18F-FDG PET/CT of Intracholecystic Papillary Neoplasm in Cystic Neck and Duct.

ABSTRACT: We report 18F-FDG PET/CT appearances of intracholecystic papillary neoplasm (ICPN) in the gallbladder neck and duct of a 74-year-old woman with a history of hepatitis B cirrhosis. The lesion presented with a large and sessile soft mass in the neck and duct of gallbladder with obvious glucose metabolism on PET/CT images, which was confirmed pathologically as ICPN (gastric foveolar type) with high-grade intraepithelial neoplasia. ICPN localized in the gallbladder neck and duct is extremely rare, and is easily misdiagnosed as gallbladder carcinoma. Our report aids in the application of PET/CT in the differential diagnosis of ICPN and guiding early surgery.

[Establish a Graded Method to Avoid HLA Class I Antibodies Corresponding Antigen and Combining HLAMatchmaker Application in Improving the CCI Value after Platelet Transfusion for Patients with IPTR].

OBJECTIVE: To establish a graded method to avoid mean fluorescence intensity (MFI) threshold of HLA Class I antibodies corresponding antigen, and the HLAMatchmaker program has been used to select the minimum mismatch value of donor-patient epitopes. Evaluate the application value of combining both methods in selecting HLA compatible platelets (PTL) for patients with immune platelet transfusion failure (IPTR) in improving platelet the corrected count increment (CCI). METHODS: A total 7 807 PLT cross-matching compatible were performed by the solid-phase red cell adherence (SPRCA) method for 51 IPTR patients. The Luminex single antigen flow cytometry was used to detect HLA Class I antibodies in patients, and detected the MFI value for different specificity antigens of HLA Class I antibodies, was graded into strong positive group (MFI>4 000, level 1), medium positive group (1 000< MFI≤4 000, 2), weak positive group (500< MFI≤1 000, 3), and one negative control group (MFI≤500). The results of 7 807 SPRCA their negative/positive reaction wells were enrolled and statistically analyzed in different grades and the four groups, the statistical differences between the four groups were compared. Multiple applications for the select HLA Class I compatible donor events were made for patients in two cases, and HLAMatchmaker program was used to calculate the number of HLA Class I epitopes mismatches between the donors and patients. The donor with the minimum number of epitopes mismatches was selected, while avoiding the corresponding antigens of HLA Class I antibodies in levels 1 and 2, the provision of HLA compatible platelets for IPTR. After the transfusions, the CCI value of the platelet transfusion efficacy evaluation index was calculated, and the clinical evaluation of the transfusion effect was obtained through statistical analysis. RESULTS: There were statistically significant differences in the positive results of SPRCA immunoassay among the strong positive group, medium positive group, and weak positive group of 51 IPTR patients with different specific of HLA -I class antibodies and corresponding antigens(all P <0.001). The positive results showed a range from high to low, with strong positive group>medium positive group>weak positive group. There were a statistical difference among between the strongly positive or moderately positive groups and the negative control group(P <0.001). There was no statistical difference between the weakly positive group and the negative control group(P >0.05). The strong positive group was set as the corresponding specific HLA Class I site corresponding antigen grade 1 avoidance threshold, the medium positive group as the grade 2 avoidance thresholds, and the weak positive group as the grade 3 avoidance threshold. In the case of donor platelet shortage, it is not necessary to avoid the weak positive group. Avoiding the strategy of donor antigens and HLAMatchmaker program scores ≤7 corresponding to HLA Class I antibodies of levels 1 and 2, with CCI values>4.5×109/L within 24 hours, can obtain effective clinical platelet transfusion conclusions. CONCLUSION: When selecting HLA Class I compatible donors for IPTR patients, the grading avoids HLA Class I antibodies corresponding to donor antigens, and the donor selection strategy with the minimum scores of HLAMatchmaker program is comprehensively selected. The negative result confirmed by platelet cross-matching experiments has certain practical application value for improving platelet count in IPTR patients.

CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma.

As a high metastatic tumor, patients having hepatocellular carcinoma (HCC) show poor prognosis. The carcinogenic roles of circMMP11 are generally described in the development of other cancers. However, there is a lack of studies on its involvement in HCC. Therefore, we investigated the potential role and molecular mechanisms of CircMMP11 in the development of HCC in vitro, providing preliminary evidence for the clinical treatment of HCC. First, we examined the expression of CircMMP11 in HCC tissues and cell lines in both clinical and in vitro experiments. We then used a loss-of-function assay to determine CircMMP11's regulatory role on the malignant characteristics of HCC cells. The results showed that high expression of CircMMP11 in HCC was associated with patient overall survival. Serum CircMMP11 had good diagnostic efficacy in distinguishing HCC patients from the control group. In vitro, inhibiting CircMMP11 suppressed the malignant characteristics of human HCC cell lines by directly sequestering miR-361-3p, which further affected the downstream gene HMGB1 expression. In addition, we knocked down CircMMP11 and found that its deletion inhibited the malignant characteristics of HCC cells through the miR-361-3p/HMGB1 axis.

