[Clinicopathological analysis of gastric adenocarcinoma with elevated serum alpha-fetoprotein and enteroblastic differentiation].

Objective: To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED). Methods: The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis. Results: Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177-GNAS, AIM1-FGFR3, and EPHA6-ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis (P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone (P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone (P＜0.05). Conclusions: Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.

[Influencing factors of visual prognosis in patients with persistent submacular fluid after successful scleral buckle surgery for macula-off retinal detachment].

Objective: To investigate the factors influencing visual outcomes in patients with rhegmatogenous retinal detachment (RRD) who developed persistent submacular fluid (PSF) after scleral buckling surgery. Methods: A retrospective case series analysis was conducted. Clinical data were collected from patients who underwent successful scleral buckling surgery for RRD at Beijing Tongren Hospital from June 2020 to December 2022 and were followed up. Patients with RRD involving the macular area preoperatively and graded as C1 or below in proliferative vitreoretinopathy (PVR) were included. Surgical procedures followed a minimally invasive scleral buckling approach. PSF was defined as subretinal fluid persisting for more than 1 month postoperatively. Regular follow-up visits were scheduled at postoperative days 1, 3, 7, 2 weeks, and 1 month, followed by monthly visits until complete PSF absorption. Best-corrected visual acuity (BCVA), intraocular pressure, refractive error, slit-lamp biomicroscopy, binocular indirect ophthalmoscopy, and optical coherence tomography (OCT) were performed at each follow-up time point. Eyes were divided into two groups based on whether the final follow-up BCVA was≥0.5 and whether the absorption time of PSF was>6 months, and statistical analysis was performed using the Wilcoxon signed-rank test, chi-squared test, and Mann-Whitney U test. Results: A total of 46 patients (46 eyes) were included in this study, comprising 25 males and 21 females, with a median age of 32.5 (21.0, 57.3) years. The preoperative equivalent spherical refractive error was (-5.27±4.05) D, and the preoperative duration of illness was 30 (14, 92) days. The preoperative BCVA (logarithm of the minimum angle of resolution,logMAR) was 2.00 (1.00, 2.50). Scleral buckle surgery was performed in 28 eyes (60.9%), and 18 eyes (39.1%) underwent scleral buckle surgery combined with encircling. External drainage was performed in 15 eyes (32.6%), while 31 eyes (67.4%) had no external drainage. BCVA (logMAR) at 1 month, 3 months, and the final follow-up postoperatively was 0.60 (0.50, 1.00), 0.40 (0.28, 0.53), and 0.15 (0.00, 0.50), respectively. In the final follow-up, 31 eyes (67.4%) achieved BCVA≥0.5, and 26 eyes (56.5%) had continuous ellipsoid zone on OCT. The differences in BCVA (logMAR) between preoperative, 1 month, 3 months, and the final follow-up were statistically significant (Z=-5.85, -5.63, -4.73;all P<0.001). The absorption time of PSF postoperatively was 6.50 (3.00, 9.00) months, ranging from 2 to 19 months. The eyes with PSF duration<3 months, 3-6 months, and>6 months were 12 eyes (26.1%), 11 eyes (23.9%), and 23 eyes (50.0%), respectively. There were statistically significant differences between the two groups in preoperative BCVA≥0.05, preoperative duration of illness within 1 month, PVR grading, surgical method, and continuous ellipsoid zone on OCT (all P<0.05), while there were no statistically significant differences between the two groups in PSF absorption time, different types of PSF, and intraoperative drainage (all P>0.05). The PSF absorption time in the two groups was 7 (3, 10) months and 6 (4, 8) months, with no statistically significant difference (P>0.05). Conclusions: Preoperative visual acuity, duration of illness, and PVR grading are factors influencing visual outcomes in patients with RRD who have undergone scleral buckling surgery and develop PSF. In contrast, intraoperative drainage, PSF absorption time, and different PSF types are not factors affecting visual prognosis. Although PSF may persist for a long time after scleral buckling surgery, it does not significantly impact long-term visual outcomes.

[A retrospective analysis of clinical characteristics and prognostic factors for 152 cases of Staphylococcus aureus bloodstream infection].

