Apparent diffusion coefficient and its standard deviation from diffusion-weighted imaging in preoperative predicting liver invasion by T3-staged resectable gallbladder carcinoma.

AIM: To evaluate apparent diffusion coefficient (ADC) and its standard deviation (SDADC) in preoperative predicting liver invasion by T3-staged gallbladder carcinoma (GBC). MATERIALS AND METHODS: Forty-one consecutive patients with T3-staged resectable GBC were included and divided into two sets with (n=27) and without (n=14) liver invasion. All patients underwent DWI at b-values of 0, 20, 50, 80, 100, 200, 400, 600, 800, and 1,000 s/mm2 with a 3 T magnetic resonance imaging scanner before surgery. ADC and SDADC of tumour-adjacent and tumour-distant liver tissues were measured on DWI, and were compared by Mann-Whitney U-tests. If there was a significant difference in any derived parameter, the area under the receiver operating characteristic curve (AUC) was used to assess performance of this parameter to predict liver invasion. RESULTS: DWI could differentiate between patients with and without liver invasion when b = 0, 1,000 s/mm2 (AUCs of ADC and SDADC were 0.697 and 0.714, respectively). In patients with liver invasion, mean ADC and SDADC of tumour-adjacent liver tissue were lower than of tumour-distant liver tissue when b = 0, 800 s/mm2, and = 0, 1,000 s/mm2 (all p-values <0.05). To differentiate tumour-adjacent from tumour-distant liver tissues in patients with liver invasion, AUCs of ADC were 0.687 (b = 0, 800 s/mm2) and 0.680 (b = 0, 1,000 s/mm2), and AUCs of SDADC were 0.673 (b = 0, 800 s/mm2) and 0.731 (b = 0, 1,000 s/mm2). CONCLUSIONS: DWI could have potential value in preoperative predicting liver invasion by T3-staged GBC.

[Cardiac amyloidosis: pathological classification and clinical analysis of 48 cases].

Objective: To investigate the histological features and clinical manifestations in different types of cardiac amyloidosis to improve diagnostic accuracy. Methods: The histopathological features and clinical manifestations of 48 patients diagnosed with cardiac amyloidosis by Congo red stain and electron microscopy through endomyocardial biopsy were collected in West China Hospital of Sichuan University from January 2018 to December 2021. Immunohistochemical stains for immunoglobulin light chains (κ and λ) and transthyretin protein were carried out, and a review of literature was made. Results: The patients age ranged from 42 to 79 years (mean 56 years) and the male to female ratio was 1.1 to 1.0. The positive rate of endomyocardial biopsy was 97.9% (47/48), which was significantly higher than that of the abdominal wall fat (7/17). Congo red staining and electron microscopy were positive in 97.9% (47/48) and 93.5% (43/46), respectively. Immunohistochemical stains showed 32 cases (68.1%) were light chain type (AL-CA), including 31 cases of AL-λ type and 1 case of AL-κ type; 9 cases (19.1%) were transthyretin protein type (ATTR-CA); and 6 cases (12.8%) were not classified. There was no significant difference in the deposition pattern of amyloid between different types (P>0.05). Clinical data showed that ATTR-CA patients had less involvement of 2 or more organs and lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) than the other type patients (P<0.05). The left ventricular stroke volume and right ventricular ejection fraction of ATTR-CA patients were better than the other patients (P<0.05). Follow-up data of 45 patients was obtained, and the overall mean survival time was 15.6±2.0 months. Univariate survival analysis showed that ATTR-CA patients had a better prognosis, while cardiac amyloidosis patients with higher cardiac function grade, NT-proBNP >6 000 ng/L, and troponin T >70 ng/L had a worse prognosis (P<0.05). Multivariate survival analysis showed that NT-proBNP and cardiac function grade were independent prognostic factors for cardiac amyloidosis patients. Conclusions: AL-λ is the most common type of cardiac amyloidosis in this group. Congo red staining combined with electron microscopy can significantly improve the diagnosis of cardiac amyloidosis. The clinical manifestations and prognosis of each type are different and can be classified based on immunostaining profile. However, there are still a few cases that cannot be typed; hence mass spectrometry is recommended if feasible.

