From clinical variables to multiomics analysis: a margin morphology-based gross classification system for hepatocellular carcinoma stratification.

OBJECTIVE: Selecting interventions for patients with solitary hepatocellular carcinoma (HCC) remains a challenge. Despite gross classification being proposed as a potential prognostic predictor, its widespread use has been restricted due to inadequate studies with sufficient patient numbers and the lack of established mechanisms. We sought to investigate the prognostic impacts on patients with HCC of different gross subtypes and assess their corresponding molecular landscapes. DESIGN: A prospective cohort of 400 patients who underwent hepatic resection for solitary HCC was reviewed and analysed and gross classification was assessed. Multiomics analyses were performed on tumours and non-tumour tissues from 49 patients to investigate the mechanisms underlying gross classification. Inverse probability of treatment weight (IPTW) was used to control for confounding factors. RESULTS: Overall 3-year survival rates varied significantly among the four gross subtypes (type I: 91%, type II: 80%, type III: 74.6%, type IV: 38.8%). Type IV was found to be independently associated with poor prognosis in both the entire cohort and the IPTW cohort. The four gross subtypes exhibited three distinct transcriptional modules. Particularly, type IV tumours exhibited increased angiogenesis and immune score as well as decreased metabolic pathways, together with highest frequency of TP53 mutations. Patients with type IV HCC may benefit from adjuvant intra-arterial therapy other than the other three subtypes. Accordingly, a modified trichotomous margin morphological gross classification was established. CONCLUSION: Different gross types of HCC showed significantly different prognosis and molecular characteristics. Gross classification may aid in development of precise individualised diagnosis and treatment strategies for HCC.

SELE Downregulation Suppresses Mast Cell Accumulation to Protect against Inflammatory Response in Chronic Idiopathic Urticaria.

BACKGROUND: Chronic idiopathic urticaria (CIU) represents a common skin disorder often characterized by mast cell activation and secretion of histamine and other proinflammatory factors. E-selectin (SELE) has been implicated in the pathogenesis of common inflammatory cutaneous disorders, while the role of SELE in CIU is yet to be fully understood. Thus, we aimed to investigate the mechanism by which SELE influences CIU in connection with the involvement of mast cells. METHODS: SELE expression was measured in blood samples obtained from CIU patients and normal individuals. A CIU mouse model was subsequently established by intradermally injecting a normal saline solution with ovalbumin IgE antiserum into the mice. Loss- and gain-of-function investigations were conducted on the mouse models. The number of degranulated mast cells and the amount of histamine release in vitro were determined. The levels of SELE, tumor necrosis factor (TNF)-α, homologous restriction factor (HRF), and interleukin (IL)-6 levels were determined. RESULTS: The CIU clinical samples exhibited upregulated SELE, while the CIU mice showed increased mast cell degranulation and an increased rate of histamine directional release, as well as an elevated expression of SELE, TNF-α, HRF, and IL-6. SELE silencing was found to decrease the number of degranulated mast cells and reduce the rate of histamine directional release, along with suppressed TNF-α, HRF, and IL-6 expression, in the serum of CIU mice. Ketotifen was observed to rescue the increased expression of TNF-α, HRF, and IL-6 caused by SELE overexpression. CONCLUSIONS: This study highlights the potential of SELE downregulation to repress inflammatory factor secretion caused by the accumulation of mast cells, which ultimately inhibits the development of CIU.

Tetramethylpyrazine Protects Against Early Brain Injury and Inhibits the PERK/Akt Pathway in a Rat Model of Subarachnoid Hemorrhage.

