Molecular dynamics-guided optimization of BGM0504 enhances dual-target agonism for combating diabetes and obesity.

The dual activation of glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) has emerged as a promising therapeutic strategy for managing type 2 diabetes and obesity. Tirzepatide, a dual agonist peptide, has exhibited superior clinical efficacy in glycemic and weight control compared to selective GLP-1R agonists. Nevertheless, the structural basis of Tirzepatide's extended half-life, attributed to an acylation side chain on the parent peptide, raises questions regarding its partial agonistic activity. Employing molecular dynamics simulations, we explored the dynamic processes of peptide-receptor interactions. We uncovered a crucial salt bridge between parent peptide and GLP-1R/GIPR at K20, a feature not discernible in cryo-electron microscopy structures. Building upon these insights, we developed an optimization strategy based on the parent peptide which involved repositioning the acylation side chain. The results of both in vitro and in vivo experiments demonstrated that the optimized peptide has twofold to threefold increase in agonistic activity compared to Tirzepatide while maintaining its extended half-life in plasma. This led to the design of BGM0504, which proved to be more effective than its predecessor, Tirzepatide, in both laboratory and animal studies.

A pan-cancer analysis identifies SOAT1 as an immunological and prognostic biomarker.

Sterol o-acyltransferase1 (SOAT1) is an enzyme that regulates lipid metabolism. Nevertheless, the predictive value of SOAT1 regarding immune responses in cancer is not fully understood. Herein, we aimed to expound the predictive value and the potential biological functions of SOAT1 in pan-cancer. Raw data related to SOAT1 expression in 33 different types of cancer were acquired from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. SOAT1 expression was significantly increased in most cancers and showed a distinct correlation with prognosis. This enhanced expression of the SOAT1 gene was confirmed by evaluating SOAT1 protein expression using tissue microarrays. In addition, we found significant positive associations between SOAT1 expression levels and infiltrating immune cells, including T cells, neutrophils, and macrophages. Moreover, the co-expression analysis between SOAT1 and immune genes showed that many immune-related genes were increased with enhanced SOAT1 expression. A gene set enrichment analysis (GSEA) revealed that the expression of SOAT1 correlated with the tumor microenvironment, adaptive immune response, interferon signaling, and cytokine signaling. These findings indicate that SOAT1 is a potential candidate marker for predicting prognosis and a promising target for tumor immunotherapy in cancers.

Preliminary clinical study of the safety of hepatectomy predicted by gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced T1 mapping magnetic resonance imaging.

BACKGROUND AND AIM: Studies have found that gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced T1 mapping magnetic resonance imaging (MRI) could assess liver fibrosis, cirrhosis, and function with high effectiveness. The aim of this study is to explore the efficacy of MRI in predicting the safety of hepatectomy. METHODS: Forty-nine patients who underwent liver resection were recruited. Gd-EOB-DTPA-enhanced MRI examination was performed 1 week before surgery, and the rate of T1 relaxation time reduction (ΔT120min%) of liver parenchyma was calculated. Posthepatectomy liver failure (PHLF) was defined by the "50-50 criteria" and International Study Group of Liver Surgery (ISGLS) classification, respectively, and posthepatectomy complications (PHC) were defined by the Clavien-Dindo grading system. The effectiveness of ΔT120min% in predicting the occurrence of PHLF and PHC was analyzed. RESULTS: The area under the curve (AUC) for ΔT120min% predicting PHLF meeting "50-50 criteria" was 0.957, with a cutoff value of 0.497, sensitivity of 100%, and specificity of 89.1%. The AUC for predicting ISGLS grade B/C (severe) PHLF was 0.84, with a cutoff value of 0.5232, sensitivity of 63.6%, and specificity of 92.6%. The AUC for predicting PHC of Clavien-Dindo grades 3-5 (severe) was 0.882, with a cutoff value of 0.5646, sensitivity of 87.5%, and specificity of 75.8%. Univariate and multivariate analyses showed that ΔT120min% < 0.4970 (P < 0.01) was an independent risk factor for the development of PHLF (50-50 criteria). Univariate and multivariate analyses showed that liver stiffness measurement and ΔT120min% were risk factors for severe PHLF and severe PHC. CONCLUSIONS: Gd-EOB-DTPA-enhanced T1 mapping MRI accurately predicts the safety of hepatectomy.