[Clinical and genetic characteristics of young patients with myeloproliferative neoplasms].

Objectives: To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN). Methods: In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients. Results: 1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion: Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.

[Read-through circular RNA rt-circ-HS promotes hypoxia inducible factor 1α expression and renal carcinoma cell proliferation, migration and invasiveness].

OBJECTIVE: To identify and characterize read-through RNAs and read-through circular RNAs (rt-circ-HS) derived from transcriptional read-through hypoxia inducible factor 1α (HIF1α) and small nuclear RNA activating complex polypeptide 1 (SNAPC1) the two adjacent genes located on chromosome 14q23, in renal carcinoma cells and renal carcinoma tissues, and to study the effects of rt-circ-HS on biological behavior of renal carcinoma cells and on regulation of HIF1α. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and Sanger sequencing were used to examine expression of read-through RNAs HIF1α-SNAPC1 and rt-circ-HS in different tumor cells. Tissue microarrays of 437 different types of renal cell carcinoma (RCC) were constructed, and chromogenic in situ hybridization (ISH) was used to investigate expression of rt-circ-HS in different RCC types. Small interference RNA (siRNA) and artificial overexpression plasmids were designed to examine the effects of rt-circ-HS on 786-O and A498 renal carcinoma cell proliferation, migration and invasiveness by cell counting kit 8 (CCK8), EdU incorporation and Transwell cell migration and invasion assays. RT-PCR and Western blot were used to exa-mine expression of HIF1α and SNAPC1 RNA and proteins after interference of rt-circ-HS with siRNA, respectively. The binding of rt-circ-HS with microRNA 539 (miR-539), and miR-539 with HIF1α 3' untranslated region (3' UTR), and the effects of these interactions were investigated by dual luciferase reporter gene assays. RESULTS: We discovered a novel 1 144 nt rt-circ-HS, which was derived from read-through RNA HIF1α-SNAPC1 and consisted of HIF1α exon 2-6 and SNAPC1 exon 2-4. Expression of rt-circ-HS was significantly upregulated in 786-O renal carcinoma cells. ISH showed that the overall positive expression rate of rt-circ-HS in RCC tissue samples was 67.5% (295/437), and the expression was different in different types of RCCs. Mechanistically, rt-circ-HS promoted renal carcinoma cell proliferation, migration and invasiveness by functioning as a competitive endogenous inhibitor of miR-539, which we found to be a potent post-transcriptional suppressor of HIF1α, thus promoting expression of HIF1α. CONCLUSION: The novel rt-circ-HS is highly expressed in different types of RCCs and acts as a competitive endogenous inhibitor of miR-539 to promote expression of its parental gene HIF1α and thus the proliferation, migration and invasion of renal cancer cells.

[Cognition and reflection on the "lateral ligament of rectum"].

As total mesorectal excision (TME) for rectal cancer is widely carried out in China, lateral ligament of rectum, as an important anatomical structure of the lateral rectum with certain anatomical value and clinical significance, has been the focus of attention. In this paper, by comparing and analyzing the characteristics about ligaments of the abdomen and pelvis, reviewing the membrane anatomy and the theory of primitive gut rotation, and combining clinical observations and histological studies, the author came to a conclusion that lateral ligament of rectum does not exist, but is only a relatively dense space on the rectal side accompanied by numerous tiny nerve plexuses and small blood vessels penetrating through it.

[Microfocal prostate cancer: a clinicopathological analysis of 206 cases].

