Alternative Splicing Factor Heterogeneous Nuclear Ribonucleoprotein U as a Promising Biomarker for Gastric Cancer Risk and Prognosis with Tumor-Promoting Properties.

Gastric cancer (GC) is a major global health concern with poor outcomes. Heterogeneous nuclear ribonucleoprotein U (HNRNPU) is a multifunctional protein that participates in pre-mRNA packaging, alternative splicing regulation, and chromatin remodeling. Its potential role in GC remains unclear. In this study, the expression characteristics of HNRNPU were analyzed by The Cancer Genome Atlas data, Gene Expression Omnibus data, and then further identified by real-time quantitative PCR and immunohistochemistry using tissue specimens. From superficial gastritis, atrophic gastritis, and hyperplasia to GC, the in situ expression of HNRNPU protein gradually increased, and the areas under the curve for diagnosis of GC and its precancerous lesions were 0.911 and 0.847, respectively. A nomogram integrating HNRNPU expression, lymph node metastasis, and other prognostic indicators exhibited an area under the curve of 0.785 for predicting survival risk. Knockdown of HNRNPU significantly inhibited GC cell proliferation, migration, and invasion and promoted apoptosis in vitro. In addition, RNA-sequencing analysis showed that HNRNPU could affect alternative splicing events in GC cells, with functional enrichment analysis revealing that HNRNPU may exert malignant biological function in GC progression through alternative splicing regulation. In summary, the increased expression of HNRNPU was significantly associated with the development of GC, with a good performance in diagnosing and predicting the prognostic risk of GC. Functionally, HNRNPU may play an oncogenic role in GC by regulating alternative splicing.

Transformation risk and associated survival outcome of marginal zone lymphoma: A nationwide study.

Histological transformation into an aggressive B-cell lymphoma indicates a poor survival outcome for patients with indolent marginal zone lymphoma (MZL), which has been less studied. Large-scale data with long-term follow-up to investigate MZL transformation is limited. Here, by reporting a US-Nationwide cohort of 30,619 MZL patients diagnosed between 2000 and 2019, we found that transformation occurred in 2.08% (N = 624) of MZL cases, with the transformation incidence of 3.1 per 1,000 person-years. Advanced Ann Arbor stage, nodal MZL (NMZL) and splenic MZL (SMZL) were associated with an elevated risk of transformation. Certain subtype-specific characteristics, such as non-gastric extra-nodal MZL (vs. gastric, HR, 1.51, 95%CI 1.13-2.04; p = 0.006), and receiving splenectomy for SMZL (HR, 2.04, 95%CI 1.28-3.26; p = 0.003), also indicated a higher risk of transformation. Besides, transformation independently increased the overall mortality risk (HR, 1.38, 95%CI 1.24-1.53, p < 0.001), especially the higher lymphoma-caused mortality risk (HR, 3.21, 95%CI 2.81-3.67, p < 0.001). Transformation was also associated with a higher percentage of lymphoma-caused deaths. The post-transformation prognostic analyses demonstrated that female gender and age ≥ 65 years independently affected patients' mortalities. These findings, based on the largest cohort to date, contribute to a better understanding of transformed MZL, and provide valuable reference points for guidelines and patient counseling.

Alteration of Thyroid Hormones in Mouse Models of Alzheimer's Disease and Aging.

INTRODUCTION: Aging is characterized by the deterioration of a wide range of functions in tissues and organs, and Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment. Hypothyroidism occurs when there is insufficient production of thyroid hormones (THs) by the thyroid. The relationship between hypothyroidism and aging as well as AD is controversial at present. METHODS: We established an animal model of AD (FAD4T) with mutations in the APP and PSEN1 genes, and we performed a thyroid function test and RNA sequencing (RNA-Seq) of the thyroid from FAD4T and naturally aging mice. We also studied gene perturbation correlation in the FAD4T mouse thyroid, bone marrow, and brain by further single-cell RNA sequencing (scRNA-seq) data of the bone marrow and brain. RESULTS: In this study, we found alterations in THs in both AD and aging mice. RNA-seq data showed significant upregulation of T-cell infiltration- and cell proliferation-related genes in FAD4T mouse thyroid. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that upregulated genes were enriched in the functional gene modules of activation of immune cells. Downregulated energy metabolism-related genes were prominent in aging thyroids, which reflected the reduction in THs. GSEA showed a similar enrichment tendency in both mouse thyroids, suggesting their analogous inflammation state. In addition, the regulation of leukocyte activation and migration was a common signature between the thyroid, brain, and bone marrow of FAD4T mice. CONCLUSIONS: Our findings identified immune cell infiltration of the thyroid as the potential underlying mechanism of the alteration of THs in AD and aging.

