Deciphering thyroid function and CIMT: a Mendelian randomization study of the U-shaped influence mediated by apolipoproteins.

Background: Carotid Intima-Media Thickness (CIMT) is a key marker for atherosclerosis, with its modulation being crucial for cardiovascular disease (CVD) risk assessment. While thyroid function's impact on cardiovascular health is recognized, the causal relationship and underlying mechanisms influencing CIMT remain to be elucidated. Methods: In this study, Mendelian Randomization (MR) was employed to assess the causal relationship between thyroid function and CIMT. Thyroid hormone data were sourced from the Thyroidomics Consortium, while lipid traits and CIMT measurements were obtained from the UK Biobank. The primary analysis method was a two-sample MR using multiplicative random effects inverse variance weighting (IVW-MRE). Additionally, the study explored the influence of thyroid hormones on lipid profiles and assessed their potential mediating role in the thyroid function-CIMT relationship through multivariate MR analysis. Results: The study revealed that lower levels of Free Thyroxine (FT4) within the normal range are significantly associated with increased CIMT. This association was not observed with free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), or TPOAb. Additionally, mediation analysis suggested that apolipoprotein A-I and B are involved in the relationship between thyroid function and CIMT. The findings indicate a potential U-shaped curve relationship between FT4 levels and CIMT, with thyroid hormone supplementation in hypothyroid patients showing benefits in reducing CIMT. Conclusion: This research establishes a causal link between thyroid function and CIMT using MR methods, underscoring the importance of monitoring thyroid function for early cardiovascular risk assessment. The results advocate for the consideration of thyroid hormone supplementation in hypothyroid patients as a strategy to mitigate the risk of carotid atherosclerosis. These insights pave the way for more targeted approaches in managing patients with thyroid dysfunction to prevent cardiovascular complications.

Next-generation sequencing-based analysis of homologous recombination repair gene variant in ovarian cancer.

Background: Ovarian cancer is the leading cause of death from gynecological malignancies. Investigating the HRR-related gene status, notably BRCA1/2 in different regions and populations is of great significance for formulating accurate target therapy. Methods: We collected 124 ovarian cancer cases from the Affiliated Hospital of.Qingdao University, detected the genomic alteration of 32 genes by NGS, including.19 HRR-related genes, 9 proto-oncogenes and 4 tumor suppressor genes. Clinicopathological characteristics, variants, clinical significance, and correlation with prognosis were analyzed. Results: The incidence of HRR-related gene mutation was 59.68 % and no statistical significance was found with multiple clinicopathological characteristics. BRCA1/2 (27.42 %) were the most frequent mutated HRR genes. 23 (18.55 %) cases harbored gBRCA1/2 mutation, with all BRCA1 mutations were pathogenic/likely pathogenic and 2 cases of BRCA2 mutation was variant of uncertain significance. Somatic BRCA1/2 mutations were found in 12 (9.68 %) cases, and sBRCA1/2 had a higher frequency in less common ovarian cancer than high-grade serous carcinoma. HRR-related gene mutation status was associated with better prognosis than HRR wild-type. Conclusions: Somatic BRCA1/2 mutation has higher incidence in less common ovarian cancer. HRR gene mutation status is an independent prognosis factor in ovarian cancer. Clarifying the HRR gene status is important for the selection of target therapy as well as the evaluation of prognosis.

MET fusions are targetable genomic variants in the treatment of advanced malignancies.