ATOH8 overexpression inhibits the tumor progression and monocyte chemotaxis in hepatocellular carcinoma.

OBJECTIVE: ATOH8 is reported to be associated with the progression of many tumors; however, there are remaining controversies. The aim of this study is to explore the role of ATOH8 in hepatocellular carcinoma (HCC) and its effect on monocyte chemotaxis. METHODS: Bioinformatics analysis was performed based on the LIHC data in GEPIA and LinkedOmic. Fresh human liver cancer and adjacent nontumor tissue specimens were collected at the Shanghai Public Health Clinical Center. qRT-PCR was performed to determine the transcript level, and western blot analysis and ELISA were used to detect protein expression. CCK8, colony formation, wound-healing, Transwell migration and invasion assays were performed to examine cell proliferation, migration and invasion. An HCC xenograft mouse model was used to determine oncogenicity in vivo. Cell apoptosis and related markers were detected by flow cytometry. Additionally, chemotaxis was assessed by the Transwell migration assay. RESULTS: ATOH8 expression is downregulated in HCC tissue and hepatoma cell lines. High expression of ATOH8 predicts a favorable prognosis. Overexpression of ATOH8 in liver cancer cells inhibits proliferation, migration and invasion in vitro, and tumor progression in nude mice. Knockdown of ATOH8 promotes proliferation of Huh7 and EMT-related proteins. Overexpression of ATOH8 increases chemosensitivity to 5-FU, which is probably caused by inhibiting the phosphorylation of AKT (Ser473). Furthermore, overexpression of ATOH8 in Huh7 reduced MCP1 to inhibit chemotactic THP-1, and promoted antitumor inflammatory cytokine (TNF-α and IFN-γ) secretion in monocytes. CONCLUSION: In addition to the intrinsic oncosuppressive function of ATOH8 in the liver, ATOH8 may modulate the microenvironment to create an immune activation state. This may partly be attributed to ATOH8 inhibition of the monocyte recruitment via suppressing MCP1 expression so as to promote antitumor inflammatory cytokine secretion in monocytes.

Actual long-term survival in HCC patients with portal vein tumor thrombus after liver resection: a nationwide study.

BACKGROUND: Liver resection for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) offers a chance of cure, although survival is often limited. The actual 3-year survival and its associated prognostic factors have not been reported. METHODS: A nationwide database of HCC patients with PVTT who underwent liver resection with 'curative' intent was analyzed. The clinicopathologic characteristics, the perioperative, and survival outcomes for the actual long-term survivors were compared with the non-long-term survivors (patients who died within 3 years of surgery). Univariable and multivariable regression analyses were performed to identify predictive factors associated with long-term survival outcomes. RESULTS: The study included 1590 patients with an actuarial 3-year survival of 16.6%, while the actual 3-year survival rate was 11.7%. There were 171 patients who survived for at least 3 years after surgery and 1290 who died within 3 years of surgery. Multivariable regression analysis revealed that total bilirubin > 17.1 µmol/l, AFP > 400 ng/ml, types of hepatectomy, extent of PVTT, intraoperative blood loss > 400 ml, tumor diameter > 5 cm, tumor encapsulation, R0 resection, liver cirrhosis, adjuvant TACE, postoperative early recurrence (< 1 year), and recurrence treatments were independent prognostic factors associated with actual long-term survival. CONCLUSION: One in nine HCC patients with PVTT reached the long-term survival milestone of 3 years after resection. Major hepatectomy, controlling intraoperative blood loss, R0 resection, adjuvant TACE, and 'curative' treatment for initial recurrence should be considered for patients to achieve better long-term survival outcomes.

A panel of five plasma proteins for the early diagnosis of hepatitis B virus-related hepatocellular carcinoma in individuals at risk.