Objective: To investigate the clinical and pathological features and prognosis of patients with microfocal prostate adenocarcinoma. Methods: Clinical and pathological data of the patients diagnosed with microfocal adenocarcinoma on prostate biopsy at the West China Hospital from 2013 to 2019 were collected. Microfocal adenocarcinoma was defined as follows: Gleason score of 3+3=6, total number of the cores ≥10, number of the positive cores ≤2, and proportion of the tumor in each positive core<50%. Clinicopathological parameters, treatment plans and follow-up data were collected. Pathological information of the biopsy and radical resection specimens was used to analyze the correlation between pathological parameters in the biopsy report and adverse pathological features of radical resection specimens, including increased Gleason score, capsule invasion, positive surgical margin and perineural invasion. Results: A total of 206 cases of microfocal adenocarcinoma were diagnosed on prostate biopsies from 2013 to 2019, accounting for 6.7% of all adenocarcinoma cases. There were 139 cases of 1 positive core and 67 cases of 2 positive cores. Patients with microfocal adenocarcinoma were younger than those with non-microfocal adenocarcinoma (69 years versus 71 years, P<0.001). Compared with patients with non-microfocal adenocarcinoma, the pre-biopsy total prostate specific antigen (tPSA) and free prostate specific antigen (fPSA) levels in patients with microfocal adenocarcinoma were both lower (11.2 µg/L2 versus 23.7 µg/L2; 1.4 µg/L2 versus 3.0 µg/L2, P<0.001), the fPSA/tPSA level was higher (12.9% versus 10.7%, P<0.05), the prostate volume was larger (38.9 mL versus 34.3 mL, P<0.05), and the PSA density was lower (0.3 µg/L2 versus 0.8 µg/L2, P<0.001). 130 patients underwent radical prostatectomy, 30 patients chose active monitoring, 31 patients chose endocrine or radiation therapy, and 15 patients were lost to follow-up. Three patients in the active surveillance group underwent radical prostatectomy for disease progression after 21-39 months observation. Biochemical relapses occurred in two patients in the radical prostatectomy group. The remaining patients have no disease progression or recurrence at present. Compared with radical prostatectomy specimens, Gleason score in the biopsy material was increased in 64/115 patients (55.7%). Among resection excision specimens, 14 cases (12.2%) had extraprostatic extension (EPE), 35 cases (30.4%) had perineural invasion, and 16 cases (13.9%) had a positive margin. Univariate and multivariate analyses showed that low fPSA/tPSA ratio and 2 positive cores were independent risk factors for Gleason score increase in the radical prostatectomy specimens. A low fPSA/tPSA ratio was an independent risk factor for perineural invasion. Low fPSA/tPSA ratio and low prostate volume were associated with a positive margin in radical prostatectomy specimens. Conclusions: In this study, patients diagnosed with microfocal adenocarcinoma on prostate biopsy account for a high proportion of the patients with increased Gleason score in the radical prostatectomy specimens, and there is a certain proportion of adverse pathological features in the radical specimens. Therefore, for the patients with only a small amount of low-grade adenocarcinoma found in biopsy, PSA levels and PSA density should be taken into consideration in treatment selection.

Supraclavicular lymph node recurrence after radical surgery: is epidermal growth factor receptor a predictive marker?

The aim of this study was to evaluate the rare postoperative supraclavicular metastasis originating from oral squamous cell carcinoma (OSCC) and to discuss epidermal growth factor receptor (EGFR) as a potential predictive marker. Tumour specimens of OSCC patients divided into three groups were included: supraclavicular metastasis (n = 8), conventional cervical metastasis (n = 28), no metastasis (n = 48). Basic information and EGFR expression were compared among these groups and the data were analysed to identify potentially related risk factors for supraclavicular metastasis. In the supraclavicular metastasis group (n = 8), all primary tumours were T1-T2 and located in the tongue and buccal region; five of eight cases were pathologically N0. The median interval from the primary tumour resection to the development of supraclavicular metastases was 21.5 months. All related deaths (5/8) occurred within 2 years. In the supraclavicular metastasis group, EGFR expression was highest in the supraclavicular metastases, followed by cervical lymph nodes, and was lowest in the primary tumours (P = 0.39). In contrast, in the conventional metastasis group and the N0 group, EGFR expression was higher in the primary tumours than in the lymph nodes (P < 0.01). Supraclavicular metastasis of OSCC is infrequent and associated with a poor prognosis. EGFR might predict the occurrence of supraclavicular metastasis.

Taurine Reduces Liver Damage in Non-Alcoholic Fatty Liver Disease Model in Rats by Down-Regulating IL-9 and Tumor Growth Factor TGF-ß.

