The emerging role of BLyS/APRIL in autoimmune diseases: Biological characteristics, functions, and therapeutic potential.

Autoimmune diseases (AIDs) are common diseases in the world. Some cases are difficult to cure and can only delay the progression of the diseases. The B lymphocyte stimulator (BLyS)/a proliferation-inducing ligand (APRIL) plays an important role in B cell homeostasis, regulation of both innate and adaptive immune responses. After binding to their receptors, BLyS/APRIL primarily affects the survival and development of marginal, transitional, and mature B cells. Of note, elevated BLyS/APRIL is seen in many AIDs, such as systemic lupus erythematosus, rheumatoid arthritis, immunoglobulin A nephropathy, etc. Moreover, there is evidence that blocking these two cytokines can control the number of serum autoantibodies, promote the depletion of B lymphocytes, inhibit the activation of T cells and dendritic lymphocytes, and reduce inflammatory stress. Currently, some clinical studies are underway targeting BLyS/APRIL inhibitors for the treatment of AIDs. However, due to the scattered knowledge on the relationship between BLyS/APRIL and AIDs, it is necessary to sort out the existing data. Therefore, in this review, we describe the basic biological characteristics and functions of BLyS/APRIL in AIDs, summarize the potential clinical applications of related inhibitors, especially monoclonal antibodies and recombinant fusion proteins targeting BLyS/APRIL in AIDs, and also outline promising research directions.

Application of nanotechnology in the treatment of glomerulonephritis: current status and future perspectives.

Glomerulonephritis (GN) is the most common cause of end-stage renal failure worldwide; in most cases, it cannot be cured and can only delay the progression of the disease. At present, the main treatment methods include symptomatic therapy, immunosuppressive therapy, and renal replacement therapy. However, effective treatment of GN is hindered by issues such as steroid resistance, serious side effects, low bioavailability, and lack of precise targeting. With the widespread application of nanoparticles in medical treatment, novel methods have emerged for the treatment of kidney diseases. Targeted transportation of drugs, nucleic acids, and other substances to kidney tissues and even kidney cells through nanodrug delivery systems can reduce the systemic effects and adverse reactions of drugs and improve treatment effectiveness. The high specificity of nanoparticles enables them to bind to ion channels and block or enhance channel gating, thus improving inflammation. This review briefly introduces the characteristics of GN, describes the treatment status of GN, systematically summarizes the research achievements of nanoparticles in the treatment of primary GN, diabetic nephropathy and lupus nephritis, analyzes recent therapeutic developments, and outlines promising research directions, such as gas signaling molecule nanodrug delivery systems and ultrasmall nanoparticles. The current application of nanoparticles in GN is summarized to provide a reference for better treatment of GN in the future.

METTL14-m6A-FOXO3a axis regulates autophagy and inflammation in ankylosing spondylitis.

The role of m6A in ankylosing spondylitis (AS) remains largely obscure. In this study, we found that m6A modification was decreased in T cells of AS, and the abnormal m6A modification was attributed to the downregulation of methyltransferase-like 14 (METTL14). METTL14 exerted a critical role in regulating autophagy activity and inflammation via targeting Forkhead box O3a (FOXO3a). Mechanistically, the loss of METTL14 decreased the expression of FOXO3a, leading to the damage of autophagic flux and the aggravation of inflammation. Inversely, the forced expression of METTL14 upregulated the expression of FOXO3a, thereby activating autophagy and alleviating inflammation. Furthermore, our results revealed that METTL14 targeted FOXO3a mRNA and regulated its expression and stability in a m6A-dependent manner. These findings uncovered the functional importance of m6A methylation mechanisms in the regulation of autophagy and inflammation, which expanded our understanding of this interaction and was critical for the development of therapeutic strategies for AS.

A proton-coupled folate transporter mutation causing hereditary folate malabsorption locks the protein in an inward-open conformation.