BACKGROUND: To improve the early diagnosis of hepatocellular carcinoma (HCC), more effective diagnostic biomarkers are needed. A combination of biomarkers is reported to distinguish individuals with early-stage HCC from at-risk individuals. METHODS: Participants in this study were recruited from six hospitals in China. Literature review was used to choose 19 candidate proteins, a case-control study in the discovery stage was used to identify five proteins (P5) that constituted a diagnostic model. In the training and validation stages, the effectiveness of P5 for detecting early-stage HCC was tested (cross-sectional study). Finally, a nested case-control study independent of the other stages was set up to evaluate the P5 in the preclinical diagnosis of HCC. FINDINGS: Between February 2013 and June 2017, a total of 1396 participants were recruited. A panel of 5 proteins (P5: OPN, GDF15, NSE, TRAP5 and OPG) showed high diagnostic accuracy when differentiating the early-stage HCC from the at-risk group, with AUCs of 0·892, 0·907 and 0·852 for the training stage, validation cohort 1 and cohort 2 data sets, respectively. In the prediction set, the sensitivity of P5 for diagnosing preclinical HCC increased with time, starting from 12 months before to the time of definitive clinical diagnosis (range, 46·15% to 86·67%). INTERPRETATION: The P5 panel has the potential to screen populations at high risk of developing HCC and can enable the early diagnosis of HCC. FUNDING: Research supported by grants from eight funds. All sources of funding were declared at the end of the text.

Upregulated calcium-binding tyrosine phosphorylation-regulated protein-a/b regulates cell proliferation and apoptosis and predicts poor prognosis in hepatocellular carcinoma.

BACKGROUND: Calcium-binding tyrosine phosphorylation-regulated protein (CABYR) is a group of isoforms produced by alternative splicing and is overexpressed in human malignancies including hepatocellular carcinoma (HCC). However, the prognostic value and biological functions of its major protein isoforms, named CABYR-a/b (combined CABYR-a and CABYR-b), in HCC remain to be established. METHODS: CABYR-a/b expression was detected in HCC tissues and cell lines by quantitative real-time polymerase chain reaction and Western blot analysis. The correlation of CABYR-a/b expression with clinical characteristics and its prognosis impact were determined by statistical analysis. Finally, the biological functions and molecular mechanism of CABYR-a/b were also investigated using molecular biology approaches. RESULTS: The present research found that CABYR-a/b was markedly elevated in HCC specimens and cell lines. Upregulated CABYR-a/b level had positive association with tumor size and differentiation in patients. Moreover, cases with elevated CABYR-a/b level had poorer overall survival (OS) and disease-free survival (DFS) than those with reduced CABYR-a/b level. Multivariate analysis and prognostic nomograms demonstrated that CABYR-a/b overexpression was an independent predictive indicator for OS and DFS. The calibration curve for the odds of OS and DFS demonstrated that the prediction by nomograms was in excellent accordance with actual situation. CABYR-a/b downregulation suppressed cell proliferation and induced G1-phase arrest via decreasing cyclin D1 and cyclin dependent kinase 4, while promoted apoptosis by reducing B-cell lymphoma 2 (Bcl-2) and increasing Bcl-2-associated death promoter. CONCLUSION: Our research indicates that CABYR-a/b exerts an oncogenic effect on HCC development and may become a new prognostic indicator for patients with HCC.

Design, synthesis and antitumor activity of a novel PEG-A6-conjugated irinotecan derivative.

A novel PEG-A6-conjugated irinotecan derivative 8 was designed and synthesized as antitumor agent by the PEGylation and A6-peptide modification of irinotecan. In vivo antitumor activity screening assay revealed that 8 exhibited better in vivo antiproliferation activity than irinotecan and its previous PEG-cRGD-conjugated derivative BGC0222 in MIA PaCa-2, NCI-H446, MDA-MB-231, HT-29 and NCI-N87 xenograft models, while the tumor of one in six mice in NCI-H446 assay and the tumors of two in six mice in MIA PaCa-2 assay completely subsided and disappeared within the 21-day period of 8-treatment, indicating that 8 should be a potential antitumor agent.