To understand the clinical characteristics of Staphylococcus aureus bloodstream infection and the main risk factors affecting clinical prognosis, providing a reference for clinical prevention and control of Staphylococcus aureus bloodstream infection. In this study, the clinical data of 152 patients with Staphylococcus aureus bloodstream infection admitted to Guangdong Provincial People's Hospital from January 2019 to December 2021 were retrospectively analyzed by reviewing the electronic medical record system, including underlying diseases, clinical characteristics, risk factors, and bacterial resistance. Statistical methods such as Chi-Squared Test and t Test were used to analyze the related risk factors that may affect the clinical characteristics and prognosis of patients with Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection, then the variables with P<0.05 in univariate analysis were included in the multivariate logistic regression model to analyze the independent risk factors of poor prognosis. The results showed among 152 patients with Staphylococcus aureus bloodstream infection, 50 patients (32.89%) were infected with MRSA. In comparison, 102 patients (67.11%) were infected with methicillin-sensitive Staphylococcus aureus (MSSA). Except for rifampicin, the resistance rate of MRSA to commonly used antibiotics was all higher than that of MSSA, and the difference was statistically significant (Chi-square values were 8.272, 11.972, 4.998, 4.776, respectively;all P-values are less than 0.05). Strains resistant to vancomycin, linezolid, and quinupristin/dalfopristin were not found. In the MRSA group, indwelling catheter and drainage tube, carbapenems, and ß-lactamase inhibitor treatment were significantly higher than the MSSA group. The difference was statistically significant (P<0.05). The incidence of poor prognosis of bloodstream infection in the MRSA group was higher than that in the MSSA group (34.00% vs 13.73%), and the difference was statistically significant (χ2=8.495, P<0.05). No independent risk factors associated with poor prognosis were found in the included patients with MRSA bloodstream infection.Multivariate Logistic regression model analysis showed that solid malignant tumors (OR=13.576, 95%CI: 3.352-54.977, P<0.05), mechanical ventilation (OR=7.468, 95%CI: 1.398-39.884, P<0.05) were the most important independent risk factors for poor prognosis in patients with Staphylococcus aureus bloodstream infection. In summary, the poor prognosis rate of MRSA bloodstream infection is higher than that of MSSA. The clinical evaluation of related risk factors should be strengthened, targeted prevention and control interventions should be taken to improve the prognosis of patients with Staphylococcus aureus bloodstream infection, and the use of antibiotics should be rational and standardized, to control bacterial infection and drug resistance effectively.

[Long non-coding RNA LINC01133 regulates cementogenic differentiation of human periodontal ligament stem cells by modulating mitochondrial functions].

Objective: To investigate the effects of long non-coding RNA (lncRNA) LINC01133 on the cementogenic differentiation of human periodontal ligament stem cells (hPDLSC) and the underlying mechanism. Methods: A total of 12 teeth were harvested from 10 patients aged 17-30 years in the Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University for impacted or orthodontic reasons from September 2021 to January 2022. The hPDLSCs were isolated from the teeth and transfected with small interfering RNA-LINC01133 (si-LINC01133) or small interfering RNA-negative control (si-NC). The si-LINC01133 was regarded as the experimental group, and the si-NC was regarded as the control one. The silencing efficiency of LINC01133 in the hPDLSCs was evaluated by real-time quantitative PCR (RT-qPCR). Western blotting was used to detect the protein expression levels of cementogenic differentiation-related factors including bone sialoprotein (BSP), cementum attachment protein (CAP), and cementum protein-1 (CEMP-1). Mitochondrial reactive oxygen species (mtROS) production was assessed using the MitoSox by flow cytometry. Mitochondrial membrane potential (MMP) was detected by JC-1 fluorescence staining. Mitochondrial respiratory chain complexes proteins including NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8 (NDUFB8), succinate dehydrogenase complex flavoprotein subunit A (SDHA), ubiquinol-cytochrome c reductase core protein 1 (UQCR1), cytochrome c oxidase subunit 4 isoform 1 (COXⅣ), and ATP synthase F1 subunit alpha (ATP5A) were evaluated by Western blotting. Results: The expression levels of LINC01133 could be suppressed by more than 60% with si-LINC01133 (control group: 1.000±0.000, experimental group: 0.385±0.128) (t=10.72, P<0.01). Suppression of LINC01133 in hPDLSCs decreased the levels of cementogenic differentiation-related proteins including BSP (control group: 1.000±0.000, experimental group: 0.664±0.179) (t=4.62, P<0.01) and CAP (control group: 1.000±0.000, experimental group: 0.736±0.229) (t=2.83, P<0.05). Suppression of LINC01133 in hPDLSCs increased the production of mtROS (control group: 1.000±0.000, experimental group: 1.458±0.185) (t=4.96, P<0.05) and the expression of NDUFB8 (control group: 1.000±0.000, experimental group: 1.683±0.397) (t=3.45, P<0.05), as well as decreased MMP levels (control group: 1.000±0.000, experimental group: 0.209±0.029) (t=53.99, P<0.01) and the expression of SDHA (control group: 1.000±0.000, experimental group: 0.428±0.228) (t=5.02, P<0.05). No significant changes in the UQCR1, COXⅣ, and ATP5A expression levels were found between the control group and exprimental group (P>0.05). Conclusions: LINC01133 regulates the cementogenic differentiation of hPDLSCs possibly via modulating the mitochondrial functions.

