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Purpose. To observe and compare the efficacy of modified trabeculectomy (TE), Ahmed drainage valve implantation (AGV), and EX-PRESS glaucoma shunt for refractory glaucoma (RG). Methods. The study population of this retrospective study comprised 73 patients (76 eyes) who were suffering from RG and treated with modified TE, AGV, and EX-PRESS glaucoma shunt in our hospital from October 2012 to October 2020. The number of cases who underwent modified TE, AVG, and EX-PRESS glaucoma shunt was 36 (38 eyes). 19 (20 eyes), and 18 patients (18 eyes), respectively. The intraocular pressure (IOP), best-corrected visual acuity (BCVA), postoperative antiglaucoma medications, filter bubble morphology, anterior chamber depth (ACD), successful rate, and postoperative complications were recorded and statistically analyzed preoperative and 1 d, 1 w, 1 mon, 3 mon, 6 mon, and the end follow-up after operation. Results. The BCVA differed insignificantly among the three cohorts before and 6 months after surgery. Compared to preoperative BCVA, the postoperative BCVA of the three groups had no statistical significance. An obvious reduction in IOP was observed in all the three group after operation ( P < 0.05 ). An obvious decrease in antiglaucoma medications was observed after surgery in all the three groups ( P < 0.05 ). The AGV group showed deeper ACD postoperatively, while no marked difference was found in postoperative ACD in the other two groups. The total success rates in modified TE and AGV groups were slightly higher than those in the EX-PRESS group. The three groups differed insignificantly in filter bubble morphology after operation. Conclusion. Modified TE, AGV, and EX-PRESS glaucoma shunt showed equivalent efficacy for RG, which could validly reduce IOP and postoperative antiglaucoma medications. However, the success rates of modified TE and AGV were slightly higher than those of EX-PRESS glaucoma shunt in the last follow-up, and their complications were slightly less than those of the EX-PRESS glaucoma shunt.

BackgroundEsophageal squamous carcinoma (ESCC) is a highly lethal malignancy with poor prognosis. The effect of transcriptome characteristics of patient immune microenvironment (TME) on the efficacy of immunosuppressive agents is still poorly understood.MethodsHere we extracted and isolated immune cells from peripheral blood of patients with PD-1 monoclonal antibody sensitivity and resistance, and conducted deep single-cell RNA sequencing to describe the baseline landscape of the composition, lineage, and functional status of infiltrating immune cells in peripheral blood of patients with esophageal cancer.ResultsThe transcriptome characteristics of immune cells were comprehensively analyzed, and the dynamic changes of cell percentage, heterogeneity of cell subtypes and interactions between cells were explained. Co-expression and pedigree tracking based on T-cell antigen receptors revealed a significant proportion of highly migratory intertissue-effector T cells. GO and KEGG enrichment pathway Analysis of CD8+ effect-T cells ESCC_S group and ESCC_D1,2 group, found that in the up-regulated enrichment pathway, ESCC_S group enriched more PD-L1 and PD-1 checkpoint pathways expressed in tumors (JUN/NFKBIA/FOS/KRAS/IFNG), which also exist in T cell receptor signaling pathways. MT2A, MT1X and MT1E were differentially expressed in ESCC patients with PD-1 monoclonal antibody resistance, which may be related to the resistance of PD-1 mMAB.ConclusionsThis study has an in-depth understanding of the influence of peripheral immune cell infiltration on the sensitivity of monoclonal antibody PD-1 in patients with esophageal cancer, which is helpful to promote the immunotherapy of patients with esophageal cancer.

The quiescent/slow-cycling state preserves the self-renewal capacity of cancer stem cells (CSCs) and leads to the therapy resistance of CSCs. The mechanisms maintaining CSCs quiescence remain largely unknown. Here, it is demonstrated that lower expression of MAN1A1 in glioma stem cell (GSC) resulted in the formation of high-mannose type N-glycan on CD133. Furthermore, the high-mannose type N-glycan of CD133 is necessary for its interaction with DNMT1. Activation of p21 and p27 by the CD133-DNMT1 interaction maintains the slow-cycling state of GSC, and promotes chemotherapy resistance and tumorigenesis of GSCs. Elimination of the CD133-DNMT1 interaction by a cell-penetrating peptide or MAN1A1 overexpression inhibits the tumorigenesis of GSCs and increases the sensitivity of GSCs to temozolomide. Analysis of glioma samples reveals that the levels of high-mannose type N-glycan are correlated with glioma recurrence. Collectively, the high mannose CD133-DNMT1 interaction maintains the slow-cycling state and tumorigenic potential of GSC, providing a potential strategy to eliminate quiescent GSCs.

Sialic acid-binding immunoglobulin-like lectin-15 (Siglec-15) has been identified as a novel potential target for cancer immunotherapy. Here, we explored the role of Siglec-15 in human hepatoma cells. In this study, we found that the expression of Siglec-15 is substantially upregulated in liver cancer tissues in comparison with the nontumor tissues. Functionally, in vitro experiments show that Siglec-15 promotes the migration of hepatoma cells. Furthermore, the data demonstrated an interaction between Siglec-15 and CD44, a transmembrane glycoprotein that mediates tumor progression and metastasis. In addition, we show that CD44 is modified by α2,6-linked sialic acids on N-glycans in hepatoma cells and that CD44 sialylation affects its interaction with Siglec-15. Removal of the sialic acid residues from CD44 resulted in suppressed interaction between Siglec-15 and CD44. We further demonstrate that Siglec-15 interacts and promotes the stability of CD44 by preventing its lysosomal-mediated degradation. Taken together, our findings demonstrate that Siglec-15 promotes the migration of hepatoma cells by regulating the CD44 protein stability.

Fenestration is a rare congenital abnormality that refers to a segmental duplication of arteries. It is still not clear about the role of fenestrations in the etiology and pathological evolution of vascular diseases. This study aims to investigate the hemodynamic influence brought by various sizes and locations of fenestration in basilar artery models. A series presumptive fenestration models were established based on a normal basilar artery model with various sizes and locations. Identical boundary conditions were utilized in the computational fluid dynamics simulations and different flow patterns in the fenestration and bifurcation regions were comprehensively analyzed. Wall shear stress (WSS)-related parameters such as oscillatory shear index (OSI) and aneurysm formation index (AFI) were computed and compared. The value of WSS on fenestration increased by the fenestration's tortuosity, and nearly-circular fenestration suffered higher WSS than narrow-strips one. Also, high OSI and low AFI value mainly occurred in the bifurcation region, indicating a high level of turbulence and high risk of aneurysm formation. The location of fenestration mainly changed the impact force of blood flow on the bifurcation and the disorder characteristics of blood flow, while the size of fenestration changed the WSS distribution on the proximal inner wall and bifurcation region of fenestration. In summary, the nearly-circular fenestration should be stratified carefully which may results in a high risk inducing unfavorable vascular wall remodeling.

Background Immune checkpoint inhibitors (ICIs) were approved to have a significant antitumor activity in various tumor types. In practice, some patients do not seem to benefit from ICIs but rather to have accelerating disease. The aim of this study was to evaluate hyperprogression in patients with malignant tumors of digestive system treated with ICIs. Methods Medical records from consecutive patients with malignant tumors of digestive system treated with ICIs in Peking University Cancer Hospital were retrospectively collected. Tumor growth kinetics (TGK) on immunotherapy and TGK pre-immunotherapy were collected and TGK ratio (TGKR) was calculated. Hyperprogression was defined as TGKR≥2. Results From August 2016 to May 2017, 25 evaluable patients were identified from 45 patients with malignant tumors of digestive system. Five patients were considered as having hyperprogression. Three of 5 were neuroendocrine carcinomas (NECs) and the other 2 were adenocarcinomas. Four of 5 were treated with programmed cell death ligand 1 (PD-L1) inhibitor, the other one was treated with PD-L1 inhibitor combined with cytotoxic T lymphocyte associated antigen-4 (CTLA-4) inhibitor. Pseudoprogression was observed in 2 patients. Conclusions Hyperprogression was observed in a fraction of patients with malignant tumors of digestive system treated with ICIs. Further investigation is urgently needed.

