell activation and relieving hepatic lesion and cirrhosis.

Chinese visible human project.

Research on the digital visible human is of great significance and has considerable application value. The US visible human project created the first digital image dataset of a complete human (one male and one female) in 1995. To promote worldwide application-oriented visible human research, additional visible human datasets, representative of different populations of the world, are needed. The Chinese visible human (CVH) male (created in October 2002) and female (created in February 2003) Project achieved greater integrity of images, better blood vessel identification, and were free of organic disease. The most noteworthy technical advance of the Chinese visible human project (CVHP) was the construction of a low temperature laboratory, which prevented loss of small structures (including teeth, nasal conchae, and articular cartilage) from the milling surface. Thus, better integrity of images was achieved. To date, we have acquired five CVH datasets and volume rendered them for visualization on a PC. 3D reconstruction of some organs and structures has been completed and work to segment a complete dataset is under way. Although there is still a long way to go to make the visible human meet the application-oriented needs in various fields, progress is being made toward acquiring new datasets, performing segmentation, and setting up a platform of computer-assisted medicine. Here, we review the history and highlights of the CVHP and foresee its future development as well.

Segmentation and three-dimension reconstruction of Chinese digitized human cerebrum.

OBJECTIVE: A 3D digitized visible model of human cerebrum was built to provide anatomical structure for making plans of cerebral surgical operation and realizing accurate simulation of cerebrum on computer. METHODS: Transverse sectional anatomy data of the cerebrum were chosen from the first Chinese visible human (one male and one female). Semi-automated segmentation and Photoshop software were selected to segment cerebral cortex, white matter, basal nuclei, lateral ventricle, hippocampus, etc. On personal computer, the segmented structures were reconstructed in 3D with volume rendering reconstruction and surface rendering reconstruction. RESULTS: Two accurately segmented images of the main structures of cerebrum were completed. The reconstructed structures can be displayed singly, in small groups or as a whole and can be continuously rotated in 3D space at different velocities. CONCLUSION: Combining volume-rendering reconstruction with surface rendering reconstruction overcomes the defects of surface rendering reconstruction that lack of internal anatomical information, which provides a new method for 3D reconstruction. The reconstructed cerebrum and the main internal structures are realistic, which demonstrates the natural shape and exact position of the structures. It provides an accurate model for the automated segmentation algorithmic study and provides a digitized anatomical mode of cerebrum.

Chinese visible human project: dataset acquisition and its primary applications.

The research on digital visible human is of great significance and application value. The US Visible Human Project (VHP) created the first digital image data set of a complete human (one male and one female) in 1995. To promote a worldwide application-oriented VHR, more visible human data sets representative of different populations of the world are in demand. The Chinese Visible Human (CVH) male (created in Oct. 2002) and female (created in Feb. 2003) project achieved greater integrity of images, easier blood vessel identification, and were free of organic lesion. The most noteworthy technical advance of CVH Project was the construction of a low temperature laboratory, which contributed to the prevention of small structures (including teeth, concha nasalis, and articular cartilage) from falling off out of the milling surface. Thus, better integrity of images can be ensured. So far, we have achieved an acquisition of five CVH data sets and the corresponding volume visualization on PC. The 3D reconstruction of some organs or structures has been finished. The work of segmentation on a complete data set is still on-going.

[Visualization and thin sectional anatomy of the laryngeal cartilages].

OBJECTIVE: To establish digitized visible model of the laryngeal cartilages of the visible human, providing morphological data for image diagnosis and laryngectomy. METHODS: Cross-sectional images of fresh tissues from the Chinese visible human data set were reviewed, and the laryngeal cartilages structures data were used, the data was on a section-by-section basis. Three-dimensional computer reconstructions of the laryngeal cartilages were generated from these data by surface rendering on a SGI workstation. RESULTS: The digital images from the visible human offer unique insights into the complex anatomy and ossification of the laryngeal cartilages, the quality of the computerized 3D-reconstructed images was distinct and perfect. CONCLUSIONS: The visible human data set can provide complete and accurate data The digitized model of the laryngeal cartilages offer unique insights into the laryngeal anatomy, could be used for resident education, rehearsal of an unfamiliar surgery and for developing a new surgical approach.

Three-dimensional computational reconstruction of lateral skull base with plastinated slices.

