Gastric cancer secreted miR-214-3p inhibits the anti-angiogenesis effect of apatinib by suppressing ferroptosis in vascular endothelial cells.

Different from necrosis, apoptosis, autophagy and other forms of cell death, ferroptosis is a mechanism that catalyzes lipid peroxidation of polyunsaturated fatty acids under the action of iron divalent or lipoxygenase, leading to cell death. Apatinib is currently used in the third-line standard treatment of advanced gastric cancer, targeting the anti-angiogenesis pathway. However, Apatinib-mediated ferroptosis in vascular endothelial cells has not been reported yet. Tumor-secreted exosomes can be taken up into target cells to regulate tumor development, but the mechanism related to vascular endothelial cell ferroptosis has not yet been discovered. Here, we show that exosomes secreted by gastric cancer cells carry miR-214-3p into vascular endothelial cells and directly target zinc finger protein A20 to negatively regulate ACSL4, a key enzyme of lipid peroxidation during ferroptosis, thereby inhibiting ferroptosis in vascular endothelial cells and reducing the efficiency of Apatinib. In conclusion, inhibition of miR-214-3p can increase the sensitivity of vascular endothelial cells to Apatinib, thereby promoting the antiangiogenic effect of Apatinib, suggesting a potential combination therapy for advanced gastric cancer.

[The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study].

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

Association of oxidative stress and Kashin-Beck disease integrated Meta and Bioinformatics analysis.

OBJECTIVE: To explore the association between oxidative stress (OS) and Kashin-Beck disease (KBD). METHODS: Terms associated with "KBD" and "OS" were searched in the six different databases up to October 2021. Stata 14.0 was used to pool the means and standard deviations using random-effect or fixed-effect model. The differentially expressed genes in the articular chondrocytes of KBD were identified, the OS related genes were identified by blasting with the GeneCards. The KEGG pathway and gene ontology enrichment analysis was conducted using STRING. RESULTS: The pooled SMD and 95% CI showed hair selenium (-4.59; -6.99, -2.19), blood selenium (-1.65; -2.86, -0.44) and glutathione peroxidases (-4.15; -6.97, -1.33) levels were decreased in KBD, whereas the malondialdehyde (1.12; 0.60, 1.64), nitric oxide (2.29; 1.31, 3.27), nitric oxide synthase (1.07; 0.81, 1.33) and inducible nitric oxide synthase (1.69; 0.62, 2.77) were increased compared with external controls. Meanwhile, hair selenium (-2.71; -5.32, -0.10) and glutathione peroxidases (-1.00; -1.78, -0.22) in KBD were decreased, whereas the malondialdehyde (1.42; 1.04, 1.80), nitric oxide (3.08; 1.93, 4.22) and inducible nitric oxide synthase (0.81; 0.00, 1.61) were elevated compared with internal controls. Enrichment analysis revealed apoptosis was significantly correlated with KBD. The significant biological processes revealed OS induced the release of cytochrome c from mitochondria. The cellular component of OS located in the mitochondrial outer membrane. CONCLUSIONS: The OS levels in KBD were significantly increased because of selenium deficiency, OS mainly occurred in mitochondrial outer membrane, released of cytochrome c from mitochondria, and induced apoptotic signaling pathway.

[Effect of HBV infection pattern on prevalence of fatty liver disease in Jinchang cohort].