The proton-coupled folate transporter (PCFT, SLC46A1) is required for folate intestinal absorption and transport across the choroid plexus. Recent work has identified a F392V mutation causing hereditary folate malabsorption. However, the residue properties responsible for this loss of function remains unknown. Using site-directed mutagenesis, we observed complete loss of function with charged (Lys, Asp, and Glu) and polar (Thr, Ser, and Gln) Phe-392 substitutions and minimal function with some neutral substitutions; however, F392M retained full function. Using the substituted-cysteine accessibility method (with N-biotinyl aminoethyl methanethiosulfonate labeling), Phe-392 mutations causing loss of function, although preserving membrane expression and trafficking, also resulted in loss of accessibility of the substituted cysteine in P314C-PCFT located within the aqueous translocation pathway. F392V function and accessibility of the P314C cysteine were restored by insertion of a G305L (suppressor) mutation. A S196L mutation localized in proximity to Gly-305 by homology modeling was inactive. However, when inserted into the inactive F392V scaffold, function was restored (mutually compensatory mutations), as was accessibility of the P314C cysteine residue. Reduced function, documented with F392H PCFT, was due to a 15-fold decrease in methotrexate influx Vmax, accompanied by a decreased influx Kt (4.5-fold) and Ki (3-fold). The data indicate that Phe-392 is required for rapid oscillation of the carrier among its conformational states and suggest that this is achieved by dampening affinity of the protein for its folate substrates. F392V and other inactivating Phe-392 PCFT mutations lock the protein in its inward-open conformation. Reach (length) and hydrophobicity of Phe-392 appear to be features required for full activity.

Antidepressant Activity of Euparin: Involvement of Monoaminergic Neurotransmitters and SAT1/NMDAR2B/BDNF Signal Pathway.

Depression is the most significant risk factor for suicide, yet the causes are complex and disease mechanism remains unclear. The incidence and disability rate of depression are very high and the efficacy of some traditional antidepressants is not completely satisfactory. Recently, some studies have found that benzofurans have anti-oxidation and anti-monoamine oxidase properties, which are related to depression. Euparin is a monomer compound of benzofuran, previous work by our team found that it improves the behavior of depressed mice. However, additional antidepressant effects and mechanisms of Euparin have not been reported. In this study, the Chronic Unpredictable Mild Stress (CUMS) model of mice was used to further investigate the effect and mechanism of Euparin on depression. Results showed that Euparin (8, 16 and 32 mg/kg) reduced depression-like behavior in mice compared with the model group. Meanwhile, all doses of Euparin were found to increase the contents of monoamine neurotransmitter and decrease monoamine oxidase and reactive oxygen species (ROS) levels in brain of depression mice. Additionally, Euparin restored CUMS-induced decrease of Spermidine/Spermine N1-Acetyltransferase 1 (SAT1), N-methyl-D-aspartate receptor subtype 2B (NMDAR2B) and brain derived neurotrophic factor (BDNF) expression. These findings demonstrate that Euparin has antidepressant properties, and its mechanism involves the SAT1/NMDAR2B/BDNF signaling pathway.

Novel molecular classification and prognosis of papillary renal cell carcinoma based on a large-scale CRISPR-Cas9 screening and machine learning.

Papillary renal cell carcinoma (PRCC) is a highly heterogeneous cancer, and PRCC patients with advanced/metastatic subgroup showed obviously shorter survival compared to other kinds of renal cell carcinomas. However, the molecular mechanism and prognostic predictors of PRCC remain unclear and are worth deep studying. The aim of this study is to identify novel molecular classification and construct a reliable prognostic model for PRCC. The expression data were retrieved from TCGA, GEO, GTEx and TARGET databases. CRISPR data was obtained from Depmap database. The key genes were selected by the intersection of CRISPR-Cas9 screening genes, differentially expressed genes, and genes with prognostic capacity in PRCC. The molecular classification was identified based on the key genes. Drug sensitivity, tumor microenvironment, somatic mutation, and survival were compared among the novel classification. A prognostic model utilizing multiple machine learning algorithms based on the key genes was developed and tested by independent external validation set. Our study identified three clusters (C1, C2 and C3) in PRCC based on 41 key genes. C2 had obviously higher expression of the key genes and lower survival than C1 and C3. Significant differences in drug sensitivity, tumor microenvironment, and mutation landscape have been observed among the three clusters. By utilizing 21 combinations of 9 machine learning algorithms, 9 out of 41 genes were chosen to construct a robust prognostic signature, which exhibited good prognostic ability. SERPINH1 was identified as a critical gene for its strong prognostic ability in PRCC by univariate and multiple Cox regression analyses. Quantitative real-time PCR and Western blot demonstrated that SERPINH1 mRNA and protein were highly expressed in PRCC cells compared with normal human renal cells. This study exhibited a new molecular classification and prognostic signature for PRCC, which may provide a potential biomarker and therapy target for PRCC patients.