MAFLD with central obesity is associated with increased risk of colorectal adenoma and high-risk adenoma.

OBJECTIVE: To analyze the risk factors associated with colorectal adenoma and to investigate the associations of metabolism-related fatty liver disease (MAFLD) with obesity, colorectal adenoma and high-risk adenoma. METHODS: A total of 1395 subjects were enrolled and divided into a colorectal adenoma group (593 subjects) and a control group (802 subjects) according to the inclusion and exclusion criteria. The characteristics of patients in the colorectal adenoma group and the control group were compared by the chi-square test. Univariate and multivariate logistic analyses were used to analyze independent risk factors and associations with different MAFLD subtypes. Colorectal adenoma characteristics and the proportion of patients with high-risk colorectal adenoma were also compared. RESULTS: High-density lipoprotein (HDL-C) was significantly lower in patients in the colorectal adenoma group than in those in the control group (P < 0.001). Logistic regression analysis revealed that age, obesity status, central obesity status, hypertension status, diabetes status, fatty liver status, smoking history, BMI, waist circumference, triglyceride level, HDL-C level, fasting blood glucose level and degree of hepatic steatosis were all independent risk factors for colorectal adenoma. Notably, MAFLD was associated with a significantly increased risk of colorectal adenoma in patients with central obesity (P < 0.001). In addition, obesity, central obesity, diabetes, fatty liver and degree of hepatic steatosis were all shown to be independent risk factors for high-risk colorectal adenoma. In addition, a greater proportion of MAFLD patients with central obesity than those without central obesity had high-risk colorectal adenoma. CONCLUSION: MAFLD and central obesity are independently associated with the development of colorectal adenoma. MAFLD with central obesity is associated with an increased risk of colorectal adenoma and high-risk adenoma.

Tri-ortho-cresyl phosphate induces hepatic steatosis by mTOR activation and ER stress induction.

Tri-ortho-cresyl phosphate (TOCP), an organophosphorus compound (OP), which is widely used as plasticizer, flame retardant and other industrial products, has been reported to cause multiple toxicities including neurotoxicity and reproductive toxicity. However, it remains to be elusive whether TOCP induces hepatotoxicity. The purpose of this study was to investigate the effect of TOCP on hepatocytes and the lipid metabolism in particular. The adult mice were given a single dose of TOCP (800 mg/kg, p.o.) and the histological changes in liver tissue and lipid content in serum were determined. The results showed that more vacuoles and lipid droplets were observed in the liver of the mice exposed to TOCP. And triglyceride concentrations in serum and liver tissue significantly increased. However, the histopathological changes of the liver and the elevated triglyceride levels in the exposed mice can be reversed by endoplasmic reticulum (ER) stress inhibitor 4-phenylbutyric acid and mTOR signal inhibitor rapamycin. It was also found that the changes of expression levels of the biomarkers of ER stress and mTOR signaling pathway, such as GRP78, CHOP, and p-mTOR, in the exposed mice were consistent with those observed in the cultured primary hepatocytes treated with the same chemicals. These results showed that TOCP activated mTOR signal and ER stress to induce de novo lipid synthesis, which led to the hepatic steatosis in mouse.

Immediate Ansa cervicalis-to-recurrent laryngeal nerve low-tension anastomosis: A new technique for phonation recovery and bilateral anastomoses to avoid tracheotomy.