[Risk factors and characteristics of gut microbiota and metabolites in inflammatory bowel diseases patients with urolithiasis].

Objective: To identify the related factors and characteristics of gut microbiota and metabolites in inflammatory bowel disease (IBD) patients with urolithiasis. Methods: A total of 68 IBD patients with urolithiasis and 136 gender-and age-matched IBD patients without urolithiasis in the Department of Gastroenterology, Peking Union Medical College Hospital from January 2014 to December 2019 were recruited. The diagnosis of urolithiasis was confirmed by plain films, ultrasonography, abdominal computed tomography or intravenous urography. The clinical data of patients were collected, and the association between the clinical characteristics and urolithiasis was further analyzed. The fecal samples were collected from 10 patients with urolithiasis and 18 patients without urolithiasis, and the gut microbiota and metabolites composition were analyzed. Results: There were 49 male and 19 female IBD patients with urolithiasis, with a mean age of (36.0±12.4) years, and 98 male and 38 female patients without urolithiasis, with a mean age of (36.1±12.5) years. Univariate analysis revealed that the rate of ileostomy and the resection of small intestine in Crohn's disease (CD) patients with urolithiasis (n=34) was significantly higher than CD patients without urolithiasis (n=68) (26.5% vs 7.4%, P=0.019). And the erythrocyte sedimentation rate was also higher [26.5 (12.0, 40.8) vs 13.0 (7.2, 32.5) mm/1 h, P=0.022] in CD patients with urolithiasis. There were no significant differences in clinical characteristics and biochemical parameters between the ulcerative colitis (UC) patients with urolithiasis (n=34) and without urolithiasis (n=68) (all P>0.05). The multivariate logistic regression analysis indicated that ileostomy and the resection of small intestine were the independent related factors for urolithiasis in CD patients (OR=4.619, 95%CI: 1.178-18.111, P=0.028). There was no significant difference in α and ß diversity between the two groups (all P>0.05). At the phylum level, there was no significant difference in the abundance of microbiota (all P>0.05). At the genus level, the abundance of Enterococcus (P=0.049), Eubacterium_eligens (P=0.036) was significantly decreased. At the species level, the abundance of Bacteroides_coprocola was increased in urolithiasis group (P=0.035), while the abundance of Blautia_caecimuris was significantly decreased (P=0.042). No significant difference was found in fecal metabolites between the two groups (all P>0.05). According to LDA effect size (Lefse) analysis, taxa including Sphingomonadales, Fenollaria, Bacteroides_coprocola contributed greatly to the difference between the two groups. Conclusions: Ileostomy and the resection of small intestine are related factors for urolithiasis in patients with CD. Gut microbiota may be involved in the occurrence of urolithiasis in patients with IBD.

[Artificial intelligence based on images in ophthalmology].

The application of artificial intelligence (AI) in ophthalmology will greatly reduce the workload of ophthalmologists. Machine learning is an important branch of AI, and deep learning is the most important algorithm in machine learning. At present, AI is well applied in the ophthalmic field. This article summarizes the use of AI in ophthalmology and discusses its inadequacy and future to provide reference for clinical practice. (Chin J Ophthalmol, 2021, 57: 465-469).

LncRNA PRNCR1 aggravates the malignancy of oral squamous cell carcinoma by regulating miR-326/FSCN1 axis.

OBJECTIVE: The important regulatory mechanism of lncRNA PRNCR1 has been emphasized in malignant tumors. However, the role of lncRNA PRNCR1 remains unclear in oral squamous cell carcinoma (OSCC). The purpose of this study is to reveal the role of lncRNA PRNCR1 in OSCC. PATIENTS AND METHODS: RT-qPCR was used to detect mRNA expression. The functional mechanism of lncRNA PRNCR1 in OSCC was investigated by CCK-8, transwell and Luciferase reporter assays. RESULTS: LncRNA PRNCR1 was upregulated in OSCC and promoted cell proliferation, migration and invasion. LncRNA PRNCR1 directly binds to miR-326. The mutual inhibition between the expressions of lncRNA PRNCR1 and miR-326 was identified in OSCC. In addition, miR-326 restrained cell proliferation, migration and invasion in OSCC. Further, miR-326 directly targets FSCN1. FSCN1 expression was positively regulated by lncRNA PRNCR1 in OSCC. And FSCN1 promoted the progression of OSCC and aggravated the carcinogenic effect of lncRNA PRNCR1 in OSCC. CONCLUSIONS: LncRNA PRNCR1 promotes the progression of OSCC by functioning as a miR-326 'sponge' to upregulate FSCN1 expression.