The role of interleukin-20 in liver disease: Functions, mechanisms and clinical applications.

Liver disease is a severe public health concern worldwide. There is a close relationship between the liver and cytokines, and liver inflammation from a variety of causes leads to the release and activation of cytokines. The functions of cytokines are complex and variable, and are closely related to their cellular origin, target molecules and mode of action. Interleukin (IL)-20 has been studied as a pro-inflammatory cytokine that is expressed and regulated in some diseases. Furthermore, accumulating evidences has shown that IL-20 is highly expressed in clinical samples from patients with liver disease, promoting the production of pro-inflammatory molecules involved in liver disease progression, and antagonists of IL-20 can effectively inhibit liver injury and produce protective effects. This review highlights the potential of targeting IL-20 in liver diseases, elucidates the potential mechanisms of IL-20 inducing liver injury, and suggests multiple viable strategies to mitigate the pro-inflammatory response to IL-20. Genomic CRISPR/Cas9-based screens may be a feasible way to further explore the signaling pathways and regulation of IL-20 in liver diseases. Nanovector systems targeting IL-20 offer new possibilities for the treatment and prevention of liver diseases.

Application of integrated problem-based learning combined with lecture-based classroom teaching in undergraduate medical education: An effective teaching model in a Medical School in China.

The problem-based learning (PBL) is increasingly used in undergraduate education. However, the application of integrated PBL to medical undergraduate education has not been well assessed. An observational study was designed to compare integrated PBL combined with lecture-based classroom (LBC) with traditional LBC teaching in 2 semesters of a Medical School in China. This study was conducted from March 2021 to July 2022. A total of 118 undergraduates majoring in clinical medicine were randomly allocated in 2 groups, 1 group receiving the integrated PBL + LBC teaching (experimental group, n = 60) and another group receiving LBC teaching (control group, n = 58). The experimental group attended the integrated PBL courses for the basic and clinical medicine conducted in the 6th and 8th semesters, respectively, as well as taking the LBC courses. The experimental group was required to preview the course materials before class, make presentations in class and take online feedback questionnaires after class, while the control group was required to preview the textbooks and listen to the traditional LBC courses. The students' scores of these 2 groups were compared, and feedback questionnaires were performed to evaluate the effectiveness of the experimental group over the control group. Results showed that the experimental group scored significantly higher than the control group in Clinical Skills (95% confidence interval [CI] 4.19-5.89), Internal Medicine I (95% CI: 1.85-9.93), Internal Medicine II (95% CI: 8.07-15.90), Introduction to Surgery (95% CI: 5.08-10.25), Surgery (General Surgery) (95% CI: 7.82-12.72), Surgery (Specialty) (95% CI: 6.47-9.97), and Clinical Medical Level Test (95% CI: 1.60-5.15) (all P < .01). In the feedback questionnaires of integrated PBL, up to 80% and 90% of students were satisfied with the teaching methods and lecturers, respectively. More than 80% of students agreed that the integrated PBL improved their abilities to learn independently, understand knowledge, and to raise, analyze and solve problems. In terms of stress in and out of class, a small number of students, <36.7%, felt stressed. The integrated PBL combined with LBC is an effective teaching approach, which may provide new ideas for teaching research and reform on undergraduate medical education in clinical medicine specialty and other medical majors.

Amorphous selenium inhibits oxidative stress injury of neurons in vascular dementia rats by activating NMDAR pathway.