Targeted therapy for malignancies has developed rapidly in recent years, benefiting patients harboring genetic mutations sensitive to relevant tyrosine kinase inhibitors (TKIs). With the development of targeted sequencing techniques, an increasing number of detectable genomic alterations in malignancies, including MET fusions, have been revealed. MET fusions, although rare among malignancies, might be functional driver genes that participate in activating downstream signaling pathways and promoting cell proliferation. Therefore, it is believed that MET fusions could be targetable genomic variants of MET, and inhibition of MET is considered an optionable therapeutic choice for patients harboring MET fusions. According to the summary presented in this review, we recommend MET-TKIs as suitable treatment agents for patients harboring primary MET fusions. For patients harboring acquired MET fusions after the development of resistance to TKIs targeting primary genomic alterations, such as sensitive EGFR mutations, treatment with a MET-TKI alone or in combination with TKIs targeting primary genomic alterations, such as EGFR-TKIs, is hypothesized to be a reasonable option for salvage treatment. In summary, MET fusions, despite their low incidence, should be taken into consideration when developing treatment strategies for cancer patients.

Is HER2 ultra-low breast cancer different from HER2 null or HER2 low breast cancer? A study of 1363 patients.

OBJECTIVE: This study aims to analyze whether there are any differences in clinicopathological features and prognosis between HER2 ultra-low, HER2-null, and HER2-low expression in Chinese breast cancer (BC) patients. METHODS: The clinicopathological data of 1363 HER2-negative BC patients were retrospectively collected (from January 2018 to December 2019). HER2 status was further classified into HER2-null, HER2 ultra-low, and HER2-low. HER2-null expression is defined as infiltrating cancer cells completely free of staining. HER2 ultra-low expression is defined as ≤10% of infiltrating cancer cells showing incomplete and faint/weak membrane staining. HER2-low expression is defined as HER2 immunohistochemistry (IHC) 1+ or 2+ with negative in situ hybridization (ISH) assay. RESULTS: Of 1363 patients, there were 86 (6.3%) HER2-null patients, 395 (29.0%) HER2 ultra-low patients, and 882 (64.7%) HER2-low patients. HER2 ultra-low patients were different from HER2-low patients in terms of N stage, hormone receptor (HR) status, Ki-67 expression, and type of surgery. There were also significant differences in histologic type and postoperative endocrine therapy between HER2 ultra-low and HER2-null patients. HR+ (81.0%) tumors was more common than HR- (19.0%) in HER2 ultra-low patients. In addition, there was a significant difference in HR status between HER2 ultra-low and HER2-low patients (P = 0.001). The survival analysis showed that HER2 status had no effect on disease-free survival (DFS) in HER2-negative patients (all P > 0.05). However, regardless of HER2 status, HR+ patients had better DFS than HR- patients (P = 0.003). Cox multivariate analysis revealed that age (HR [95% CI] = 0.950 [0.928, 0.972], P < 0.001), HR status (HR [95% CI] = 3.342 [1.658, 6.736], P = 0.001), and postoperative endocrine therapy (HR [95% CI] = 0.048 [0.048, 0.023], P < 0.001) were important influencing factors of DFS in HER2-negative BC patients. CONCLUSION: HER2 ultra-low BC patients demonstrated distinct clinicopathological features from HER2-null and HER2-low tumors; while, HER2 status (null, ultra-low, or low) had no prognostic value in these HER2-negative BC population. Consistent with the published literature, HR status was an independent prognostic factor for DFS in HER2-negative BC patients.

Regulation of the Ca2+ Channel CaV1.2 Supports Spatial Memory and Its Flexibility and LTD.

Widespread release of norepinephrine (NE) throughout the forebrain fosters learning and memory via adrenergic receptor (AR) signaling, but the molecular mechanisms are largely unknown. The ß2 AR and its downstream effectors, the trimeric stimulatory Gs-protein, adenylyl cyclase (AC), and the cAMP-dependent protein kinase A (PKA), form a unique signaling complex with the L-type Ca2+ channel (LTCC) CaV1.2. Phosphorylation of CaV1.2 by PKA on Ser1928 is required for the upregulation of Ca2+ influx on ß2 AR stimulation and long-term potentiation induced by prolonged theta-tetanus (PTT-LTP) but not LTP induced by two 1-s-long 100-Hz tetani. However, the function of Ser1928 phosphorylation in vivo is unknown. Here, we show that S1928A knock-in (KI) mice of both sexes, which lack PTT-LTP, express deficiencies during initial consolidation of spatial memory. Especially striking is the effect of this mutation on cognitive flexibility as tested by reversal learning. Mechanistically, long-term depression (LTD) has been implicated in reversal learning. It is abrogated in male and female S1928A knock-in mice and by ß2 AR antagonists and peptides that displace ß2 AR from CaV1.2. This work identifies CaV1.2 as a critical molecular locus that regulates synaptic plasticity, spatial memory and its reversal, and LTD.SIGNIFICANCE STATEMENT We show that phosphorylation of the Ca2+ channel CaV1.2 on Ser1928 is important for consolidation of spatial memory and especially its reversal, and long-term depression (LTD). Identification of Ser1928 as critical for LTD and reversal learning supports the model that LTD underlies flexibility of reference memory.