Objective: To investigate the influence of HBV infection on the prevalence of fatty liver disease in Jinchang cohort and provide theoretical evidence for the prevention and treatment of fatty liver disease. Methods: Epidemiological investigation, laboratory examination and abdominal ultrasound were conducted in the baseline population of Jinchang cohort to collect the basic data, the differences in the prevalence of fatty liver disease under different HBV infection patterns were described and compared and the influence of different HBV infection patterns on the prevalence of fatty liver disease were evaluated by using logistic regression analysis. Results: The baseline Jinchang cohort population totaled 45 605, including 27 917 males and 17 688 females. The male to female ratio was 1.6∶1. The mean age of the overall population was 46.49 years. Among the 8 common HBV infection modes in the Jinchang cohort, the prevalence of fatty liver was low in HBsAg, HBeAg and HBcAb positive, HBsAg and HBcAb positive, and HBsAg, HBeAb and HBcAb positive groups. For 4 serum markers of HBV infection, the prevalence of fatty liver disease in HBsAg and HBeAg positive groups was lower than that in HBsAg and HBeAg negative groups. Logistic regression analysis showed that being HBsAg and HBcAb positive (OR=0.61, 95%CI: 0.39-0.98) and HBsAg, HBeAg and HBcAb positive (OR=0.52, 95%CI: 0.30-0.89) could reduce the risk for fatty liver disease. Conclusion: Acute HBV infection reduces the prevalence of fatty liver disease, and the reason may be related to the disturbance of the body's fat metabolism by active HBV replication.

[Analysis on influencing factors for nonalcoholic fatty liver disease in Jinchang cohort].

Objective: To explore the influencing factors for non-alcoholic fatty liver disease (NAFLD) in Jinchang cohort, and provide scientific basis for the prevention and control of NAFLD. Methods: A total of 20 051 patients without fatty liver at baseline survey and met the inclusion criteria in Jinchang cohort were selected as study subjects. Prospective cohort study and Cox regression analysis were used to investigate the influencing factors for NAFLD, and the dose-response relationship between related biochemical indicators and NAFLD risk was studied by restricted cubic spline method. Results: The incidence of NAFLD was 42.37/1 000 person years. Multivariate Cox regression analysis showed that being worker and technical personnel (being worker:HR=0.84,95%CI:0.70-0.99;being technical personnel:HR=0.73,95%CI:0.56-0.95), tea drinking (current drinking:HR=0.86,95%CI:0.78-0.94;previous drinking: HR=0.52,95%CI: 0.31-0.86), exercise (occasionally: HR=0.79, 95%CI: 0.68-0.91;frequently:HR=0.60,95%CI:0.52-0.69), low body weight (HR=0.10, 95%CI: 0.05-0.22), daily intake of dairy products >300 ml/day (HR=0.78, 95%CI: 0.71-0.87) and HBV infection (HR=0.77, 95%CI: 0.60-0.99) were the protective factors for NAFLD, while being internal or office workers (HR=1.84, 95%CI: 1.46-2.31), income ≥2 000 yuan (2 000- yuan: HR=1.32, 95%CI: 1.04-1.66; ≥5 000 yuan: HR=1.72, 95%CI:1.11-2.66), bachelor degree or above (HR=1.35,95%CI:1.03-1.76), overweight (HR=2.31, 95%CI:2.08-2.55), obesity (HR=3.95, 95%CI: 3.42-4.56), impaired fasting blood glucose (HR=1.31, 95%CI:1.17-1.47), diabetes (HR=1.53, 95%CI: 1.30-1.80), increased TC (HR=1.37,95%CI:1.24-1.52), increased TG (HR=1.79,95%CI: 1.62-1.98), decreased HDL-C (HR=1.29, 95%CI: 1.14-1.45), increased ALT (HR=1.13, 95%CI: 1.01-1.26) and high-fat diet (HR=1.24, 95%CI: 1.11-1.40) were the risk factors for NAFLD. Moreover, TC, TG, HDL-C, ALT and FPG all showed good dose-response relationship with the incidence of NAFLD. Conclusion: Occupation, education level, income level, tea drinking, exercise, BMI, FPG, blood lipid, ALT, HBV infection and diet were related to the incidence of NAFLD.

[Correlation between nUGT1A1 gene polymorphisms and adverse events of irinotecan plus S-1 for patients with recurrent or metastatic esophageal squamous cell carcinoma: a prospective, open-label, randomized controlled trial (ESWN 01)].