Management of esophageal squamous cell carcinoma remains challenging, because detection often occurs at advanced stages and because of the high incidence of lymph node metastasis. This article focuses on whether lymphopenia is associated with response and tumor progression in patients with advanced esophageal squamous cell carcinoma who received concurrent chemotherapy., Background. Lymphopenia occurs commonly in esophageal squamous cell carcinoma (ESCC) and may influence treatment outcomes. We aimed to examine its association with treatment response and tumor progression in patients with locally advanced ESCC treated with concurrent chemoradiotherapy (CCRT). Materials and Methods. A total of 286 patients with stage II–IVa ESCC treated with CCRT between 2015 and 2017 were analyzed. Total lymphocyte counts were assessed at baseline, weekly, and 4 weeks after CCRT. Pretreatment lymphopenia was defined as total lymphocyte count

The tumor-initiating cell (TIC) marker CD133 promotes TIC self-renewal and tumorigenesis through the tyrosine phosphorylation of its c-terminal domain. Therefore, finding compounds that target the phosphorylation of CD133 will provide an effective method for inhibiting TICs characteristics. Here, through small molecule microarray screening, compound LDN193189 was found to bind to the c-terminus of CD133 and influenced its tyrosine phosphorylation. LDN193189 inhibited the interaction between CD133 and p85, accompanied by a reduction in the self-renewal and tumorigenicity of liver TIC. In addition, LDN193189 inhibited the expression and transcription of Galectin-3 by reducing the tyrosine phosphorylation of CD133. Galectin-3 secreted by liver TICs inhibited the proliferation of activated CD8+ T cells by binding to PD-1. LDN193189 suppressed the immune escape ability of liver TICs by downregulating Galectin-3. Taken together, LDN193189 suppressed the tumorigenesis and immune escape of liver CSCs by targeting the CD133-Galectin-3 axis.

BACKGROUND Despite the promising results of immunotherapy in cancer treatment, new response patterns, including pseudoprogression and hyperprogression, have been observed. Radiomics is the automated extraction of high-fidelity, high-dimensional imaging features from standard medical images, allowing comprehensive visualization and characterization of the tissue of interest and corresponding microenvironment. This study assessed whether radiomics can predict response to immunotherapy in patients with malignant tumors of the digestive system. MATERIAL AND METHODS Computed tomography (CT) images of patients with malignant tumors of the digestive system obtained at baseline and after immunotherapy were subjected to radiomics analyses. Radiomics features were extracted from each image. The formula of the screened features and the final predictive model were obtained using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm. RESULTS Imaging analysis was feasible in 87 patients, including 3 with pseudoprogression and 7 with hyperprogression. One hundred ten radiomics features were obtained before and after treatment, including 109 features of the target lesions and 1 of the aorta. Four models were constructed, with the model constructed from baseline and post-treatment CT features having the best classification performance, with a sensitivity, specificity, and AUC of 83.3%, 88.9%, and 0.806, respectively. CONCLUSIONS Radiomics can predict the response of patients with malignant tumors of the digestive system to immunotherapy and can supplement conventional evaluations of response.

BackgroundThis retrospective study was to assess and compare the toxicity and efficacy of concurrent chemoradiotherapy (CCRT) with S-1 or docetaxel and cisplatin in patients with locally advanced esophageal squamous cell carcinoma (ESCC).MethodsPatients with locally advanced ESCC who received CCRT with S-1 (70 mg/m2twice daily on days 1–14, every 3 weeks for 2 cycles, S-1 group) or docetaxel (25 mg/m2) and cisplatin (25 mg/m2) on day 1 weekly (DP group) between 2014 and 2016 were retrospectively analyzed. Radiotherapy was delivered in 1.8–2.0 Gy per fraction to a total dose of 50–60 Gy. Treatment-related toxicities (Common Terminology Criteria for Adverse Events version 4.0), response rate, and survival outcomes were compared between groups.ResultsA total of 175 patients were included in this study (72 in the S-1 group and 103 in the DP group). Baseline characteristics were well balanced between the two groups. The incidence of grade 3–4 adverse events were significantly lower in the S-1 group than that of the DP group (22.2% vs. 45.6%,p = 0.002). In the DP group, elderly patients (> 60 years) had a significantly higher rate of grade 3–4 adverse events than younger patients (58.1% vs. 31.3%,p = 0.01). The objective overall response rate (complete response + partial response) was 68.1% in the S-1 group, and 73.8% the DP group (p = 0.497). The 3-year overall survival was 34.7% in the S-1 group, and 38.8% in the DP group (p = 0.422). The 3-year progression free survival in the DP group was higher than that in the S-1 group but without significant difference (33.0% vs. 25.0%,p = 0.275).ConclusionCCRT with S-1 is not inferior to CCRT with docetaxel and cisplatin and is better tolerated in in elderly patients with locally advanced ESCC.

Background Betahistine is a clinical medication for the treatment of benign paroxysmal positional vertigo (BPPV). Otolin, a secreted glycoprotein with a C-terminal globular domain homologous to the immune complement C1q, has been identified as a biomarker for BPPV. However, the role of complement C1q/TNF-related proteins (CTRPs) with a C-terminal globular domain in BPPV is unclear, so we explored the change of CTRPs in betahistine treated BPPV. Methods We treated BPPV patients with Betahistine (12 mg/time, 3 times/day) for 4 weeks and observed the clinical efficacy and the expression of CTRP family members in BPPV patients. Then, we constructed a vertigo mice model of vestibular dysfunction with gentamicin (150 mg/Kg) and a BPPV model of Slc26a4loop/loop mutant mice. Adenoviral vectors for CTRP expression vector and small interfering RNA were injected via the intratympanic injection into mice and detected the expression of CTRP family members, phosphorylation levels of ERK and AKT and the expression of PPARγ. In addition, we treated mice of vestibular dysfunction with Betahistine (10 mg/Kg) and/or ERK inhibitor of SCH772984 (12 mg/Kg) and/or and PPARγ antagonist GW9662 (1 mg/Kg) for 15 days, and evaluated the accuracy of air righting reflex, the time of contact righting reflex and the scores of head tilt and swimming behavior. Results After treatment with Betahistine, the residual dizziness duration and the score of the evaluation were reduced, and the expression of CTRP1, 3, 6, 9 and 12 were significantly increased in BPPV patients. We also found that Betahistine improved the accuracy of air righting reflex, reduced the time of contact righting reflex and the scores of head tilt and swimming behavior in gentamicin-treated mice and Slc26a4loop/loop mutant mice. The expression levels of CTRP1, 3, 6, 9 and 12, phosphorylation levels of ERK and AKT, and PPARγ expression were significantly increased, and the scores of head tilt and swimming behavior were decreased in vestibular dysfunction mice with overexpression of CTRPs. Silencing CTRPs has the opposite effect. SCH772984 reversed the effect of Betahistine in mice with vestibular dysfunction. Conclusion Betahistine alleviates BPPV through inducing production of multiple CTRP family members and activating the ERK1/2-AKT/PPARy pathway.

Ankyloglossia is a congenital condition characterized by a short lingual frenulum, which may result in the restriction of tongue movement and function. Considerable controversy regarding the diagnosis, clinical significance, and management of the condition remains, and great variations in practice have been recorded. Indeed, attitudes toward ankyloglossia differ among professional groups, and opinions may vary remarkably even among those within the same specialty. This article reviews the embryology, genetics, diagnosis, clinical presentation, and treatment of ankyloglossia to help physicians better understand and treat the condition.舌系带过短是一种先天性异常，可能会限制舌尖的活动能力，削弱舌的功能，然而对舌系带过短的诊断、临床表现、治疗存在的争议历史已久。不仅不同专业群体对舌系带过短的态度不同，甚至在同一专业的人之间观点也不同。本文对舌系带过短的胚胎学、遗传学、诊断、临床表现、治疗作一综述，以帮助各科医师更好地认识和治疗舌系带过短。.

Objective. Vagus nerve stimulation (VNS) is a nonpharmacologic therapeutic option for patients who have pharmaco-resistant Dravet syndrome (DS). Plentiful efforts have been made for delivering VNS to DS patients, but its effectiveness still requires further verification. We investigated the effectiveness of the VNS treatment of DS patients using brain connectivity analysis with electroencephalography (EEG). Approach. Twenty pharmaco-resistant DS patients were selected to undergo VNS implantation and classified into responder and non-responder groups after 24 months post-VNS. The effect of VNS between 6 months pre- and 6, 12, and 24 months post-VNS in all patients, responders, and non-responders on four different frequency categories of four brain parameters were compared using resting-state EEG. Main results. In alpha and beta bands, all patients showed positive results for characteristic path length (CPL), global efficiency (GE), and transitivity after VNS treatment, and changes in betweenness centrality (BC) were not significant. The difference in transitivity between responders and non-responders is more pronounced than those in CPL and GE are, in both the alpha (p < 0.015) and beta (p < 0.001) bands. There was an obvious change in BC, especially in the alpha band, as the hubs tended to move from frontal lobe to parietal lobe for responders; however, there was no change for the non-responders. Significance. We investigated the alteration in brain connectivity of DS patients in alpha and beta bands during a long-term follow-up and found the responders have a decreased transitivity after the VNS treatment. Moreover, the hubs with high values in the alpha band tended to move from frontal lobe to parietal lobe for responders after VNS treatment.