Neuronal apoptosis is a potentially fatal pathological process that occurs in early brain injury (EBI) after subarachnoid hemorrhage (SAH). There is an urgent need to identify effective therapeutics to alleviate neuronal apoptosis. Tetramethylpyrazine (TMP), as an important component of the Chinese traditional medicinal herb Ligusticum wallichii, has been widely used in China to treat cerebral ischemic injury and confer neuroprotection. In the present work, we investigate whether TMP can reduce EBI following SAH in rats, specifically via inactivating the PERK/Akt signaling cascade. One hundred twenty-five male Sprague-Dawley rats were used in the present study. TMP was administered by intravenous (i.v.) injection, and the Akt inhibitor MK2206 was injected intracerebroventricularly (i.c.v.). SAH grade, neurological scores, and brain water content were measured 24 h after SAH. Neuronal apoptosis was visualized by Fluoro-Jade C (FJC) staining. Western blotting was used to measure the levels of PERK, p-PERK, eIF2α, p-eIF2α, Akt, p-Akt, Bcl-2, Bax, and cleaved caspase-3. Our results showed that TMP effectively reduced neuronal apoptosis and improved neurobehavioral deficits 24 h after SAH. Administration of TMP reduced the abundance of p-PERK and p-eIF2α. In addition, TMP increased the p-Akt level and the Bcl-2/Bax ratio and decreased the level of cleaved caspase-3. The selective Akt inhibitor MK2206 abolished the anti-apoptotic effect of TMP at 24 h after SAH. Collectively, these results indicate that Akt-related anti-apoptosis through the PERK pathway is a major, potent mechanism of EBI. Further investigation of this pathway may provide a basis for the development of TMP as a clinical treatment.

Painless Jaundice Caused by Clonorchis sinensis Infection: A Case Report.

A man with only yellowing of the skin and eye sclera was diagnosed with clonorchiasis, which rarely manifested jaundice as the initial symptom. However, because of a lack of evidence for a diagnostic gold standard, the time until definitive diagnosis was more than a week. The diagnostic process relied on inquiring about the patient's history, including the place of residence, dietary habits, and symptoms, as well as on serological findings, an imaging examination, and pathological findings. MRCP and CT results showed mild dilatation of intrahepatic ducts and increased periductal echogenicity. The eggs were ultimately found in stool by water sedimentation method after the negative report through direct smear. DNA sequencing of PCR production of the eggs demonstrated 98-100% homology with ITS2 of Clonorchis sinensis. After anti-parasite medical treatment, the patient's symptoms were gradually relieved. Throughout the diagnostic procedure, besides routine examinations, the sedimentation method or concentration method could be used as a sensitive way for both light and heavy C. sinensis infection in the definite diagnosis.

CD44 but not CD24 expression is related to poor prognosis in non-cardia adenocarcinoma of the stomach.

BACKGROUND: Recent studies have focused on the diagnostic and prognostic significance of CD24 and CD44 expression in human cancers. This study aimed to explore changes in CD44 and CD24 expression levels in patients with gastric cancer and to assess their prognostic values. METHODS: CD44 and CD24 expression levels were investigated immunohistochemically in tumor samples from 290 patients with non-cardia gastric adenocarcinoma, of whom 77 had paired adjacent normal gastric mucosa. CD24 and CD44 mRNA levels were determined by quantitative polymerase chain reaction in 34 patients. Serum anti-Helicobacter pylori IgG was detected by enzyme-linked immunosorbent assay. Relationships between CD44 and CD24 protein expression levels and tumor parameters were analyzed and their prognostic values were evaluated by Cox proportional hazards models. RESULTS: CD24 and CD44 expression levels were significantly higher in patients with gastric cancer compared with those in paired controls (45.5% vs. 0.0%, and 61.0% vs. 0.0%, P < 0.001). Among 290 patients, the overall survival rate was significantly higher in CD44(-) compared with CD44(+) patients (log-rank test, P = 0.035). However, there was no significant correlation between CD24 expression and overall survival time (log-rank test, P = 0.115). Multivariate regression analysis indicated that positive CD44 expression (P = 0.029), TNM staging (P < 0.001), and lymphovascular invasion (P = 0.016), but not CD24 expression (P = 0.065), were independent prognostic factors in gastric cancer. CONCLUSIONS: Individual expression of CD44 was associated with poor survival in patients with gastric carcinoma.

Melanotic Neuroectodermal Tumor of Infancy in the Epididymis: A Case Report.

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare, benign neoplasm of neural crest origin that predominantly involves the craniofacial region, involvement of the epididymis being extremely rare, with about 30 cases reported. We report an unusual case of a 5-month-old male with MNTI in the epididymis. The patient underwent orchiectomy. Half a year later, there was no sign of recurrence. Whether preoperative examination or intraoperative frozen examination, the tumor may easily be misdiagnosed as malignancy. Melanotic neuroectodermal tumor of infancy should be included in differential diagnosis in infants presenting with fast-growing scrotal swelling.

