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Background The prognosis for patients with colorectal-cancer liver metastases (CRLM) after curative surgery remains poor and shows great heterogeneity. Early recurrence, defined as tumor recurrence within 6 months of curative surgery, is associated with poor survival, requiring earlier detection and intervention. This study aimed to develop and validate a bedside model based on clinical parameters to predict early recurrence in CRLM patients and provide insight into post-operative surveillance strategies. Material and methods A total of 202 consecutive CRLM patients undergoing curative surgeries between 2012 and 2019 were retrospectively enrolled and randomly assigned to the training (n = 150) and validation (n = 52) sets. Baseline information and radiological, pathological, and laboratory findings were extracted from medical records. Predictive factors for early recurrence were identified via a multivariate logistic-regression model to develop a predictive nomogram, which was validated for discrimination, calibration, and clinical application. Results Liver-metastases number, lymph-node suspicion, neurovascular invasion, colon/rectum location, albumin and post-operative carcinoembryonic antigen, and carbohydrate antigen 19–9 levels (CA19–9) were independent predictive factors and were used to construct the nomogram for early recurrence after curative surgery. The area under the curve was 0.866 and 0.792 for internal and external validation, respectively. The model significantly outperformed the clinical risk score and Beppu’s model in our data set. In the lift curve, the nomogram boosted the detection rate in post-operative surveillance by two-fold in the top 30% high-risk patients. Conclusion Our model for early recurrence in CRLM patients after curative surgeries showed superior performance and could aid in the decision-making for selective follow-up strategies.

Background Bilateral herpes zoster (BHZ) is an atypical presentation of herpes zoster (HZ), with few cases reported before. Ramsay Hunt syndrome (RHS) is an uncommon complication of VZV infection. Cases of BHZ with RHS in immunocompetent adults have been reported rarely. Case presentation We described an immunocompetent adult who suffered from left-sided thoracic herpes zoster and contralateral RHS simultaneously, and summarizes the characteristics of BHZ. Conclusions Cases of BHZ with RHS in immunocompetent adults have not been reported previously. Antivirus - glucocorticoid combination therapy showed a good effect in this case.

The myocyte enhancer factor 2 (MEF2) factors act as lynchpins in cell differentiation and organogenesis through transcriptional circuits and thus potentiate development of vertebrate. Nevertheless, the association between mutations in Myocyte enhancer factor 2 (MEF2s) especially MEF2C (Myocyte enhancer factor 2C) and livestock growth remains largely unknown. Here, in Nanjiang Yellow goat population (female, n = 219), we identified 10 single nucleotide variations (SNVs) in MEF2C using direct Sanger sequencing PCR product from DNA and cDNA. Among which eight were located in exons while two (g.143180 T>G and g.143666 C>T) were in introns, and the only one mutation embedded in coding region (g. 143515 C>T) led to a Pro 148 Ser exchange. In this goat population, all these ten SNVs presented lower to moderate polymorphism (0.28 0.05). Notably, four SNVs including g.76303 A>G, g.143180 T>G, g.176090 A>G, and g.176845 T>C significantly associated with goat growth (p G variation even exceeded those H3H4 animals by over ~20% from birth to 12-mon old (p G variation exhibited no connection with exon α splicing of MEF2C, but in silicon analysis revealed that T to G mutation potentially increased DNA accessibility of g.143180 T>G per se and the following 14-bp region by 2 to 22 fold, which directly relates the binding of dlx5 (Distal-Less Homeobox 5). These results confirm the close relationship between MEF2C and animal development, and also provide an important option guiding study in elucidating the substantial mechanisms that MEF2C exerts in promoting mammal growth.

Purpose: Colorectal liver metastasis (CRLM) is the major cause of death due to colorectal cancer. Although great efforts have been made in treatment of CRLM, about 60–70% of patients will develop hepatic recurrence. Hepatic steatosis was reported to provide fertile soil for metastasis. However, whether hepatic steatosis predicts higher incidence of CRLM recurrence is not clear. Therefore, we aimed to determine the role of hepatic steatosis in CRLM recurrence in the present study.Methods: Consecutive CRLM patients undergoing curative treatment were retrospectively enrolled and CT liver-spleen attenuation ratio was used to detect the presence of hepatic steatosis. In patients with hepatic steatosis, we also detected the presence of fibrosis. Besides, a systematic literature search was performed to do meta-analysis to further analyze the association between hepatic steatosis and CRLM recurrence.Results: A total of 195 eligible patients were included in our center. Patients with hepatic steatosis had a significantly worse overall (P = 0.0049) and hepatic recurrence-free survival (RFS) (P = 0.0012). Univariate and multivariate analysis confirmed its essential role in prediction of RFS. Besides, hepatic fibrosis is associated with worse overall RFS (P = 0.039) and hepatic RFS (P = 0.048). In meta-analysis, we included other four studies, with a total of 1,370 patients in the case group, and 3,735 patients in the control group. The odds ratio was 1.98 (95% CI: 1.25–3.14, P = 0.004), indicating that patients with steatosis had a significantly higher incidence of CRLM recurrence.Conclusion: In summary, patients with hepatic steatosis had a significantly worse overall and hepatic RFS and it's associated with higher incidence of CRLM recurrence.