STAT gene family mRNA expression and prognostic value in hepatocellular carcinoma.

BACKGROUND: Signal transducer and activator of transcription (STAT) proteins are well-known transcription factors that play an important role in the progression of cancer. However, the association between STAT family genes and hepatocellular carcinoma (HCC) remains unclear. This study investigates the expression level, the prognostic value and the potential mechanism of STAT family genes in HCC. METHODS: Data from 365 HCC patients in The Cancer Genome Atlas (TCGA) database and 241 HCC patients in the Gene Expression Omnibus (GEO) database were used to investigate the diagnostic and prognostic values of STAT genes by survival analysis and nomogram. Gene set enrichment analysis (GSEA) was used to investigate the potential mechanism of the STAT genes in the development of HCC. RESULTS: Our results showed that STAT4/5B mRNA expression levels in HCC tissues were lower than those in normal tissues. Importantly, our results indicated that high expression of STAT5A, STAT5B and STAT6 was associated with better overall survival in HCC patients. Joint effects analysis of STAT5A, STAT5B and STAT6 suggested that the prognosis difference for any combination of genes was more significant than that for any individual gene. Then, we developed a risk score model could predict HCC prognosis and the nomogram visualized gene expression and clinical factors of probability for HCC prognosis. The ROC and calibration curves showed good performance in survival prediction in both the TCGA and the GEO databases. GSEA suggested that high expression of STAT5A, STAT5B and STAT6 were involved in immune-related biological processes, drug metabolism cytochrome P450, JAK-STAT signalling pathway, and PPAR signalling pathways. CONCLUSION: Our data suggest that STAT5A, STAT5B and STAT6 expression may be potential prognostic markers of HCC and, in combination, have a better predictive value for HCC prognosis.

Design, synthesis and pharmacological evaluation of a novel PEG-cRGD-conjugated irinotecan derivative as potential antitumor agent.

A novel PEG-cRGD-conjugated irinotecan derivative BGC0222 was designed and synthesized as antitumor agent. Antitumor activity screening assay indicated that BGC0222 exhibited better in vitro antiproliferation activity than irinotecan and NKTR-102 against HT29, MIA PaCa-2 and MCF-7 tumor cell lines, with IC50 of 1.83 ±â€¯0.09 µM, 3.95 ±â€¯0.16 µM and 0.68 ±â€¯0.04 µM, respectively, while it displayed better in vivo antiproliferation activity than irinotecan and NKTR-102 in HT-29, MIA PaCa-2, NCI-H446, U-87 MG and MDA-MB-231 xenograft models. The action mechanism of BGC0222 was then investigated by integrin-binding competition (IBC) and chick chorioallantoic membrane (CAM) angiogenesis assays, which indicated that BGC0222 may exert antitumor activity by binding to αvß3 target and consequently inducing neovascularization effect. Pharmacokinetic analysis showed that BGC0222 could slowly and steadily release irinotecan, which was subsequently metabolized into 7-ethyl-10-hydroxycamptothecin (SN-38) in the whole blood.

Protective effect of electro-acupuncture on liver ischemia-reperfusion injury in rats.