Relations between antinuclear, antineutrophil cytoplasmic, anticardiolipin antibodies and degree of neurological deficit, cerebrovascular stenosis in cerebral infarction patients.

Objective: To investigate the correlation of antinuclear antibody (ANA), antineutrophil cytoplasmic antibody (ANCA) and anticardiolipin antibody (ACA) with the degree of the neurological defect and cerebrovascular stenosis in patients with cerebral infarction. Methods: Clinical data of 99 patients with acute cerebral infarction (ACI) admitted to the Department of Neurology of Baoding First Central Hospital from June 2020 to December 2021 were retrospectively analyzed, and their ANA, ACA, ANCA, neurological deficit (NIHSS) scores as well as cerebrovascular stenosis were detected and assessed. Moreover, the correlation between the positive expression rates of ANA, ANCA, ACA and the degree of the neurological deficit, as well as the location and degree of cerebrovascular stenosis, were analyzed. Results: All patients had ANA, ACA, ANCA antibodies with positive rates of 68.69%, 70.71%, 69.70%, and mild, moderate, and severe cerebrovascular stenosis with incidence rates of 28.28%, 32.32%, and 39.39% respectively; Moreover, their incidence of mild, moderate, and severe neurological deficits were 15.15%, 44.44%, and 40.40%, respectively. Statistically significant differences could be observed in the degree of cerebrovascular stenosis and neurological deficit between the ANA, ACA and ANCA antibody positive group and the negative group (p<0.05). ANA, ACA, ANCA antibody positive was moderately positively correlated with cerebrovascular stenosis rate and NIHSS score (0.40

PCK1 activates oncogenic autophagy via down-regulation Serine phosphorylation of UBAP2L and antagonizes colorectal cancer growth.

Phosphoenolpyruvate carboxykinase 1 (PCK1) is the rate-limiting enzyme in gluconeogenesis. PCK1 is considered an anti-oncogene in several human cancers. In this study, we aimed to determine the functions of PCK1 in colorectal cancer (CRC). PCK1 expression in CRC tissues was tested by western blot and immunohistochemistry analyses and associations of PCK1 level with clinicopathological characteristics and disease survival evaluated. Further, we studied the effect of PCK1 on CRC cell proliferation and the underlying mechanisms. Our results show that PCK1 is expressed at significantly lower levels in CRC than in control tissues. High PCK1 expression was correlated with smaller tumor diameter and less bowel wall invasion (T stage). Overexpression and knockdown experiments demonstrated that PCK1 inhibits CRC cell growth both in vitro and in vivo. Mechanistically, PCK1 antagonizes CRC growth via inactivating UBAP2L phosphorylation at serine 454 and enhancing autophagy. Overall, our findings reveal a novel molecular mechanism involving PCK1 and autophagy, and highlight PCK1 as a promising candidate therapeutic target in CRC.

Tumor-to-tumor metastasis: A case report of metastasis of nasopharyngeal carcinoma to meningioma and review of the literature.