Objective: To investigate the correlation between UGT1A1 polymorphisms and the irinotecan plus S-1 regimen-induced toxicities in Chinese advanced esophageal squamous cell carcinoma (ESCC) patients. Methods: A total of 46 recurrent or metastatic ESCC patients selected from ESWN 01 trial were randomly assigned to irinotecan plus S-1 group [intravenous infusion of irinotecan (160 mg/m(2)) on day 1 and oral S-1 (80-120 mg) on days 1-10, repeated every 14 days]. Peripheral venous blood at baseline was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6 and UGT1A1*28 were analyzed by polymerase chain reaction (PCR) amplification. Irinotecan plus S-1 regimen-induced toxicities of patients with different UGT1A1 polymorphisms were observed. The correlation between UGT1A1 polymorphisms and the adverse effects was analyzed. Results: Among the 46 patients, the numbers of UGT1A1*6 wild type genotype (GG), mutant heterozygote (GA) and mutant homozygote (AA) were 30, 15 and 1, while those with UGT1A1*28 wild type genotype (TA6/6), mutant heterozygote (TA6/7) and mutant homozygote (TA7/7) were 36, 8 and 2, respectively. Only one patient with UGT1A1*6 AA genotype occurred grade 3 diarrhea, while one of the 2 patients with UGT1A1*28 TA7/7 genotype occurred grade 4 diarrhea. No neutropenia was observed in the patient with UGT1A1*6 AA genotype, however, both of the two patients with UGT1A1*28 TA7/7 genotype occurred grade 3-4 neutropenia. Patients with UGT1A1*28 genetic polymorphism (TA 6/7 or TA7/7) had a higher response rate compared with wild-type TA6/6 carriers. (55.6% versus 26.5%). Conclusions: The homozygous genotype of UGT1A1*6 AA and UGT1A1*28 TA7/7 are rare (<5%) in Chinese ESCC population. Not all homozygous AA and TA7/7 carriers occur severe dose limited toxicities (DLT) when treated with irinotecan (160 mg/m(2)) plus S-1 regimen for 2 weeks. However, it's still necessary torigorously observe the occurrence of severe diarrhea and neutropenia in patients with UGT1A1*6 AA and UGT1A1*28 TA7/7 and adjust the dose timely.

[Value of serum parathyroid hormone in the diagnosis of primary aldosteronism].

Objective: To explore the value of serum parathyroid hormone (PTH) in the diagnosis of primary aldosteronism (PA) and to investigate an optimal cut-off of serum PTH to distinguish PA from nonfunctional adrenal tumor (NFA). Methods: The clinical data of patients with adrenal incidentaloma in Chinese PLA General Hospital from January 1, 2017 to December 31, 2019 were collected. The data of PA and NFA by clinical characteristics and evaluation on endocrine function were retrospectively analyzed. The logistic regression model was used to find the potential risk factors of elevated PTH. The receiver operating characteristic(ROC) curve was used to evaluate the efficacy of PTH in diagnosis of PA and to explore the best cut-off value. Results: A total of 773 patients were included. There were 356 PA patients (203 males, 57.0%), aged (50±11) years and 417 NFA patients (219 males, 52.5%), aged (51±12) years. The serum PTH level in patients with PA was significantly higher than that in patients with NFA [63.1 (48.4, 80.3) ng/L vs 41.7 (34.1, 51.7) ng/L, P<0.05], as well as the proportion of patients with elevated PTH level (47.8% vs 7.2%, P<0.05). Logistic regression analysis showed that having PA and deficiency of Vitamin D were risk factors for PTH elevation (both P<0.05). The ROC curve showed that the best cut-off value of PTH for the diagnosis of PA in patients with vitamin D deficiency was 56.44 ng/L, with a sensitivity of 66.5% and a specificity of 83.0%, and that in patients with normal vitamin D was 48.81 ng/L, with a sensitivity of 70.5% and a specificity of 72.6%. Conclusions: Patients with PA tend to show increased levels of serum PTH compared with NFA patients. The level of serum PTH can be used as one of the valuable indexes in screening of PA.