Knockdown of microRNA-181a inhibits osteosarcoma cells growth and invasion through triggering NLRP3-dependent pyroptosis.

The article "Knockdown of microRNA-181a inhibits osteosarcoma cells growth and invasion through triggering NLRP3-dependent pyroptosis, by B.-G. Tian, Z. Hua, Z.-J. Wang, J. Li, published in Eur Rev Med Pharmacol Sci 2020; 24 (3): 1030-1040-DOI: 10.26355/eurrev_202002_20153-PMID: 32096182" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20153.

A relationship between MAPK/ERK pathway expression and neuronal apoptosis in rats with white matter lesions.

OBJECTIVE: The aim of this study was to explore the association between the expression of mitogen-activated protein kinase (MAPK)/extracellular regulated protein kinase (ERK) pathway and neuronal apoptosis in rats with white matter lesions (WML). MATERIALS AND METHODS: Sprague-Dawley (SD) rats were selected as the research objects. Rat models of ischemic WML were established by bilateral common carotid artery ligation. Subsequently, brain tissues were collected from rats in sham operation group and WML group, respectively. Hematoxylin-eosin (HE) staining assay was conducted to observe the pathological changes in white matters (WMs) (callosum, internal capsule, and optic nerve) and apoptotic cells in brain tissues. The protein expression levels of phosphorylated ERK (p-ERK) and ERK, phosphorylated MAPK (p-MAPK), and MAPK in tissues were measured by Western blotting. Immunohistochemistry was employed to detect the expression levels of p-ERK, ERK, p-MAPK, and MAPK in brain tissues of the two groups. Next, nerve cells were isolated from rats with WML as research objects. The phosphorylation of the MAPK/ERK pathway was suppressed using PD03259019 (a chemical drug, hereafter referred to as PD). Then, the changes in the protein expressions of apoptosis proteins B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were determined before and after MAPK/ERK pathway inhibition. Meanwhile, changes in the messenger ribonucleic acid (mRNA) expression levels were detected via real-time fluorescent quantitative polymerase chain reaction (PCR), and changes in apoptosis were observed. RESULTS: HE staining revealed that in sham operation group, WMs had normal structure and intact morphology. The cells were regularly arranged, with little apoptosis of the nuclei in the center. However, there were abnormally arranged nerve cells, loose cortical structure, swollen cells, aberrant nuclear membrane, pyknosis, signs of cell degeneration and necrosis, apoptotic cells filled most of the field of vision, and relatively evident lesions in WML group. Besides, WML group exhibited significantly up-regulated expressions of p-ERK and p-MAPK, as well as basically unchanged expressions of ERK and MAPK (p<0.05). After PD was added for 1 d, 2 d, and 3 d, the MAPK/ERK pathway was repressed, which was the most significantly at 3 d. Furthermore, the anti-apoptotic phenotype of neurons was detected, which was more pronounced at 3 d (p<0.05). CONCLUSIONS: Rats with WML exhibited elevated MAPK/ERK activity and evident apoptosis. After inhibiting the phosphorylation site of MAPK/ERK in rat neuronal cells, the expression of pro-apoptotic protein decreased, and the apoptosis was relieved. In rats with WML, neuronal apoptosis is promoted by activating the MAPK/ERK pathway, thus worsening the condition.

Knockdown of microRNA-181a inhibits osteosarcoma cells growth and invasion through triggering NLRP3-dependent pyroptosis.