OBJECTIVE: This case series study investigated the outcomes of an innovative approach, ansa cervicalis nerve (ACN)-to-recurrent laryngeal nerve (RLN) low-tension anastomosis. METHODS: Patients who received laryngeal nerve anastomosis between May 2015 and September 2021 at the facility were enrolled. The inclusion criteria were patients with RLN dissection and anastomosis immediately during thyroid surgery. Exclusion criteria were cases with anastomosis other than cervical loop-RLN anastomosis or pronunciation recovery time > 6 months. Patients admitted before January 2020 were assigned to group A which underwent the conventional tension-free anastomosis, and patients admitted after January 2020 were group B and underwent the innovative low-tension anastomosis (Dong's method). RESULTS: A total of 13 patients were included, 11 patients received unilateral surgery, and 2 underwent bilateral surgery. For patients who underwent unilateral anastomosis, group B had a significantly higher percentage of normal pronunciation via GRBAS scale (83.3 % vs. 0 %, p = 0.015) and voice handicap index (66.7 % vs. 0 %, p = 0.002), and shorter recovery time in pronunciation (median: 1-day vs. 4 months, p = 0.001) than those in group A after surgery. CONCLUSIONS: ACNs-to-RLN low-tension anastomosis with a laryngeal segment ≤1 cm (Dong's method) significantly improves postoperative pronunciation and recovery time. The results provide clinicians with a new strategy for ACN -to-RLN anastomosis during thyroid surgery.

Development and validation a radiomics nomogram for predicting thymidylate synthase status in hepatocellular carcinoma based on Gd-DTPA contrast enhanced MRI.

OBJECTIVES: The purpose of this study was to develop and validate a radiomics nomogram for predicting thymidylate synthase (TYMS) status in hepatocellular carcinoma (HCC) by using Gd-DTPA contrast enhanced MRI. METHODS: We retrospectively enrolled 147 consecutive patients with surgically confirmed HCC and randomly allocated to training and validation set (7:3). The TYMS status was immunohistochemical determined and classified into low TYMS (positive cells ≤ 25%) and high TYMS (positive cells > 25%) groups. Radiomics features were extracted from the arterial phases and portal venous phase of Gd-DTPA contrast enhanced MRI. Least absolute shrinkage and selection operator (LASSO) were applied for generating the Rad score. Clinical data and MRI findings were assessed to build a clinical model. Rad score combined with clinical features was used to construct radiomics nomogram. RESULTS: A total of 2260 features were extracted and reduced to 7 features as the most important discriminators to build the Rad score. InAFP was identified as the only independent clinical factors for TYMS status. The radiomics nomogram showed good discrimination in training (AUC, 0.759; 95% CI 0.665-0.838) and validation set (AUC, 0.739; 95% CI 0.585-0.860), and showed better discrimination capability (P < 0.05) compared with clinical model in training (AUC, 0.656; 95% CI 0.555-0.746) and validation set (AUC, 0.622; 95% CI 0.463-0.764). CONCLUSIONS: The radiomics nomogram shows favorable predictive efficacy for TYMS status in HCC, which might be helpful for the personalized treatment of HCC.

Bone Microarchitecture and Volumetric Mineral Density Assessed by HR-pQCT in Patients with 21- and 17α-Hydroxylase Deficiency.

Due to disturbances in hormones and long-term glucocorticoid replacement therapy (GRT), congenital adrenocortical hyperplasia (CAH) patients are at risk of impaired bone structure and metabolism. This cross-sectional, case-control study aims to investigate for the first time bone microarchitecture features in 21-hydroxylase deficiency (21OHD; N = 38) and 17α-hydroxylase deficiency (17OHD; N = 16) patients using high-resolution peripheral quantitative computed tomography (HR-pQCT) by matching the same sex and similar age [21OHD vs. control: 29.5 (24.0-34.3) vs. 29.6 (25.9-35.2) years; 17OHD vs. controls: 29.0 (21.5-35.0) vs. 29.7 (24.6-35.3) years] with healthy controls (1:3). All patients underwent HR-pQCT scans of the nondominant radius and tibia, and had received GRT. Compared with corresponding controls, 17OHD cases had higher height (P < 0.001), weight (P = 0.013) and similar body mass index (BMI), while 21OHD had lower height (P < 0.001), similar weight and higher BMI (P < 0.001). 17OHD and 21OHD patients demonstrated various significant bone differences in most HR-pQCT indices, suggesting abnormalities in bone microarchitectures from healthy people. Further correlation analyses revealed that some characteristics, such as height and hormones, may contribute to the bone differences in HR-pQCT indices between two diseases. However, treatment dosage and time were not correlated, indicating that the current glucocorticoid doses may be within safety limits for bone impairment. Overall, our study for the first time revealed changes of bone microarchitecture in CAH patients and their potential relations with clinical characteristics. Further longitudinal researches are required to confirm these findings.