The study employed a rat model to examine the effects of taurine (Tau) on prevention and therapy of non-alcoholic fatty liver disease (NAFLD). In model rats maintained on a high-fat diet (HFD), the serum levels of ALT, AST, triglycerides, cholesterol, and LDL were higher than the corresponding levels in normal control and NP groups (p<0.05). In Tau-prevention and Tau-treatment groups, the serum levels of AST and triglycerides were lower than in HFD rats (p<0.05). In HFD rats, diffuse fatty degeneration and infiltration with inflammatory cells was observed in the liver; in the ileal mucosa, the villi were fractured or absent, the epithelium was exfoliated and infiltrated with inflammatory cells. The levels of TGF-ß, IL-9, and their mRNA in the liver and ileal mucosa of HFD rats were significantly higher than in normal control and NP groups (p<0.05). In Tau-prevention and Tau-treatment groups, these levels were significantly lower than in HFD rats (p<0.05). Thus, TGF-ß and IL-9 can be implicated in NAFLD genesis, while Tau can preventively or therapeutically diminish the damage to the liver and ileal mucosa in rats with this disease by down-regulating the expression of TGF-ß and IL-9.

[Health-related quality of life and its associated variables in Chinese patients with Philadelphia-negative myeloproliferative neoplasms].

Objectives: To explore health-related quality of life (HRQoL) and identify its associated variables in Chinese patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) . Methods: In this cross-sectional study, anonymous questionnaires were distributed to adult patients with MPNs to assess symptom burden measured by MPN-10 and HRQoL measured by Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) . Results: The data from 1405 respondents with MPNs, including 645 (45.9%) with essential thrombocythemia (ET) , 297 (21.1%) with polycythemia vera (PV) , and 463 (33.0%) with myelofibrosis (MF) , were analyzed. 646 (46.0%) respondents were male. The median age was 56 (range, 18-99) years. The mean MPN-10 scores were 13.0±12.7, 15.0±14.7, and 21.0±16.6 (P<0.001) , and the physical component summary (PCS) and mental component summary (MCS) scores were 48.0±8.5, 47.0±9.0, and 42.0±10.0 (P<0.001) and 51.0±11.0, 50.0±10.8, and 49.0±11.1 (P=0.002) for respondents with ET, PV, and MF, respectively. Respondents with MF reported the lowest score of physical functioning, role functioning, emotional functioning, cognitive functioning, social function, and global health status (all P<0.01) and the highest score of fatigue, pain, dyspnea, appetite loss, diarrhea, and financial problems (all P<0.05) in EORTC QLQ-C30. Multivariate analyses revealed that higher MPN-10 scores were significantly associated with lower PCS (-0.220 to -0.277, P<0.001) and MCS (-0.244 to -0.329, P<0.001) scores; increasing age (-1.923 to -4.869; all P<0.05) , lower PCS score. Additionally, comorbidity (ies) , symptom at diagnosis, splenomegaly, anemia, unknown driver gene, and higher annual out-of-pocket cost were significantly associated with lower PCS and/or MCS scores. However, age ≥ 60 years, urban household registration, concomitant medication, and receiving ruxolitinib therapy in respondents with MF were associated with higher MCS scores. Weak correlations were found between MPN-10 score (except the subscale of appetite loss and constipation) and EORTC QLQ-C30 score in majority of subscales in respondents with ET (|r| = 0.193-0.457, all P<0.001) , PV (|r| = 0.192-0.529, all P<0.01) , and MF (|r| = 0.180-0.488, all P<0.001) , respectively. Conclusions: HRQoL in patients with MPN was significantly reduced, especially in patients with MF. Sociodemographic and clinical variables were significantly associated with the HRQoL in patients with MPNs.

Dysregulation of microRNA-770-5p influences pancreatic-ß-cell function by targeting TP53 regulated inhibitor of apoptosis 1 in gestational diabetes mellitus.