RATIONALE: Tumor to tumor metastasis is a rare phenomenon clinically, especially tumor to meningioma metastasis. Here, we present an unusual case of metastasis of nasopharyngeal carcinoma to meningioma. PATIENT CONCERNS: A 55-year-old man, with a history of nasopharyngeal carcinoma, developed neurological symptoms. DIAGNOSIS: Computed tomography and magnetic resonance imaging revealed a mass on left temporoparietal lobe, indicating the presence of meningioma. The pathologist diagnosed the metastasis of nasopharyngeal carcinoma (differentiated non-keratinizing squamous cell carcinoma) to meningioma. INTERVENTIONS: Chemotherapy and immunotherapy were performed following the resection. OUTCOMES: The patient has been well and no relapses has been observed. LESSONS: Doctors should be aware of the presence of tumor-to-tumor metastasis, which is a rare phenomenon. A positive history of primary extracranial tumor should raise the suspicion of potential tumor-to-tumor metastasis.

Silencing TRAIP suppresses cell proliferation and migration/invasion of triple negative breast cancer via RB-E2F signaling and EMT.

TRAIP, as a 53 kDa E3 ubiquitin protein ligase, is involved in various cellular processes and closely related to the occurrence and development of tumors. At present, few studies on the relationship between TRAIP and triple negative breast cancer (TNBC) were reported. Bioinformatic analysis and Western blot, immunohistochemistry (IHC), CCK-8, colony formation, flow cytometry, wound healing, Transwell, and dual-luciferase reporter assays were performed, and xenograft mouse models were established to explore the role of TRAIP in TNBC. This study showed that the expression of TRAIP protein was upregulated in TNBC tissues and cell lines. Silencing of TRAIP significantly inhibited the proliferation, migration, and invasion of TNBC cells, whereas opposite results were observed in the TRAIP overexpression. In addition, TRAIP regulated cell proliferation, migration, and invasion through RB-E2F signaling and epithelial mesenchymal transformation (EMT). MiR-590-3p directly targeted the TRAIP 3'-UTR, and its expression were lower in TNBC tissues. Its mimic significantly downregulated the expression of TRAIP and subsequently suppressed cell proliferation, migration, and invasion. Rescue experiments indicated that TRAIP silencing reversed the promotion of miR-590-3p inhibitor on cell proliferation, migration, and invasion. TRAIP overexpression could also reverse the inhibition of miR-590-3p mimic on tumorigenesis. Finally, TRAIP knockdown significantly inhibited tumor growth and metastasis in animal experiments. In conclusion, TRAIP is an oncogene that influences the proliferation, migration, and invasion of TNBC cells through RB-E2F signaling and EMT. Therefore, TRAIP may be a potential therapeutic target for TNBC.

BAG2-activated cell autophagy and mir-27b dynamic regulation mechanism during Mycobacterium tuberculosis infection.

Tuberculosis is a highly contagious infectious disease. Mycobacterium tuberculosis infection is the main cause of tuberculosis. During the infection of M. tuberculosis, the expression of the resistance gene BAG2 will change, and miR-27b will play a certain role in dynamic regulation. The purpose of this article is to explore in-depth the effect of BAG2 on cell autophagy during M. tuberculosis infection and the dynamic regulatory mechanism of miR-27b on BAG2 activated cell autophagy. Fifty rats were used as experimental subjects, and M. tuberculosis strains H37Ra and H37Rv were implanted into the rats. Fluorescence quantitative PCR was used to detect the dynamic changes of BAG2 and miR-27b expression levels in rats and the regulatory effect of miR-27b on BAG2, and the effect of changes in BAG2 expression levels on cell autophagy was studied by immunoblotting. The results showed that after M. tuberculosis-infected macrophages, the expression level of BAG2 decreased from (284.24±6.31) to (156.48.24±4.49), and the expression level of miR-27b was increased from (43.72±3.35) to (78.35± 4.17), the apoptosis rate increased by 17.8%, and the autophagy rate increased by 20.6%. Therefore, it can be seen that the up-regulation of miR-27b expression level during M. tuberculosis infection will inhibit BAG2 expression, thereby promoting cell autophagy and apoptosis to reduce the survival rate of M. tuberculosis.