Liver ischemia-reperfusion injury is an important clinical complication in which excessive inflammation is a key factor; however, few studies have provided effective means of its regulation. As previous studies suggested that electro-acupuncture (EA) is able control excessive inflammation, the present study aimed to explore its effects on liver ischemia-reperfusion injury in experimental rats. The animals were randomly divided into surgery and sham groups, which were further divided into four sub-groups, including a non-treatment (NT), a non-point acupuncture (NPA), the non-selective nicotinic acetylcholine receptor (AChR) agonist 1,1-dimethyl-4-phenyl L-pioperazinium iodide (DMPPI) and an EA group. The alanine aminotransferase (ALT), serum cytokine and myeloperoxidase (MP) levels and the tissue pathology were evaluated after 90 min of ischemia followed by a 4, 8 or 24 h reperfusion. The results demonstrated that EA and DMPPI suppressed serum ALT elevation at 4 and 8 h reperfusion, whereas NPA did not. I/R induced hepatocellular necrosis, and cytoplasmic vacuolization and sinusoidal congestion was ameliorated by EA treatment after an 8 and 24 h reperfusion. In addition, EA also inhibited liver neutrophil accumulation, evidenced by a decreased MPO level at 8 h reperfusion. EA also suppressed the release of serum inflammatory factors TNF-α and IL-6 for the duration of reperfusion. However, little influence on IL-10 was observed. Mechanistically, vagus block by subphrenic vagotomy or mecamylamine hydrochloride abolished EA effect on liver damage, neutrophil accumulation and inflammatory factor release. In conclusion, it was demonstrated that EA protects the liver against I/R induced injury by inhibiting the inflammatory response, which is associated with the vagus.

Metabolic syndrome relates to high risk in hepatocellular carcinoma: a meta-analysis.

Metabolic syndrome (MetS) has been linked to the development of cancer. The relationship between MetS and hepatocellular carcinoma (HCC) remains controversial. Studies up to September 2017 of MetS and HCC were systematically identified and meta-analyzed. Ten studies (nine cohorts and one case-control) were included in this meta-analysis. It was found that MetS patients are significantly more likely to develop HCC (RR = 1.60, 95%CI = 1.12-2.28, P = 0.01). Additionally, when only cohort studies were included, MetS is a potential risk factor for HCC occurrence (RR = 1.52, 95%CI = 1.01-2.30, P = 0.05). Interestingly, subgroup analysis showed that male patients with MetS are more likely to develop HCC compared with female patients (RR = 1.91, 95%CI = 1.38-2.65, P < 0.0001 in male and RR = 2.1, 95%CI = 0.69-6.37, P = 0.19 in female). Additionally, MetS could significantly increase the risk of HCC in the Euro-US population (RR = 1.71, 95%CI = 1.09-2.67, P = 0.02). In conclusion, metabolic syndrome might be associated with a high risk of HCC occurrence, especially in male and the Euro-US population. However, no statistical significances were found between MetS and HCC clinicopathological features including capsule, vascular invasion, and moderate-poor differentiation, and between MetS and HCC survivals. Prospectively, well-designed trials with large numbers of samples should be conducted to evaluate the links between MetS and HCC.

A novel wireless and temperature-compensated SAW vibration sensor.

A novel wireless and passive surface acoustic wave (SAW) based temperature-compensated vibration sensor utilizing a flexible Y-cut quartz cantilever beam with a relatively substantial proof mass and two one-port resonators is developed. One resonator acts as the sensing device adjacent to the clamped end for maximum strain sensitivity, and the other one is used as the reference located on clamped end for temperature compensation for vibration sensor through the differential approach. Vibration directed to the proof mass flex the cantilever, inducing relative changes in the acoustic propagation characteristics of the SAW travelling along the sensing device, and generated output signal varies in frequency as a function of vibration.  A theoretical mode using the Rayleigh method was established to determine the optimal dimensions of the cantilever beam. Coupling of Modes (COM) model was used to extract the optimal design parameters of the SAW devices prior to fabrication. The performance of the developed SAW sensor attached to an antenna towards applied vibration was evaluated wirelessly by using the precise vibration table, programmable incubator chamber, and reader unit.  High vibration sensitivity of ~10.4 kHz/g, good temperature stability, and excellent linearity were observed in the wireless measurements.

Liver-to-spleen ratio as an index of chronic liver diseases and safety of hepatectomy: a pilot study.