Paternal chromosome elimination of inducer triggers induction of double haploids in Brassica napus.

A synthetic octoploid rapeseed, Y3380, induces maternal doubled haploids when used as a pollen donor to pollinate plant. However, the mechanism underlying doubled haploid formation remains elusive. We speculated that double haploid induction occurs as the inducer line's chromosomes pass to the maternal egg cell, and the zygote is formed through fertilization. In the process of zygotic mitosis, the paternal chromosome is specifically eliminated. Part of the paternal gene might have infiltrated the maternal genome through homologous exchange during the elimination process. Then, the zygote haploid genome doubles (early haploid doubling, EH phenomenon), and the doubled zygote continues to develop into a complete embryo, finally forming doubled haploid offspring. To test our hypothesis, in the current study, the octoploid Y3380 line was back bred with the 4122-cp4-EPSPS exogenous gene used as a marker into hexaploid Y3380-cp4-EPSPS as paternal material to pollinate three different maternal materials. The fertilization process of crossing between the inducer line and the maternal parent was observed 48 h after pollination, and the fertilization rate reached 97.92% and 98.72%. After 12 d of pollination, the presence of cp4-EPSPS in the embryo was detected by in situ PCR, and at 13-23 d after pollination, the probability of F1 embryos containing cp4-EPSPS gene was up to 97.27%, but then declined gradually to 0% at 23-33 d. At the same time, the expression of cp4-EPSPS was observed by immunofluorescence in the 3rd to 29th day embryo. As the embryos developed, cp4-EPSPS marker genes were constantly lost, accompanied by embryonic death. After 30 d, the presence of cp4-EPSPS was not detected in surviving embryos. Meanwhile, SNP detection of induced offspring confirmed the existence of double haploids, further indicating that the induction process was caused by the loss of specificity of the paternal chromosome. The tetraploid-induced offspring showed infiltration of the induced line gene loci, with heterozygosity and homozygosity. Results indicated that the induced line chromosomes were eliminated during embryonic development, and the maternal haploid chromosomes were synchronously doubled in the embryo. These findings support our hypothesis and lay a theoretical foundation for further localization or cloning of functional genes involved in double haploid induction in rapeseed.

APEX1 predicts poor prognosis of gallbladder cancer and affects biological properties of CD133+ GBC-SD cells via upregulating Jagged1.

Although APEX1 is associated with the tumorigenesis and progression of some human cancer types, the function of APEX1 in gallbladder cancer (GBC) is unclear. In this study, we found that APEX1 expression is up-regulated in GBC tissues, and APEX1 positive expression is related to aggressive clinicopathological features and poor prognosis of GBC. APEX1 was an independent risk factor of GBC prognosis, and presented some pathological diagnostic significance in GBC. Furthermore, APEX1 was overexpressed in CD133+ GBC-SD cells in comparison with GBC-SD cells. APEX1 knockdown increased the sensitivity of CD133+ GBC-SD cells to 5-Fluorouracil via facilitating cell necrosis and apoptosis. APEX1 knockdown in CD133+ GBC-SD cells dramatically inhibited cell proliferation, migration, and invasion, and promoted cell apoptosis in vitro. APEX1 knockdown in CD133+ GBC-SD cells accelerated tumor growth in the xenograft models. Mechanistically, APEX1 affected these malignant properties via upregulating Jagged1 in CD133+ GBC-SD cells. Thus, APEX1 is a promising prognostic biomarker, and a potential therapeutic target for GBC.