OBJECTIVE: The purpose of this study was to investigate the role of microRNA-770-5p (miR-770-5p) in gestational diabetes mellitus (GDM). MATERIALS AND METHODS: In the present study, the expression levels of miR-770-5p in the peripheral blood from GDM women and healthy women were investigated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The relationship between TP53 regulated inhibitor of apoptosis 1 (TRIAP1) and miR-770-5p was determined using dual-luciferase reporter assay. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry were used to detect pancreatic ß-cell proliferation and apoptosis. Enzyme-linked immunosorbent assay (ELISA) was used to measure total insulin content and insulin secretion. RESULTS: Our data indicated that miR-770-5p was up-regulated in GDM patients. TRIAP1 was a direct target of miR-770-5p and it was down-regulated in GDM patients. Besides, miR-770-5p negatively regulated the expression of TRIAP1 in INS-1 cells. Then, we explored the effects of miR-770-5p down-regulation on the insulin secretion of pancreatic ß-cells, and the results showed that miR-770-5p inhibitor promoted the generation of insulin secretion or total insulin content in INS-1 cells, while these effects were significantly inhibited by TRIAP1-siRNA. Moreover, we found that miR-770-5p inhibitor enhanced INS-1 cell proliferation and suppressed cell apoptosis, whereas these effects were eliminated by TRIAP1-siRNA. Accordingly, miR-770-5p inhibitor decreased the expression of Bax, apoptotic peptidase activating factor 1 (APAF1) and increased Bcl-2 level in INS1 cells. These results were all reversed by TRIAP1-siRNA. CONCLUSIONS: The data demonstrated that miR-770-5p was a vital regulator in pancreatic ß-cell proliferation, apoptosis and insulin secretion by targeting TRIAP1, and dysregulation of miR-770-5p resulted in the development of GDM via APAF1 signaling pathway.

[Semiquantitative parameters of 18F-FDG PET/CT, gene mutation states of epidermal growth factor receptor and anaplastic lymphoma kinase in prognosis evaluation of patients with lung adenocarcinoma].

OBJECTIVE: To explore the valuable predictors for evaluating progression-free survival (PFS) in patients with lung adenocarcinoma, we analyzed the potential roles of standardized uptake value (SUV)-derived parameters from 18F-FDG PET/CT, combining with the gene mutation states of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and other clinical characteristics. METHODS: Data of 84 lung adenocarcinoma patients pre-treated, who underwent 18F-FDG PET/CT scans, EGFR gene mutations test, ALK rearrangement assay and other relative tests, were retrospectively collected. Then a series of clinical parameters including EGFR/ALK mutation status and SUV-derived features [maximum standardized uptake value (SUVmax), average of standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were evaluated. Best possible cutoff points for all measuring parameters were calculated using receiver operating characteristic curve (ROC) analysis. Survival analysis was performed using Cox proportional hazards model to determine the prognostic markers for progression-free survival (PFS). Survival curves were obtained through Log-rank test and Kaplan-Meier curve. RESULTS: The median follow-up period was 31 months (24 to 58 months). It was found that SUVmax (≥3.01), SUVmean (≥2.25), MTV (≥25.41 cm3), and TLG (≥55.02) of the primary tumors were significantly associated with PFS in univariate Cox proportional hazards regression. Then regardless of age, gender, co-morbidity, EGFR/ALK mutation status, and treatment program, TLG (≥ 55.02, HR=4.965, 95%CI: 1.360-18.133), TNM stage (Ⅲ/Ⅳ, HR=7.811, 95%CI: 2.977-20.489), pro-gastrin releasing peptide (proGRP) (≥45.65 ng/L, HR=4.070, 95%CI: 1.442-11.487), tissue polypeptide antigen (TPA) (≥68.20 U/L, HR=6.996, 95%CI: 1.458-33.574), alkaline phosphatase (ALP) (≥82.50 IU/L, HR=4.160, 95%CI: 1.416-12.219) and ratio of activated partial thromboplastin time (aPTTR) (≥1.16: HR=4.58, 95%CI: 1.913-10.946) showed the independently relevant to PFS through multivariate Cox proportional hazards analysis. The EGFR mutant (P=0.343) and ALK rearrangement (P=0.608) were not significant either in survival analysis. CONCLUSION: High SUV-derived parameters (SUVmax, SUVmean, MTV and TLG) might provide prognostic value to some extent. Especially, TLG, and other clinical features [TNM stage, proGRP, TPA, ALP, and aPTTR] could be independently and significantly associated with PFS of lung adenocarcinoma patients. However, EGFR/ALK gene status could not be effectively relevant to PFS in lung adenocarcinoma patients.

