Background This study aimed to investigate the implementation and quality control of the quantitative detection of serum Helicobacter pylori (H. pylori) antibody in clinical laboratories in China. Methods Online external quality assessment (EQA) questionnaires were distributed to the clinical laboratories by National Center for Clinical Laboratories (NCCL) of China. We collected information on the quantitative detection procedures of serum H. pylori antibody in clinical laboratories, including detection reagents, methods, instruments, calibrators, and internal quality control (IQC). We distributed quality control products to some select laboratories that conducted quantitative detection and analyzed the obtained test data. We evaluated the quantitative detection procedure based on the standard evaluation criteria set at a target value of +/- 30%. Results 70.9% (146/206) of the laboratories conducted quantitative detection of H. pylori antibody; 29.1% (60/206) of the laboratories performed qualitative detection. Domestic reagents and matching calibrators accounted for more than 97.1% (200/206) of all reagents. Latex-enhanced immunoturbidimetry was used in 89.7% (131/146) of the laboratories for quantitative determination, while the colloidal gold method was used in 66.7% (40/60) of the laboratories for qualitative determination. A total of 130 laboratories participated in the EQA; 123 completed the assessment, and the pass rate was 75.6% (93/123). Conclusion Clinical quantitative detection of serum H. pylori antibody is performed at a high rate in China. Thus, further studies on the specificity of commercial detection reagents are needed. EQAs are useful to monitor and improve the detection quality of H. pylori antibodies.

Objective: Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disease with many manifestations, and it involves any organ. In this study, we report a TSC patient with new type skin lesions. Methods: A 7-month-old TSC boy with multiple cutaneous nodules was admitted in our hospital. We collected the clinical data of the patient. We performed biopsy of cutaneous nodules and whole-exome sequencing in both paraffin block tissue and blood samples. Results: The patient presented with a 2 month history of gradual growth multiple cutaneous nodules. He had cardiac rhabdomyoma, subependymal giant cell astrocytoma (SEGA) and hypomelanotic macules. The pathological finding of cutaneous nodules was consistent with juvenile xanthogranuloma (JXG). After 3 months of sirolimus treatment, the multiple nodules disappeared. The whole-exome sequencing identified TSC1 (c.2356C>T, p.R786*) mutation in both paraffin block tissue and blood samples. We overturned the original pathological diagnosis and finally identified JXG as a new type of skin lesions in TSC. Conclusion: This is the first report on the occurrence of JXG skin lesions in TSC patient. Genetic testing is necessary in JXG. These findings expand the phenotype of skin in patients with TSC and contribute to the elucidation of JXG pathogenesis and treatment.

Previous studies have found that alpha-fetoprotein (AFP) can promote the proliferation of hepatoma cells and accelerate the progression of hepatocellular carcinoma (HCC). However, the exact mechanism of action remains unclear. Recent bioinformatics studies have predicted the possible interaction between AFP and retinoic acid receptors (RARs). Thus, the purpose of this study was to investigate the molecular mechanism through which AFP promotes tumour cell proliferation by interfering with the RA-RAR signal pathway. Our data indicated that AFP could significantly promote the proliferation and weaken ATRA-induced apoptosis of hepatoma cells. Besides, cytoplasmic AFP interacts with RAR, disrupting its entrance into the nucleus, which in turn affects the expression of the Bcl-2 gene. In addition, knockdown of AFP in HepG2 cells was synchronously associated with an incremental increase of RAR binding to DNA, as well as down-regulation of Bcl-2; the opposite effect was observed in AFP gene-transfected HLE cells. Moreover, a similar effect of AFP was detected in tumour tissues with high serum AFP, but not in adjacent non-cancerous liver tissues, or HCC tissues with low serum AFP levels. These results indicate that AFP acts as signalling molecule and prevents RAR from entering into the nucleus by interacting with RAR, thereby promoting the expression of Bcl-2. Our data reveal a novel mechanism through which AFP regulates Bcl-2 expression and further suggest that AFP may be used as a novel target for treating HCC.

Rationale: Pseudo progression is a noted phenomenon of immune checkpoint inhibitors therapy, which has been defined as a response after an initial enlargement of the tumor followed by tumor reduction. In July 2017, the Food and Drug Administration granted accelerated approval of nivolumab for the treatment of metastatic colorectal cancer patients whose tumor harbors deficient mismatch repair. Patient concerns and diagnosis: We present a patient who received nivolumab for heterogeneity of right-sided metastatic colon carcinoma. Intervention: The patient was treated with nivolumab combined with chemotherapy. Outcome: The computed tomography showed mass lesion in the left lobe of liver remained stable while metastasis tumors under envelop of liver were exacerbated after 6 cycles of nivolumab combined with chemotherapy, and later regressed. Lessons: The status of mismatch repair in primary tumor and metastatic liver carcinoma is contradictory but using nivolumab demonstrated encouraging efficacy. This is the first case of pseudo progression undergoing immunotherapy for heterogeneity of right-sided metastatic colon carcinoma.