Immunogenomic landscape analyses of immune molecule signature-based risk panel for patients with triple-negative breast cancer.

Triple-negative breast cancer (TNBC) presented as high heterogeneous immunogenicity that lacks useful clinical signatures to risk-stratify immune-benefit subtypes. We hypothesized that molecular-based phenotypic characterization of TNBC tumors and their immunity may overcome these challenges. We enrolled 1,145 patients with TNBC for analysis. Through combining algorithm integration analysis and TNBC datasets, a tumor immune risk score (TIRS) panel consisting of 8 potential biomarkers was identified. The TIRS panel represented excellent effectiveness as an independent predictor. High- and low risk stratification of patients was further achieved by TIRS, and significant survival and immune-infiltration pattern differences were found in each cohort, both at the transcriptome and protein levels. Non-negative matrix factorization clustering further identified four different tumor immune microenvironment types (TIMTs), among which TIMT-II was associated with the best prognosis and immune status, whereas TIMT-IV had the opposite effect, TIMT-III was associated with highly unstable genomes, and TIMT-I displayed stem-cell-related characteristics along with high stromal scores and may have extensive enrichment of tumor-associated fibroblasts and vascular cells. In conclusion, our TIRS panel could serve as a robust prognostic signature and provide therapeutic benefits for immunotherapy. Additionally, coordinating four TIMTs may be helpful for clinical decision-making in TNBC patients.

Clinicopathological characteristics and prognostic analysis of tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ (DCIS) and DCIS with microinvasion (DCIS-Mi) of the breast.

OBJECTIVE: Our purpose is to evaluate the correlation of TILs with clinicopathological characteristics and disease free survival (DFS) in DCIS and DCIS-Mi breast cancer (BC) patients. METHODS: We retrospectively reviewed the data of 360 DCIS patients and 125 DCIS-Mi patients treated by a single institution from 2016 to 2019. TILs are regarded as continuous variables and are divided into low (≤ 5%), medium (5-40%) and high (≥ 40%) for statistical analysis. RESULTS: In DCIS and DCIS-Mi patients, larger tumor size, higher nuclear grade, hormone receptor (HR) negativity and human epidermal growth factor receptor 2(HER2) overexpression are all related to high TILs (P < 0.05). In addition, compared with DCIS, DCIS-Mi patients were significantly associated with high TILs (P < 0.001). Based on the different results of the subtypes, we further studied the correlation between TILs and DFS in 279 cases of HER2+ patients (204 of DCIS; 75 of DCIS-Mi). In HER2+ group, DCIS-Mi was significantly associated with HR negativity (P = 0.015) and high TILs (P = 0.002) compared with DCIS patients. In the survival analysis, we found that TILs had no effect on the DFS of DCIS (P = 0.938), DCIS-Mi (P = 0.807), and HER2+ (P = 0.379) BC patients. In the univariate and multivariate cox regression analysis, the correlation between TILs and the prognosis of DFS has not been confirmed in the three BC groups (P > 0.05). CONCLUSION: TILs have played an non-negligible role in the progress of DCIS to DCIS-Mi, especially in HER2+ BC. The predictive and prognostic value of TILs still needs further research to confirm.

Clinicopathological characteristics and treatment of patients with high-grade endometrial stromal sarcoma: A retrospective study of 40 cases.