Calcium-sensing receptor bridges calcium and telomerase reverse transcriptase in gastric cancers via Akt.

PURPOSE: Human telomerase reverse transcriptase (hTERT) and calcium-sensing receptor (CaSR) act as an oncogene in gastric cancers, however, their relationship in the progression of gastric cancers is yet to be elucidated. Herein, we aimed to access the potential interaction between hTERT and CaSR in the development of gastric cancers. METHODS: The clinical data of 41 patients with gastric cancers were analyzed regarding the expressions of hTERT and CaSR by immunohistochemistry. Among them, five patients' specimens were also analyzed by Western blotting. The regulation of calcium on the expression level of hTERT and the possible underlying mechanism via CaSR were explored in gastric cancer cell lines MKN45 and SGC-7901. RESULTS: Both hTERT and CaSR were increased and positively correlated in human gastric cancers, which also occurs in gastric cancer cells MKN45 and SGC-7901. Calcium induced hTERT expression at the transcriptional level in a CaSR-dependent manner followed by an increase in telomerase activity, as either a CaSR shRNA or the CaSR antagonist NPS2143 abolished the calcium-mediated regulation of hTERT and telomerase activity. Further studies showed that CaSR-mediated cytosolic calcium rise followed by Akt activation was involved in the regulation of hTERT by extracellular calcium. Finally, neither CaSR overexpression nor shRNA-mediated CaSR downregulation had an effect on the expression level of hTERT. CONCLUSIONS: Our findings established a functional linkage between CaSR and hTERT in the development of gastric cancers and CaSR-hTERT coupling might serve as a novel target for therapeutic strategy against human gastric cancers.

Circ-DB participates in the progression of gastric cancer by competitively binding microRNA-34a to regulate the expression of MET.

OBJECTIVE: To figure out the possible role and mechanism of circ-DB in the pathogenesis of gastric cancer (GCa). PATIENTS AND METHODS: 32 cases of postoperative GCa tissue samples and adjacent ones were collected and divided into groups of ≥ 5 cm and < 5 cm according to tumor diameter. Circ-DB, microRNA-34a, and MET expressions were detected by real time-quantitative PCR (RT-qPCR) in GCa tissues and adjacent tissues. To determine the main mode of action of circ-DB, the subcellular localization of circ-DB was examined by dividing the cells into the nucleus and cytoplasmic fractions. The binding of microRNA-34a to circ-DB was demonstrated by a Dual-Luciferase reporter gene assay. The expression of circ-DB in HGC-27 and AGS cells was overexpressed and knocked down to evaluate the migration function of the cells by transwell. The protein expression of MET, as well as the target gene of microRNA-34a, was detected by Western blot. RESULTS: The expression of circ-DB and MET in GCa tissues was significantly higher than that in the corresponding adjacent tissues. Circ-DB was positively correlated with MET expression, while microRNA-34a expression was negatively correlated with circ-DB and MET expression. Circ-DB was mainly located in the cytoplasm, and the Dual-Luciferase reporter gene demonstrated that microRNA-34a can bind to circ-DB. The down-regulation of circ-DB expression inhibited the migration of HGC-27 and AGS cells. In vitro cell experiments showed that low expression of circ-DB inhibited cell migration, which could be recovered by the co-transfection with microRNA-34a inhibitor. CONCLUSIONS: Circ-DB may regulate MET level through microRNA-34a and affect the proliferative ability and migration of GCa cells.

[Rapamycin in the treatment of renal diseases associated with tuberous sclerosis complex].