Diagnostic significance of DOG-1 and PKC-θ expression and c-Kit/PDGFRA mutations in gastrointestinal stromal tumours.

OBJECTIVE: To investigate discovered on gastrointestinal stromal tumor (GIST)-1 (DOG-1) and protein kinase C-θ (PKC-θ) expression in a series of GISTs and determine the sensitivity, specificity, and diagnostic value of these two antigens. METHODS: Immnunohistochemistry (IHC) was used to detect CD117, DOG-1, PKC-θ, CD34, Ki-67, α-smooth muscle actin (SMA), S100, and Desmin expression in 147 GISTs and 51 non-GISTs. c-Kit gene (exons 9, 11, 13, and 17) and platelet-derived growth factor receptor-alpha (PDGFRA) gene (exons 12 and 18) mutations were also detected. RESULTS: About 94.5% GISTs were CD117 positive, 96% were DOG-1 positive, and 90.5% were PKC-θ positive. DOG-1 had a specificity of 100%, while CD117 and PKC-θ had a specificity of 90% and 80%, respectively. There was no significant difference between DOG-1 and PKC-θ expressions when compared to CD117 expression. In 30 out of 42 (71.5%) GISTs, a c-Kit gene mutation was found, and in 3 out of 42 cases (7%), PDGFRA was mutated. Wild-type c-Kit/PDGFRA genes accounted for 21.5% (9/42). Most c-Kit gene mutations were found to be located at exon 11, mainly as in-frame deletions. Mutations in exon 9 were all missense mutations. Most PDGFRA gene mutations were found in exon 18, codon 842. c-Kit gene mutations in exons 13 and 17, and the PDGFRA gene mutation in exon 12 were not detected. CONCLUSIONS: Compared to CD117, DOG-1 is a biomarker with higher sensitivity and specificity. The combination of CD117 and DOG-1 can be used to improve the diagnosis of GIST. Although PKC-θ has a lower specificity than DOG-1, it can be a useful biomarker, especially in CD117(-) and/or DOG-1(-) cases.

Renal primitive malignant tumor with endocrine activity.

OBJECTIVE: To report a hypertensive and systematically pigmented female with primitive neuroectodermal tumors. CLINICAL PRESENTATION AND INTERVENTION: A female patient presented with a complaint of right flank pain. She had a right renal space-occupying lesion, underwent right radical nephrectomy, and returned to normotensive postoperatively. The pathological examination identified typical primitive neuroectodermal tumor histology. During a 60-month follow-up period, she remained normotensive and demonstrated normal renal and adrenal functions. CONCLUSION: Early diagnosis and definitive surgery led to the patient's long-term survival.

Significance of FNAC, BRAF mutation, and intraoperative frozen section in surgical decision-making of thyroid nodules.

BACKGROUND: A preoperative method is desired to discriminate benign from malignant thyroid nodules. This retrospective study evaluated the diagnostic performance of BRAF (B-Raf proto-oncogene) mutation (BRAFV600E ) positivity and fine-needle aspiration cytology (FNAC) relative to intraoperative frozen section pathology. METHODS: Patients underwent preoperative FNAC of thyroid nodules. Cytology specimens were classified according to the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), and analyzed for BRAFV600E using an amplification-refractory mutation system (ARMS). Thyroid tissue was surgically removed and frozen sections processed for histology. The sensitivities and specificities of each analysis were compared, alone and in combination. RESULTS: Among 346 patients, 333/358 FNACs (93%) showed malignant nodules; 322 (93%) patients received a pathological diagnosis of papillary thyroid carcinoma (PTC). The sensitivity and specificity of BSRTC VI for malignancy was the highest among the BSRTC categories. Compared with FNAC, the BRAFV600E analysis had significantly higher sensitivity and specificity. The diagnostic efficacy of frozen section pathology was significantly higher than that of either BSRTC category or BRAFV600E analysis alone. Combining methods variably improved diagnostic performance. BRAFV600E was not associated with capsule infiltration, neurovascular infiltration, mono- or multifocal PTC, lymph node metastasis, or clinical stage. CONCLUSION: The diagnostic performance of preoperative BRAFV600E determination was better than that of the BSRTC-FNAC category; combining both improved sensitivity and specificity. Patients with positive malignancy scores from both should be recommended for surgery; those with negative scores require close monitoring. Surgical treatment should include comprehensive intraoperative frozen section assessment. BRAF mutations cannot indicate aggressive treatment.