OBJECTIVE: This study aimed to investigate the physiological function and molecular mechanism of microRNA-181a (miRNA-181a) in the carcinogenesis of osteosarcoma. MATERIALS AND METHODS: The relative expression of miRNA-181a in tissues and cultured cells was detected by quantitative real time-polymerase chain reaction (qRT-PCR). MiR-181a inhibitor and miR-181a mimics were used to manipulate its level in cells. Cell proliferation and invasion were measured using Cell Counting Kit-8 (CCK-8) assay and transwell assay, respectively. The protein levels of the targeted genes were detected by Western blotting and immunohistochemistry. Terminal Deoxynucleotidyl Transferase (TdT)-mediated dUTP Nick-End Labeling (TUNEL) assay was employed to detect cell apoptosis. Moreover, a xenograft tumor bearing mice model was used to evaluate the effect of miR-181a in vivo. RESULTS: We found that miRNA-181a was aberrantly elevated in osteosarcoma tissues and cells. Moreover, the overexpression of miRNA-181a could facilitate cell proliferation and migration. By contrast, miRNA-181a knockdown reverses these effects. Additionally, downregulation of miRNA-181a could activate NOD-like receptor protein 3 (NLRP3)-dependent pyroptosis, as evidenced by the increase of pyroptosis-related genes (NLRP3, caspase-1, interleukin-18, and interleukin-1ß) in miRNA-181a inhibitor transfected cells compared with the control. Further mechanistic studies identified that miRNA-181a knockdown suppresses cell proliferation and invasion by activating NLRP3-dependent pyroptosis. Silencing NLRP3 could effectively reverse the effects mediated by miRNA-181a inhibitor. Consistently, in vitro results also demonstrated that blockade of miRNA-181a notably suppresses tumor growth via activating pyroptosis. CONCLUSIONS: These results provide that miRNA-181a might serve as potential therapeutic target for osteosarcoma patients.

[Evaluation of the efficacy and safety of a foldable capsular vitreous body in the treatment of severe retinal detachment].

Objective: To determine the efficacy and safety of vitrectomy combined with implantation of a foldable capsular vitreous body in the treatment of severe retinal detachment with early ocular atrophy in human eyes. Methods: This study was a prospective, multicenter, and one-arm phase Ⅱ clinical trial. Patients with severe retinal detachment and early eyeball atrophy attending Beijing Tongren Eye Center from April 2011 to July 2012 were included. A standard three-port pars plana vitrectomy was performed, and a foldable capsular vitreous body was folded and sent into the vitreous cavity; silicone oil was injected into the capsule. Measurement of visual acuity and intraocular pressure, corneal endothelium count, color fundus photography, optical coherence tomography, and ocular ultrasonography were performed to observe retinal reattachment and adverse reactions after surgery. Wilcoxon signed rank test was performed to compare the baseline and postoperative visual acuity, intraocular pressure and corneal endothelium count. Results: A total of 26 patients were enrolled, including 23 males and 3 females. The age was (37.5±11.5) years, with an average follow-up of 33 months. For each patient, only the left or right eye was included (13 left eyes and 13 right eyes). Retinal reattachment was found in all 24 eyes, and the eyeball atrophy was controlled in all patients. Visual acuity was improved in 4 patients (15.4%) and unchanged in 5 patients (19.2%). The mean intraocular pressure [(14.4±3.9) mmHg(1 mmHg=0.133 kPa)] at the last follow-up was higher than the baseline intraocular pressure [(12.0±6.5) mmHg], but the difference was not statistically significant (Z=-1.859, P=0.063). For the 16 patients with ocular atrophy at baseline, the last follow-up intraocular pressure [(14.6±3.9) mmHg] was significantly higher than the preoperative intraocular pressure [(8.5±2.4) mmHg] (t=-5.326, P<0.001). No obvious adverse reactions were observed. Conclusions: Implantation of a foldable capsular vitreous body is an effective way to treat severe retinal detachment with early eyeball atrophy. It can help to reattach the retina, control eyeball atrophy, maintain the eye shape and intraocular pressure, while visual acuity improvement is limited. (Chin J Ophthalmol, 2019, 55: 259-266).

[Incidence of postoperative venous thromboembolism after thoracic surgery and its characteristic: a single center, prospective cohort study].