The goals of this study were to build the 3D reconstructed model of lateral skull base and to explore the spatial relationships of the important structures for providing the morphological basis for lateral skull base surgery and clinical image diagnosis. Blocks with edges of about 80 mm containing the lateral skull base region and adjacent structures were sawn out from both sides of the heads and sectioned on transverse plane at a thickness of 700 microm using a plastination technique. On an SGI workstation, a Contours-Marching cubes algorithm was selected to reconstruct the 3D model of the lateral skull base. Accurate alignment of the structures in the serial macroscopic sections was obtained by the employment of the plastination technique. The quality of the reconstructed images was distinct and perfect, specifically, the spatial positions and complicated adjacent relationships of various structures of the lateral skull base can be shown in direct viewing when they are displayed in background of the cranial bony substance. The time spent in displaying or rotating one image including 50 sections was 1.5 sec; all reconstructed structures can be represented individually or jointly and rotated in any plane. The plastination technique and computer-aided 3D reconstruction have an obvious advantage in the study of the complex anatomy of the lateral skull base. Plastination technique provides cross-section images of a higher resolution than those obtained from CT scanning. The computerized 3D reconstruction is important in studying the spatial anatomy of the lateral skull base and can serve as a standard for models created with other techniques.

The Chinese Visible Human (CVH) datasets incorporate technical and imaging advances on earlier digital humans.

We report the availability of a digitized Chinese male and a digitzed Chinese female typical of the population and with no obvious abnormalities. The embalming and milling procedures incorporate three technical improvements over earlier digitized cadavers. Vascular perfusion with coloured gelatin was performed to facilitate blood vessel identification. Embalmed cadavers were embedded in gelatin and cryosectioned whole so as to avoid section loss resulting from cutting the body into smaller pieces. Milling performed at -25 degrees C prevented small structures (e.g. teeth, concha nasalis and articular cartilage) from falling off from the milling surface. The male image set (.tiff images each of 36 Mb) has a section resolution of 3072 x 2048 pixels ( approximately 170 micro m, the accompanying magnetic resonance imaging and computer tomography data have a resolution of 512 x 512, i.e. approximately 440 micro m). The Chinese Visible Human male and female datasets are available at http://www.chinesevisiblehuman.com. (The male is 90.65 Gb and female 131.04 Gb). MPEG videos of direct records of real-time volume rendering are at: http://www.cse.cuhk.edu.hk/~crc

Creation of the Chinese visible human data set.

The United States Visible Human Project (VHP) created a digital image data set of complete human male (data acquisition finished in November 1994) and female (data acquisition finished in December 1995) cadavers in magnetic resonance imaging (MRI), computed tomography (CT), and anatomical (anatomic serial section) modes. VHP aroused worldwide enthusiasm for Visible Human Research (VHR), and the data set is being used in a variety of research and educational domains. The Visible Korean Human (VKH) male was produced in March 2001. To accelerate worldwide VHR and to promote virtual anatomy as a revolutionary break with conventional anatomy, more visible human data sets representative of different populations of the world are in demand. The Chinese Visible Human (CVH) male (created in October 2002) and female (created in February 2003) project achieved greater integrity of images, easier blood vessel identification, and were free of organic lesion (unlike the other visible human projects). We performed data acquisition, three-dimensional (3D) reconstruction, and visualization with improved technology to create CVH male and female. CVH is the first volumetric data representing a complete normal adult human male and female of an Asian population. This article presents the history of Chinese Visible Human cadavers and the methods and technology used to produce the data set.

Plastination and computerized 3D reconstruction of the temporal bone.

The purpose of this study was to generate a computerized 3D reconstruction of the temporal bone and intratemporal structures. A plastination technique was used to obtain equidistant serial thin sections of 1.2 mm thickness and, on an SGI workstation, a Contour-Marching Cubes algorithm was selected to reconstruct the temporal bone and intratemporal structures in three dimensions. All reconstructed structures can be represented individually or jointly and rotated in any plane. Any diameter and angle of a structure can be conveniently measured. The capability of reconstructing individual and combined images of intratemporal structures, viewing them from all surgical angles, and accurately measuring their spatial relationships gives skull base and otologic surgeons important guidance. The reconstructed model can also be used for resident education, rehearsal of an unfamiliar surgery, and for developing a new surgical approach.