Evogliptin attenuates bleomycin-induced lung fibrosis via inhibiting TGF-ß/Smad signaling in fibroblast.

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a pulmonary interstitial fibrosis disease. Excessive activation of fibroblasts in the lung contributes to severe alveoli dysfunction and histological destruction. Evogliptin, a dipeptidyl peptidase IV inhibitor, has been widely used to reduce glucose level in type 2 diabetes, whereas evogliptin treatment to fibrosis process of lung IPF is elusive. The study aimed to investigate the mechanism of evogliptin in transforming growth factor-beta (TGF-ß)-activated lung fibroblasts and evaluate the efficacy of evogliptin in lung fibrosis model. MATERIALS AND METHODS: In lung fibroblast culture, the RNA expression of α-SMA in lung fibroblasts was detected, and α-SMA/COL-1 immunofluorescence co-staining after TGF-ß stimulation and evogliptin administration was displayed. Mechanically, the phosphorylation level of Smad2/3 protein in cells was analyzed using Western blotting, and the scratch assay was used to reflect fibroblast proliferation. Furthermore, bleomycin was employed to induce lung fibrosis in mice, and IHC staining and hematoxylin and eosin (HE) & Masson staining were carried out to examine the extracellular matrix (ECM) expression and tissue fibrosis. RESULTS: The results demonstrated that evogliptin treatment attenuated the activation of fibroblasts and collagen deposition following TGF-ß stimulation. Furthermore, the extracellular matrix expression was descended via evogliptin restraining the TGF-ß/Smad pathway. Besides, it was also found that evogliptin affected the proliferation degree of lung fibroblasts. In vivo, the COL-1 and α-SMA were significantly reduced through evogliptin treatment compared with the bleomycin group, and fibroblasts and collagenous fiber were remarkably decreased. CONCLUSIONS: Evogliptin exerts an anti-fibrosis effect on TGF-ß induced lung fibroblast activation, which restrains ECM formation and decreases cell proliferation level in fibroblasts. Moreover, the fibroblast infiltration and collagen deposition were ameliorated following evogliptin administration. Therefore, evogliptin serves as a potential implication to protect lung fibrosis.

[Threshold effects of body mass index on the bone mineral density of Chinese rural women in fluorosis area].

To explore the threshold effect of body mass index (BMI) on bone mineral density (BMD) in Chinese women living in the fluorosis area, we conducted a cross-sectional study and recruited 722 women in rural areas in Henan Province, China. After detection and analyses, we found that compared with the normal BMI group, the risk of osteoporosis in the overweight and obese groups were reduced by 32% and 69%, respectively. Threshold effect analysis showed that BMD was positively correlated with BMI when BMI was 16.8-31.2 kg/m2; while when BMI was greater than 31.2 kg/m2, the correlation reached saturation. The correlation observed between low-to-moderate fluoride exposure and BMD in rural women was not significant.

[Analysis of sugammadex for antagonistic neuromuscular block in patients with radical resection of lung cancer under thoracoscope].