Background. Stage II colorectal cancer patients had heterogeneous prognosis, and patients with recurrent events had poor survival. In this study, we aimed to identify stage II colorectal cancer recurrence associated genes by microarray meta-analysis and build predictive models to stratify patients’ recurrence-free survival. Methods. We searched the GEO database to retrieve eligible microarray datasets. The microarray meta-analysis was used to identify universal recurrence associated genes. Total samples were randomly divided into the training set and the test set. Two survival models (lasso Cox model and random survival forest model) were trained in the training set, and AUC values of the time-dependent receiver operating characteristic (ROC) curves were calculated. Survival analysis was performed to determine whether there was significant difference between the predicted high and low risk groups in the test set. Results. Six datasets containing 651 stage II colorectal cancer patients were included in this study. The microarray meta-analysis identified 479 recurrence associated genes. KEGG and GO enrichment analysis showed that G protein-coupled glutamate receptor binding and Hedgehog signaling were significantly enriched. AUC values of the lasso Cox model and the random survival forest model were 0.815 and 0.993 at 60 months, respectively. In addition, the random survival forest model demonstrated that the effects of gene expression on the recurrence-free survival probability were nonlinear. According to the risk scores computed by the random survival forest model, the high risk group had significantly higher recurrence risk than the low risk group (HR = 1.824, 95% CI: 1.079–3.084, p = 0.025). Conclusions. We identified 479 stage II colorectal cancer recurrence associated genes by microarray meta-analysis. The random survival forest model which was based on the recurrence associated gene signature could strongly predict the recurrence risk of stage II colorectal cancer patients.

Background Angiopoietin-like protein 1 (ANGPTL1) has been proved to suppress tumor metastasis in several cancers. However, its extracellular effects on the pre-metastatic niches (PMNs) are still unclear. ANGPTL1 has been identified in exosomes, while its function remains unknown. This study was designed to explore the role of exosomal ANGPTL1 on liver metastasis in colorectal cancer (CRC). Methods Exosomes were isolated by ultracentrifugation. The ANGPTL1 level was detected in exosomes derived from human CRC tissues. The effects of exosomal ANGPTL1 on CRC liver metastasis were explored by the intrasplenic injection mouse model. The liver PMN was examined by vascular permeability assays. Exosomal ANGPTL1 localization was validated by exosome labeling. The regulatory mechanisms of exosomal ANGPTL1 on Kupffer cells were determined by RNA sequencing. qRT-PCR, Western Blot, and ELISA analysis were conducted to examine gene expressions at mRNA and protein levels. Results ANGPTL1 protein level was significantly downregulated in the exosomes derived from CRC tumors compared with paired normal tissues. Besides, exosomal ANGPTL1 attenuated liver metastasis and impeded vascular leakiness in the liver PMN. Moreover, exosomal ANGPTL1 was mainly taken up by KCs and regulated the KCs secretion pattern, enormously decreasing the MMP9 expression, which finally prevented the liver vascular leakiness. In mechanism, exosomal ANGPTL1 downregulated MMP9 level in KCs by inhibiting the JAK2-STAT3 signaling pathway. Conclusions Taken together, exosomal ANGPTL1 attenuated CRC liver metastasis and impeded vascular leakiness in the liver PMN by reprogramming the Kupffer cell and decreasing the MMP9 expression. This study suggests a suppression role of exosomal ANGPTL1 on CRC liver metastasis and expands the approach of ANGPTL1 functioning.

PSTPIP1-associated myeloid-related proteinaemia inflammatory (PAMI) syndrome has been described as a rare and distinct clinical phenotype of PSTPIP1-associated inflammatory diseases. We report PSTPIP1 mutation in both father and son who have leukopenia and acne-like lesions. Through whole-exome sequencing on blood DNA, it is found a heterozygous mutation of PSTPIP1 gene c.748G>A on the father and son. The diagnosis of PAMI is made based on DNA sequencing results and clinical characteristics of typical lesions, leukopenia, and the markedly increased serum S100A8/A9 (calprotectin).