To investigate the effects of electroacupuncture (EA) at Taichong (LR 3) and Baihui (DU 20) on myocardial hypertrophy in spontaneously hypertensive rats (SHRs).Thirty-six SHRs were randomly assigned to model, EA, and Losartan groups, with twelve rats per group. Twelve Wistar Kyoto rats were selected as the normal control group. Systolic blood pressure (SBP) and cardiac function were measured in all rats. Expression levels of factors associated with the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway were evaluated by Western blotting and real-time PCR. Pathological changes of the heart tissue were observed by hematoxylin-eosin staining.After treatment, enhanced SBP was significantly decreased in the EA and Losartan groups compared with the model group (P0.01). Echocardiographic and morphological analyses revealed that enhanced end-diastolic interventricular septal thickness and left ventricular posterior wall thickness, as well as ratio of left ventricular weight to body weight were markedly diminished in the EA and Losartan groups (P0.01 or P0.05), while reduced left ventricular end-diastolic dimension and left ventricular ejection fraction were significantly ameliorated (P0.01). Real-time PCR and western blotting analyses showed that the expression levels of PI3K, Akt, and mTOR in SHRs were significantly up-regulated by EA and Losartan (P0.01), while the expression levels of PTEN and ANP were down-regulated (P0.01).EA at Taichong (LR 3) and Baihui (DU 20) inhibited the development of cardiac hypertrophy and improved the cardiac function in SHRs, possibly through regulation of the PI3K/Akt/mTOR signalling pathway.

Background Ferroptosis is a novel mode of non-apoptotic cell death induced by build-up of toxic lipid peroxides (lipid-ROS) in an iron dependent manner. Cancer-associated fibroblasts (CAFs) support tumor progression and drug resistance by secreting various bioactive substances, including exosomes. Yet, the role of CAFs in regulating lipid metabolism as well as ferroptosis of cancer cells is still unexplored and remains enigmatic. Methods Ferroptosis-related genes in gastric cancer (GC) were screened by using mass spectrum; exosomes were isolated by ultra-centrifugation and CAF secreted miRNAs were determined by RT-qPCR. Erastin was used to induce ferroptosis, and ferroptosis levels were evaluated by measuring lipid-ROS, cell viability and mitochondrial membrane potential. Results Here, we provide clinical evidence to show that arachidonate lipoxygenase 15 (ALOX15) is closely related with lipid-ROS production in gastric cancer, and that exosome-miR-522 serves as a potential inhibitor of ALOX15. By using primary stromal cells and cancer cells, we prove that exosome-miR-522 is mainly derived from CAFs in tumor microenvironment. Moreover, heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was found to mediate miR-522 packing into exosomes, and ubiquitin-specific protease 7 (USP7) stabilizes hnRNPA1 through de-ubiquitination. Importantly, cisplatin and paclitaxel promote miR-522 secretion from CAFs by activating USP7/hnRNPA1 axis, leading to ALOX15 suppression and decreased lipid-ROS accumulation in cancer cells, and ultimately result in decreased chemo-sensitivity. Conclusions The present study demonstrates that CAFs secrete exosomal miR-522 to inhibit ferroptosis in cancer cells by targeting ALOX15 and blocking lipid-ROS accumulation. The intercellular pathway, comprising USP7, hnRNPA1, exo-miR-522 and ALOX15, reveals new mechanism of acquired chemo-resistance in GC. Graphical abstract

Koebner phenomenon refers to the emergence of new psoriatic lesions in the healthy skin regions following an injury/trauma to psoriatic patients. The occurrence of psoriatic lesions at unusual areas of the body regions such as on penis, around eyes and on keloids suggest that the Koebner phenomenon may be responsible for these lesions. A number of agents/triggers have been reported to induce the development of new psoriatic lesions in healthy skin areas and these include, tattooing skin, radiations, skin incision, viral infections and striae etc. The different mechanisms that contribute in inducing the development of new psoriatic lesions as Koebernization include the involvement of mast cell-derived inflammatory mediators such as tryptase, IL-6, IL-8, IL-17, and IL-36γ. Moreover, an increased expression of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) also contribute in Koebernization. Apart from these, there is a critical role of α 2 β1 integrins, S100A7 (psoriasin) and S100A15 (koebnerisin), change in the ratio of CD4+/CD8+ T cells, down-regulation of mechanosensitive polycystin 1 protein, decrease in inflammation controlling atypical chemokine receptor 2 (ACKR2), reduced expression of N-methyl-d-aspartate (NMDA) receptors (NMDARs) on the keratinocytes and increase in levels of chemokines (CXCL8 and CCL20) in inducing formation of new psoriatic lesions. The present review discusses the role of Koebner phenomenon in the development of new psoriatic lesions. Moreover, it also describes the mechanisms involved in Koebernization in the form of discussion of different key targets that may be potentially modulated pharmacologically to attenuate/halt the development of new psoriatic lesions.

Four controversial types of simplex reinforcing-reducing manipulation of acupuncture and their possible meanings were summarized to explore several key elements of reinforcing-reducing manipulation of acupuncture, in addition, the simplex reinforcing-reducing manipulation of acupuncture was classified by single factor. It is concluded that the definition of simplex reinforcing-reducing manipulation of acupuncture should try not to include other non-manipulative elements. According to single factor, it can be divided into: needle-oriented reinforcing-reducing manipulation, twisting reinforcing-reducing manipulation, lifting and interpolating reinforcing-reducing manipulation, fast and slow reinforcing-reducing manipulation, breathing reinforcing-reducing manipulation, opening and closing reinforcing-reducing manipulation. In addition, after considering the effect and principle of number reinforcing-reducing manipulation, it can be considered.

Background:Epidemiologic studies have investigated the association between nut intake and risk for multiple cancers. However, current findings are inconsistent and no definite conclusion has been drawn from prospective studies. We therefore conducted this meta-analysis to evaluate the relationship between nut consumption and risk of cancer.Methods:Prospective studies reporting associations between nut intake and risk for all types of cancer were identified by searching Web of Science and PubMed databases up to June 2019. Risk ratios (RR) and 95% confidence intervals (CI) were extracted and then pooled across the studies using a random-effect model. A dose–response analysis was modeled by performing restricted cubic splines when data were available.Results:Thirty-three studies that included more than 50,000 cancer cases were eligible for the analysis. When comparing the highest with the lowest category of nut intake, high consumption of nuts was significantly associated with decreased risk of overall cancer (RR = 0.90; 95% CI, 0.85–0.95). The protective effect of nut consumption was especially apparent against cancers from the digestive system (RR = 0.83; 95% CI, 0.77–0.89). Among different nut classes, significant association was only obtained for intake of tree nuts. We also observed a linear dose–response relationship between nut consumption and cancer: Per 20 g/day increase in nut consumption was related to a 10% (RR = 0.90; 95% CI, 0.82–0.99) decrease in cancer risk.Conclusions:Our analysis demonstrated an inverse association of dietary nut consumption with cancer risk, especially for cancers from the digestive system.Impact:This study highlights the protective effect of nuts against cancer.

RBM15, an RNA-binding protein, plays important roles in the growth and apoptosis of cells, especially blood cells through regulating multiple signal pathways such as Notch and Wnt. An increasing body of evidence has suggested that RBM15 may play a key function on the development of various blood diseases, such as acute/chronic myeloid leukemia and kaposi's sarcoma. In this review, we will focus on the progress of the association between RBM15 and its related blood diseases.

Bisphenol A (BPA), a well-known endocrine disruptor, was reported to promote migration and invasion of lung cancer cells, but findings in human study is absent. A case-control study in Chinese population was conducted to evaluate the association between BPA exposure and non-small cell lung cancer (NSCLC), and explore the interaction between BPA exposure and estrogen-related genetic polymorphism on NSCLC. BPA concentrations were measured in urine samples using an UHPLC-MS method and rs2046210 in estrogen receptor α (ESR1) gene was genotyped by TaqMan genotyping system. Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the association analyses. As a result, 615 NSCLC cases and 615 healthy controls were enrolled from Wuhan, central China. The mean age was 58.0 (SD: 7.9) years old for controls and 59.2 (SD: 8.8) years old for cancer cases. The creatinine-adjusted BPA levels were significantly higher in NSCLC cases than that in healthy controls (median: 0.97 vs 0.73 μg/L, P 0.001). Exposure to high levels of BPA was significantly associated with NSCLC (adjusted OR = 1.91, 95%CI: 1.39-2.62, P 0.001 for the highest quartile). We also observed a shallow concave dose-response relationship about the overall association between BPA and NSCLC. Moreover, interaction analyses showed that BPA exposure interacted multiplicatively with rs2046210, with a marginal P value (P = 0.049), to contribute to NSCLC. In conclusion, exposure to high levels BPA may be associated with NSCLC and the relationship may be modified by genetic polymorphism in ESR1.