BACKGROUND: Hepatic failure is a main cause of death after hepatectomy. Accurate preoperative evaluation of functional liver reserve is the key to ensure safe resection. Studies have found that the spleen would gradually enlarge as chronic liver disease worsened. This study was designed to determine whether preoperative liver-to-spleen ratio (LSR) would be an indicator to evaluate severity of liver disease and predict safety of hepatectomy. METHODS: The volumes of liver and spleen were evaluated on computed tomography scan in 67 patients who received partial hepatectomy. Preoperative LSR was calculated. Statistical analysis was conducted to examine the relationship between LSR and the degree of chronic liver disease. Ability of LSR to predict the safety of hepatectomy also was evaluated. RESULTS: LSR had a negative correlation with the degree of chronic liver diseases (r = -0.606, P < 0.0001). LSR = 3.22 was the cutoff point for predicting posthepatectomy complications and inadequacy. AUC, sensitivity, and specificity for predicting posthepatectomy complications and inadequacy respectively were 0.830 (95 % confidence interval [CI] 0.715-0.950, P < 0.0001), 69.6, 93.2 %, and 0.863 (95 % CI 0.777-0.949, P < 0.0001), 68.8, 84.3 %. Multivariate analysis showed that LSR = 3.22 was the factor that affected both posthepatectomy complications and liver inadequacy. CONCLUSIONS: Preoperative LSR score correlated well with the degree of chronic liver diseases, and it probably help us to improve the safety of hepatectomy.

A near-vision chart for children aged 3-5 years old: new designs and clinical applications.

AIM: To introduce a new near-vision chart for children aged 3-5 years old and its clinical applications. METHODS: The new near-vision chart which combined the Bailey-Lovie layout with a newly devised set of symmetry symbols was designed based on Weber-Fechner law. It consists of 15 rows of symmetry symbols, corresponding to a visual acuity range from 1.3 to 0.1 logMAR. The optotypes were red against a white background and were specially shaped four basic geometric symbols: circle, square, triangle, and cross, which matched the preschool children's cognitive level. A regular geometric progression of the optotype sizes and distribution was employed to arrange in 15 lines. The progression rate of the optotype size between two lines was 1.2589 and two smaller groups of optotypes ranging from 0.7 to -0.1 logMAR were included for repetitive testing. A near visual acuity was recorded in logMAR or decimal, and the testing distance was 25 cm. RESULTS: This new near-vision chart with pediatric acuity test optotypes which consists of 4 different symbols (triangle, square, cross, and circle) met the national and international eye chart design guidelines. When performing the near visual acuity assessment in preschoolers (3-5 years old). It overcame an inability to recognize the letters of the alphabet and difficulties in designating the direction of black abstract symbols such as the tumbling 'E' or Landolt 'C', which the subjects were prone to lose interest in. Near vision may be recorded in different notations: decimal acuity and logMAR. These two notations can be easily converted each other in the new near-vision chart. The measurements of this new chart not only showed a significant correlation and a good consistency with the Chinese national standard logarithmic near-vision chart (r=0.932, P<0.01), but also indicated good test-retest reliability (89% of retest scores were within 0.1 logMAR units of the initial test score) and a high response rate. CONCLUSION: The results of this study support the validity and reliability of near visual acuity measurements using the new near-vision chart in children aged 3-5y over a wide range of visual acuities, and the new eye chart was especially suitable for the detection of amblyopia risk factors and low vision examination in children (3-5y of age). It can be applied in routine clinical practice.

Bevacizumab attenuates hepatic fibrosis in rats by inhibiting activation of hepatic stellate cells.

Angiogenesis is a fundamental part of the response to tissue injury, which is involved in the development of hepatic fibrosis. Vascular endothelial growth factor plays an important role in angiogenesis. The expression of VEGF is increased during hepatic fibrogenesis and correlates with the micro-vessel density. In this study, we investigated the effects of bevacizumab, an anti-angiogenetic drug, on the formation of hepatic fibrosis. We found that bevacizumab could attenuate the development of hepatic fibrosis and contribute to the protection of liver function. Bevacizumab was also found to downregulate the expression α-SMA and TGF-ß1, which have been reported to be profibrogenic genes in vivo. We also observed that the expression of VEGF increased significantly during the development of hepatic fibrosis and CCl4 was found to induce hepatocytes to secrete VEGF, which led to the activation and proliferation of HSCs. Bevacizumab was also found to block the effects of the hepatocytes on the activation and proliferation of HSCs. Our results suggest that bevacizumab might alleviate liver fibrosis by blocking the effect of VEGF on HSCs. Bevacizumab might be suitable as a potential agent for hepatic fibrosis therapy.