Objective: To evaluate the incidence of postoperative venous thromboembolism (VTE) after thoracic surgery and its characteristic. Methods: This was a single-center, prospective cohort study. Patients undergoing major thoracic surgeries between July 2016 and March 2017 at Department of Thoracic Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University were enrolled in this study. Besides the routine examination, all patients were screened for deep venous thrombosis (DVT) by using noninvasive duplex lower-extremity ultrasonography after surgery. CT pulmonary angiography (CTPA) was carried out if patients had one of the following conditions including typical symptoms of PE, high Caprini score (>9 points) or new diagnosed postoperative DVT. Caprini risk assessment model was used to detect high risk patients. No patients received any prophylaxis of VTE before surgery. Further data was analyzed for identifying the incidence of postoperative VTE. The t-test, χ2 test or Wilcoxon rank-sum test was used to analyze the quantitative data and classification data, respectively. Results: Totally 345 patients who undergoing major thoracic surgery were enrolled in this study including 145 benign diseases and 200 malignant diseases.There were 207 male and 138 female, aging from 15 to 85 years. Surgery procedures included 285 lung surgeries, 27 esophagectomies, 22 mediastinal surgeries and 11 other procedures. The overall incidence of VTE was 13.9% (48 of 345) after major thoracic surgery including 39 patients with newly diagnosed DVT (81.2%), 1 patient with PE (2.1%) and 8 patients with DVT+ PE (16.7%). The median time of VTE detected was 4.5 days postoperative. There were 89.6% (43/48) VTE cases diagnosed in 1 week. The incidence of VTE was 9.0% in patients with benign diseases, while 17.5% in malignant diseases (χ2=5.112, P<0.05). The incidence of VTE in patients with pulmonary diseases was 12.6%, among that, in patients with lung cancer and benign lung diseases was 16.4% and 7.5 % (χ2=4.946, P<0.05), respectively. Regarding to Caprini risk assessment model, the incidence of VTE in low risk patients, moderate risk patients (Caprini score 5 to 8 points)and high risk patients(≥9 points)were 0(0/77), 15.2%(33/217) and 29.4%(15/51), respectively(Z=-12.166, P<0.05). In patients with lung cancer, 98.2% of patients were moderate risk or high risk; only 3 cases scored low risk. The incidence of VTE in moderate risk and high risk patients was 13.4%(18/134) and 32.1%(9/28), respectively, while it was 0(0/3) in low risk patients. Conclusions: The overall incidence of VTE after major thoracic surgeries is 13.9%, and the incidence of VTE after lung cancer surgeries was 16.4%. Most of the VTE cases occurr within one week after the surgery. Caprini risk assessment model can identify high risk patients effectively.

Positron emission tomography modalities prevent futile radical resection of pancreatic cancer: A meta-analysis.

BACKGROUND: Numerous distant metastases were not detected preoperatively. Positron emission tomography (PET) has been used for oncology diagnosis recently. However, it remains controversial whether PET modality is a more efficient way in detecting unresectable features for radical resection of pancreatic cancer (PC). This meta-analysis aims to validate the efficiency of PET modalities (including PET and PET/CT) in preoperative assessment of PC, and compare them with computed tomography (CT). METHODS: PubMed, EMBASE, Science Citation Index and The Cochrane Library were searched to identify relevant studies. Both PET modality and CT had been performed for all the included patients. A meta-analysis was performed to compare the ability of PET modalities in detecting occult distant metastases and regional lymph nodes invasion with that of CT. RESULTS: 17 clinical studies that recruited 1343 patients were included. This meta-analysis indicated that PET modalities were more efficient in detecting true positive distant metastases compared with CT (OR = 1.52, 95%CI: 1.23-1.88). In subgroup analysis, when compared with CT alone, PET/CT also showed greater utility in detecting distant metastases (OR = 1.66, 95%CI: 1.31-2.08). There was no definite difference in detecting regional lymph nodes invasion between PET modalities and CT (OR = 0.97, 95%CI: 0.63-1.47). CONCLUSION: Compared with CT, PET/CT provides extensive possibility to avoid futile radical resection by detecting occult metastases of PC preoperatively. Surgeons, especially in developing countries, should take PET modalities as a routine preoperative assessment before making operative plan for PC patients.

[Survey of current status of prevention of venous thromboembolism after thoracic surgery in China].

Objective: To investigate the current status of prevention and treatment of venous thromboembolism (VTE) after thoracic surgery in China. Method: Chinese thoracic surgeons were investigated by the online questionnaire which was based on the Chinese version of International VTE questionnaire added with 6 extra questions with Chinese characteristics. Results: A total of 1 150 valid questionnaires were retrieved, accounting for about 20% of all the Chinese thoracic surgeons. The surgeons participating in this survey came from all over the country, most of whom were experienced professionals with high academic titles.For lung cancer patients, 66.96% (770/1 150) of the surgeons suggested that VTE prophylaxis should start 1 day after lung cancer resection, and 64.61% (743/1 150) of the surgeons suggested extending after discharge. For esophagestomy patients, and 48.35% (514/1 063) of the surgeons suggested that there was no need for patients to extend VTE prophylaxis after discharge. More than half of the surgeons participating in this survey made decision of the method and duration of VTE prophylaxis after lung cancer resection (53.91% (620/1 150)) or esophagectomy (52.49% (558/1 063)) depending on the clinical experience.Low molecular weight heparin was the common choice of most surgeons in VTE prophylaxis. More than half of the surgeons thought that previous history of VTE, advanced age, complicated with thrombophilia, obesity (body mass index>30 kg/m2), duration of surgery longer than 6 hours and family history of VTE were key risk factors of the occurrence of postoperative VTE. Conclusions: The results of this survey are highly credible and are a good reflection of the current status of VTE prevention and treatment after thoracic surgery in China. This survey will play an important role in promoting VTE prevention and treatment in Chinese thoracic surgery department, it will also provide data support for government setting new policies, hospital construction of VTE prevention and control as well as raising physicians' awareness.