Astaxanthin is a natural product gaining increasing attention due to its safety and anti-cancer properties. In this study, we investigated the mechanisms of the anti-cancer effects of astaxanthin on prostate cancer (PCa) cell lines using aggressive PCa DU145 cells. Also an instantaneous silenced cell line (si-STAT3) derived from DU145 and a control cell line (si-NK) were used for the MTT and colony formation assays to determine the role of astaxanthin in proliferation and colony formation abilities. Flow cytometry assays were used to detect the apoptosis of tumor cells. Migration and invasion assays detected the weakening of the respective abilities. Western blot and RT-PCR tests detected the levels of STAT3 protein and mRNA. Astaxanthin resulted in suppression of the proliferation of DU145 cells and the level of STAT3. The treatment of DU145 cells with astaxanthin decreased the cloning ability, increased the apoptosis percentage and weakened the abilities of migration and invasion of the cells. Furthermore, astaxanthin reduced the expression of STAT3 at protein and mRNA levels. The effects were enhanced when astaxanthin and si-STAT3 were combined. The results of animal experiments were consistent with the results in cells. Thus, astaxanthin inhibits the proliferation of DU145 cells by reducing the expression of STAT3.

Oncogenic alterations in the BRAF gene are identified in an estimate of 50% of melanomas and cause melanoma development. BRAF kinase inhibitors (BRAFi), including vemurafenib and dabrafenib, were discovered and used in the clinical treatment of BRAF-mutant metastatic melanoma. Though, BRAFi's therapeutic advantages are short term and short-lived associated with drug resistance. Although a few pathways of developed BRAFi resistance have also been established, in approximately 40% of melanomas, the cause for inherited resistance remains unclear. Recognizing a new process of developed BRAFi resistance might provide new possibilities to successfully treat BRAF mutant melanoma. In this study, we are exploring the compensatory alternative pathway followed by BRAFi/MEKi treated resistant cell for maintaining the long-term integrity and survival.

Background Genome-wide association studies (GWAS) have identified 5p15.33 as a susceptible locus for lung cancer. However, for non-small cell lung cancer (NSCLC), low-frequency risk variants in this region have not been systematically studied. We intended to explore the associations between low-frequency variants on 5p15.33 and NSCLC using a next-generation sequencing based approach in this study. Methods We have acquisited the variation spectrum of 400 NSCLC patients on 5p15.33 by sequencing the targeted region before. Candidate variants were primarily selected by restricting the minor allele frequency (MAF 1–5%) and then by comparing their frequency in 400 NSCLC patients with 1008 East Asians from The genome Aggregation Database (gnomAD). The associations between candidate variants and NSCLC were discovered and replicated in two case-control sets: discovery stage with 960 cases and 916 controls, and replication stage with 1596 cases and 1614 controls in total. Results Five low-frequency variants were selected as our candidates and subsequent association analyses showed that 2 polymorphisms were significantly associated with risk of NSCLC, including rs33963617 (OR = 0.63, 95% CI: 0.53–0.76, P = 3.80 × 10−7) in TERT and rs77518573 (OR = 0.73, 95% CI: 0.63–0.84, P = 2.00 × 10−5) in upstream of CLPTM1L. When stratified by histologic subtype, a significant association was only investigated in adenocarcinoma for rs77518573. We also observed an obvious cumulative effect of the two significant variants. Conclusions We newly identified two NSCLC related variants on chromosome 5p15.33. Both TERT-rs33963617 and CLPTM1L-rs77518573 conferred reduced risk for NSCLC in Chinese Han population.

Background: The chromosome 5p15.33 has been reported as a susceptibility locus for lung cancer, but causal variants have not been fully investigated. We intended to explore functional polymorphisms associated with non-small cell lung cancer (NSCLC) susceptibility and their relationship with telomere length in Chinese population. Methods: We conducted a targeted sequencing at 5p15.33 with 400 patients. Comparing with genotypic frequency in 1000 Genomes Project, we selected candidate variants and validated their associations with NSCLC in 985 cases and 970 controls. The relationships between susceptibility SNPs and telomere length were evaluated in 774 healthy subjects. Luciferase assays and electrophoretic mobility shift assays were performed to reveal potential mechanisms. Findings: we identified 1478 variants through targeted sequencing and selected 17 candidate variants. Four polymorphisms exhibited prominent associations with lung cancer risk, including rs7726159 (OR = 1.34, 95% CI: 1.18-1.52, P = 7.78 × 10-6 )，rs10054203 (OR = 1.29, 95% CI: 1.13-1.46, P = 1.37 × 10-4 )，rs2736107 (OR = 1.28, 95% CI: 1.11-1.47, P = 5.14 × 10-4 ) and rs2853677 (OR = 1.23, 95% CI: 1.08-1.39, P = 0.002). The minor allele of rs7726159 and rs10053203 were associated with long telomeres (P = 0.008 and 0.036, respectively). Functional exploration characterized rs7726159 promoted TERT transcription through disrupting transcription factor binding. Interpretation: The functional polymorphism, rs7726159, confers lung cancer susceptibility by disturbing telomere biology. Our study illustrated the functional significance of this variant in lung cancer initiation, which provides a new insight into the important role of telomere dysfunction in tumor progression. Funding Statement: This work was supported by the National Natural Science Foundation of China (81572071). Declaration of Interests: The authors declare that they have no potential conflicts of interest. Ethics Approval Statement: Written informed consent was obtained from each individual, and this study was approved by the Institutional Review Board of the Tongji Medical College, HUST.

The aim of this study was to evaluate the early and sustained effects of tinnitus educational counseling on chronic primary tinnitus and related problems. A descriptive longitudinal cohort study was conducted with 159 adult patients suffering from chronic primary tinnitus and sleep problems. All patients received tinnitus educational counseling, sleep adjustment, and vegan dietary advice. At short-term assessment within 3 months and long-term follow-up at 6–26 months, perceived changes in tinnitus were assessed with the Tinnitus Handicap Inventory (THI) and the Tinnitus Evaluation Questionnaire (TEQ), respectively. In TEQ, the volume of subjective tinnitus was scored according to realistic environments in which tinnitus could be heard. Sleep quality was assessed with questionnaires developed in our laboratory. Most of the subjects showed significant early improvement in their THI scores (96/159, 60.38%; from 46.11 ± 22.74 to 31.94 ± 20.41,t= 11.16,p< 0.001, Cohen’sd= 0.66). Tinnitus volume (39/159, 24.53%, from 2,2 to 2,1,z= -3.56,p< 0.001) and sleep quality (68/159, 42.77%; from 7.13 ± 3.11 to 6.31 ± 2.75,t= 3.73,p< 0.001, Cohen’sd= 0.28) were also improved. Long-term follow-up TEQ results indicated that tinnitus loudness, the impact of tinnitus on sleep, concentration, and emotional state were all improved since the prior consultation (p= 0.001, 0.026, 0.012, and p= 0.002), initial THI score (OR = 1.02, 95% CI: 1.01 to 1.04,p= 0.006), compliance with sleep advice (OR = 2.27, 95% CI: 1.02–5.05,p= 0.044), and nervous disposition (OR = 2.80, 95% CI: 1.25–6.30,p= 0.013). A future randomized controlled trial would be carried out to examine the effect of sole tinnitus educational counseling.

The present study explores the correlation of human epidermal growth factor receptor-2 (HER-2) protein expression with sentinel lymph node (SLN) metastasis and prognosis of breast cancer. The breast cancer tissues and adjacent tissues were obtained from patients with primary breast cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the mRNA level of HER-2. Spearman correlation analysis was used to analyze the correlation of HER-2 expression with SLN metastasis. The disease-free survival (DFS) and overall survival (OS) of breast cancer patients were investigated. Univariate and multivariate analyses were performed to explore factors influencing SLN metastasis and prognosis of breast cancer. Compared with adjacent tissues, HER-2 expression was significantly up-regulated in breast cancer tissues. HER-2 expression was correlated with the pathological type, tumor node metastasis (TNM) staging, histological grade, blood vessel invasion, SLN metastasis, estrogen receptor (ER), and progesterone receptor (PR). The expression level of HER-2 was positively related to the SLN metastasis (r=0.548). Median DFS and OS were longer in patients with negative HER-2 expression than in patients with positive HER-2 expression. TNM staging, SLN metastasis, and expression levels of HER-2 and ER were independent factors for DFS of breast cancer patients, while TNM staging, blood vessel invasion, histological grade, SLN metastasis, and expression levels of HER-2 and PR were independent factors for OS of breast cancer patients. Our study suggests that high expression of HER-2 promoted SLN metastasis. HER-2 expression and SLN metastasis were the independent factors for the prognosis of breast cancer.

