Problem-based learning (PBL) is a unique form of pedagogy dedicated to developing students' self-learning and clinical practice skills. After several decades of development, although applications vary, PBL has been recognized all over the world and implemented by many medical schools. This review summarizes and updates the application and study of PBL in medical education through the literature published between 1993 and early 2017. It focuses on understanding real medical PBL courses and ways to improve PBL to achieve better learning outcomes. PBL aims to develop lifelong skills to solve practical problems rather than limiting learning to theoretical knowledge. To achieve this goal, strict and reasonable procedures need to be designed and implemented. Rigorous monitoring and timely feedback and evaluation are indispensable to constant improvements and perfecting of the process. © 2017 by The International Union of Biochemistry and Molecular Biology, 46(2):186-194, 2018.

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ZCCHC9 is a type of CCHC type zinc-finger containing protein which was found to be expressed in some tissues including brain and testicles in mice. Expression and function of ZCCHC9 in human tissues including cancer was largely unknown. In this study, we investigated the expression and function of ZCCHC9 in human non-small cell lung cancer (NSCLC) and the related molecular mechanism. Immunochemistrical standing showed that ZCCHC9 was mainly located in the nucleus in bronchial epithelial cells and epithelial cells of submucosal glands (58.3% [14/24]). But in NSCLC cells ZCCHC9 was mainly located in the cytoplasm and the positive rate was 54.5% (60/110). Ectopic cytoplasmic expression of ZCCHC9 in cancer tissues was significantly associated with advanced TNM stages (III+IV), lymph node metastasis, and poor clinical outcome (P < 0.05). Overexpression of cytoplasmic ZCCHC9 using transfection of ZCCHC9 cDNA in A549 and NCI-H1299 cells significantly upregulated the proliferation and invasion of these cancer cells in vitro (P < 0.05). Western blot study showed that overexpression of cytoplasmic ZCCHC9 significantly upregulated expression of p-JNK, Cyclin D1, and MMP7 (P < 0.05). Next we used the inhibitor of JNK pathway to inhibit the activity of the JNK pathway and the results showed that co-addition of SP600125 significantly abolished the function of ZCCHC9 to promote the proliferation and invasion of cancer cells. These results indicate that cytoplasmic ZCCHC9 could promote the proliferation and invasion of NSCLC through the JNK pathway and may be a promising cancer maker. K E Y W O R D S JNK, lung cancer, NSCLC, ZCCHC9

Background Homocysteine (Hcy) is considered to be a risk factor for cardiovascular and cerebrovascular diseases. Few studies have evaluated the distribution of Hcy on a large-scale health examination. Accordingly, this study aimed to investigate the level and distribution of Hcy in the population with healthy physical examination and the correlation with other biomarkers, and analyzed for cardiovascular and other diseases. Methods Measurements of serum Hcy, TC, TG, LDL-c, HDL-c, ALT, ALP, γ-GT, TBIL, GLU, urea, Cr, UA, and related metabolic risk factors were selected for analysis from 8063 medical examination samples collected from February 2017 to April 2020. The relationship between Hcy and other biochemical indicators were evaluated with the multivariate regression model of age, gender, smoking, drinking, body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Results Among 8063 cases, the age, BMI, SBP, and DBP of the high-Hcy group were higher than those of the low-Hcy group, the difference was statistically significant (P < 0.001), and the proportion of males, smoking, and drinking were higher than the low-Hcy group, the difference was statistically significant (P < 0.001); Hcy of the abnormal GLU group is higher than the normal GLU group (P = 0.002) and the Hcy of abnormal TG and HDL is higher than that of the normal blood lipid group (P < 0.001); Hcy of people with abnormal UA and Urea was higher than that of people with normal renal function (P < 0.001, P = 0.007). In multivariate analysis, lnHDL-C was negatively correlated with lnHcy (β = − 0.038, SE = 0.016, P = 0.019), lnCr was positively correlated with lnHcy (β = 0.055, SE = 0.016, P < 0.001), lnUA and lnHcy were positive correlated (β = 0.043, SE = 0.019, P = 0.022). Conclusion Hcy is closely related to HDL-c, Cr, and UA, which indicates that Hcy may affect the metabolism of HDL-c and UA, and can also be used as an auxiliary diagnostic index for kidney injury.