Identification and Quantitative Assessment of Different Components of Intracranial Atherosclerotic Plaque by Ex Vivo 3T High-Resolution Multicontrast MRI.

BACKGROUND AND PURPOSE: High-resolution 3T MR imaging can visualize intracranial atherosclerotic plaque. However, histologic validation is still lacking. This study aimed to evaluate the ability of 3T MR imaging to identify and quantitatively assess intracranial atherosclerotic plaque components ex vivo with histologic validation. MATERIALS AND METHODS: Fifty-three intracranial arterial specimens with atherosclerotic plaques from 20 cadavers were imaged by 3T MR imaging with T1, T2, and proton-density-weighted FSE and STIR sequences. The signal characteristics and areas of fibrous cap, lipid core, calcification, fibrous tissue, and healthy vessel wall were recorded on MR images and compared with histology. Fibrous cap thickness and maximum wall thickness were also quantified. The percentage of areas of the main plaque components, the ratio of fibrous cap thickness to maximum wall thickness, and plaque burden were calculated and compared. RESULTS: The signal intensity of the lipid core was significantly lower than that of the fibrous cap on T2-weighted, proton-density, and STIR sequences (P < .01) and was comparable on T1-weighted sequences (P = 1.00). Optimal contrast between the lipid core and fibrous cap was found on T2-weighted images. Plaque component mean percentages were comparable between MR imaging and histology: fibrous component (81.86% ± 10.59% versus 81.87% ± 11.59%, P = .999), lipid core (19.51% ± 10.76% versus 19.86% ± 11.56%, P = .863), and fibrous cap (31.10% ± 11.28% versus 30.83% ± 8.51%, P = .463). However, MR imaging overestimated mean calcification (9.68% ± 5.21% versus 8.83% ± 5.67%, P = .030) and plaque burden (65.18% ± 9.01% versus 52.71% ± 14.58%, P < .001). CONCLUSIONS: Ex vivo 3T MR imaging can accurately identify and quantitatively assess intracranial atherosclerotic plaque components, providing a direct reference for in vivo intracranial plaque imaging.

Targeting Chromatin Remodeling in Inflammation and Fibrosis.

Mucosal surfaces of the human body are lined by a contiguous epithelial cell surface that forms a barrier to aerosolized pathogens. Specialized pattern recognition receptors detect the presence of viral pathogens and initiate protective host responses by triggering activation of the nuclear factor κB (NFκB)/RelA transcription factor and formation of a complex with the positive transcription elongation factor (P-TEFb)/cyclin-dependent kinase (CDK)9 and Bromodomain-containing protein 4 (BRD4) epigenetic reader. The RelA·BRD4·P-TEFb complex produces acute inflammation by regulating transcriptional elongation, which produces a rapid genomic response by inactive genes maintained in an open chromatin configuration engaged with hypophosphorylated RNA polymerase II. We describe recent studies that have linked prolonged activation of the RelA-BRD4 pathway with the epithelial-mesenchymal transition (EMT) by inducing a core of EMT corepressors, stimulating secretion of growth factors promoting airway fibrosis. The mesenchymal state produces rewiring of the kinome and reprogramming of innate responses toward inflammation. In addition, the core regulator Zinc finger E-box homeodomain 1 (ZEB1) silences the expression of the interferon response factor 1 (IRF1), required for type III IFN expression. This epigenetic silencing is mediated by the Enhancer of Zeste 2 (EZH2) histone methyltransferase. Because of their potential applications in cancer and inflammation, small-molecule inhibitors of NFκB/RelA, CDK9, BRD4, and EZH2 have been the targets of medicinal chemistry efforts. We suggest that disruption of the RelA·BRD4·P-TEFb pathway and EZH2 methyltransferase has important implications for reversing fibrosis and restoring normal mucosal immunity in chronic inflammatory diseases.

MicroRNA-125b promotes tumor growth and suppresses apoptosis by targeting DRAM2 in retinoblastoma.