BACKGROUND:Lin28B and its paralog Lin28A are small RNA binding proteins that have similar inhibitory effects, although they target separate steps in the maturation of let-7 miRNAs in mammalian cells. Because Lin28B participates in the promotion and development of tumors mostly by blocking the let-7 tumor suppressor family members, we sought to explore the associated mechanisms to gain insights into how Lin28B might be decreased in human cancer cells to increase let-7 levels and reverse malignancy.RESULTS:We demonstrated that the histone acetyltransferase PCAF, via its cold shock domain, directly interacts with and subsequently acetylates Lin28B in lung adenocarcinoma-derived H1299 cells. RT-qPCR assays showed that both let-7a-1 and let-7g were increased in PCAF-transfected H1299 cells. Lin28B is acetylated by ectopic PCAF and translocates from the nucleus to the cytoplasm in H1299 cells.CONCLUSIONS:The effects of acetylated Lin28B on let-7a-1 and let-7g are similar to that of stable knockdown of Lin28B in H1299 cells. The new role of PCAF in mediating Lin28B acetylation and the specific release of its target microRNAs in H1299 cells may shed light on the potential application of let-7 in the clinical treatment of lung cancer patients.

Purpose: Pyruvate kinase M2 (PKM2) was found overexpressed in tumor cells and played a significant role in tumor formation and growth. We sought to explore the correlation of PKM2 expression with cell proliferation, invasion, and apoptosis in bladder cancer cell line. Materials and Methods: Real-time polymerase chain reaction and Western blot were performed to determine the expression level of PKM2 at mRNA and protein level. MTT and flow cytometry were respectively used to explore the proliferation, invasion, and apoptosis in bladder cancer cell line in vitro. Results: The results suggested that suppression of PKM2 significantly decreased the proliferation rate, invasive cell number, and migration ability of bladder cancer cells compared with blank group. Moreover, proteins such as MMP2 and MMP9 as well as P38 expression were also affected by the PKM2 expression changes. These results proved that PKM2 could be involved in the progression of bladder cancer by mitogen-activated protein kinases signaling pathway. Conclusion: The data presented in this study revealed that PKM2 up-regulation may promote the development and metastasis of bladder cancer through promoting cell proliferation, migration and invasion via MAPK signal pathway.

Abstract. Aims:. Catechol-O-methyltransferase (COMT) plays a role in many kinds of cancer, and its high expression in pancreatic cancer has been found to be related to better prognosis. However, the expression and biological significance of COMT in multistep pancreatic cancerogenesis is not clear. Main methods:. Six LSL-KrasG12D-positive and Pdx1-Cre-positive mice (KrasG12D mice), 6 wild-type mice and 1 human tissue microarray were used in this study. COMT protein expression was measured by immunohistochemistry, and DNA chips were made for use in COMT mRNA assays. Key findings:. The expression of COMT in pancreatic intraepithelial neoplasias (PanINs) from KrasG12D mice was significantly higher than that in normal pancreatic tissue from wild-type mice, both in terms of protein level and mRNA expression. The median COMT immunohistochemistry expression scores in human PanIN-1 and PanIN-2 were 70 and 160, respectively, which were significantly lower than the score of 170 observed in pancreatic ductal adenocarcinoma (PDAC) (P = .024 and .037, respectively) and significantly higher than the score of 25 observed in pancreatitis (P = .01 and .008, respectively). Significance:. In the development of pancreatic cancer from chronic pancreatitis and in the transition of PanIN to PDAC, we observed significantly increased expression of COMT. These data predict that the overexpression of COMT is an early event in the multistep process of pancreatic cancerogenesis.

Rationale: Case reports concerning the value of dopamine agonists in the treatment of patients with thyrotropin-secreting pituitary adenoma (TSHoma) are limited. Herein, we present a rare case of octreotide-insensitive TSHoma responding to bromocriptine therapy.Patient concerns: A 45-year-old Chinese man was admitted to Peking Union Medical College Hospital with marked clinical manifestations of hyperthyroidism.Diagnoses: Thyroid function tests demonstrated elevated concentrations of free thyroid hormones in the presence of normal thyrotropin. Magnetic resonance imaging findings showed a pituitary microadenoma on the right side of the sellar region. Based on characteristic endocrine results and neuroimaging findings, the patient was diagnosed with TSHoma.Interventions: Most patients with TSHomas are significantly responsive to somatostatin analog treatment. However, our patient was orally administered with bromocriptine to normalize thyroid function as assessed by suppression tests conducted prior to surgery. A transsphenoidal surgery was performed by an experienced neurosurgeon for tumor removal.Outcomes: The pituitary lesion was totally resected. Following the operation, the results of thyroid function tests were immediately within reference limits. During the follow-up, there was no residual or recurrent tumor.Lessons: Attention should be paid to the role of dopamine agonists such as bromocriptine and cabergoline as adjuvant therapy for TSHomas that are insensitive to traditional medical treatment by somatostatin analogs.