Association of polymorphism of PTPN 11 encoding SHP-2 with gastric atrophy but not gastric cancer in Helicobacter pylori seropositive Chinese population.

BACKGROUND: The interaction between Src homology 2 domain-containing protein tyrosine phosphatase (SHP-2) of gastric epithelial cells and cagA from H. pylori plays a crucial role in developments of gastric atrophy and gastric cancer. This study aimed to investigate the association of haplotype tagging SNPs (htSNPs) in the PTPN11 gene encoding SHP-2 with gastric atrophy and gastric cancer in Chinese population. METHODS: The subjects comprised 414 patients with gastric cancer, 109 individuals with gastric atrophy and 923 healthy controls. Blood was collected from October 2008 to October 2010. Five htSNPs rs2301756, rs12423190, rs12229892, rs7958372 and rs4767860 from the PTPN11 gene were selected and genotyped by Taqman assay. Serum Ig G antibodies to H. pylori were detected by ELISA. Gastric atrophy was screened by the levels of serum pepsinogenIandII, and confirmed by endoscopy and histopatholgical examinations. Odds ratio (ORs) and 95% confidence intervals (CIs) were calculated by a multivariate logistic regression. RESULTS: Among H. pylori seropositive subjects, age and gender-adjusted OR of gastric atrophy was 2.47 (95%CI 1.13-4.55, P = 0.02) for CC genotype compared with CT/TT genotypes, suggesting a recessive model of genetic risk for rs12423190. The prevalence of H. pylori seropositivity were significantly higher in groups of gastric cancer and gastric atrophy compared to the control group (70.3% vs. 75.2% vs. 49.7%, P <0.001). However, the distributions of genotypes and haplotypes in patients with gastric cancer were not significantly different from healthy controls. CONCLUSIONS: Our study provides the first evidence that rs12423190 polymorphism of the PTPN11 gene is significantly associated with an increased risk of gastric atrophy in H. pylori infected Chinese Han population, suggesting that rs12423190 polymorphism could be used as a useful marker of genetic susceptibility to gastric atrophy among H. pylori infected subjects. The biological roles of this polymorphism require a further investigation.

Inactivation of the Gastrokine 1 gene in gastric adenomas and carcinomas.

Gastrokine 1 (GKN1) plays a role in the gastric mucosal defence mechanism and may be a gastric tumour suppressor. We have investigated whether inactivation of the GKN1 gene is involved in the development and/or progression of gastric cancers. GKN1 protein expression was examined in gastric adenomas and cancer and we also analysed GKN1 mutation and epigenetic alteration, DNA copy number change and mRNA transcript expression. The effect of GKN1 on cell proliferation and death was examined in wild-type GKN1-transfected AGS gastric cancer cells. Reduced or loss of GKN1 expression was detected in 36 (90%) and 170 (89.5%) of 40 adenomas and 190 gastric cancers, respectively. Statistically, there was no significant relationship between altered expression of GKN1 protein and clinicopathological parameters, including depth of invasion, location and lymph node metastasis (χ(2) test, p > 0.05). In western blot analysis, absence or reduced expression was found in 21 (84.0%) of 25 gastric carcinomas. No mutation was detected in gastric tumours, and hypermethylation of GKN1 gene was found in two tumours. DNA copy number and mRNA transcript of GKN1 were significantly decreased in gastric cancers. In functional analysis, AGS gastric cancer cells transfected with GKN1 wild-type showed marked inhibition of cell proliferation and induction of cell death. These data suggest that inactivation of the GKN1 gene may play an important role in the development of sporadic gastric cancers, as an early event.

Leiomyosarcoma of the inferior vena cava level II involvement: curative resection and reconstruction of renal veins.