Patients with low body mass index are more likely to develop shoulder pain after laparoscopy.

INTRODUCTION: Shoulder pain is one of the most common complications after laparoscopy. Previous studies have found a number of methods to reduce shoulder pain after laparoscopic surgery, but these methods have not been targeted to specific populations. The purpose of this study was to identify people who are more likely to develop shoulder pain. MATERIAL AND METHODS: A total of 203 patients underwent laparoscopy for benign gynecological diseases between July 2020 and February 2021. Patients were divided into two groups according to the Chinese overweight standard, body mass index less than 24 kg/m2 group and 24 kg/m2 or more group. The baseline characteristics and intraoperative data between the two groups were compared. The intensity of the shoulder pain was quantified using a visual analog scale (VAS). RESULTS: The incidence and the VAS scores of shoulder pain were significantly higher in the less than 24 kg/m2 group (63.64% vs 38.03%, p < 0.001 in incidence; median 5 (interquartile range [IQR] 3-7) vs 3 (IQR 2-5), p < 0.001 in VAS scores), and the chance of shoulder pain within 24 hours after laparoscopy was higher in the less than 24 kg/m2 group (89.29% vs 66.67%, p = 0.013). In univariate and multivariate logistic regression analysis, BMI less than 24 kg/m2 was an independent risk factor of shoulder pain after laparoscopic surgery (p = 0.001, p = 0.031, respectively). Shoulder pain scores were inversely correlated with BMI (r = -0.300, p = 0.001). CONCLUSIONS: Patients with low body mass index are more likely to develop shoulder pain after laparoscopy, with earlier onset and higher pain scores.

Pyroptosis related genes signature predicts prognosis and immune infiltration of tumor microenvironment in hepatocellular carcinoma.

Little is known on the relationship between the expression of pyroptosis related genes (PRGs) and prognosis of hepatocellular carcinoma (HCC). In this study, a specific PRGs prognostic model was developed with an aim to improve therapeutic efficiency among HCC patients. In total, 42 PRGs that were differentially expressed between HCC tissues and adjacent tissues and we exhibited the mutation frequency, classification, the location of copy number variation (CNV) alteration and the CNV variation frequency of PRGs. Two clusters were distinguished by the consensus clustering analysis based on the 42 differentially expressed genes (DEGs). There were significant differences in clinical features including T stage, grade, gender, and stage among different clusters. Kaplan-Meier curve analysis showed that cluster 1 had a better prognosis than cluster 2. The prognostic value of PRGs for survival was evaluated to construct a multigene signature using The Cancer Genome Atlas (TCGA) cohort. Based on the univariate analysis and multivariate analysis, a 10-gene signature was built and all HCC patients in the TCGA cohort were divided into low-risk group and high-risk group. HCC patients in the high-risk group showed significantly lower survival possibilities than those in the low-risk group (P < 0.001). Utilizing the median risk score from the TCGA cohort, HCC patients from International Cancer Genome Consortium (ICGC)-LIRI-JP cohort and Gene Expression Omnibus (GEO) cohort (GSE14520) were divided into two risk subgroups. The result showed that overall survival (OS) time was decreased in the high-risk group. Combined with the clinical characteristics, the risk score was an independent factor for predicting the OS of HCC patients. Then, ROC curve and survival analysis were performed to evaluate the prognostic prediction value of the model. Finally, we constructed a PRGs clinical characteristics nomogram to further predict HCC patient survival probability. There were significant differences in immune cell infiltration, GSEA enrichment pathway, IC50 of chemotherapeutics, PRGs mutation frequency between high-risk group and low-risk group. This work suggests PRGs signature played a crucial role in predicting the prognosis, infiltration of cancer microenvironment, and sensitivity of chemotherapeutic agents.