Objective: To investigate the efficacy and safety of rapamycin in children with tuberous sclerosis complex (TSC) associated renal disease. Methods: A prospective self-control study was conducted. The clinical data of 92 children diagnosed with tuberous sclerosis complex associated kidney disease at the People's Liberation Army General Hospital from January 2011 to January 2019 were collected. The long-term rapamycin treatment for all patients initiated at 1 mg/(m(2)·d), which was gradually adjusted to reach a blood concentration of 5-10 µg/L. The changes of the maximum diameter of renal lesions in children after rapamycin treatment were observed and analyzed with Wilcoxon test. Results: Ninety-two children, including 52 males and 40 females, who met the criteria were analyzed. Sixty patients had only renal angiomyolipoma(RAML), while 24 patients had only multiple renal cysts(MRC), and 8 patients had both lesions. The age of TSC diagnosis was 16.0 (7.0, 42.0) months, and the age of initial treatment with rapamycin was 63.5 (21.0, 103.0) months. The follow-up lasted for 12.0 (4.0, 23.0) months. Sequencing of TSC1 and TSC2 genes was performed in 54 children with TSC, including 3 patients (6%) with mutations in TSC1 gene and 51 patients (94%) with mutations in TSC2 gene. The maximum RAML diameter before treatment was 7.0 (4.0, 9.0) mm. The best effect reached at 3 months of treatment, with the diameter of 4.0 (0,7.0) mm. The maximum diameters at 6 months, 1 year and 1-2 years were 5.0 (0,9.8) mm, 5.0 (1.5, 8.5) mm, 5.5 (3.0, 9.0) mm, respectively, and were significantly different from the baseline (Z=-2.404,-2.350,-2.750,P=0.016,0.019,0.006, respectively). The maximum diameter after 2-3 years, and ≥3 years were 5.0 (3.9,7.0) mm and 6.0 (1.0, 11.0) mm, without significant difference from the baseline (Z=-0.856,-0.102,P=0.393,0.919, respectively).The maximum diameters of MRC after 3 months, 6 months, 1 year,1-2 years, 2-3 years, and ≥3 years were 11.0 (5.0, 14.0) mm,3.0 (0.0,11.0) mm,5.0 (0,21.0) mm,0 (0,14.0) mm,0 (0,10.0) mm, and 0 (0,18.3) mm, respectively, but were not significantly different rom the baseline (7.0 (5.0, 15.7) mm)(Z=-0.944,-1.214,-1.035,-1.896,-1.603,-1.214,P=0.345,0.225,0.301,0.058,0.109,0.225, respectively).Twenty-nine patients (32%) had oral ulcers during the entire treatment period, and no serious adverse reactions were observed. Conclusions: Rapamycin could decrease the diameter of TSC-related RAML, but could not inhibit the growth of cysts. It is well tolerated in the treatment of renal diseases associated with tuberous sclerosis complex.

[The subgroup analysis of the prognostic value of the intraductal carcinoma of the prostate in patients with metastatic prostate cancer].

Objective: To determine the prognostic value of the intraductal carcinoma of the prostate IDC-P in metastatic prostate cancer (mPCa) patients of different subgroups. Methods: Data of 582 de novo mPCa patients between January 2011 and December 2017 diagnosed at Departments of Urology, West China Hospital, Sichuan University were retrospectively analyzed. The age was (70±8) years (range: 45 to 89 years). IDC-P was identified from 12-core prostate biopsy. The prognostic role of IDC-P was assessed by Kaplan-Meier curves and Cox regression. Subgroup analysis was conducted by the forest plot. The endpoints were castration-resistant prostate cancer free survival (CFS) and overall survival (OS). Results: In total, 177/582 (30.4%) patients harbored IDC-P. Patients with IDC-P had poorer CFS and OS than those without IDC-P (mCFS: 12.1 months vs. 16.9 months, P=0.000; mOS: 39.7 months vs. not reached, P=0.000). Multivariate Cox regression analysis indicated that, the existence of IDC-P was an independent prognosticator of both CFS (HR=1.40, 95% CI: 1.10 to 1.79, P=0.006) and OS (HR=1.51, 95% CI: 1.02 to 2.25, P=0.041). Subanalysis indicated that, in most subgroups, IDC-P was an adverse prognosticator of both CFS and OS. Even in subgroups with adverse clinicopathological features, e.g. Gleason score 9 to 10 (CFS: HR=1.467, P=0.007; OS: HR=1.807, P=0.013), baseline prostate specific antigen≥50 µg/L (CFS: HR=1.616, P=0.000; OS: HR=1.749, P=0.006), anemia (CFS: HR=1.653, P=0.036; OS: HR=2.100, P=0.038), alkaline phosphatase≥160 U/L (CFS: HR=1.326, P=0.038; OS: HR=1.725, P=0.010) or abnormal lactate dehydrogenase level (CFS: HR=1.614, P=0.001; OS: HR=1.900, P=0.003), IDC-P was still closely associated with shorter CFS and OS. Conclusions: The presence of IDC-P was closely related to poor survival outcomes for patients with mPCa. IDC-P was an adverse prognosticator in most subgroup patients. The description of IDC-P in the pathological report of prostate biopsy would help clinicians to evaluate the prognosis of mPCa patients more accurately and make better treatment choices.