A novel method, real-time reverse transcription PCR (real-time RT-PCR) coupled with probe-melting curve analysis, has been established to detect two kinds of samples within one fluorescence channel. Besides a conventional TaqMan probe, this method employs another specially designed melting-probe with a 5' terminus modification which meets the same label with the same fluorescent group. By using an asymmetric PCR method, the melting-probe is able to detect an extra sample in the melting stage effectively while it almost has little influence on the amplification detection. Thus, this method allows the availability of united employment of both amplification stage and melting stage for detecting samples in one reaction. The further demonstration by simultaneous detection of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) in one channel as a model system is presented in this essay. The sensitivity of detection by real-time RT-PCR coupled with probe-melting analysis was proved to be equal to that detected by conventional real-time RT-PCR. Because real-time RT-PCR coupled with probe-melting analysis can double the detection throughputs within one fluorescence channel, it is expected to be a good solution for the problem of low-throughput in current real-time PCR.

Interleukin (IL)-17 signaling serves an important role in the development and pathogenesis of psoriasis; a chronic skin disease characterized by increased dermal vascularity and the hyperproliferation of keratinocytes. microRNA (miR)‑203 is preferentially expressed in the skin and is an important regulator of keratinocyte differentiation. miR‑203 has been implicated in a number of skin diseases, including psoriasis. However, the role of miR‑203 in IL‑17‑induced vascular endothelial growth factor (VEGF) secretion has yet to be elucidated. The present study demonstrated that miR‑203 expression was upregulated in the ears of IL‑17‑stimulated mice and IL‑17‑treated HaCaT cells. In addition, the IL‑17‑induced increase in miR‑203 expression activated the Janus kinase/signal transducer and activator of transcription signaling pathway and promoted VEGF secretion in HaCaT cells. Furthermore, miR‑203 was observed to bind to the 3'‑untranslated region of suppressor of cytokine signaling 3 (SOCS3) and inhibited SOCS3 expression. The results suggest that miR‑203 expression may be upregulated by IL‑17 stimulation, and miR‑203 is a positive regulator of IL‑17‑induced VEGF secretion. The present study may support potential therapeutic strategies for the treatment of psoriasis.

To compare the efficacy and toxicity of intensity- modulated radiation therapy plus chemotherapy (IMRT-TP) with simple intensity-modulated radiation therapy (IMRT) in the treatment of locally advanced esophageal carcinoma.A total of 170 eligible patients with locally advanced esophageal carcinoma were recruited prospectively from September 2004 to April 2008 and randomly divided into IMRT-TP group and IMRT group. Two groups were treated with IMRT of 6MV-X. The radiation dose was 60 Gy in 30 fractions in IMRT-TP group and 66 Gy in 30 fractions in IMRT group. The regimen of chemotherapy consisted of docetaxel and cisplatin in IMRT-TP group for 2 cycles.Of 170 patients, 160 completed the trial, including 75 patients of IMRT-TP group and 85 of IMRT group. As compared to IMRT group, total recurrence rate [69.3% (52/75) vs. 84.7% (72/85), P=0.020] and local recurrence rate [50.7% (38/75) vs. 67.1% (57/85), P=0.035] decreased in IMRT-TP group, the 5-year overall survival (29.3% vs. 15.3%, P=0.031) and 5-year recurrence free survival (24.0% vs. 10.6%, P=0.015) increased in IMRT-TP group. While severe side effect ratio increased obviously in IMRT-TP group [54.7% (41/75) vs. 4.7% (4/85), P=0.000].As compare to simple IMRT, IMRT plus docetaxel and cisplatin can decrease the local recurrence rate, prolong the overall survival and regression-free survival, but bring more side effects.

Objective The efficacy of postoperative concurrent radiochemotherapy (POCRT) on IIIA-pN2 non-small cell lung cancer (NSCLC) is still unclear. The aim of this randomized controlled trial was to compare POCRT with postoperative chemotherapy (POCT) alone in terms of survival and relapse patterns. Methods Patients with completely resected IIIA-pN2 NSCLC were randomized into POCRT or POCT groups. Chemotherapy consisted of paclitaxel (175mg/m 2 ) and cisplatin (60mg/m 2 ) administered intravenously for four cycles on day 1, 22, 43, and 64. Patients in the POCRT group received radiotherapy (50.4Gy/28 fractions) concurrently with the first 2 cycles of chemotherapy. Results This study recruited 140 participants and was closed early because of slow accrual. Data were analyzed for 135 of them including 66 cases in the POCRT group and 69 cases in the POCT group. Patients were followed-up for a median period of 45months. The POCRT group had a median survival (MS) of 40months and a 5-year overall survival (OS) rate of 37.9%. The POCT group had a MS of 28months and a 5-year OS rate of 27.5%. The hazard ratio for death in the POCRT group was 0.69 (95% CI: 0.457–1.044, P =0.073). We observed a disease-free survival (DFS) of 28months and a 5-year DFS rate of 30.3% in the POCRT group. Likewise, we observed a DFS of 18months and a 5-year DFS rate of 18.8% in the POCT group. The recurrence hazard ratio in the POCT group was 1.49 (95% CI: 1.008–2.204, P =0.041). Subgroup analysis revealed that POCRT significantly increased the OS rate of the patients with ⩾2 pN2 lymph nodes ( P =0.021). The POCRT group had a significantly lower local relapse ( P =0.009) and distant metastasis ( P =0.05) rates as compared to that of the POCT group. One case died of pyemia and 9 cases suffered from grade 3 and 4 acute radiation esophagitis. The two groups had similar and tolerable hematologic toxicities. Conclusions Compared with POCT, POCRT increased both local/regional and distant DFS rate of the patients with IIIA-pN2 NSCLC, but not the OS rate. Considering the relatively small sample size of the current study, caution should be taken when adopting the conclusions.

This study explored whether docetaxel/cisplatin and radiotherapy (TP-R) increases overall survival (OS) and recurrence-free survival (RFS) compared to single-agent cisplatin and radiotherapy (C-R) in patients with high-risk early-stage cervical cancer post surgery.Patients with clinical stage IB and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or the diameter of the primary tumor ≥4 cm and/or depth of interstitial infiltration ≥1/2 and/or lymphovascular space invasion were eligible for this study. Patients were randomized to receive C-R or TP-R. Radiotherapy in both groups was external radiation (46-54 Gy) followed by high-dose rate brachytherapy (12-24 Gy). Patients were given cisplatin (40 mg/m(2)) every week for five cycles (C-R group) or docetaxel (30 mg/m(2)) and cisplatin (30 mg/m(2)) every week for five cycles (TP-R group).Between 2003 and 2008, 320 patients were entered onto the study. Final analyses included 285 patients. One hundred and forty patients comprised the C-R group and 145 were in the TP-R group. The 5-year OS were 74.3 % in the C-R group and 82.8 % in the TP-R group. The hazard ratio (HR) for death was 0.65 in the TP-R group (95 % CI: 0.39-1.09, P = 0.098). The RFS were 69.3 % in the C-R group and 79.3 % in the TP-R group, and the HR for recurrence was 0.64 in the TP-R group (95 % CI: 0.40-1.03, P = 0.061). Recurrence rates were similar in both groups (27 in the C-R group and 18 in the TP-R group, P = 0.112). The seriousness of late side effects was similar in the two groups, with a higher rate of reversible hematological effects in the TP-R group.Compared with single-agent cisplatin and radiotherapy, docetaxel/cisplatin in combination with radiotherapy does not increase OS but has the trend of increasing RFS in patients with high-risk early-stage cervical cancer. However, docetaxel/cisplatin in combination with radiotherapy is associated with a higher incidence of side effects, this effect was reversible, and the incidence of late side effects was similar in the two treatment groups.