Preparation of multifunctional mesoporous SiO2nanoparticles and anti-tumor action.

A targeted drug delivery system was developed to accumulate specific drugs around tumor cells based on the redox, temperature, and enzyme synergistic responses of mesoporous silica nanoparticles. Mesoporous silica nanoparticles (MSN-NH2) and Doxorubicin (DOX) for tumor therapy were prepared and loaded into the pores of MSN- NH2 to obtain DOX@MSN(DM NPs). Hyaluronic acid (HA) was used as the backbone and disulfide bond was used as the linker arm to graft carboxylated poly (N-isopropylacrylamide)(PNIPAAm-COOH) to synthesize the macromolecular copolymer (HA-SS-PNIPAAm), which was modified to DM NPs with capped ends to obtain the nano-delivery system DOX@MSN@HA-SS-PNIPAAm(DMHSP NPs), and a control formulation was prepared in a similar way. DMHSP NPs specifically entered tumor cells via CD44 receptor-mediated endocytosis; the high GSH concentration (10 mM) of cells severed the disulfide bonds, the hyaluronidase sheared the capped HA to open the pores, and increased tumor microenvironment temperature due to immune response can trigger the release of encapsulated drugs in thermosensitive materials.In vitroandin vivoantitumor and hemolysis assays showed that DMHSP NPs can accurately target hepatocellular carcinoma cells with a good safety profile and have synergistic effects, which meant DMHSP NPs had great potential for tumor therapy.

Risk of second primary malignancies associated with radiotherapy in prostate cancer patients: competing risk analysis.

Background: The effect of radiotherapy (RT) for second primary malignancies (SPMs) among prostate cancer survivors is controversial. Methods: Applying logistic regression, competing risk analysis and propensity score matching method, this study analyzed clinical data from the Surveillance, Epidemiology, and End Results program to compare the risk for SPMs between patients receiving RT and non-RT. Results: In this study, prostate cancer patients treated with RT developed more SPMs in the anus, bladder, rectum, liver, lung and bronchus and lymphoma than non-RT groups. Conclusion: More intensive surveillance should be adopted for these cancers among prostate cancer survivors.

Plain language summary Patients with prostate cancer have the highest 5-year survival rate, which increases the risk for developing second primary malignancies (SPMs). The effect of radiotherapy (RT) for SPMs is controversial among prostate cancer survivors. This study analyzed a mass of prostate cancer patients from a public database to compare risk for SPMs between RT and non-RT groups. RT indeed increased certain categories of SPM and intensive surveillance should be considered.

Development and validation of nomogram to predict very early recurrence of combined hepatocellular-cholangiocarcinoma after hepatic resection: a multi-institutional study.

BACKGROUND AND OBJECTIVES: Combined hepatocellular cholangiocarcinoma (cHCC) has a high incidence of early recurrence. The objective of this study is to construct a model predicting very early recurrence (VER) (i.e., recurrence within 6 months after surgery) of cHCC. METHODS: One hundred thirty-one consecutive patients from Eastern Hepatobiliary Surgery Hospital served as a development cohort to construct a nomogram predicting VER by using multi-variable logistic regression analysis. The model was internally and externally validated in a validation cohort of 90 patients from Mengchao Hepatobiliary Hospital using the C concordance statistic, calibration analysis, and decision curve analysis (DCA). RESULTS: The VER nomogram contains microvascular invasion (MiVI), macrovascular invasion (MaVI), and CA19-9 > 25 mAU/mL. The model shows good discrimination with C-indexes of 0.77 (95% CI: 0.69-0.85) and 0.76 (95% CI: 0.66-0.86) in the development cohort and validation cohort respectively. Decision curve analysis demonstrated that the model is clinically useful and the calibration of our model was favorable. Our model stratified patients into two different risk groups, which exhibited significantly different VER. CONCLUSIONS: Our model demonstrated favorable performance in predicting VER in cHCC patients.