The effects of metformin on anti-Müllerian hormone levels in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

OBJECTIVE: To analyze whether metformin treatment in patients with polycystic ovary syndrome (PCOS) results in a decrease of anti-Müllerian hormone (AMH) levels, we reviewed and analyzed PCOS studies which evaluated serum AMH levels before and after metformin treatment. METHODS: This is a systematic review and meta-analysis of self-controlled clinical trials. Databases including PubMed, Embase, and Web of Science library were searched to identify eligible studies published before February 2023. Random-effects models were applied to assess standardized mean differences (SMDs) with 95% confidence intervals (95% CI). RESULTS: The electronic-based search retrieved 167 articles of which 14 studies (12 publications) involving 257 women with PCOS were included. In general, AMH levels decreased significantly after metformin treatment [SMD (95% CI) of -0.70 (-1.13 to -0.28); P = 0.001]. Metformin exhibited a strong inhibitory effect on AMH levels for PCOS patients with age less than 28 [SMD - 1.24, 95% CI - 2.15 to - 0.32, P = 0.008]. Additionally, AMH levels significantly slid down in PCOS patients with no more than 6 months metformin treatment [SMD - 1.38, 95% CI - 2.18 to - 0.58, P = 0.0007], or with no more than a dose of 2000 mg/day [SMD -0.70, 95% CI -1.11 to -0.28; P = 0.001]. Notably, suppressive effects of metformin treatment were merely observed in patients with AMH levels at baseline higher than 4.7 ng/ml [SMD - 0.66, 95% CI - 1.02 to - 0.31, P = 0.0003]. CONCLUSION: This meta-analysis provided quantitative evidence demonstrating that metformin significantly decreased AMH levels, especially for young patients and those with AMH levels at baseline higher than 4.7 ng/ml. TRIAL REGISTRATION: PROSPERO CRD42020149182.

Tumor metabolism derived from 18F-FDG PET/CT in predicting the macrotrabecular-massive subtype of hepatocellular carcinoma.

Background: The recently described pathological subtype of hepatocellular carcinoma (HCC), named macrotrabecular massive (MTM), is associated with an unfavorable prognosis. This study aimed to evaluate the potential for tumor metabolism obtained by ß-2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) to be used as a preoperative imaging indicator for predicting MTM-HCCs. Methods: This study was designed to be cross-sectional. Patients who underwent preoperative 18F-FDG PET/CT and who had surgically-diagnosed HCC between June 2015 and June 2021 were retrospectively included. Tumor metabolism was determined by the tumor-to-normal liver standardized uptake value ratio (TLR) of the primary tumor as shown on 18F-FDG PET/CT. Clinical, pathological, and PET/CT characteristics were compared between non-MTM-HCCs and MTM-HCCs. Univariate analyses were used to screen the predictive factors of MTM-HCCs, then multivariate binary logistic regression analyses were performed. A regression-based diagnostic model was then established. Substantial necrosis was assessed to compare the predictive performance between traditional imaging and TLR measured on 18F-FDG PET/CT. The receiver operating characteristic (ROC) curve analyses and the DeLong test were used to assess the predictive performance. Results: A total of 93 patients (mean age, 52.6±11.3 years; 81 male) with 36 MTM-HCCs were included. Multivariate binary logistic regression analyses identified higher platelet count [PLT; ≥118.5×103/µL; odds ratio (OR), 3.63; 95% confidence interval (CI), 1.13-12.87; P=0.035], higher aspartate transaminase (AST; ≥52 IU/L; OR, 4.15; 95% CI: 1.34-14.33; P=0.017), and larger TLR (≥2.2; OR, 5.55; 95% CI: 1.90-17.56; P=0.002) as independent predictors of MTM-HCCs. A TLR ≥2.2 helped to identify 72.2% of the MTM-HCCs with a specificity of 75.4%. The AUC of the regression-based diagnostic model for predicting MTM-HCCs was 0.835 (95% CI: 0.746-0.923), with a sensitivity of 80.6% and a specificity of 78.9%. Substantial necrosis enabled the identification of MTM-HCCs with 52.8% sensitivity and 87.7% specificity, with an AUC of 0.702 (95% CI: 0.588-0.817). There was no statistical difference between TLR and substantial necrosis in predicting MTM-HCCs using the DeLong test (P>0.05). Conclusions: Tumor metabolism determined by TLR on 18F-FDG PET/CT is a valuable imaging indicator for MTM-HCCs. Noninvasive prediction of this subtype can achieve good sensitivity and excellent predictive performance based on the regression model of AST, PLT, and TLR.

18F-FDG PET/CT-based radiomics nomogram for preoperative prediction of macrotrabecular-massive hepatocellular carcinoma: a two-center study.