Leiomyosarcoma of the inferior vena cava (IVCL) is a rare retroperitoneal tumor. We report two cases of level II (middle level, renal veins to hepatic veins) IVCL, who underwent en bloc resection with reconstruction of bilateral or left renal venous return using prosthetic grafts. In our cases, IVCL is documented to be occluded preoperatively, therefore, radical resection of tumor and/or right kidney was performed and the distal end of inferior vena cava was resected and without caval reconstruction. None of the patients developed edema or acute renal failure postoperatively. After surgical resection, adjuvant radiation therapy was administrated. The patients have been free of recurrence 2 years and 3 months, 9 months after surgery, respectively, indicating the complete surgical resection and radiotherapy contribute to the better survival. The reconstruction of inferior vena cava was not considered mandatory in level II IVCL, if the retroperitoneal venous collateral pathways have been established. In addition to the curative resection of IVCL, the renal vascular reconstruction minimized the risks of procedure-related acute renal failure, and was more physiologically preferable. This concept was reflected in the treatment of the two patients reported on.

Lymphoepithelioma­Like Cholangiocarcinoma with Hepatitis C Virus Infection Treated by Microwave Ablation: A Literature Review and Case Report.

Background: Lymphoepithelioma-like cholangiocarcinoma (LELCC) is a rare type of intrahepatic tumor that is poorly understood. It is not associated with specific physical findings and is usually diagnosed incidentally, resulting in tumors that are often large-sized at diagnosis. At present, the main treatment approach is surgical resection. Case Presentation: Here, we report the case of a patient with LELCC treated with microwave ablation (MWA). Our patient was a Chinese man with chronic hepatitis C and a 51 mm-diameter intrahepatic tumor. Despite blood testing, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging, and abdominal ultrasound, the tumor was not well diagnosed. However, the histopathological findings of ultrasound-guided percutaneous tumor biopsy led to a diagnosis of LELCC. The patient was treated with MWA, and no new lesions had occurred at 9 months after treatment. Conclusion: To our knowledge, this is the first patient with LELCC treated using MWA. Our experience suggests that MWA is an effective new therapeutic method for this disease.

Non-invasive evaluation of NAFLD and the contribution of genes: an MRI-PDFF-based cross-sectional study.

OBJECTIVE: To investigate the clinical, laboratory and genetic features of NAFLD patients based on MRI-PDFF in China. DESIGN: Patients with high ALT and with a diagnosis of fatty liver were included in this cross-sectional study. Fasting blood was collected to test biomarkers and SNPs. A total of 266 patients underwent MRI-PDFF and FibroScan examinations, and 38 underwent liver biopsy. Diagnostic models (decision tree, LASSO, and elastic net) were developed based on the diagnosis from MRI-PDFF reports. RESULTS: Approximately, 1/3 of the patients were found to have NASH and fibrosis. After quantifying liver steatosis by MRI-PDFF (healthy: n = 47; mild NAFLD: n = 136; moderate/severe NAFLD: n = 83; liver fat content (LFC): 3.6% vs. 8.7% vs. 19.0%), most biomarkers showed significant differences among the three groups, and patients without obesity were found to have a similar LFC as those with obesity (11.1% vs. 12.3%). Models including biomarkers showed strong diagnostic ability (accuracy: 0.80-0.91). Variant alleles of PNPLA3, HSD17B13 and MBOAT7 were identified as genetic risk factors causing higher LFC (8.7% vs. 12.3%; 11.0% vs. 14.5%; 8.5% vs. 10.2%, p < 0.05); those with the UQCC1 rs878639 variant allele showed lower LFC (10.4% vs. 8.4%; OR = 0.58, p < 0.05). Patients with more risk alleles had higher LFCs (8.1% vs. 10.7% vs. 11.6% vs. 14.5%). CONCLUSIONS: Based on MRI-PDFF, a combination of several specific biomarkers can accurately predict disease status. When the effects of genes on liver steatosis were first quantified by MRI-PDFF, the UQCC1 rs878639 G allele was identified as a protective factor, and the MBOAT7 T allele was identified as a risk only among nonobese individuals.

PTEN Expression Was Significantly Associated with PD-L1 Score but Not with EBV Infection in Gastric Cancer.