Surgical strategies for patients with second primary non-small cell lung cancer lesions 2 cm or less in diameter.

BACKGROUND AND PURPOSE: The wide application of low-dose computed tomography (CT) has led to an increase in the detection of small lung cancer lesions. Moreover, surgical recommendations for second primary non-small cell lung cancer (NSCLC) lesions ≤ 2 cm are obscure. This study compares the efficacy of wedge resection, lobectomy, and segmentectomy for small second primary NSCLC lesions. METHODS: The cohort was established based on the SEER database. Univariate and multivariate cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression, and restricted mean survival time (RMST) values were applied to identify prognostic factors. We used the Kaplan-Meier method to plot the survival curves of the different subgroups according to propensity score matching (PSM) analysis to then compare the therapeutic efficacy of the surgical procedures. RESULTS: A total of 568 patients were enrolled in this study. Age, sex, grade, and lymph node ratio were selected as independent prognostic factors (p < 0.05). No significant differences were observed in survival probabilities among the groups of patients who underwent segmentectomy, wedge resection, or lobectomy (p > 0.05). We also established a nomogram model based on the four prognostic factors to guide clinical treatment. CONCLUSIONS: Based on the findings of our study, segmentectomy was more appropriate than lobectomy for patients with a second primary NSCLC lesion ≤ 2 cm in diameter. The evidence to support other recommendations is insufficient.

[Large-scale Hospital Material Supply Chain Practice under Closed-loop Management].

In the context of public health emergencies, a Hospital used the existing SPD supply chain model as a basis, research and practice proceeded simultaneously and formed a set of "three-group three-port" emergency plan by itself. The program played a positive role and effectiveness in this emergency incident, assisting the hospital to obtain a valuable experience in closed-loop management of emergency supplies. This article elaborated on how the hospital can supply materials in case of emergency medical supplies shortage after emergencies by focusing on the three groups of closed-loop working group, inventory management group, and material procurement group, and the three ports of material storage port, logistics receiving and dispatching port, and closed-loop releasing port. In the case of emergency medical supplies being in short supply after emergencies, how can hospitals ensure adequate and balanced supply of supplies; barrier-free demand information; command and dispatch without chaos and reasonable deployment; materials receiving and dispatching are efficient and distributed in an orderly manner.

Model constructions of chemosensitivity and prognosis of high grade serous ovarian cancer based on evaluation of immune microenvironment and immune response.

BACKGROUND: The prognosis of high grade serous ovarian cancer (HGSOC) patients is closely related to the immune microenvironment and immune response. Based on this, the purpose of this study was to construct a model to predict chemosensitivity and prognosis, and provide novel biomarkers for immunotherapy and prognosis evaluation of HGSOC. METHODS: GSE40595 (38 samples), GSE18520 (63 samples), GSE26712 (195 samples), TCGA (321 samples) and GTEx (88 samples) were integrated to screen differential expressed genes (DEGs) of HGSOC. The prognosis related DEGs (DEPGs) were screened through overall survival analysis. The DEGs-encoded protein-protein interaction network was constructed and hub genes of DEPGs (DEPHGs) were generated by STRING. Immune characteristics of the samples were judged by ssGSEA, ESTIMATE and CYBERSORT. TIMER was used to analyze the relationship between DEPHGs and tumor-infiltrating immunocytes, as well as the immune checkpoint genes, finally immune-related DEPHGs (IDEPHGs) were determined, and whose expression in 12 pairs of HGSOC tissues and tumor-adjacent tissues were analyzed by histological verification. Furthermore, the chemosensitivity genes in IDEPHGs were screened according to GSE15622 (n = 65). Finally, two prediction models of paclitaxel sensitivity score (PTX score) and carboplatin sensitivity score (CBP score) were constructed by lasso algorithm. The area under curve was calculated to estimate the accuracy of candidate gene models in evaluating chemotherapy sensitivity. RESULTS: 491 DEGs were screened and 37 DEGs were identified as DEPGs, and 11 DEPHGs were further identified. Among them, CXCL13, IDO1, PI3, SPP1 and TRIM22 were screened as IDEPHGs and verified in the human tissues. Further analysis showed that IDO1, PI3 and TRIM22 could independently affect the chemotherapy sensitivity of HGSOC patients. The PTX score was significantly better than TRIM22, PI3, SPP1, IDO1 and CXCL13 in predicting paclitaxel sensitivity, so was CBP score in predicting carboplatin sensitivity. What's more, both of the HGSOC patients with high PTX score or high CBP score had longer survival time. CONCLUSIONS: Five IDEPHGs identified through comprehensive bioinformatics analysis were closely related with the prognosis, immune microenvironment and chemotherapy sensitivity of HGSOC. Two prediction models based on IDEPHGs might have potential application of chemotherapy sensitivity and prognosis for patients with HGSOC.