ABSTRACT: To investigate the clinicopathological characteristics of patients with high-grade endometrial stromal sarcoma (HG-ESS).The clinicopathological characteristics, treatments, and prognostic information of consecutive HG-ESS patients were collected from medical records and then evaluated.A total of 40 women were included in the analysis. The immunohistochemical profiles indicated that HG-ESS tumors tend to be locally or weakly positive for vimentin (100%) and CD10 (72.0%) but mostly negative for desmin (7.7%) and AE1/AE3 (9.1%). The progression-free survival intervals and the clinical benefit rates of patients receiving radiotherapy and/or chemotherapy were slightly longer and higher than those receiving simple observation (progression-free survival: 6 and 5 months vs 2 months; clinical benefit rate: 83.3% and 75.0% vs 28.6%). The 1-year disease-specific survival (DSS) rate was 62.7%. Tumor size, myometrial invasion, lymphovascular space invasion, cervical involvement, Federation International of Gynecology and Obstetrics (FIGO) stage, and residual disease all significantly affected the DSS rate (P < .001, =.002, <.001, =.004, <.001, and <.001, respectively). For patients with stage I disease, the 1-year DSS rate was as high as 91.7%, in contrast to 66.7%, 26.7%, and 0% for those with stage II, III, and IV disease, respectively.HG-ESS is associated with an adverse prognosis. FIGO stage could effectively predict the prognosis of patients with this lethal disease. Immunohistochemical markers, vimentin+/CD10+ (local or very weak), in combination with desmin-/AE1/AE3-, may be helpful for improving the diagnostic accuracy of this lethal condition. The therapeutic roles of adjuvant chemotherapy and radiotherapy warrant further investigation.

Gastrointestinal Goblet Cell Adenocarcinomas Harbor Distinctive Clinicopathological, Immune, and Genomic Landscape.

Goblet cell adenocarcinoma (GCA) is a rare amphicrine tumor and difficult to diagnose. GCA is traditionally found in the appendix, but extra-appendiceal GCA may be underestimated. Intestinal adenocarcinoma with signet ring cell component is also very rare, and some signet ring cell carcinomas are well cohesive, having some similar morphological features to GCAs. It is necessary to differentiate GCA from intestinal adenocarcinomas with cohesive signet ring cell component (IACSRCC). The goal of this study is to find occurrence of extra-appendiceal GCA and characterize the histological, immunohistochemical, transcriptional, and immune landscape of GCA. We collected 12 cases of GCAs and 10 IACSRCCs and reviewed the clinicopathologic characters of these cases. Immunohistochemical stains were performed with synaptophysin, chromogranin A, CD56, somatostatin receptor (SSTR) 2, and Ki-67. Whole transcriptome RNA-sequencing was performed, and data were used to analyze differential gene expression and predict immune cell infiltration levels in GCA and IACSRCC. RNA-sequencing data for colorectal adenocarcinoma were gathered from TCGA data portal. Of the 12 patients with GCA, there were 4 women and 8 men. There were three appendiceal cases and nine extra-appendiceal cases. GCAs were immunohistochemically different from IACSRCC. GCA also had different levels of B-cell and CD8+ T-cell infiltration compared to both colorectal adenocarcinoma and cohesive IACSRCCs. Differential gene expression analysis showed distinct gene expression patterns in GCA compared to colorectal adenocarcinoma, with a number of cancer-related differentially expressed genes, including upregulation of TMEM14A, GOLT1A, DSCC1, and HSD17B8, and downregulation of KCNQ1OT1 and MXRA5. GCA also had several differentially expressed genes compared to IACSRCCs, including upregulation of PRSS21, EPPIN, RPRM, TNFRSF12A, and BZRAP1, and downregulation of HIST1H2BE, TCN1, AC069363.1, RP11-538I12.2, and REG4. In summary, the number of extra-appendiceal GCA was underestimated in Chinese patients. GCA can be seen as a distinct morphological, immunohistochemical, transcriptomic, and immunological entity. The classic low-grade component of GCA and the immunoreactivity for neuroendocrine markers are the key points to diagnosing GCA.

Mesenchymal-Epithelial Transition Exon 14 Skipping Mutation and Amplification in 5,008 Patients With Lung Cancer.