Vascular dementia (VD) is one of the most common causes of dementia, taking account for about 20% of all cases. Although studies have found that selenium supplementation can improve the cognitive ability of Alzheimer's patients, there is currently no research on the cognitive impairment caused by VD. This study aimed to investigate the role and mechanism of Amorphous selenium nanodots (A SeNDs) in the prevention of VD. The bilateral common carotid artery occlusion (BCCAO) method was used to establish a VD model. The neuroprotective effect of A SeNDs was evaluated by Morris water maze, Transcranial Doppler TCD, hematoxylin-eosin (HE) staining, Neuron-specific nuclear protein (Neu N) staining and Golgi staining. Detect the expression levels of oxidative stress and Calcium-calmodulin dependent protein kinase II (CaMK II), N-methyl-D-aspartate receptor subunit NR2A, and postsynaptic dense protein 95 (PSD95). Finally, measure the concentration of calcium ions in neuronal cells. The results showed that A SeNDs could significantly improve the learning and memory ability of VD rats, restore the posterior arterial blood flow of the brain, improve the neuronal morphology and dendritic remodeling of pyramidal cells in hippocampal CA1 area, reduce the level of oxidative stress in VD rats, increase the expression of NR2A, PSD95, CaMK II proteins and reduce intracellular calcium ion concentration, but the addition of selective NR2A antagonist NVP-AAMO77 eliminated these benefits. It suggests that A SeNDs may improve cognitive dysfunction in vascular dementia rats by regulating the NMDAR pathway.

Cardioprotective role of A-cycloglycosylated derivative of Rubiadin in diabetic cardiomyopathy in rats.

Diabetic cardiomyopathy (DCM) is a kind of idiopathic heart disease, which is one of the main complications of diabetes and seriously threatens the life of diabetic patients. Rubiadin, an anthraquinone compound extracted from the stems and roots of rubiaceae, has been widely discussed for its anti-diabetes, anti-oxidation and other pharmacological effects. However, Rubiadin can cause drug-induced liver injury. Therefore, A-cycloglycosylated derivative of Rubiadin (ACDR) was obtained by modifying its structure. The purpose of this study was to investigate the effect of ACDR on DCM cardiac injury and its mechanism. The DCM animal model was established by streptozotocin, and the success of DCM was verified by blood glucose level, echocardiographic evidence of impaired myocardial functions along with enhanced myocardial fibrosis. We performed liver function tests, morphological staining of the heart and tests for oxidative stress to evaluate cardiac functional and structural changes. Finally, the expression of Na+/H+ exchanger (NHE1) protein was analyzed by immunohistochemistry and western bolt, and the expression of hairy/enhancer-of-split related with YRPW motif 1 (Hey1) and P-p38 protein was detected by immunofluorescence chemistry and western blotting. The results showed that ACDR can improve cardiac dysfunction, reduce myocardial injury, reduce oxidative stress, and protect the liver in DCM rats. Interestingly, all variations were countered by LiCl. Our study suggests that, along with controlling hyperglycemia, ACDR may improve DCM by reducing NHE1 expression, further inhibiting P-p38 activity and increasing Hey1 expression to reduce oxidative stress.

Citronellal Attenuates Oxidative Stress-Induced Mitochondrial Damage through TRPM2/NHE1 Pathway and Effectively Inhibits Endothelial Dysfunction in Type 2 Diabetes Mellitus.

In type 2 diabetes mellitus (T2DM), oxidative stress induces endothelial dysfunction (ED), which is closely related to the formation of atherosclerosis. However, there are few effective drugs to prevent and cure it. Citronellal (CT) is an aromatic active substance extracted from citronella plants. Recently, CT has been shown to prevent ED, but the underlying mechanism remains unclear. The purpose of this study was to investigate whether CT ameliorated T2DM-induced ED by inhibiting the TRPM2/NHE1 signal pathway. Transient receptor potential channel M2 (TRPM2) is a Ca2+-permeable cation channel activated by oxidative stress, which damages endothelial cell barrier function and further leads to ED or atherosclerosis in T2DM. The Na+/H+ exchanger 1 (NHE1), a transmembrane protein, also plays an important role in ED. Whether TRPM2 and NHE1 are involved in the mechanism of CT improving ED in T2DM still needs further study. Through the evaluations of ophthalmoscope, HE and Oil red staining, vascular function, oxidative stress level, and mitochondrial membrane potential evaluation, we observed that CT not only reduced the formation of lipid deposition but also inhibited ED and suppressed oxidative stress-induced mitochondrial damage in vasculature of T2DM rats. The expressions of NHE1 and TRPM2 was up-regulated in the carotid vessels of T2DM rats; NHE1 expression was also upregulated in endothelial cells with overexpression of TRPM2, but CT reversed the up-regulation of NHE1 in vivo and in vitro. In contrast, CT had no inhibitory effect on the expression of NHE1 in TRPM2 knockout mice. Our study show that CT suppressed the expression of NHE1 and TPRM2, alleviated oxidative stress-induced mitochondrial damage, and imposed a protective effect on ED in T2DM rats.