Prognostic value and predication model of microvascular invasion in patients with intrahepatic cholangiocarcinoma: a multicenter study from China.

BACKGROUND: At present, hepatectomy is still the most common and effective treatment method for intrahepatic cholangiocarcinoma (ICC) patients. However, the postoperative prognosis is poor. Therefore, the prognostic factors for these patients require further exploration. Whether microvascular invasion (MVI) plays a crucial role in the prognosis of ICC patients is still unclear. Moreover, few studies have focused on preoperative predictions of MVI in ICC patients. METHODS: Clinicopathological data of 704 ICC patients after curative resection were retrospectively collected from 13 hospitals. Independent risk factors were identified by the Cox or logistic proportional hazards model. In addition, the survival curves of the MVI-positive and MVI-negative groups before and after matching were analyzed. Subsequently, 341 patients from a single center (Eastern Hepatobiliary Hospital) in the above multicenter retrospective cohort were used to construct a nomogram prediction model. Then, the model was evaluated by the index of concordance (C-Index) and the calibration curve. RESULTS: After propensity score matching (PSM), Child-Pugh grade and MVI were independent risk factors for overall survival (OS) in ICC patients after curative resection. Major hepatectomy and MVI were independent risk factors for recurrence-free survival (RFS). The survival curves of OS and RFS before and after PSM in the MVI-positive groups were significantly different compared with those in the MVI-negative groups. Multivariate logistic regression results demonstrated that age, gamma-glutamyl transpeptidase (GGT), and preoperative image tumor number were independent risk factors for the occurrence of MVI. Furthermore, the prediction model in the form of a nomogram was constructed, which showed good prediction ability for both the training (C-index = 0.7622) and validation (C-index = 0.7591) groups, and the calibration curve showed good consistency with reality. CONCLUSION: MVI is an independent risk factor for the prognosis of ICC patients after curative resection. Age, GGT, and preoperative image tumor number were independent risk factors for the occurrence of MVI in ICC patients. The prediction model constructed further showed good predictive ability in both the training and validation groups with good consistency with reality.

Predicting occult lymph node metastasis by nomogram in patients with lung adenocarcinoma ≤2 cm.

Background: Previous researches had not proposed any prediction models for occult lymph node metastasis (OLNM). Considering the occurrence of OLNM and the importance of OLNM management, we aimed to develop a nomogram to predict OLNM of patients with lung adenocarcinoma ≤2 cm. Methods: Characteristics of patients with lung adenocarcinoma of ≤2 cm diameter at the Peking Union Medical College Hospital were retrospectively reviewed. Univariate and multivariate logistic regressions were performed. A nomogram model was developed. The concordance index (C-index) and calibration and decision curves were used to evaluate the predictive ability. Results: A total of 473 patients were enrolled, with an OLNM incidence of 7.4%. Four factors were selected as risk factors. The model had a C-index of 0.932. Calibration and decision curves were determined. Conclusion: Patients with pure ground-glass opacity (pGGO) or noninvasive adenocarcinoma have significantly lower risk of OLNM. SUVmax, CEA, micropapillary and solid component were identified as independent risk factors. The nomogram model was effective in predicting OLNM preoperatively.