PurposeIt is known that microRNAs (miRNAs) are a class of small, noncoding RNAs that act as key regulators in various physiological and pathological processes. However, the regulatory mechanisms involving miRNAs in retinoblastoma (RB) remain largely unknown. The miRNA miR-125b is dysregulated in various human cancers such as breast cancer, human hepatocellular carcinoma, ovarian cancer, and colorectal cancer. However, the significance of miR-125b in RB has not been sufficiently investigated. Our objective was to explore the role of the miR-125b in RB.MethodsIn this study, we measured miR-125b levels using real-time polymerase chain reaction in human RB cell lines, including HXO-Rb44, Y79, SO-RB50, and the normal human retinal pigment epithelial cell line ARPE-19; a total of 38 pairs of primary RB tissues and adjacent noncancerous tissues were also measured. In addition, overexpression of miR-125b in RB cell lines was performed to determine the role of miR-125b in RB.ResultsWe found that miR-125b is significantly upregulated in RB, and closely associated with tumor cell proliferation and apoptosis. In addition, overexpression of miR-125b apparently promotes RB cell proliferation and migration in vitro. Gain-of-function in vitro experiments further showed that the miR-125b mimic significantly suppressed RB cell apoptosis. A subsequent dual-luciferase reporter assay identified the suppressor gene DRAM2 as direct target of miR-125b.ConclusionsOur data collectively demonstrate that miR-125b is a suppressor gene miRNA that can promote RB cell proliferation and migration by downregulating the suppressor gene DRAM2, indicating that miR-125b may represent a new potential diagnostic and therapeutic target for RB treatment.

Eosinophil differentiation in the bone marrow is promoted by protein tyrosine phosphatase SHP2.

SHP2 participates in multiple signaling events by mediating T-cell development and function, and regulates cytokine-dependent granulopoiesis. To explore whether and how SHP2 can regulate bone-marrow eosinophil differentiation, we investigate the contribution of SHP2 in the bone-marrow eosinophil development in allergic mice. Blockade of SHP2 function by SHP2 inhibitor PHPS-1 or conditional shp2 knockdown by adenovirus-inhibited bone-marrow-derived eosinophil differentiation in vitro, with no detectable effects on the apoptosis of eosinophils. Furthermore, SHP2 induced eosinophil differentiation via regulation of the extracellular signal-regulated kinase pathway. Myeloid shp2 conditional knockout mice (LysM(cre)shp2(flox/flox)) failed to induce eosinophilia as well as airway hyper-responsiveness. The SHP2 inhibitor PHPS-1 also alleviated eosinophilic airway inflammation and airway hyper-responsiveness, accompanied by significantly reduced levels of systemic eosinophils and eosinophil lineage-committed progenitors in allergic mice. We demonstrate that inhibition of eosinophil development is SHP2-dependent and SHP2 is sufficient to promote eosinophil formation in vivo. Our data reveal SHP2 as a critical regulator of eosinophil differentiation, and inhibition of SHP2 specifically in myeloid cells alleviates allergic airway inflammation.

Discovery of a BTK/MNK dual inhibitor for lymphoma and leukemia.

Bruton's tyrosine kinase (BTK) kinase is a member of the TEC kinase family and is a key regulator of the B-cell receptor (BCR)-mediated signaling pathway. It is important for B-cell maturation, proliferation, survival and metastasis. Pharmacological inhibition of BTK is clinically effective against a variety of B-cell malignances, such as mantle cell lymphoma, chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML) and activated B-cell-diffuse large B-cell lymphoma. MNK kinase is one of the key downstream regulators in the RAF-MEK-ERK signaling pathway and controls protein synthesis via regulating the activity of eIF4E. Inhibition of MNK activity has been observed to moderately inhibit the proliferation of AML cells. Through a structure-based drug-design approach, we have discovered a selective and potent BTK/MNK dual kinase inhibitor (QL-X-138), which exhibits covalent binding to BTK and noncovalent binding to MNK. Compared with the BTK kinase inhibitor (PCI-32765) and the MNK kinase inhibitor (cercosporamide), QL-X-138 enhanced the antiproliferative efficacies in vitro against a variety of B-cell cancer cell lines, as well as AML and CLL primary patient cells, which respond moderately to BTK inhibitor in vitro. The agent can effectively arrest the growth of lymphoma and leukemia cells at the G0-G1 stage and can induce strong apoptotic cell death. These primary results demonstrate that simultaneous inhibition of BTK and MNK kinase activity might be a new therapeutic strategy for B-cell malignances.