Hes3 is a basic helix-loop-helix factor gene, which was found to be involved in neural cell differentiation. Expression and clinicopathological significance of Hes3 in non-small cell lung cancer was not clear. In this study, we used immunohistochemistry to examine Hes3 expression in normal human lung and non-small cell lung cancer tissues. Hes3 expression was detected in cytoplasm and nucleus. Hes3 expression in bronchial epithelial cells and epithelial cells of submucosal glands was relatively weak and the positive rate was of 30.3% (10/33). Hes3 expression in non-small cell lung cancer tissues (51.8% (58/112)) was significantly higher than that in normal lung tissues (p < 0.05). Hes3 expression in cancer tissues was significantly associated with poor differentiation, advanced TNM stages, lymph node metastasis, and a shorter patient survival time (p < 0.05). In vitro study showed that overexpression of Hes3 in A549 cells significantly promoted cancer cell proliferation and invasion, while inhibition of Hes3 expression significantly downregulated cancer cell proliferation and invasion (p < 0.05). Western blotting showed that overexpression of Hes3 significantly upregulated expression of Cyclin D1, Cyclin D3, and MMP7 in A549 cells, while inhibition of Hes3 expression in LK2 cells significantly downregulated the expression of these molecules (p < 0.05). These results indicated that Hes3 may contribute to the malignant phenotype of non-small cell lung cancer, possibly through regulation of Cyclin D1, Cyclin D3, and MMP7, and may be a promising cancer marker.

Multiple myeloma (MM) is a hematologic malignancy caused by abnormal proliferation of bone marrow plasma cells, which lacks diagnostic markers and has a general prognosis. At present, the understanding of its pathogenesis provides the basis for the combined diagnosis and new targeted therapy of the disease. In this study, quantitative real-time PCR was used to detect 136 MM patients and 74 healthy controls, and the clinical application value of hsa_circ_0087776 as a new tumor marker and combined diagnosis was evaluated. The results showed that the expression of hsa_circ_0087776 was significantly lower in serum of MM patients ( P -value < 0.0001), and the expression was consistent in MM cells. In the analysis of clinicopathological parameters, it was found that there were significant statistical differences with MM stage and renal injury. In addition, it significantly increased the sensitivity with ALB, β₂-MG joint diagnosis, to provide a basis for diagnosis, improve the prognosis of the disease, improve the survival of patients and quality of life. These studies suggest that hsa_circ_0087776 can be used as a new oncology marker for the combined diagnosis of MM. Impact statement: Various evidences have shown that the role of circRNA in the occurrence and development of diseases is potentially unknown and untapped. Therefore, it has a broad prospect to find circRNA specifically expressed in MM patients for combined diagnosis and targeted therapy of MM. However, MM lacks such specific tumor markers. Therefore, the discovery of new specific tumor markers for combined diagnosis is an important milestone in the development of medical history. In the research, we founded hsa_circ_0087776 can be used as a new oncology marker for combined diagnosis of MM.

The established UHPLC-MS/MS method for absolute quantification of uCysC is helpful for accurate diagnosis of early acute kidney injury.

BackgroundHepatocellular Carcinoma (HCC) is the most common primary carcinoma of the liver, which mainly metastasizes through the portal vein system.Case presentationHere, we report an extremely rare case in which HCC metastasized to the capsule of an undescended testis in the right inguinal area of the patient. A tumor approximately 8.8 × 7.0 cm in size was found in the patient’s liver during a health check-up. Initially, it was considered a metastatic tumor because the patient was found to have cryptorchidism, which had been left untreated before he presented to our hospital. The patient underwent a radical orchiectomy via inguinal approach, and the resected testis in the right inguinal region was examined via microscopy. The cancer cells were arranged in nests and showed abundant red or clear cytoplasm and marked nuclear atypia. Immunohistochemical staining showed that the tumor cells were positive for CK, CK8/18, AFP, hepatocyte, GCP3, but negative for PLAP, CD10, CD30, CD34, and vimentin.ConclusionAccording to these findings, the tumor in the inguinal region was considered a metastatic HCC arising from the liver, rather than a seminoma that had originated in the undescended testis. We suggest that during the diagnosis of malignancies, metastatic tumors should always be considered in the differential diagnosis even if the original presentation is at rare metastatic sites or concurrent with other disease(s).