Lay abstract Lung cancer was once the leading cause of death among tumors. Today, as routine examination has become more common, the incidence of lung cancers ≤2 cm diameter has been increasing. Much research had explored treatment for these patients. Lobectomy and lymph node dissection in particular were recommended. Furthermore, lymph node dissection was strongly recommended for lymph-node-positive patients. During treatment, occult lymph node metastasis (OLNM) had been observed in some cases. And OLNM referred to a postoperative positive pathological result among preoperative imaging-negative cases. The study was designed to establish a model for predicting OLNM. In a cohort of 473 patients, we found certain risk factors for OLNM and established a predictive model. Relevant findings were shown in the 'Conclusion' section.

Identification of lipid metabolism-related genes as prognostic indicators in papillary thyroid cancer.

Lipid metabolism plays important roles not only in the structural basis and energy supply of healthy cells but also in the oncogenesis and progression of cancers. In this study, we investigated the prognostic value of lipid metabolism-related genes in papillary thyroid cancer (PTC). The recurrence predictive gene signature was developed and internally and externally validated based on PTC datasets including The Cancer Genome Atlas (TCGA) and GSE33630 datasets. Univariate, LASSO, and multivariate Cox regression analysis were applied to assess prognostic genes and build the prognostic gene signature. The expression profiles of prognostic genes were further determined by immunohistochemistry of tissue microarray using in-house cohorts, which enrolled 97 patients. Kaplan-Meier curve, time-dependent receiver operating characteristic curve, nomogram, and decision curve analyses were used to assess the performance of the gene signature. We identified four recurrence-related genes, PDZK1IP1, TMC3, LRP2 and KCNJ13, and established a four-gene signature recurrence risk model. The expression profiles of the four genes in the TCGA and in-house cohort indicated that stage T1/T2 PTC and locally advanced PTC exhibit notable associations not only with clinicopathological parameters but also with recurrence. Calibration analysis plots indicate the excellent predictive performance of the prognostic nomogram constructed based on the gene signature. Single-sample gene set enrichment analysis showed that high-risk cases exhibit changes in several important tumorigenesis-related pathways, such as the intestinal immune network and the p53 and Hedgehog signaling pathways. Our results indicate that lipid metabolism-related gene profiling represents a potential marker for prognosis and treatment decisions for PTC patients.

Tri-ortho-cresyl phosphate exposure leads to low egg production and poor eggshell quality via disrupting follicular development and shell gland function in laying hens.

Tri-ortho-cresyl phosphate (TOCP) has been used commercially as a plasticizer and a flame retardant, which has been reported to cause multiple toxicities in humans and other animals. However, the effect of TOCP on female reproductive system is still unclear. The aim of this investigation was to evaluate the reproductive toxicity of TOCP in female avian and investigate its molecular mechanism. In the current study, 50 adult hens were given a single oral dose of TOCP (750 mg/kg). Egg laid by the hens were harvested and counted. Egg quality is assessed by determining the shell strength and thickness. Samples of ovary, shell gland, and serum were collected on day 0, 2, 7, and 21 after the administration. The morphological and pathological changes in tissues were examined. Cell death, follicular development, and steroidogenesis were determined to assess the toxicity of TOCP on laying hens. The results showed that egg production, egg weight, and eggshell strength significantly decreased after TOCP exposure. The calcium levels in serum and eggshell decreased and the expression levels of the eggshell formation-related genes calbindin-D28k (CaBP-D28k) and carbonic anhydrase 2 (CA2) were downregulated. The inhibitory effects of TOCP on follicular development and steroidogenesis were observed with changes in the levels of the related proteins such as forkhead box O1 (FoxO1) and mothers against decapentaplegic homolog 2/3 (Smad2/3). Cell death was identified, which might lead to follicular development disorder. Taken together, TOCP reduced the quantity and quality of the eggs laid by the hens through disrupting follicular development, steroidogenesis, and shell gland function.