[Effect of lactuside B on the expression of bcl-2 and bax mRNA and their protein in rats' cerebral cortex after cerebral ischemia-reperfusion injury].

This study is to investigate the effect of the major chemical composition in rhizome of Pterocypsela elata, lactuside B, on expression of bcl-2, bax mRNA and their protein in rats' cerebral cortex after cerebral ischemia-reperfusion injury. First, middle cerebral artery ischemia-reperfusion injury model was established, and each group was treated with the corresponding medicines. Animals were separately sacrificed at 24 h and 72 h. The brain infarct volumes were detected by TTC dye, bcl-2 and bax mRNA expression was checked by RT-PCR, and the proteins of bcl-2 and bax were explored by two-step immunohistochemistry in cerebral cortex of rats. Lactuside B can reduce brain infarct volume of cerebral cortex of rats, increase the expression of bcl-2 mRNA and decrease that of bax mRNA. Moreover, the ratio of bcl-2 to bax mRNA is higher in 12.5 and 25 mg kg(-1) dose group, respectively, which is significantly different from that of model group (P < 0.05 or P < 0.01). Generally, either 12.5 or 25 mg kg(-1) dose group is better than positive control medicine nimodipine (P < 0.05 or P < 0.01). In addition, the expression of bcl-2 and bax protein is consistent with their gene expression. Infarct volume and the ratio of bcl-2 to bax mRNA expression are significantly different (P < 0.05 or P < 0.01) between 72 h and 24 h group. The results demonstrated that lactuside B could play a good role in resisting cerebral ischemia by upregulating the expression of bcl-2 mRNA and protein and downregulating that of bax mRNA and protein.

[Follicular variant of peripheral T-cell lymphoma: a clinicopathologic and genetic study of 2 cases].

OBJECTIVE: To observe the clinicopathologic and genetic features of follicular variant of peripheral T-cell lymphoma (FV-PTCL), with particular attention to the relationship of this type of lymphoma with angioimmunoblastic T-cell lymphoma (AITL). METHODS: The clinical data, hematoxylin and eosin-stained sections of lymph node biopsies from 2 FV-PTCL cases were reviewed. Immunohistochemical phenotyping and detection of EBV-encoded RNAs (EBER) through in situ hybridization (ISH) were performed. The EnVision two-step method was used for all antibodies except CXCL13 (by using three-step streptavidin immunoperoxidase method). Analysis of clonality and ITK/SYK gene rearrangement was conducted using PCR and RT-PCR assays, respectively. RESULTS: Clinically, the two patients presented with superficial lymphadenopathy similarly. Histologically, case 1 showed a follicular/nodular lymphoid proliferation without marked germinal centers. The neoplastic cells comprised mainly medium sized cells with abundant, sometimes clear cytoplasms. Similar histologic findings were seen in case 2 in addition to a concurrent component mimicking typical AITL noticed. Of both cases, the neoplastic cells showed positive reactivity to CD3, CD4, CD10, PD1, and CXCL13. Positive hybridization signals for EBER were only seen in case 2, and double stains demonstrated that those EBV-positive cells were mostly the reactive transformed B-cells. Monoclonal T-cell proliferation was proved by the rearranged TCR gene detection in both cases. Neither of the current cases expressed ITK/SYK fusion transcripts. CONCLUSION: FV-PTCL shows the similar or overlapped morphological and immunophenotypic features to those of AITL, possibly suggesting the presence of a potential relationship between these two types of lymphomas.