Objective: To investigate the efficacy and safety of sugammadex for antagonistic neuromuscular block in patients with radical resection of lung cancer under thoracoscope. Methods: One hundred patients undergoing radical resection of lung cancer under thoracoscope in Affiliated Cancer Hospital of Zhengzhou University from March to September in 2019, were randomly divided into control group (group C) and sugammadex group (group S). All patients were anaesthetized (induced and maintained) with intravenous target-controlled infusion of propofol and remifentanil, and intermittent intravenous injection of the neuromuscular block of rocuronium. During the operation, the bispectral index (BIS) was used to monitor the depth of anesthesia, and the neuromuscular block was assessed with TOF. Single-lung mechanical ventilation and double-lumen endotracheal intubation were carried out, and patient-controlled analgesia after operation were enforced. Patients in group C received neostigmine (2 mg) combined with atropine (0.5-1.0 mg) after thoracic closure, while patients in group S received sugammadex (2 mg/kg) at TOF count (≥2) after thoracic closure, and then double-lumen endotracheal tubes were extubated according to extubation indications. At these time points: T(0) (immediate before anesthesia induction), T(1) (immediate before tracheal intubation), T(2) (immediately after thoracic closure), T(3) (1 h after operation), T(4) (6 h after operation), T(5) (24 h after operation), T(6)(48 h after operation), the heart rate(HR) and mean arterial pressure (MAP) were recorded, QT interval (V3 ECG) were measured and calculated, indicators of liver function [alanine transaminase (ALT), aspartate transaminase(AST)], renal function [blood urea nitrogen (BUN), creatinine (Cre)] and clotting function [thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB)] were detected. The duration of operation, postoperative conditions within 48 hours after operation(the time of tracheal tube extubation, respiratory suppression/dysfunction, allergy, nausea and vomiting, itching of skin, abnormal sensation), pathological types and the postoperative hospital stay were recorded. Results: There were no significant differences of the age, sex ratio, body mass index (BMI), American Society of Anesthesiologists (ASA) grading ratio, duration of operation, pathological types and the postoperative hospital stay, HR, MAP and QT interval between two groups (all P>0.05). There were no remarkable differences of the levels of serum histamine, ALT, AST, BUN, Cre, TT, PT, APTT and FIB before and after administration of neuromuscular blockade antagonists (neostigmine or Sugammadex) in the same group patients (all P>0.05), also no significant differences between group C and group S at the same time points (all P>0.05). Average time of tracheal tube extubation in group S [(3.7±1.3) min] was sharply shorter than that in group C [(14.5±4.4) min, t=2.266, P<0.05)]. There were no patients with allergy, skin itching, sensory abnormality in these two groups. There were no significant difference of the incidence of postoperative nausea and vomiting between these two groups. There were 5 patients with respiratory depression in group C and no respiratory depression patient in group S, the difference was statistically significant between these two groups (χ(2)=5.263, P<0.05). Conclusion: Sugammadex is effective for antagonizing the neuromuscular blockade of rocuronium in patients with radical resection of lung cancer under thoracoscope, and can shorten the time of tracheal tube extubation after surgery.

[Prognosis factors analysis of 56 cases of non-Hodgkin's lymphoma originating from the nasopharynx].

Objective:To investigate the prognosis of non-Hodgkin's lymphoma originating from the nasopharynx.Method:The clinical data of 56 patients with a primary diagnosis of non-Hodgkin's lymphoma originating from the nasopharynx treated between January 2010 and December 2015 were studied.The association between clinical parameters and survival rate was evaluated by Kaplan-Meier method and Cox regression model.Result:The 1,3,5-year overall survival were 91.1%, 73.1%,and 49.6% respectively.Single factor analysis displayed that age,Ann-Arbor staging,iactate dehydrogenase,combined with B symptoms at the time of diagnosis,international prognostic index and the expression level of Ki-67 were related to the prognosis factors.Multivariate analysis showed that the international prognostic index greater than or equal to 2 points and the positive rate of Ki-67 greater than or equal to 60% were the independent risk factors for the prognosis of non-Hodgkin's lymphoma originating from the nasopharynx.Conclusion:International prognostic index and the expression level of Ki-67 may be independent prognostic factors for non-Hodgkin's lymphoma originating from the nasopharynx.

Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemo-refractory gastric cancer treated with toripalimab, a PD-1 antibody in phase Ib/II clinical trial NCT02915432.