Purpose: Gastric cancer (GC) remains a prevalent aggressive tumor with high morbidity and mortality globally. The identification of GC subtypes based on molecular features improved the prediction of prognosis and the selection of targeted therapies. PTEN is a characteristic tumor suppressor, while its association with different GC subtypes was unknown. Patients and Methods: The cohort consisted of 248 patients diagnosed with gastric cancer who were hospitalized and received radical gastrectomy. In addition, PTEN gene expression matrix of STAD was retrieved from TCGA. The mRNA and protein levels of PTEN and PD-L1 were detected using qRT-PCR and IHC staining. Multivariate logistic regression and Kaplan-Meier analysis were used to examine the relationship between PTEN expression and clinical characteristics. Results: In our study, PTEN was downregulated in gastric tumors both in mRNA and protein levels. Its inactivation was closely linked to higher histological grade (P = 0.005), neural invasion (P = 0.012), depth of invasion (P = 0.021), lymph metastasis (P = 0.026), and TNM stage (P = 0.001) of GC in the present study. Moreover, according to the molecular subtypes, high PTEN expression was related to high TPS score of PD-L1 positively (P = 0.010) but was not associated with MSI and EBV infection. Further, TCGA data validated that PTEN was indeed correlated with histological grade and invasion depth and positively related to PD-L1 expression (R = 0.29, adjusted P < 0.001). Conclusion: The above results suggested that PTEN expression was a useful marker in gastric carcinogenesis and progression and in the selection of immunotherapy-based treatments for GC patients.

[Spermatic cord liposarcoma: a case report and review of the literature].

OBJECTIVE: To explore the clinical features and treatment of spermatic cord liposarcoma (SCL). METHODS: We retrospectively analyzed the clinical data of a case of SCL, reviewed the related literature and investigated the diagnosis and treatment of the disease. RESULTS: The patient underwent tumor resection and left inguinal orchidectomy. Postoperative pathology confirmed the case to be s SCL. Neither recurrence nor metastasis was found during the five-month follow-up. CONCLUSION: SCL is a rare medical condition with no specific imaging and laboratory features. Radical orchidectomy with wide local excision of the mass is recommended for its treatment, and adjuvant radiotherapy can be considered in intermediately or highly differentiated tumors and recurrent liposarcomas, while the role of chemotherapy is not well-defined.

Application of propofol combined with sevoflurane anesthesia in staged hepatectomy liver detachment and portal vein ligation.

The aim of the present study was to investigate the application of propofol combined with sevoflurane anesthesia in associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). A retrospective analysis of 40 patients with liver cancer who underwent ALPPS was performed. The study included 21 (control group) and 19 (observation group) patients who were administered propofol anesthesia and propofol in combination with sevoflurane anesthesia, respectively. Changes in liver function indicators, routine blood parameters and blood coagulation function, as well as cognitive function (mini-mental state examination) were recorded. The total bilirubin and direct bilirubin levels and the alanine aminotransferase (ALT) level after the first- and second-stage operation in the two groups was also higher than that prior to the first-stage operation (P<0.05), and the ALT level was significantly lower in the two groups after the second-stage operation compared with that prior to the second-stage operation (P<0.05). The AST level after the first- and second-stage operation was lower than that prior to the first- and second-stage operation, respectively (P<0.05). The white blood cell count after the second-stage operation was significantly lower compared with that prior to the second-stage operation (P<0.05). The plasma fibrinogen (FIB) level was higher after the first-stage operation compared with that prior to the first-stage operation (P<0.05). The prothrombin time in the two groups of patients was higher after the second-stage operation compared with that prior to the second-stage operation (P<0.05), whereas the FIB level was lower (P<0.05) and the international normalized ratio was not significantly different (P>0.05). The degree of cognitive decline prior to the first/second-stage operation, according to mini-mental state examination scores, was different from that after the first/second-stage operation (P<0.05). In conclusion, propofol combined with sevoflurane has a good application value in ALPPS.

miR-383 reduces keratinocyte proliferation and induces the apoptosis in psoriasis via disruption of LCN2-dependent JAK/STAT pathway activation.