TFEB promotes BCL-2 expression by upregulating its promoter activity in the t(6;11) translocation renal cell carcinomas.

t(6;11) translocation renal cell carcinoma (RCC) is classified as a subset of the MiT family translocation RCCs and characterized by harboring the Alpha-TFEB fusion gene. However, the development mechanism of this tumor and its effective treatment have not been fully identified yet. The purpose of this study was to explore the relationship between TFEB and BCL-2 in Alpha-TFEB stably transfected cell lines and in t(6;11) RCC tumor tissue. An Alpha-TFEB eukaryotic expression vector was constructed and stably transfected into CaKi-2 and HK-2 cells. RT-PCR and real-time RT-PCR were used to measure the mRNA expressions of TFEB and BCL-2, and immunohistochemistry, Western blot and dual immunofluorescence assays were used to evaluate the TFEB and BCL-2 protein expressions. MTT proliferation assays and flow cytometry were also performed. Furthermore, luciferase reporter assays were used to evaluate the BCL-2 promoter activity. An Alpha-TFEB eukaryotic expression vector was successfully constructed and stably transfected into CaKi-2 and HK-2 cells (named CaKi-2-TFEB and HK-2-TFEB cells). Compared with the CaKi-2 and HK-2 groups, the TFEB and BCL-2 mRNA expression levels were significantly upregulated in the CaKi-2-TFEB and HK-2-TFEB groups respectively. The TFEB and BCL-2 protein expressions showed a similar result. The overexpression of TFEB and BCL-2 promoted cell proliferation and inhibited cell apoptosis. Moreover, the overexpression of TFEB upregulated the promoter activity of BCL-2. Our data suggest that the overexpression of TFEB promotes BCL-2 expression by upregulating its promoter activity and ultimately results in the development of t(6;11) translocation RCC. BCL-2 inhibitors may serve as potential therapeutic targets for t(6;11) translocation RCC.

15α,20ß-Dihydr-oxy-6ß-meth-oxy-6,7-seco-6,20-ep-oxy-1,7-olide-ent-kaur-16-ene.

The title compound, C(21)H(30)O(6), a natural ent-kaurane diterpenoid, was obtained from the medicinal plant Isodon serra. The five rings in the mol-ecule exhibit the expected cis and trans junctions. The three six-membered rings adopt chair, twist-boat and boat conformations, while two five-membered rings adopt envelope conformations. There are two mol-ecules in the asymmetric unit, related by a non-crystallographic twofold screw axis; the main difference is in the different degrees of distortion of ring B. In the crystal, the mol-ecules are linked by inter-molecular O-H⋯O hydrogen bonds, forming chains along the b axis.

Alpha gene upregulates TFEB expression in renal cell carcinoma with t(6;11) translocation, which promotes cell canceration.

Renal cell carcinoma (RCC) with t(6;11) translocation has been characterized by the fusion of the Alpha gene with the TFEB gene. However, the underlying molecular mechanisms remain greatly uncharacterized and effective targeted therapy has yet to be identified. In this study, we examined the role of the Alpha gene in this tumor entity and the function of the fusion gene Alpha-TFEB product in vitro and in vivo. Our results revealed that the luciferase activity of Alpha1, Alpha2, Alpha3, Alpha4 and Alpha5 significantly increased compared with that of the pGL3-Basic group (P<0.01). The luciferase activity also increased significantly in the Alpha1, Alpha2 and Alpha5 groups compared with that of the normal TFEB gene group (P<0.01). In addition, the luciferase activity of Alpha5 was the strongest located in the 643-693 base sequence. The stable transfection of Alpha-TFEB into HK-2 and CaKi-2 cells promoted the expression of Alpha-TFEB mRNA and TFEB protein. Furthermore, the overexpression of TFEB increased cell proliferation and enhanced the cell invasive ability, and decreased cell apoptosis in the Alpha-TFEB stably transfected cells in vitro. In vivo experiments revealed that the overexpression of TFEB promoted tumorigenicity in nude mice, which was consistent with our in vitro results. On the whole, these data indicate that the overexpression of TFEB confers a potent oncogenic signal and may thus be a novel therapeutic target in RCC with t(6;11) translocation.

[Expression of human Sel-1-like gene and its significance in esophageal cancer].