PURPOSE: To explore the potential of ß-2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the evaluation of macrotrabecular-massive (MTM) hepatocellular carcinoma (HCC) and to apply radiomics approach to build a radiomics nomogram for predicting MTM-HCC. METHODS: This study included 140 (training cohort:101; validation cohort:39) HCC patients who underwent preoperative 18F-FDG PET/CT at two institutions. The clinical features and tumor FDG metabolism measured by the tumor-to-liver ratio (TLR) via 18F-FDG PET/CT were retrospectively collected. Radiomics features were extracted from 18F-FDG PET/CT images and a radiomics score (Rad-score) was calculated. A radiomics nomogram was then constructed by combining Rad-score and independent clinical features and was assessed with a calibration curve. The performance of the radiomics nomogram, Rad-score and TLR was evaluated by receiver operating characteristic (ROC) curves and decision curve analysis (DCA). RESULTS: A total of six top weighted radiomics features were selected from PET/CT images by the least absolute shrinkage and selection operator (LASSO) regression algorithm and were used to construct a Rad-score. Multivariate analysis identified Rad-score (OR = 2.183, P = 0.004), age ≤ 50 years (OR = 3.136, P = 0.036), AST > 40U/L (OR = 0.270, P = 0.017) and TLR (OR = 1.641, P = 0.049) as independent predictors of MTM-HCC. The radiomics nomogram had a higher area under the curves (AUCs) than the Rad-score and TLR for predicting MTM-HCC in both training (0.849 [95% CI 0.774-0.924] vs. 0.764 [95% CI 0.669-0.843], 0.763 [95% CI 0.668-0.842]) and validation (0.749 [95% CI 0.584-0.873] vs. 0.690 [95% CI 0.522-0.828], 0.541 [95% CI 0.374-0.701]) cohorts. DCA showed the radiomics nomogram to be more clinically useful than Rad-score and TLR. CONCLUSIONS: Tumor FDG metabolism is significantly associated with MTM-HCC. A 18F-FDG PET/CT-based radiomics nomogram may be useful for preoperatively predicting the MTM subtype in primary HCC patients, contributing to pretreatment decision-making.

FOXP1 and FOXO3a Are Prognostic Markers in Gallbladder Squamous Cell/Adenosquamous Carcinomas and Adenocarcinomas.

The pathologic characteristics of squamous cell/adenosquamous carcinomas (SC/ASC) have not been well clarified. As a rare subtype of gallbladder cancer (GBC), no biological markers for diagnosis and prognosis are available. This research evaluated the expression of FOXP1 and FOXO3a in 69 SC/ASC, and 146 adenocarcinoma (AC) samples were analyzed via immunohistochemistry. SC/ASCs were associated with higher rates of lymph node metastasis, invasion, and patients older than 45 years comparing to ACs. FOXP1 and FOXO3a positivity rates were significantly lower in SC/ASC and AC samples from patients with large tumor size, a high TNM stage, lymph node metastasis, invasion, and no history of tumor resection (biopsy only). Positive FOXP1 expression levels were significantly decreased in cases of poorly differentiated AC. The univariate Kaplan-Meier analysis revealed that negative FOXP1 and FOXO3a expression, poor differentiation, large tumor size, high TNM stage, lymph node metastasis, invasion, and an inability to undergo curative resection were all closely associated with decreased overall survival in SC/ASC and AC patients. The multivariate cox regression analysis showed that negative FOXP1 and FOXO3a expression levels were independent predictors of poor prognosis in SC/ASC and AC patients. Our results indicate that negative FOXP1 and FOXO3a expression are closely associated with the pathogenesis, clinicopathologic properties, and prognosis of GBC patients. FOXP1 and FOXO3a may thus be biomarkers of GBC carcinogenesis, progression, and prognosis.

Identifying patterns of immune related cells and genes in the peripheral blood of acute myocardial infarction patients using a small cohort.

BACKGROUND: The immune system plays a vital role in the pathophysiology of acute myocardial infarction (AMI). However, the exact immune related mechanism is still unclear. This research study aimed to identify key immune-related genes involved in AMI. METHODS: CIBERSORT, a deconvolution algorithm, was used to determine the proportions of 22 subsets of immune cells in blood samples. The weighted gene co-expression network analysis (WGCNA) was used to identify key modules that are significantly associated with AMI. Then, CIBERSORT combined with WGCNA were used to identify key immune-modules. The protein-protein interaction (PPI) network was constructed and Molecular Complex Detection (MCODE) combined with cytoHubba plugins were used to identify key immune-related genes that may play an important role in the occurrence and progression of AMI. RESULTS: The CIBERSORT results suggested that there was a decrease in the infiltration of CD8 + T cells, gamma delta (γδ) T cells, and resting mast cells, along with an increase in the infiltration of neutrophils and M0 macrophages in AMI patients. Then, two modules (midnightblue and lightyellow) that were significantly correlated with AMI were identified, and the salmon module was found to be significantly associated with memory B cells. Gene enrichment analysis indicated that the 1,171 genes included in the salmon module are mainly involved in immune-related biological processes. MCODE analysis was used to identify four different MCODE complexes in the salmon module, while four hub genes (EEF1B2, RAC2, SPI1, and ITGAM) were found to be significantly correlated with AMI. The correlation analysis between the key genes and infiltrating immune cells showed that SPI1 and ITGAM were positively associated with neutrophils and M0 macrophages, while they were negatively associated with CD8 + T cells, γδ T cells, regulatory T cells (Tregs), and resting mast cells. The RT-qPCR validation results found that the expression of the ITGAM and SPI1 genes were significantly elevated in the AMI samples compared with the samples from healthy individuals, and the ROC curve analysis showed that ITGAM and SPI1 had a high diagnostic efficiency for the recognition of AMI. CONCLUSIONS: Immune cell infiltration plays a crucial role in the occurrence and development of AMI. ITGAM and SPI1 are key immune-related genes that are potential novel targets for the prevention and treatment of AMI.