Psoriasis is a chronic and relapsing disorder with considerable negative effects on patients' quality of life. The finer details associated with the molecular mechanism of psoriasis and its pathogenesis remain somewhat elusive. Extensive studies have highlighted the crucial role of microRNAs (miRNAs) in the development of psoriasis. Hence, the current study aimed to investigate the effect of miR-383 on a psoriasis rat model and elucidate the underlying molecular mechanism. The rat psoriasis model was established via imiquimod (IMQ) induction followed by verification of miR-383 and LCN2 expression in the skin tissues of the models. ELISA was conducted to determine the secretion of inflammatory factors. Keratinocyte proliferation and apoptosis was evaluated by MTT assay and flow cytometric analysis. Down-regulation of miR-383 and up-regulation of LCN2 were detected in the psoriasis rat model. Our data indicated that miR-383 targeted LCN2 by binding to its 3'UTR and inhibited JAK/STAT pathway activation. Notably, miR-383 overexpression or LCN2 knockdown attenuated psoriasis-like symptoms, suppressed inflammatory response, reduced the expression of JAK3 and STAT3, ceased keratinocyte proliferation, and promoted the apoptosis. The findings of our study suggest that miR-383 may inhibit LCN2 and inactivate the JAK/STAT pathway, suppressing the progression of psoriasis in a rat model. This study provided novel insights into the pathogenesis of psoriasis and offered potential targets for psoriasis treatment.

[Retracted] miR­137 acts as a tumor suppressor in papillary thyroid carcinoma by targeting CXCL12.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the western blotting data shown in Figs. 4D and 5B were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Oncology Reports 35: 2151-2158, 2016; DOI: 10.3892/or.2016.4604].

Microsatellite instability and Epstein-Barr virus combined with PD-L1 could serve as a potential strategy for predicting the prognosis and efficacy of postoperative chemotherapy in gastric cancer.

BACKGROUND: Microsatellite instability (MSI) and Epstein-Barr virus (EBV)-positive molecular subtypes exhibit complex immune responses in gastric cancer (GC), and PD-L1 has emerged as a prognostic biomarker associated with the cancer immune microenvironment. This study aimed to determine the prognostic value of molecular subtypes and whether the addition of PD-L1 would accurately predict the prognosis and guide postoperative chemotherapy for GC patients. METHODS: We performed molecular subtyping of tissue microarray slides from 226 GC patients who were treated with radical gastrectomy. The MSI status and PD-L1 expression were evaluated through immunohistochemistry (IHC) and EBV status through situ hybridization. Multiplex polymerase chain reaction (PCR) was also performed on 50 cases to validate the accuracy of IHC in defining MSI status. Differences in overall survival (OS) were assessed using the Kaplan-Meier method, log-rank test and Cox proportional hazards regression model. RESULTS: Among the 226 GC patients, 52 (23.2%) patients were classified as the MSI subtype, 11 (4.9%) were EBV+ subtype, and 161 (71.9%) were MSS (Microsatellite stable) /EBV subtype according to TCGA analysis. Two patients were both positive for MSI and EBV infection. EBV+ cases showed higher PD-L1 positivity than MSI cases and MSS/EBV cases (81.8% vs. 50.0% vs. 35.4%, P = 0.003). Compared with the non-MSS/EBV (MSI or EBV+ cases) subgroup, GC patients with MSS/EBV were associated with the worst outcomes (HR = 1.610, 95% CI [1.0462.479], P = 0.031). MSS/EBV GCs alone could benefit from postoperative chemotherapy (HR = 0.452, 95% CI [0.2990.682], P<0.001), and PD-L1-positive expression could also predict a better prognosis (HR = 0.612, 95% CI [0.3890.962], P = 0.033) in this subgroup. Considering both chemotherapy efficacy and PD-L1 expression in the MSS/EBV subgroup, chemotherapy could improve the prognosis for PD-L1-negative MSS/EBV GCs (HR = 0.357, 95% CI [0.2170.587], P <0.001) but not PD-L1-positive MSS/EBV GCs. CONCLUSIONS: Molecular subtyping combined with PD-L1 expression could serve as a potential strategy to better predict prognosis and guide postoperative chemotherapy of GC patients.