BACKGROUND: Lung cancer is a major health concern worldwide because of its increasing incidence and mortality. This study aimed to clarify the association between mesenchymal-epithelial transition (MET) genomic alterations and clinical characteristics of lung cancer. METHOD: We collected data from 5,008 patients with lung cancer diagnosed and treated between January 2017 and July 2021 at the Affiliated Hospital of Qingdao University. Genomic alterations in the MET gene, including the exon 14 skipping mutation and amplification, were detected using amplification refractory mutation system-polymerase chain reaction (2,057 cases) and next-generation sequencing (2,951 cases). Clinical characteristics such as age, sex, tumor location, tumor stage, smoking, pleural invasion, and histology were statistically analyzed for MET exon 14 skipping mutation and amplification. The DNA splicing sites causing the MET exon 14 skipping mutation at the mRNA level were also investigated. RESULTS: The incidence of the MET exon 14 skipping mutation was 0.90% (41/4,564) in adenocarcinoma, 1.02% (3/294) in squamous cell carcinoma, and 8.33% (1/12) in sarcomatoid carcinoma specimens. It was more frequently observed in patients over 60 years of age than the MET exon 14 skipping mutation wildtype. The MET exon 14 skipping mutation co-occurred with epidermal growth factor receptor (EGFR) L858R, EGFR 19-Del, and BRAF V600E mutations. At the DNA level, single nucleotide mutation and small fragment deletion (1-38 base pairs) upstream and downstream of MET exon 14 led to MET exon 14 skipping mutation at the mRNA level. MET amplification occurred in 0.78% (21/2,676) adenocarcinoma and 1.07% (2/187) squamous cell carcinoma specimens and was significantly associated with advanced tumor stages (III + IV) compared to the MET amplification wildtype. MET amplification primarily co-occurred with the EGFR mutation. CONCLUSIONS: Our study found that MET genomic alterations were statistically related to age and tumor stage and co-existed with mutations of other oncogenic driver genes, such as EGFR and BRAF. Moreover, various splicing site changes at the DNA level led to the exon 14 skipping mutation at the mRNA level. Further studies are required to clarify the association between MET genomic alterations and prognosis.

Construction of a survival prediction model for high-and low -grade UTUC after tumor resection based on "SEER database": a multicenter study.

BACKGROUND: There are differences in survival between high-and low-grade Upper Tract Urothelial Carcinoma (UTUC). Our study aimed to develop a nomogram to predict overall survival (OS) of patients with high- and low-grade UTUC after tumor resection, and to explore the difference between high- and low-grade patients. METHODS: Patients confirmed to have UTUC between 2004 and 2015 were selected from the Surveillance, Epidemiology and End Results (SEER) database. The UTUCs were identified and classified as high- and low-grade, and 1-, 3- and 5-year nomograms were established. The nomogram was then validated using the Chinese multicenter dataset (patients diagnosed in Shandong, China between January 2010 and October 2020). RESULTS: In the high-grade UTUC patients, nine important factors related to survival after tumor resection were identified to construct nomogram. The C index of training dataset was 0.740 (95% confidence interval [CI]: 0.727-0.754), showing good calibration. The C index of internal validation dataset was 0.729(95% CI:0.707-0.750). On the other hand, Two independent predictors were identified to construct nomogram of low-grade UTUC. The C index was 0.714 (95% CI: 0.671-0.758) for the training set,0.731(95% CI:0.670-0.791) for the internal validation dataset. Encouragingly, the nomogram was clinically useful and had a good discriminative ability to identify patients at high risk. CONCLUSION: We constructed a nomogram and a corresponding risk classification system predicting the OS of patients with an initial diagnosis of high-and low-grade UTUC.

Establishment and Clinical Application of an Artificial Intelligence Diagnostic Platform for Identifying Rectal Cancer Tumor Budding.