Immune-Related RNA-Binding Protein-Based Signature With Predictive and Prognostic Implications in Patients With Lung Adenocarcinoma.

Background: Dysregulation of RNA-binding proteins (RBPs) in cancers is associated with immune and cancer development. Here, we aimed to profile immune-related RBPs in lung adenocarcinoma (LUAD) and construct an immune-related RBP signature (IRBPS) to predict the survival and response to immunotherapy. Methods: A correlation analysis was performed to establish a co-expression network of RBPs and immune-related genes (IRGs) to characterize immune-related RBPs in the TCGA-LUAD cohort (n = 497 cases). Then, a combination of the Random survival forest (RSF) and Cox regression analysis was performed to screen the RBPs and establish IRBPS. This was followed by independent validation of IRBPS in GSE72094 (n = 398 cases), GSE31210, (n = 226 cases), and GSE26939 (n = 114 cases). Differences between the low- and high-risk groups were compared in terms of gene mutations, tumor mutation burden, tumor-infiltrating lymphocytes, and biomarkers responsive to immunotherapy. Results: DDX56, CTSL, ZC3H12D, and PSMC5 were selected and used to construct IRBPS. The high-risk scores of patients had a significantly worse prognosis in both training and testing cohorts (p < 0.0001 and p < 0.05, respectively), and they tended to be older and have an advanced TNM stage. Furthermore, IRBPS was a prognostic factor independent of age, gender, smoking history, TNM stage, and EGFR mutation status (p = 0.002). In addition, high-risk scores of IRBPS were significantly correlated with tumor-infiltrating lymphocytes (p < 0.05). They also had a high level of PD-L1 protein expression (p < 0.01), number of neoantigens (p < 0.001), and TMB (p < 0.001), implying the possible prediction of IRBPS in the immunotherapy of LUAD. Conclusion: The currently established IRBPS encompassing immune-related RBPs might serve as a promising tool to predict survival, reflect the immune microenvironment, and predict the efficacy of immunotherapy among LUAD patients.

Efficacy evaluation of intravitreal ranibizumab therapy for three types of retinopathy of prematurity.

AIM: To evaluate efficacy of intravitreal ranibizumab (IVR) therapy for aggressive posterior retinopathy of prematurity (ROP), threshold ROP disease and type 1 pre-threshold ROP. METHODS: A retrospective analysis was performed on 40 patients (76 eyes) who had IVR as the primary treatment for ROP from April 2017 to January 2018. According to disease pathogenic features, the 76 eyes were divided into three groups: aggressive posterior ROP (AP-ROP) group (16 eyes), threshold ROP group (28 eyes) and type 1 pre-threshold ROP group (32 eyes). The characteristics of patients and lesions situation before the first intravitreal injection, and posttreatment fundus outcomes determined by wide-angle RetCam fundus imaging were recorded. RESULTS: The birth weight and postmenstrual age of first IVR treatment in AP-ROP, threshold ROP, and type 1 pre-threshold ROP groups were significant difference (1087.50±246.78, 1103.75±168.30, 1257.03±210.82 g, P=0.005; 34.50±1.46, 36.89±2.97, 36.50±2.36wk, P=0.008), while the gestational age was not difference (28.00±2.00, 28.54±1.90, 28.59±1.43wk, P=0.510). The retina hemorrhage ratio (with/without: 14/2, 8/20, 5/27), iris neovascularization or vascular engorgement ratio (with/without: 12/4, 11/17, 6/26), and the zone I (inside/outside: 16/0, 2/26, 5/27) in AP-ROP, threshold ROP, and type 1 pre-threshold ROP group were difference significantly (all P<0.05). The regression rates were 37.5%, 92.86%, and 100%, and the recurrence rates were 62.5%, 7.14%, and 0 in AP-ROP, threshold ROP, and type 1 pre-threshold ROP group, respectively (both P<0.05). The recurrence eyes were cured by secondary IVR or retinal laser photocoagulation. CONCLUSION: IVR is an effective treatment for all types of ROP. The regression of AP-ROP is significantly lower than type 1 pre-threshold and threshold disease. Birth weight, retinal hemorrhage, iris neovascularization or vascular engorgement and lesions located in zone I may be associated with AP-ROP recurrence and retreatment, which should be noted in follow-up.