To investigate chronic hepatitis B (CHB) patients infected with the antiviral-resistant rtA181 mutation hepatitis B virus (HBV) who have been unresponsive to general therapy to determine the effects of individualized therapy.Fifty-four patients with confirmed rtA181 mutation and who experienced virological breakthrough during nucleus(t)ide analogue (NUC) treatment were enrolled in this prospective cohort study. Their serum levels of HBV DNA, hepatitis B surface antigen (HBsAg), and alanine transaminase (ALT) were tested. Each patient was genotyped by pyrosequencing for 10 mutation sites in the HBV P gene that have been previously correlated to NUC efficacy. Each patient's antiviral therapy and response history was analyzed in regard to their particular mutation pattern. The serological index was determined for carriers of the rtA181T/V mutation. The secondary individualized treatment included adding/switching to entecavir (ETV; group A) or adding telbivudine (LdT; group B) upon confirmation of drug resistance. Effect of individualized treatment was analyzed by T test and Mann-Whitney U test for continuous variables with normal or skewed distributions, respectively. Categorical variables were analyzed by the Chi-squared ( x² ) or Fisher's exact tests.The rtA181T mutation was found in 64.8% (35/54) of patients with rtA181 mutation HBV. The most frequent previously administered medications were adefovir dipivoxil (ADV) and lamivudine (LAM). Multi-site rtA181 mutations occurred more frequently in the patients with multi-NUCs history (57.6%) than in those with single NUCs history (28.6%) (x²=4.342, P less than 0.05). Serum HBV DNA level at virological breakthrough was lower than that at baseline of the first antiviral treatment (5.66+/-1.01 vs. 6.75+/-0.81 log10 copies/ml; t=-4.210, P less than 0.01). The serum HBsAg level was higher in carriers of the rtA181T mutation than in carriers of the rtA181V mutation (3.80+/-0.45 vs. 3.46+/-0.60 log10 IU/ml; t=2.109, P less than 0.05). In patients with serum HBV DNA more than or equal to 6 log10 copies/ml at viral breakthrough, 100% (8/8) of patients in the secondary treatment group A and 75% (3/4) patients in the secondary treatment group B exhibited virological response at week 24 after intervention. Undetectable HBV DNA was achieved in three patients of group A and one patient of group B. In patients with serum HBV DNA less than 6 log10 copies/ml at viral breakthrough, 100% (14/14) of patients in group A and 71.4% (5/7) of patients in group B exhibited biological response at week 24 after intervention. The serum HBV DNA level decreased to undetectable levels in 12 patients of group A and four patients of group B.The rtA181 mutation pattern correlates with previous antiviral therapy response. In addition, multi-site rtA181 mutations occur more frequently in patients with a history of multi-NUCs therapy. Adding or switching rtA181 carriers to ETV produces a more robust virological suppression than adding LdT.

Background and purpose The role of postoperative chemoradiotherapy in the treatment of patients with gastric cancer with D2 lymph node curative dissection is not well established. In this study, we compared postoperative intensity-modulated radiotherapy plus chemotherapy (IMRT-C) with chemotherapy-only in this patient population. Materials and methods We randomly assigned patients with D2 lymph node dissection in gastric cancer to IMRT-C or chemotherapy-only groups. The adjuvant IMRT-C consisted of 400mg of fluorouracil per square meter of body-surface area per day plus 20mg of leucovorin per square meter of body-surface area per day for 5days, followed by 45Gy of IMRT for 5weeks, with fluorouracil and leucovorin on the first 4 and the last 3days of radiotherapy. Two 5-day cycles of fluorouracil and leucovorin were given 4weeks after the completion of IMRT. Chemotherapy-only group was given the same chemotherapy regimens as IMRT-C group. Results The median overall survival (OS) in the chemotherapy-only group was 48months, as compared with 58months in the IMRT-C group; the hazard ratio for death was 1.24 (95% confidence interval, 0.94–1.65; P =0.122). IMRT-C was associated with increases in the median duration of recurrence-free survival (RFS) (36months vs. 50months), the hazard ratio for recurrence was 1.35 (95% confidence interval, 1.03–1.78; P =0.029). COX multivariate regression analysis showed that lymph node metastasis and TNM stage were both the independent prognostic factors. Rates of all grade adverse events were similar in the two treatment groups. Conclusions IMRT-C improved RFS, but did not significantly improve OS among patients with D2 lymph node dissection in gastric cancer. Using IMRT plus chemotherapy was feasible and well tolerated in patients with gastric cancer after D2 resection.

To investigate the clinical effect of orbit blowout fracture reconstruction under nasal endoscope.Forty-one cases of orbit fracture were reconstructed for lost or damaged orbit under nasal endoscope through maxillary sinus, ethmoidal sinus or the both.Among the 35 cases of orbit blowout fracture, enophthalmos in 33 cases were completely improved, 29 cases were symmetrical to normal eye after operation without diplopia except that 6 cases had slight enophthalmos accompanied with slight diplopia. Among these 6 cases, 4 cases returned to normal without diplopia 6 months after operation. In the 6 cases of orbit non-blowout fracture, 4 cases were symmetrical to normal eye after operation without enophthalmos, diplopia and facial malformation. One case had slight enophthalmos and diplopia, 1 case had slight enophthalmos with slight facial malformation.The surgery under nasal endoscope is safe and credible. The method can be easily mastered and its complication is less.

Recent evidences indicate that retinal muller cells exhibit retinal progenitor characteristics under certain condition in chick, rat and human. However, there is no report on nonhuman primate, a close relative to human. In this study, we first established a muller cell line of rhesus monkey expressing GS, vimentin, CRALBP, EGFR, barely GFAP, which resemble the expression profile of human muller cells, differ from that of rodent. Expression of pax6, nestin, sox2, otx2, six6, and six3 was detected after one week culture in neural stem cell medium. Further culture with retinoic acid induced some cells differentiate toward neuron. These results suggest that primate muller cell is capable of dedifferentiating to retinal progenitors, which may serve as a potential cell source for cell therapy to treat retinal degenerative diseases.

Rhesus monkey embryonic stem (rES) cells have similar characteristics to human ES cells, and might be useful as a substitute model for preclinical research. Notch signaling is involved in the formation of bile ducts, which are composed of cholangiocytes. However, little is known about the role of Notch signaling in cholangiocytic commitment of ES cells. We analyzed the effect of Notch signaling on the induction of cholangiocyte-like cells from rES cells. About 80% of definitive endoderm (DE) cells were generated from rES cells after treatment with activin A. After treatment with BMP4 and FGF1 on matrigel coated wells in serum-free medium, rES-derived DE gave rise to cholangiocyte-like cells by expression of cholangiocytic specific proteins (CK7, CK18, CK19, CK20, and OV-6) and genes (GSTPi, IB4, and HNF1β). At the same time, expression of Notch 1 and Notch 2 mRNA were detected during cell differentiation, as well as their downstream target genes such as Hes 1 and Hes 5. Inhibition of the Notch signal pathway by L-685458 resulted in decreased expression of Notch and their downstream genes. In addition, the proportion of cholangiocyte-like cells declined from approximately 90% to approximately 20%. These results suggest that Notch signaling may play a critical role in cholangiocytic development from ES cells.

To investigate changes of T lymphocytes subsets in children with infectious mononucleosis (IM) and the effects of different interventions.Forty-eight children with IM were enrolled, 28 cases were assigned to the group treated with intravenous immunoglobulin (IVIG) 400 mg/(kg x d) for 5 continuous days or IVIG 1 g/(kg x d) for 2 continuous days, the remaining 20 cases were treated with ganciclovir (GCV) 5-10 mg/(kg x d) for 5 consecutive days. All these children were given general supportive therapies. Twenty healthy children from healthcare clinic serviced as control group.CD4 (%), CD8 (%) and the CD4/CD8 ratio in healthy control group were (34.12 +/- 3.53)%, (26.22 +/- 4.43)% and (1.41 +/- 0.3), in IVIG group were (24.2 +/- 4.3)%, (36.4 +/- 6.8)% and (0.72 +/- 0.12), and in GCV group were (23.7 +/- 5.1)%, (37.3 +/- 7.8)% and (0.67 +/- 0.13), respectively. CD4 (%), CD8 (%) and the ratio CD4/CD8 in the control group were significantly different from those in both groups with IM (P0.05). Compared with pre-treatment levels, the 28 cases treated with IVIG had significant improvement, the CD4 (%) increased, CD8 (%) decreased and the ratio of CD4/CD8 increased after treatment (P0.05). However, 20 cases in GCV treatment group made less changes (P0.05) . Meanwhile, the clinical symptoms and signs in the IVIG group were improved faster than that in the GCV group (P0.05). The rate of remission in IVIG group was 88.7% vs. 59.2% of GCV group (P0.05); the hospital days in IVIG group were (9.2 +/- 4.3) days vs. (13.8 +/- 5.1) days in the GCV (P0.05).It is indicated that the subsets of T lymphocytes in peripheral blood are obviously abnormal in children with IM caused by EBV infection in acute phase. IVIG can regulate the immunological derangements of T lymphocytes subsets, on which anti-viral therapy alone may have little impact.