OBJECTIVE: To study the expression of SEL1L (human Sel-1-like gene) mRNA and protein and its significance in esophageal cancer. METHODS: Immunohistochemical staining (S-P method) for SEL1L protein was performed in 90 samples of esophageal squamous cell carcinoma, 35 samples of normal esophageal mucosa 5 cm away from the tumor, 60 samples of esophageal mucosa adjacent to the tumor and 20 samples of esophageal squamous dysplasia. In situ hybridization for SEL1L mRNA was also carried out in the esophageal carcinoma cases and normal esophageal mucosa distant from and adjacent to the tumor. RESULTS: The positive rate of SEL1L mRNA was higher in esophageal carcinoma (80.0%, 72/90), as compared with that in normal esophageal mucosa distant from (14.3%, 5/35) and adjacent to (16.7%, 10/60) the tumor (P < 0.01). The positive rate of SEL1L mRNA in tumors with lymph node metastasis (92.7%, 38/41) was higher than that in tumors without lymph node metastasis (69.4%, 34/49) (P < 0.01). On the other hand, the expression rate of SEL1L protein was higher in esophageal carcinoma (87.8%, 79/90) and esophageal dysplasia (90.0%, 18/20), as compared with that in normal esophageal mucosa distant from (14.3%, 5/35) and adjacent to (13.3%, 8/60) the tumor (P < 0.01). The expression of SEL1L protein in esophageal cancer however did not correlate with age and sex of the patient, tumor location, tumor size, degree of differentiation, depth of tumor invasion, lymph node metastasis and tumor clinical stage (P > 0.05). A positive correlation was found between the expression of SEL1L mRNA and SEL1L protein (r = 0.492, P < 0.01). CONCLUSIONS: L1L protein expression is regulated at the transcriptional level. The high SEL1L protein expression is mainly the result of increased transcription. Overexpression of SEL1L protein is likely an early event during the pathogenesis of esophageal squamous cell carcinoma. SEL1L protein may serve as an important biomarker in identifying patients with higher risk of developing esophageal cancer.

Probiotics for prevention of radiation-induced diarrhea: A meta-analysis of randomized controlled trials.

BACKGROUND: Radiotherapy is commonly used for abdominal or pelvic cancer, and patients receiving radiotherapy have a high risk developing to an acute radiation-induced diarrhea. Several previous studies have discussed the effect of probiotics on prevention of radiation-induced diarrhea, but the results are still inconsistent. OBJECTIVE: We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of probiotic supplementation for prevention the radiation-induced diarrhea. METHODS: Relevant RCTs studies assessing the effect of probiotic supplementation on clinical outcomes compared with placebo were searched in PubMed, EMBASE, and the Cochrane Library databases (up to March 30 2016). Heterogeneity was assessed with I2 and H2, and publication bias was evaluated using sensitive analysis. RESULTS: Six trials, a total of 917 participants (490 participants received prophylactic probiotics and 427 participants received placebo), were included in this meta-analysis. Compared with placebo, probiotics were associated with a lower incidence of radiation-induced diarrhea (RR: 0.55; 95% CI: 0.34-0.88; P = 0.01; I2: 87%; 95% CI: 75%-94%; H2: 2.8; 95% CI: 2.0-4.0). However, there is no significant difference in the anti-diarrheal medication use (RR: 0.68; 95% CI: 0.40-1.14; P = 0.14) or bristol scale on stool form (RR: 0.64; 95% CI: 0.35-1.17; P = 0.14). CONCLUSION: Probiotics may be beneficial to prevent radiation-induced diarrhea in patients who suffered from abdominal or pelvic cancers during radiotherapy period.

A case of PSF-TFE3 gene fusion in Xp11.2 renal cell carcinoma with melanotic features.

Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) with PSF-TFE3 gene fusion is a rare neoplasm. Only 22 cases of Xp11.2 RCCs with PSF-TFE3 have been reported to date. We describe an additional case of Xp11.2 RCC with PSF-TFE3 showing melanotic features. Microscopically, the histologic features mimic clear cell renal cell carcinoma. However, the dark-brown pigments were identified and could be demonstrated as melanins. Immunohistochemically, the tumor cells were widely positive for CD10, human melanoma black 45, and TFE3 but negative for cytokeratins, vimentin, Melan-A, microphthalmia-associated transcription factor, smooth muscle actin, and S-100 protein. Genetically, we demonstrated PSF-TFE3 fusion between exon 9 of PSF and exon 5 of TFE3. The patient was free of disease with 50 months of follow-up. The prognosis of this type of tumor requires more cases because of limited number of cases and follow-up period. Xp11.2 RCC with PSF-TFE3 inevitably requires differentiation from other kidney neoplasms. Immunohistochemical and molecular genetic analyses are essential for accurate diagnosis.