Tumor organoids recapitulate pathological properties and would serve as an excellent ex vivo model for drug discovery. Here, we performed an unbiased drug screening on drivers-defined tumor organoids from mouse endometrial cancer, the most prevalent gynecological malignancy in human, with a small molecule library targeting epigenetic factors. Among them, menin-MLL inhibitors MI-136 and MI-463 scored. The therapeutic capacity of MI-136 was further validated in tumor organoids in vitro and an orthotopic model in vivo. CRISPR/cas9-mediated mutations of major components of the menin-MLL complex, Men1, Kmt2a and Ash2l, inhibited the growth of tumor organoids, suggesting that the complex was the target of MI-136. Transcriptome analysis showed that the hypoxia-inducible factor (HIF) pathway was the most significantly downregulated pathway by MI-136 treatment. Consistently, Men1, Kmt2a, and Ash2l knockout also repressed the expressions of the HIF target genes. Loss of Hif1a or Hif1b partially phenocopied the inhibition of the menin-MLL complex by MI-136 or mutations in term of tumor organoid growth. Further, we found that MEN1 was upregulated in human endometrial cancers, which were tightly correlated with the expression levels of HIF1A, and associated with poor prognosis. Importantly, MI-136 also significantly inhibited the growth of endometrial cancer organoids derived from patients. Thus, our study identified MI-136 as a potential inhibitor for endometrial cancer through regulating the HIF pathway, a novel molecular mechanism distinguished from those in AML and prostate cancer.

Objective To achieve universal access to medical resources—a partial goal of the second ambitious health reform since 2010—the Chinese government aimed to build a regional medical consortium and enhance the efficiency of health information exchange (HIE). We analyzed the experience of constructing a medical consortium in Chinese hospitals, which was based on regional health information technology (RHIT) promoted by HIE. Method In this longitudinal study, we analyzed the results of the annual surveys that were conducted by the China Hospital Information Management Association from 2006 to 2015. The survey results mainly concerned whether hospitals should join the regional medical consortium, the methods used for sharing inter-hospital medical data, and the out-of-hospital information interaction system. The Bass diffusion model was adopted to fit and predict the proportion of Chinese hospitals joining the consortium from 2006 to 2025. Result As of 2015, the survey results of 7272 hospitals were obtained. The proportion of hospitals in partnership systems increased from 3.0% in 2007 to 57.2% in 2015. There has been a rapid development in the electronic sharing of medical data between hospitals. The proportion of hospitals that relied solely on paper documents for data interaction decreased from 43.3% in 2011 to 8.0% in 2015. There was a strong positive linear correlation between hospitals joining the consortium and the accessibility of electronic medical data exchange within hospitals (r = 0.925). The proportions of hospitals that supported dual referral systems and appointments, data browsing between hospitals and regional information systems, and remote consultation services increased to 65.0%, 61.6%, and 81.9% in 2015, as compared to 18.8%, 16.8%, and 10.9% in 2011, respectively. The Bass prediction model showed that the goal of recruiting 90% of the hospitals to the consortium by 2020 will likely be achieved (adjusted R2 = 0.93). Conclusion The Chinese government has applied a top-down, high-level design model to promote the rapid development of a medical consortium, in which the RHIT technologies are crucial technical enabler.

Background To achieve universal access to medical resources, China introduced its second health care reform in 2010, with health information technologies (HIT) as an important technical support point. Objective This study is the first attempt to explore the unique contributions and characteristics of HIT development in Chinese hospitals from the three major aspects of hospital HIT—human resources, funding, and materials—in an all-around, multi-angled, and time-longitudinal manner, so as to serve as a reference for decision makers in China and the rest of the world when formulating HIT development strategies. Methods A longitudinal research method is used to analyze the results of the CHIMA Annual Survey of Hospital Information System in China carried out by a Chinese national industrial association, CHIMA, from 2007 to 2018. The development characteristics of human resources, funding, and materials of HIT in China for the past 12 years are summarized. The Bass model is used to fit and predict the popularization trend of EMR in Chinese hospitals from 2007 to 2020. Results From 2007 to 2018, the CHIMA Annual Survey interviewed 10,954 hospital CIOs across 32 administrative regions in Mainland China. Compared with 2007, as of 2018, in terms of human resources, the average full time equivalent (FTE) count in each hospital’s IT center is still lower than the average level of US counterparts in 2014 (9.66 FTEs vs. 34 FTEs). The proportion of CIOs with a master’s degree or above was 25.61%, showing an increase of 18.51%, among which those with computer-related backgrounds accounted for 64.75%, however, those with a medical informatics background only accounted for 3.67%. In terms of funding, the sampled hospitals’ annual HIT investment increased from ¥957,700 (US $136,874) to ¥6.376 million (US $911,261), and the average investment per bed increased from ¥4,600 (US $658) to ¥8,100 (US $1158). In terms of information system construction, as of 2018, the average EMR implementation rate of the sampled hospitals exceeded the average level of their US counterparts in 2015 and their German counterparts in 2017 (85.26% vs. 83.8% vs. 68.4%, respectively). The results of the Bass prediction model show that Chinese hospitals will likely reach an adoption rate of 91.4% by 2020 (R2=0.95). Conclusions In more than 10 years, based on this top-down approach, China’s medical care industry has accepted government instructions and implemented the unified model planned by administrative intervention. With only about one-fifth of the required funding, and about one-fourth of the required human resources per hospital as compared to the US HITECH project, China’s EMR coverage in 2018 exceeded the average level of its US counterparts in 2015 and German counterparts in 2017. This experience deserves further study and analysis by other countries.