Rapid and Synchronous Breeding of Cytoplasmic Male Sterile and Maintainer Line Through Mitochondrial DNA Rearrangement Using Doubled Haploid Inducer in Brassica napus.

When homozygously fertile plants were induced using doubled haploid (DH) induction lines Y3380 and Y3560, the morphology of the induced F1 generation was basically consistent with the female parent, but the fertility was separated, showing characteristics similar to cytoplasmic male sterile (CMS) and maintainer lines. In this study, the morphology, fertility, ploidy, and cytoplasm genotype of the induced progeny were identified, and the results showed that the sterile progeny was polima cytoplasm sterile (pol CMS) and the fertile progeny was nap cytoplasm. The molecular marker and test-cross experimental results showed that the fertile progeny did not carry the restorer gene of pol CMS and the genetic distance between the female parent and the offspring was 0.002. This suggested that those inductions which produced sterile and fertile progeny were coordinated to CMS and maintainer lines. Through the co-linearity analysis of the mitochondrial DNA (mtDNA), it was found that the rearrangement of mtDNA by DH induction was the key factor that caused the transformation of fertility (nap) into sterility (pol). Also, when heterozygous females were induced with DH induction lines, the induction F2 generation also showed the segregation of fertile and sterile lines, and the genetic distance between sterile and fertile lines was approximately 0.075. Therefore, the induction line can induce different types of female parents, and the breeding of the sterile line and the maintainer line can be achieved through the rapid synchronization of sister crosses and self-crosses. The induction of DH inducer in B. napus can provide a new model for the innovation of germplasm resources and open up a new way for its application.

18F-FDG PET/CT Imaging in Sarcomatoid Hepatocellular Carcinoma.

Sarcomatoid hepatocellular carcinoma is a rare subtype of hepatocellular carcinoma. We present a 53-year-old man with a hepatic IV/VIII segment neoplasm whose tumor markers were all in the reference range. The neoplasm presented intense uptake of 18F-FDG and was confirmed as sarcomatoid hepatocellular carcinoma by immunohistochemistry. After 6 cycles of PD-1 treatment, no recurrence or metastasis was found by follow-up CT over 2 years. Thus, we reported a case of sarcomatoid hepatocellular carcinoma with complete remission to PD-1 treatment and provided some help for the diagnosis and treatment of sarcomatoid hepatocellular carcinoma.

Rapid Creation of Interspecific Hybrid Progeny to Broaden Genetic Distance through Double Haploid (DH) Inducer in Brassica napus.

Interspecific hybridization of rapeseed is an important way to innovate breeding resources. This research used Brassica napus and Brassica rapa for artificial synthesis interspecific hybridization of F1. The F1 self-fruiting rate was particularly low. By comparing the fertilization rate and seed setting rate of nine crosses and selfing combinations of interspecific hybrid progeny F1 and control B. napus, the results proved that the genetic stability of egg cells was greater than that of sperm cells, so the F1 could get seed by artificial pollination with other normal pollen. Based on these results, interspecific maternal inbred offspring (induced F1) from egg cells was obtained by emasculation and pollination with the pollen of DH inducer Y3380. It was found through morphological analysis, flow cytometry identification, and meiotic observation of induced F1, the plants had most normal fertile tetraploid and the meiosis was normal. The FISH results showed that the induced F1 were B. napus (2n = 4x = 38, AACC), 20 A and 19 C chromosomes. The results of SNP chip detection and genetic cluster analysis found that the genetic variation between interspecies could be preserved or broadened in the induced F1. The use of DH inducer created special breeding resources for interspecific hybridization and distant hybridization of rapeseed while shortening time, improving efficiency, and providing a new insight into innovate breeding resources.

Postoperative radioiodine therapy impact on survival in poorly differentiated thyroid carcinoma: a population-based study.