A new specialized visual acuity chart for amblyopic children aged 3-5 years old: development and its clinical applications.

AIM: To introduce a new specialized visual acuity chart for amblyopic children aged 3-5 years old and its clinical applications. METHODS: The new visual acuity chart and notations were designed based on Weber-Fechner law. The optotypes were red against a white background and were specially shaped four basic geometric symbols: circle, square, triangle, and cross. A regular geometric progression of the optotype sizes and distribution was employed to arrange in 14 lines. The progression rate of the optotype size between two lines was 1.2589 and the testing distance was 3m. Visual acuity score could be recorded as logMAR notation or decimal notation. Age-stratified diagnostic criteria for amblyopia established by consensus statement on diagnosis of amblyopia (2011) among members of the Strabismus and Pediatric Ophthalmology Group, Ophthalmology Society, Chinese Medical Association (SPOGOSCMA) were illustrated in the new visual acuity chart. RESULTS: When assessing visual acuity in children aged 3-5 years old, this new visual acuity chart that consists of four symmetrical shapes (triangle, square, cross, and circle) overcame an inability to recognize the letters of the alphabet and difficulties in designating the direction of black abstract symbols such as the tumbling 'E' or Landolt 'C', which the subjects were prone to lose interest in. The visual acuity score may be recorded in different notations: decimal acuity and logMAR. These two notations can be easily converted each other in the new eye chart. The measurements of this new chart not only showed a significant correlation and a good consistency with the international standard logarithmic visual acuity chart (r=0.932, P<0.01), but also indicated a high test-retest reliability (89% of retest scores were within 0.1logMAR units of the initial test score). CONCLUSION: The results of this study support the validity and reliability of distance visual acuity measurements using the new eye chart in children aged 3 to 5 years over a wide range of visual acuities, and the new eye chart is great for early detection of amblyopia. It can be applied in various clinical settings.

Primary retroperitoneal carcinosarcoma in a child: a case report.

Carcinosarcoma is a rare biphasic malignancy consisting of intermixed epithelial and mesenchymal elements. Carcinosarcoma is particularly rare among children. We accepted a 7 year old patient with retroperitoneal carcinosarcoma. The tumor was totally resected and no recurrence is found 11 months after operation. Literatures has been reviewed and there are few reports of primary retroperitoneal carcinosarcoma in children up to date. So we report the patient's clinical character, surgical resection, pathological and immunohistochemical analysis.

Primary hepatic neuroendocrine carcinoma: clinical analysis of 11 cases.

BACKGROUND: Primary hepatic neuroendocrine carcinoma (PHNEC) is extremely rare, and fewer than 300 cases have been reported in the English/Chinese-language literature, therefore it is difficult to make a proper diagnosis and determine a therapeutic approach. METHODS: Eleven PHNEC patients were admitted to our hospital between January 1996 and May 2008. Laboratory examination, digestive endoscopy, B-ultrasonography, CT, MRI, or PET-CT were performed on the patients for preoperative diagnosis. All patients received liver resection. Some patients received transcatheter arterial chemoembolization (TACE), percutaneous ethanol injection treatment (PEIT), or octreotide injection when a recurrence was found. The patients' clinical data were recorded and all patients were followed up. RESULTS: The patients were confirmed pathologically as having PHNEC . Their median follow-up time was 33 months (12-107 months). All patients survived, and the longest post-operative survival time was 107 months, the longest disease-free survival time was 98 months, the 1-year survival rate was 100%, and the 1-year recurrence rate was 45.5% (5/11). CONCLUSIONS: Since PHNEC is easy to confuse with hepatocellular carcinoma, careful screening of symptoms is needed to avoid misdiagnosis. Resection is the first choice of treatment for PHNEC and provides the most favorable outcomes including long-term survival. Other treatment such as TACE and PEIT can be considered as well, especially when a tumor recurs.