To determine the role of serum leptin in infants with wheezing after respiratory syncytial virus infected.43 infants infected with RSV were given blood samples to detect leptin concentration with radioimmunoassays (RIA) within 24 hours after admission into hospital, discharged and 12 weeks later. Then, they were followed up for 2 years. 10 healthy children of the same age served as controls.41.9% infants developed asthma after infected with RSV. Compared to control group, the serum level of leptin in the asthma group and non-asthma group were significantly higher before treatment (t = 3.41 and 2.64 respectively, P0.05). When they were discharged, the serum level of leptin in the asthma group was significantly higher than that in non-asthma group and control group (t = 5.74 and 6.23, respectively, P0.05). 12 weeks later, the serum level of leptin in the asthma group was still significantly higher than that in non-asthma group and control group (t = 6.32 and 6.11, respectively, P0.05), but there were no difference between non-asthma group and control group (t = 0.81, P0.05).The serum level of leptin in infants with asthma after RSV infected was higher than that in healthy and non-asthma children. Persistent higher level of leptin may play an important role in infants with asthma after RSV infected.

To investigate the effects of Dermatophagoides pteronyssinus allergen-specific immunotherapy (SIT) on the prognosis of asthmatic children.Sixty-five children with established diagnosis of allergic asthma to dust mite were enrolled in this study, of whom 42 children received treatment with standardized SIT for 12 month and the other 23 served as the control group with inhaled corticosteroids according to Global Initiative for Asthma (GINA). The serum levels of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) were detected and the pulmonary functions examined before and after the one-year treatment in all the patients.After the one-year treatment with SIT, the asthmatic children showed obviously reduced serum levels of IL-4, significantly increased IFN-gamma levels and the IFN-gamma/IL-4 ratio (P0.05), and markedly improved pulmonary functions (FVC, pre-FEV1% and pre-PEF%) (P0.05). In the control group, the children exhibited significantly increased IFN-gamma levels and IFN-gamma/ IL-4 ratio (P0.05) without obvious reduction of serum IL-4 levels or pulmonary function improvement (P0.05). With comparable basic pulmonary functions in the two groups before the treatment, the children in SIT group showed significantly greater improvement in the pulmonary functions than those in the control group after the one-year treatment.The one-year treatment with SIT can significantly improve the pulmonary functions of children with allergic asthma, and this effect is attributed to the regulation of Th1/Th2 cell balance and inhibition of asthmatic airway remodeling by SIT.

Airway remodeling is the specific pathological characteristics of asthma, which is related to the clinical symptoms, pulmonary function, and airway hyperreactivity. This study aimed at exploring the effects of dermatophagoides pteronyssinus allergen-specific immunotherapy (SIT) on the serum interleukin (IL)-13 and pulmonary functions in asthmatic children.Fifty-eight pediatric asthma patients allergic to dust mite participated in this study. Thirty-five children received SIT with a standardized dermatophagoides pteronyssinus extract for one year (SIT group), and the other 23 children treated with inhaled corticosteroids (ICS group) according to the Global Initiative for Asthma (GINA) for one year. Serum levels of IL-13, IL-4 and interferon (IFN)-gamma were examined and the pulmonary functions were checked before and after the treatment.After the treatment, the number of emergency visiting for asthma attack in SIT group was significantly less than that in ICS group. The serum levels of IL-4 and IL-13 were clearly reduced, IFN-gamma and the ratio of IFN-gamma/IL-4 were significantly increased, the pulmonary functions (forced vital capacity (FVC), forced expiratory volume in one second percentage (FEV(1)%) and peak expiratory flow percentage (PEF%) were significantly improved in the SIT group. Meanwhile, IFN-gamma and the ratio of IFN-gamma/IL-4 were greatly increased, but serum levels of IL-4 and IL-13 had less changes, the pulmonary functions (FVC, FEV(1)% and PEF%) were poorly improved in ICS group. The basic pulmonary functions in both groups were at the same level, which had made more improvement in SIT group than in ICS group one year later.One year of dermatophagoides pteronyssinus SIT can significantly reduce the frequencies of emergency visiting for asthma attack and improve the pulmonary functions of children with allergic asthma, and that is attributed to SIT, which can reduce the levels of IL-4 and IL-13 and regulate the imbalance of the Th1/Th2 cells in asthmatic children. All of these might be effective in preventing the asthmatic airway from remodeling.

To evaluate the efficacy of 3 commonly used protocols for management of acute exacerbation of asthma in children.Totally 113 asthmatic children were randomized into 3 groups. In group A (53 cases), the children were treated with inhalation of nebulized budesonide suspension plus salbutamol and ipratropium bromide twice daily for 5 days; in group B (41 cases), budesonide plus salbutamol and ipratropium aerosol was administered, and in group C (29 cases), dexathmisone plus aminophylline injection was given once daily for 5 days. All the children received basic treatment with fluid infusion, antibiotics or/and anti-virus medications.The children in both groups A and C showed effectively controlled asthma attack, with significant differences in the therapeutic effects (P0.05). In contrast, only a few children showed improvement in group B, suggesting the ineffectiveness of the treatment.Nebulized medicine is one of the best means for management of acute asthma exacerbation in children, and inhalation of budesonide suspension plus salbutamol and ipratropium bromide can effectively relieve the asthmatic symptoms in these children with good compliance and convenient administration.

To investigate changes in the levels of Th2 cytokine interleukin-4 (IL-4), Th1 cytokine interferon-gamma (IFN-gamma), and TNF-alpha in serum of newborn infants with cytomegalovirus (CMV) pneumonia.Twenty-five neonatal cases who were positive for serum IgM antibody to CMV by ELISA were divided into IVIG intervention group and ganciclovir intervention group, and 15 healthy neonates were enrolled into the control group. The levels of IL-4, IFN-gamma, and TNF-alpha were detected by using double antibody ELISA for the control group and the intervention groups at the beginning and end of treatment.The levels of IFN-gamma and TNF-alpha in patients with CMV pneumonia were higher than that in the healthy neonates, while the levels of IL-4 were lower(t= 2.65 and 3.16, p less than 0.05). The level of IL-4 in patients with CMV pneumonia was significantly lower than that of the healthy neonates (t= 2.49, p less than 0.05). There was no significant difference in the levels of IFN-gamma, IL-4 and TNF-alpha between IVIG intervention group and ganciclovir intervention group at the beginning of treatment (t= 1.85, 1.71, 1.76, p greater than 0.05). In IVIG intervention group, the levels of IFN-gamma and TNF-alpha significantly decreased after treatment (t=3.98, 5.16, p less than 0.01), the level of IL-4 in this group was higher than that before treatment (t= 2.55, p less than 0.05). In ganciclovir group, the level of IFN-gamma and TNF-alpha did not change after treatment (t=1.75, 1.16, p greater than 0.05), the level of IL-4 in this group was higher than that before treatment (t= 2.39, p less than 0.05).There seems to be an imbalance of Th1 and Th2 cytokines secretion in the infants with CMV pneumonia and, which may lead to immune-inflammation injury. IVIG can regulate imbalanced Th1/Th2 activities, therefore, immunomodulatory treatment should be applied besides antiviral therapy.

To investigate the effect of polysaccharide nucleic acid of BCG (BCG-PSN) injection on immune and pulmonary function in asthmatic children complicated with allergic rhinitis.Thirty-seven cases were separated at random into two groups, the BCG-PSN group (17 cases) was treated with BCG-PSN plus inhaled glucocortisteriods, and the control group (20 cases) was treated with inhaled glucocortisteriods only. The children in both groups were followed up for 6 months to record their lung function, allergic rhinitis scores, frequency of asthmatic attacks and respiratory infection. The levels of interleukin (IL)-4, interferon-gamma (IFN-g) and plasma total IgE were detected by using double antibody sandwich ELISA at the beginning and the end of treatment.In comparison with the control group, after treatment, the levels of IFN-g and the ratio of IFN-g/IL4 in the BCG-PSN group significantly increased, whereas the level of IL-4 and the plasma total IgE significantly decreased (P less than 0.05), while those of the control group had no significant change. The lung function of both groups had significant improvement (p less than 0.05). The frequencies of asthmatic attacks in BCG-PSN and control groups were 0.81 +/- 0.20 vs. 1.72 +/- 0.80, and the difference was statistically significant. The frequencies of respiratory tract infection in BCG-PSN and control groups were 1.15 +/- 0.55 vs. 3.21 +/- 0.73, the difference was significant.BCG-PSN may be able to correct the imbalance of Th1/Th2 and improve the lung function of children with asthma complicated with allergic rhinitis, which suggest that the immune adjusting treatment should be emphasized besides anti-inflammation therapy.