PURPOSE: The true impact of postoperative radioiodine therapy on survival has been controversial for patients with poorly differentiated thyroid carcinoma (PDTC). We aimed to determine the impact of postoperative radioiodine on survival in PDTC through a population-based study. METHODS: Data on patients with PDTC were collected from the US SEER database (2004 to 2015). Patients were divided into the radioiodine group and nonradioiodine group. Survival comparison between groups was evaluated by Kaplan-Meier curves, log-rank test and multivariate Cox regression analysis. Akaike information criterion was used to select variables in the nomogram. The performance of the nomogram was assessed by discrimination (C-index) and calibration plots. RESULTS: The radioiodine group had more aggressive features, such as advanced tumor node metastasis stage and radical surgery, compared to the nonradioiodine group. PDTC patients receiving radioiodine therapy had a significant survival advantage in terms of overall survival (OS) (P = 0.001) but not in terms of cancer-specific survival (P = 0.083). Multivariate analysis revealed radioiodine therapy was an independent favorable factor for OS in PDTC patients (hazard ratio = 0.57; 95% CI, 0.44-0.75, P < 0.001). Subgroup analysis identified patients' characteristics favoring radioiodine therapy. The nomogram (age, tumor size, extension, neck lymph nodes metastasis and radioiodine therapy) of OS for predicting 3-, 5- and 10-year OS probability showed good discrimination (C-index, 0.797) and calibration power. CONCLUSION: Postoperative radioiodine therapy can prolong the long-term OS in patients with PDTC, and is an independent favorable prognostic factor for those patients. Further prospective studies are warranted.

Machine learning-based prediction of invisible intraprostatic prostate cancer lesions on 68 Ga-PSMA-11 PET/CT in patients with primary prostate cancer.

PURPOSE: 68 Ga-PSMA PET/CT has high specificity and sensitivity for the detection of both intraprostatic tumor focal lesions and metastasis. However, approximately 10% of primary prostate cancer are invisible on PSMA-PET (exhibit no or minimal uptake). In this work, we investigated whether machine learning-based radiomics models derived from PSMA-PET images could predict invisible intraprostatic lesions on 68 Ga-PSMA-11 PET in patients with primary prostate cancer. METHODS: In this retrospective study, patients with or without prostate cancer who underwent 68 Ga-PSMA PET/CT and presented negative on PSMA-PET image at either of two different institutions were included: institution 1 (between 2017 and 2020) for the training set and institution 2 (between 2019 and 2020) for the external test set. Three random forest (RF) models were built using selected features extracted from standard PET images, delayed PET images, and both standard and delayed PET images. Then, subsequent tenfold cross-validation was performed. In the test phase, the three RF models and PSA density (PSAD, cut-off value: 0.15 ng/ml/ml) were tested with the external test set. The area under the receiver operating characteristic curve (AUC) was calculated for the models and PSAD. The AUCs of the radiomics model and PSAD were compared. RESULTS: A total of 64 patients (39 with prostate cancer and 25 with benign prostate disease) were in the training set, and 36 (21 with prostate cancer and 15 with benign prostate disease) were in the test set. The average AUCs of the three RF models from tenfold cross-validation were 0.87 (95% CI: 0.72, 1.00), 0.86 (95% CI: 0.63, 1.00), and 0.91 (95% CI: 0.69, 1.00), respectively. In the test set, the AUCs of the three trained RF models and PSAD were 0.903 (95% CI: 0.830, 0.975), 0.856 (95% CI: 0.748, 0.964), 0.925 (95% CI:0.838, 1.00), and 0.662 (95% CI: 0.510, 0.813). The AUCs of the three radiomics models were higher than that of PSAD (0.903, 0.856, and 0.925 vs. 0.662, respectively; P = .007, P = .045, and P = .005, respectively). CONCLUSION: Random forest models developed by 68 Ga-PSMA-11 PET-based radiomics features were proven useful for accurate prediction of invisible intraprostatic lesion on 68 Ga-PSMA-11 PET in patients with primary prostate cancer and showed better diagnostic performance compared with PSAD.

The expression of Aquaporin-1 and Aquaporin-3 in extrahepatic cholangiocarcinoma and their clinicopathological significance.