Tumor budding is considered a sign of cancer cell activity and the first step of tumor metastasis. This study aimed to establish an automatic diagnostic platform for rectal cancer budding pathology by training a Faster region-based convolutional neural network (F-R-CNN) on the pathological images of rectal cancer budding. Postoperative pathological section images of 236 patients with rectal cancer from the Affiliated Hospital of Qingdao University, China, taken from January 2015 to January 2017 were used in the analysis. The tumor site was labeled in Label image software. The images of the learning set were trained using Faster R-CNN to establish an automatic diagnostic platform for tumor budding pathology analysis. The images of the test set were used to verify the learning outcome. The diagnostic platform was evaluated through the receiver operating characteristic (ROC) curve. Through training on pathological images of tumor budding, an automatic diagnostic platform for rectal cancer budding pathology was preliminarily established. The precision-recall curves were generated for the precision and recall of the nodule category in the training set. The area under the curve = 0.7414, which indicated that the training of Faster R-CNN was effective. The validation in the validation set yielded an area under the ROC curve of 0.88, indicating that the established artificial intelligence platform performed well at the pathological diagnosis of tumor budding. The established Faster R-CNN deep neural network platform for the pathological diagnosis of rectal cancer tumor budding can help pathologists make more efficient and accurate pathological diagnoses.

Graphene Oxide-Gold Star Construct on Triangular Electrodes for Alzheimer's Disease Identification.

Nanotechnology is playing a major role in the field of medical diagnosis, in particular with the biosensor and bioimaging. It improves the performance of the desired system dramatically by displaying higher selectivity and sensitivity. Carbon nanomaterial, gold nanostructure, magnetite nanoparticle, and silica substrate are the most popular nanomaterials greatly contributed to make the affordable and effective biosensor at low-cost. This research work is introducing a new sensing strategy with graphene oxide-constructed triangular electrodes to diagnose Alzheimer's disease (AD). MicroRNA-137 (miRNA-137) was found as a suitable biomarker for AD, and the sensing method was established here to detect miRNA-137 on the complementary sequence. To enhance the immobilization of capture miRNA-137, gold nanostar (GNS) was conjugated with capture miRNA and immobilized on the GO-modified surface through an amine linker. This immobilization process enhanced the hybridization of the target and reaches the detection limit at 10 fM with the sensitivity of 1 fM on the linear curve with a regression coefficient of 0.9038. Further control sequences of miRNA-21 and single and triple base mismatched miRNA-137 did not show a significant response in current changes, indicating the specific miRNA-137 detection for diagnosing AD.

Changes in clinical trials of endocrine disorder and metabolism and nutrition disorder drugs in mainland China over 2010-2019.

With the improvements in relevant policies, laws, and regulations regarding drug clinical trials in China, the quantity and quality of drug clinical trials have gradually improved, and the development prospects of drug clinical trials for endocrine disorders and metabolism and nutrition disorders are promising. Based on information from the clinical trials from the online drug clinical trial registration platform of the National Medical Products Administration, we aimed to review and evaluate the development of clinical trials of drugs for endocrine disorders and metabolism and nutrition disorders in mainland China from 2010 to 2019, as well as the trends over time. A total of 861 trials were carried out on 254 types of drugs for endocrine disorders and metabolism and nutrition disorders, among which 531 (61.67%) involved endocrine disorders, and 330 (38.33%) addressed metabolism and nutrition disorders. The annual number of clinical trials has been increasing gradually, with a significant increase in 2017. Among them, the proportion of clinical trials with Chinese epidemiological characteristics was relatively large (Wu, Annual Report on Development Health Management and Health Industry in China, 2018). The largest number of trials were for diabetes drugs (55.63%), followed by trials of drugs for hyperlipidemia (19.4%) and those for hyperuricemia (7.9%). It was found that the geographical area of the leading units also showed obvious unevenness according to the analysis of the test unit data. Based on the statistics and evaluation of the data, comprehensive information is provided to support the cooperation of global pharmaceutical R&D companies and research units in China and the development of international multicenter clinical trials in China. This work additionally provides clinical trial units with a self-evaluation of scientific research competitiveness and hospital development strategies. At the same time, it provides a reference with basic data for sponsors and stakeholders in these trials to determine their development strategy goals.