To assess the value of immunoregulants in improving the prognosis of infants with wheezing.Forty-three infants with wheezing with given oxygen support, injection or inhalation of glucocorticosteroids or bronchodilatator to relieve the symptoms. Of these infants, 24 received immunoregulant treatment with bronchovaxom at the daily dose of 3.5 mg for 10 days every a month for a treatment course of 3 months. The other 19 infants were managed with budesonide aerosol at 200 microg once or twice daily for 3 months (basic treatment group). All the infants were followed up for 1 year to record the number of wheezing episode and infections. Ten healthy infants were also included in this study as the control group.In infants with bronchovaxom treatment, 25% reported more than 3 wheezing episodes within the 1-year follow-up, a rate significantly lower than that in the control group (63.2%, Chi(2)=6.344, P0.05). The episodes of respiratory infection were similar between bronchovaxom group and the healthy control group (t=0.72, P0.05), but significantly higher in the basic treatment group than in bronchovaxom and the healthy control group (t=3.11 and 3.92, respectively. P0.05).Bronchovaxom can effectively reduce the recurrence of wheezing and respiratory infections in the infants with wheezing attack to reduce the risks of asthma development.

To investigate the effects of leukotriene receptor antagonist on the levels of Th1 and Th2 cytokines and the serum cysteinyl leukotrenes (CysLTs) in infants and young children with respiratory syncytial virus (RSV) pneumonia.Thirty-seven infants and young children with RSV pneumonia were divided into two groups after discharge. The cases in group 1 (n=24) were treated with a leukotriene receptor antagonist, Singulair 4 mg once daily for 12 weeks; the cases in group 2 (n=13) were treated with budesonide aerosol 200 ug once or twice daily for 12 weeks. The serum CysLTs, IFN-gamma and IL-4 were detected with enzyme_linked immunosorbent assays (ELISA) for all the 37 cases, and 10 healthy infants of the same age served as controls.The serum CysLTs level in the cases with RSV pneumonia was significantly higher than that in controls (P0.05). There was an imbalance in expression of Th1 and Th2 cytokines (IFN-gamma and IL-4 ) in these cases. Both Singulair and budesonide aerosol could correct the imbalance of Th1 and Th2 cytokines. The serum CysLTs level declined after treatment with Singulair in 24 cases, but no significant change occurred after treatment with budesonide aerosol in the remaining 13 cases.The serum CysLTs level in children with RSV pneumonia was higher than that in healthy children, and there was an imbalance of Th1 and Th2 cytokines in these infants, which was similar to those with asthma. Leukotriene receptor antagonist may be effective in preventing children with RSV pneumonia from evolving into asthma.

To investigate the correlation between the reticular basement membrane thickness and the airway wall remolding in asthma patients.Lung tissues were obtained from 5 patients who died from asthma, 3 males and 2 females, aged 45 +/- 16 (fatal asthma group), 5 asthmatics who died of diseases unrelated to asthma, 3 males and 2 females, aged 47 +/- 13, (non-fatal asthma group), and 5 dead patients without asthma, 3 males and 2 females, aged 24 +/- 14 (control group) to select 41, 38, and 43 transverse sections of tracheae respectively. The samples of tracheae were divided into cartilaginous and membranous airways by light microscopy (x100). The thickness of reticular basement membrane and the dimensions of the airway wall, including the smooth muscle area, submucosal gland area, inner and outer wall areas, and lumen area were measured. The correlations of reticular basement membrane thickness with the airway changes were analyzed.The reticular basement membrane was significantly thicker in both cartilaginous and membranous airways in the fatal and non-fatal asthma groups than in the control group (all P0.05). The submucosal gland area of the fatal asthma group was significantly larger than those of the non-fatal asthma group and control group (both P0.05). The inner wall area of the cartilaginous airway of the fatal asthma group was significantly larger than that of the non-fatal asthma group (P0.05); however, the inner wall area of the membranous airway of the fatal asthma group was not significantly different from that of the non-fatal asthma group. The outer wall areas of cartilaginous and membranous airways of the fatal asthma group were both significantly larger than those of the other 2 groups (all P0.05). There was no significant difference in the lumen areas of cartilaginous and membranous airways between the fatal and non-fatal asthma groups. The reticular basement membrane thickness was correlated with the smooth muscle area (P0.05), submucosal gland area (P0.05), and inner wall area (P0.01) of the corresponding bronchi in regard to the cartilaginous airway; and was correlated with the smooth muscle area (P0.05) and inner wall area (P0.01) of the corresponding bronchi in regard to the membranous airway, but was not correlated with the airway size, lumen area, and outer wall area in regard to the 2 kinds of airways.The reticular basement membrane thickness of central airway reflects the airway remolding of the central airway and the changes of smooth muscle and inner wall of the peripheral airway. It is worthwhile to do end bronchial biopsy to measure the reticular basement membrane thickness so as to assess the pathology of the airway and to conduct long-term follow-up among the asthma patients.

To investigate the effective therapeutic method of human cytomegalovirus (HCMV) hepatitis in children.Twenty-five children with HCMV hepatitis were randomly assigned to a treated group (n=13) or a control group (n=12). Both groups were treated with prednisone, glucurone, luminal and Xiaoyanlidanpian. But the treated group was given ganciclovir (GCV) + intravenous immunoglobulin (IVIG) in addition. Each infant of the two groups was checked for blood routine, liver function and HCMV copy numbers on admission and before discharge. They were seen at the third, sixth and ninth month after discharge. On each visit blood specimens were collected for HCMV copy numbers (fluorescence quantitative PCR, FQ-PCR).The viral load of the treated group decreased significantly. A significant difference in viral copy numbers was found between the two groups on admission, discharge, and third, sixth and ninth month after discharge (P less than 0.001). The number of HCMV DNA copy fell to 10(3) copies/ml on discharge while that of the control group fell to the same level after the third month. The differences between the two groups in the length of hospitalization, time of initial jaundice disappearance and complete disappearance were statistically significant (P less than 0.05). The need for transfusion in the treated group was significantly less than that in the control group (chi-square=4.012, P less than 0.05).Combination of GCV with a high dosage of IVIG to treat HCMV active infection could decrease viral load remarkably; The duration of disease, severity of symptoms, degree of anemia and the need for blood transfusion were reduced. No adverse effects related to the combination of GCV with IVIG therapy were observed.

AIM: To investigate the photodynamic inhibitory effects of Elsinochrome A (EA), Hypocrellin A (HA) and Hypocrellin B (HB) on human colorectal carcinoma Hce-8693 cells and rhesus monkey embryonic stem R366.4 cells, via inducing apoptosis. METHODS: EA, HA and HB were extracted from metabolites of Hypomyces (Fr) Tul.Sp. R366.4 cells or Hce-8693 cells were cultured with different concentrations of EA, HA or HB respectively, irradiated and incubated with fresh medium for 2 h. Cell cycle analysis was performed by flow cytometry (FCM). Data were expressed as means ± SD and analysis of variance and Student’ t-test for individual comparisons. RESULTS: The photodynamic bioactivity of EA was first reported in this study. After irradiation for 5 min, 6 min, 10 min or 20 min, photoactivated EA at lower concentrations, which were 10-7 Mol/L, 10- 6 Mol/L, 10 - 5 Mol/L respectively, had no cytotoxic effects on R366.4 ES cells. Whereas, all of the three perylenequinones could induce apoptosis with a dose-dependent manner when Hce-8693 cells were incubated with photoactivated EA, HA and HB respectively. When Hce-8693 cells were incubated with EA at 10-6 Mol/L and irradiated 5 min, 6 min, 10 min and 20 min respectively, the rates of EA-induced apoptosis were 0, 0, 13.4% and 40.5%. While the rates of HA-induced apoptosis were 29.5%, 32.0%, 40.2% and 22.6%. And the rates of HB-induced apoptosis were 0, 0, 0 and 13.7% respectively. Meanwhile, after 10-5 Mol/L treatment, the rates of EA-induced apoptosis were 32.7%, 19.3%, 26.4% and 52.7%, the rates of HA-induced apoptosis were 47.2%, 39.1%, 45.2% and 56.6%, and the rates of HB-induced apoptosis were 0, 0, 20.0% and 13.9% respectively. CONCLUSION: EA, HA and HB have significant anti-cancer activity. The order of photodynamic inhibitory effects on tumor cells would be approximately HA > EA > HB. The molecular mechanisms of apoptosis may not be induced by reactive oxygen species and are worth further investigation.