BACKGROUND: The aim of the study was to evaluate the expression and clinicopathological significance of Aquaporin-1 (AQP1) and Aquaporin-3 (AQP3) in extrahepatic cholangiocarcinoma (EHCC). METHODS: Immunostaining of AQP1 and AQP3 was performed by EnVision immunohistochemistry in benign and malignant biliary tract tissues. RESULTS: The expression of AQP1 and AQP3 protein were significantly higher in EHCC tumor tissues (P < 0.05 or P < 0.01). Adenoma and paracancerous tissues with positive AQP1 and/or AQP3 protein expression exhibited atypical hyperplasia. AQP1 expression was positive correlated with AQP3 expression in EHCC (P < 0.01). TNM I + II stage and radical surgery, the positive expression of AQP1 and AQP3 In patients with well-differentiation, no invasion, no lymph metastasis, is lower (P < 0.05 or P < 0.01). Average overall survival time of those with positive expression of AQP1 and AQP3 was significant shorter (P < 0.01). Both AQP1 and AQP3 positive expressions were proved to be an independent prognostic factors in EHCC by cox multivariate analysis. The AUC calculated for AQP1 was 0.769 (95% confidence interval [CI]: 0.618-0.920), and that for AQP3 was 0.758 (95%CI: 0.605-0.911, while that for AQP1 and AQP3 was 0.825 (95%CI: 0.658-0.991). CONCLUSIONS: Positive expression of AQP1 and AQP3 is closely related to the pathogenesis, severe clinicopathological characteristics, aggressive biological behaviors, and dismal prognoses in EHCC.

Genetic characteristics and ploidy trigger the high inducibility of double haploid (DH) inducer in Brassica napus.

BACKGROUND: Our recently reported doubled haploid (DH) induction lines e.g., Y3380 and Y3560 are allo-octoploid (AAAACCCC, 2n = 8× ≈ 76), which can induce the maternal parent to produce DH individuals. Whether this induction process is related to the production of aneuploid gametes form male parent and genetic characteristics of the male parent has not been reported yet. RESULTS: Somatic chromosome counts of DH inducer parents, female wax-less parent (W1A) and their F1 hybrid individuals revealed the reliability of flow cytometry analysis. Y3560 has normal chromosome behavior in metaphase I and anaphase I, but chromosome division was not synchronized in the tetrad period. Individual phenotypic identification and flow cytometric fluorescence measurement of F1 individual and parents revealed that DH individuals can be distinguished on the basis of waxiness trait. The results of phenotypic identification and flow cytometry can identify the homozygotes or heterozygotes of F1 generation individuals. The data of SNP genotyping coupled with phenotypic waxiness trait revealed that the genetic distance between W1A and F1 homozygotes were smaller as compared to their heterozygotes. It was found that compared with allo-octoploids, aneuploidy from allo-octoploid segregation did not significantly increase the DH induction rate, but reduced male infiltration rate and heterozygous site rate of induced F1 generation. The ploidy, SNP genotyping and flow cytometry results cumulatively shows that DH induction is attributed to the key genes regulation from the parents of Y3560 and Y3380, which significantly increase the induction efficiency as compared to ploidy. CONCLUSION: Based on our findings, we hypothesize that genetic characteristics and aneuploidy play an important role in the induction of DH individuals in Brassca napus, and the induction process has been explored. It provides an important insight for us to locate and clone the genes that regulate the inducibility in the later stage.

CXCR4 protects bone marrow-derived endothelial progenitor cells against hypoxia through the PI3K/Akt signaling pathway.

The present study aimed to investigate the regulatory mechanism of chemokine (C-X-C motif) receptor 4 (CXCR4) on endothelial progenitor cells (EPCs) through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway under hypoxic conditions. Mononuclear cells were isolated from the bone marrow (BM) of young Sprague-Dawley (SD) rats. Bone marrow-derived endothelial progenitor cells (BM-EPCs) were characterized by using Dil-labeled acetylated low-density lipoprotein (Dil-ac-LDL) and fluorescein isothiocyanate-labeled UEA (FITC-UEA-1). Phenotype identification of BM-EPCs was based on red cytoplasm and green cytomembrane. Flow cytometry was employed to examine the markers CD14, CD34, and KDR. Expression level of the EPC-specific surface marker CD14 was found to be negative, while the expression level of CD34 and KDR was positive. In addition, CXCR4 was stably overexpressed in BM-EPCs after transfection with adenovirus-CXCR4. Cell proliferation, migration and apoptosis abilities were measured through the application of CCK-8, followed by Transwell and flow cytometry assays. The expression level of CXCR4, PI3K and Akt was determined by reverse transcription-quantitative PCR and western blotting assays. Functional experiments demonstrated that hypoxia inhibited BM-EPC proliferation and migration, while accelerating BM-EPC apoptosis. Additionally, CXCR4 was found to promote proliferation and migration, and suppress apoptosis in BM-EPCs with or without hypoxia treatment. Evidence also demonstrated that CXCR4 markedly upregulated the expression levels of PI3K and Akt. Furthermore, PI3K inhibitor (LY294002) and CXCR4 inhibitor (AMD3100) effectively inhibited the proliferation, migration and resistance to apoptosis of CXCR4-mediated BM-EPCs under hypoxic conditions.