Role and mechanism of Dvl3 in the esophageal squamous cell carcinoma.

OBJECTIVE: The purpose of this project was to investigate the expression of Dishevelled-3 (Dvl3) in esophageal squamous cell carcinoma and cultured cells, and to determine the consequence of Dvl3 silencing in the tumorous properties of esophageal squamous cell carcinoma cells. PATIENTS AND METHODS: The expression of Dvl3 mRNA and protein in 50 cases of esophageal squamous cell carcinoma was detected. The expression of Dvl3 mRNA and protein was significantly elevated in esophageal squamous cell carcinoma tissues compared with atypical hyperplasia and normal esophageal mucosa. RESULTS: Dvl3 promoted the proliferation of esophageal squamous cell carcinoma cells and cell migration of cells expressing Dvl3 siRNA was significantly lower than that of the non-transfected cells. Flow cytometry showed that silencing Dvl3 promoted apoptosis of esophageal squamous cell carcinoma. Dvl3 overexpression cells in the subcutaneous tissue of nude mice promoted the formation of tumors. The expression of Dvl3 was associated with invasion and metastasis of the esophageal squamous cell carcinoma. CONCLUSIONS: Overall, down-regulation of Dvl3 expression can control the progression of esophageal squamous cell carcinoma, inhibit the growth and promote the apoptosis of tumor cells. Thus, Dvl3 has potential applications for early diagnosis, prognosis and therapeutics in the esophageal squamous cell carcinoma.

[Prognostic significance of combined TERT and IDH gene mutation analysis in diffusely infiltrating gliomas].

Objective: To investigate the status and prognostic significance of TERT and IDH1/2 genes mutations in diffusely infiltrating gliomas. Methods: Hot spot mutations of TERT and IDH1/2 genes were detected by DNA sequencing in 236 cases of gliomas at West China Hospital from 2012 to 2016, including pilocytic astrocytoma (WHO grade Ⅰ, 16 cases), diffuse astrocytoma and oligodendroglioma (WHO grade Ⅱ, 89 cases), anaplastic astrocytoma and oligodendroglioma (WHO grade Ⅲ, 72 cases) and glioblastoma (WHO grade Ⅳ, 59 cases). The prognostic significance of TERT and IDH1/2 hot spot mutations was evaluated. Results: No IDH or TERT mutations were detected in pilocytic gliomas. TERT promoter mutation frequency was higher in patients aged ≥40 years(60.8%, 93/153) than in patients aged <40 years (32.8%, 22/67; P<0.01). TERT promoter mutation rate was also significantly higher in oligodendroglioma (87.5% , 56/64) than that in astrocytoma(37.8%, 59/156; P<0.01). Young age (<40 years), oligodendroglioma and IDH1 mutation were favorable prognostic factors for diffusely infiltrating astrocytic and oligodendroglial tumors. TERT mutation alone was not of prognostic significance. Diffusely infiltrating astrocytic and oligodendroglial tumors were divided into four molecular subtypes according to TERT and IDH1 mutation status: IDH(+ )/TERT(+ ), IDH(+ )/TERT(-), IDH(-)/TERT(-) and IDH(-)/TERT(+ ). There was significant prognostic difference among the 4 subtypes. Conclusions: Combined IDH and TERT gene mutation analysis may be useful for prognostic subgrouping. Notably, IDH1 wild-type cases can be further subdivided into TERT(+ ) or (-) subgroups with significant prognostic difference.