Hepatocellular carcinoma (HCC) is the most common type of hepatic cancer and is particularly a problem in China. Bio-molecular markers have been demonstrated to be of prognostic significance and might help predict tumor behavior. In our study, we aimed to assess the prognostic values of DNA methyltransferase 1 (DNMT1), HLA-DRα, and β-catenin, as well as the combined use of molecular biomarkers, clinicopathological parameters and the TNM staging system to find a method for superior prognostic performance for HCC by analyzing a Chinese HCC cohort. We revealed the significant prognostic roles of DNMT1 (OR: 2.570; 95% CI: 1.401-4.715; P = 0.002) and HLA-DRα (0.350; 0.189-0.616; 0.001), and further developed an estimation formula to predict prognosis in HCC patients after curative resection, based on TNM staging, operative blood loss, abnormal total bilirubin, DNMT1 and HLA-DRα. The receiver operating characteristic curve analysis showed that prediction from the multivariate logistic regression had an area of 0.847 and performed better than the conventional TNM staging system, as well as other current HCC staging systems. Our study demonstrated the prognostic values of DNMT1 and HLA-DRα in HCC patients after curative resection. Additionally, we developed a prognostic estimation formula featured better stratification ability than the conventional TNM staging and provided a practicable stratification method for HCC patients after curative resection.

PURPOSE:Studies have reported limited evidence of the benefits and harms of various regimens, such as liver resection and medical therapy, for the treatment of pancreatic neuroendocrine tumors (pNETs) with liver metastases. This meta-analysis aimed to evaluate the efficacy of liver resection versus nonsurgical treatments in patients with pNET.METHODS:Relevant studies published in English were retrieved from the computerized databases Medline, Embase, and Cochrane. A meta-analysis was performed to investigate the differences in the efficacy of liver resection and nonsurgical treatments based on the evaluation of 30-day mortality, symptom relief rate, median survival time, and 2-, 3-, or 5-year survival using a random-effects model. Studies were independently reviewed by two investigators. Data from eligible studies were extracted, and the meta-analysis was performed using the comprehensive meta-analysis program version 2.RESULTS:A total of seven studies were included in the analysis. The results demonstrated that liver resection was significantly associated with a higher rate of symptom relief, longer median survival time, higher 2- or 3-year survival rates, as well as a higher 5-year survival rate. There was no significant difference in 30-day mortality among patients with pNETs who were treated by liver resection and nonsurgical therapy or survival between functional and nonfunctional pNETs. No publication bias was detected.CONCLUSIONS:Liver resection has a favorable prognostic outcome in terms of higher postoperative symptom relief rates and longer survival rates. Further randomized, controlled trials with longer follow-up periods are required to confirm the advantages of liver resection for pNETs.

Alpha-fetoprotein (AFP) represents the most important biomarker for hepatocellular carcinoma (HCC). The aim of this study was to identify the optimal staging system to predict the survival of AFP-negative and AFP-positive patients. This study analyzed the data of 431 AFP-negative HCC patients who had previously undergone surgery and 471 AFP-positive HCC candidates. Kaplan–Meier (K-M) survival estimates were plotted, and the P values were assessed using log-rank tests. The Akaike information criterion (AIC) was calculated using the results of a Cox’s regression to compare the overall assessment of the seven different staging systems. The AFP-positive group displayed characteristics of poor tumor biological behavior (tumor multiplicity [ P = 0.032], low grade differentiation [ P = 0.000] and carcinoma cell embolus [ P = 0.031]), poor liver function (Child–Pugh B classification [ P = 0.003], abnormal prothrombin time activity [ P = 0.037] and moderate/severe cirrhosis [ P = 0.000]) and increased operative difficulties (transfusion; P = 0.001). TNM7th staging showed the lowest AIC value (1,279.528) for the AFP-negative group, while the Barcelona Clinic Liver Cancer (BCLC) staging system revealed the lowest AIC value (1,991.233) for the AFP-positive group. In conclusion, among the seven favorable staging systems, BCLC staging was superior for the AFP-positive group, while the TNM7th was a more appropriate staging model for the AFP-negative group.