BACKGROUND: High tumor mutational burden (TMB-H) is correlated with enhanced objective response rate (ORR) and progression-free survival (PFS) for certain cancers receiving immunotherapy. This study aimed to investigate the safety and efficacy of toripalimab, a humanized programmed death-1 (PD-1) antibody, in advanced gastric cancer (AGC), and the predictive survival benefit of TMB and PD-L1. PATIENTS AND METHODS: We reported on the AGC cohort of phase Ib/II trial evaluating the safety and activity of toripalimab in patients with AGC, oesophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma. In cohort 1, 58 chemo-refractory AGC patients received toripalimab (3 mg/kg d1, Q2W) as a monotherapy. In cohort 2, 18 chemotherapy-naive AGC patients received toripalimab (360 mg d1, Q3W) with oxaliplatin 130 mg/m2 qd, d1, capecitabine 1000 mg/m2 b.i.d., d1-d14, Q3W as first-line treatment. Primary end point was ORR. Biomarkers such as PD-L1 and TMB were evaluated for correlation with clinical efficacy. RESULTS: In cohort 1, the ORR was 12.1% and the disease control rate (DCR) was 39.7%. Median PFS was 1.9 months and median OS was 4.8 months. The TMB-H group showed significant superior OS than the TMB-L group [14.6 versus 4.0 months, HR = 0.48 (96% CI 0.24-0.96), P = 0.038], while PD-L1 overexpression did not correlate with significant survival benefit. A 77.6% of patients experienced at least one treatment-related adverse event (TRAE), and 22.4% of patients experienced a grade 3 or higher TRAE. In cohort 2, the ORR was 66.7% and the DCR was 88.9%. A 94.4% of patients experienced at least one TRAE and 38.9% of patients experienced grade 3 or higher TRAEs. CONCLUSIONS: Toripalimab has demonstrated a manageable safety profile and promising antitumor activity in AGC patients, especially in combination with XELOX. High TMB may be a predictive marker for OS of AGC patients receiving toripalimab as a single agent. TRIAL REGISTRATION: ClinicalTrials.gov NCT02915432.

Characterization of bacterial microbiota diversity in Tibetan pigs fed with green forage in Linzhi of the Tibet autonomous region.

The acute shortage of forage resources is a serious problem for Tibetan pigs in the Tibet region, and the composition of feed can change the structure of the intestinal flora. This study first reported the effect of Alfalfa and Chenopodium glaucum feeding on the microbial diversity in Tibetan pigs, contributing to the forage exploitation of Tibetan pigs in the Tibet region.

Potential of piperine in modulation of voltage-gated K+ current and its influences on cell cycle arrest and apoptosis in human prostate cancer cells.

OBJECTIVE: Piperine is an attractive therapeutic alkaloid from black pepper that exhibits a broad spectrum of pharmacological properties over various pathological disorders including cancer. Voltage-gated K+ channels (KV) play an important role in regulating cancer cell proliferation and are considered as potential targets for the treatment of cancer. However, there is a paucity of information with regard to the implication of piperine in KV associated anticancer activities on human prostate cancer cells LNCaP and PC-3 cells. Therefore, the primary objective of the present study was to elucidate the anticancer action of piperine that might be mediated via voltage-gated K+ current (IK) blockade. PATIENTS AND METHODS: Whole-cell patch clamp was used to record the modulatory effects of piperine on IK expressed in LNCaP and PC-3 cells. Moreover, the anticancer activity of piperine was evaluated by MTT assay, flow cytometry and live/dead assay. RESULTS: Piperine significantly inhibited IK in a dose-dependent manner with an effective IC50 dose 39.91 µM in LNCaP and 49.45 µM in PC-3 cells. Also, piperine induced a positive shift in the relative activation curve in both cells. Blockade of IK by piperine exerted G0/G1 phase cell cycle arrest that led to inhibition of cell proliferation and induced apoptosis in a dose-dependent manner. CONCLUSIONS: We showed that the anticancer effects of piperine are directly correlated with the blockade of IK in LNCaP and PC-3 cells. The study also confirmed that IK inhibition by piperine might be responsible for its anticancer activities in prostate cancer cells.

[CD23 on B cells determines Breg-facilitated IL-10 secretion as well as activation of T cells].

Objective:To explore whether or not the IL-10 mediated by Bregs modulate the secreting T cells activation by the anti-CD23 antibody, to find a new target for the treatment of allergic rhinitis. Method:The rat model of allergic rhinitis was established. Anti-CD23 antibody was used to observe the behavioral changes, passive skin allergen test, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, immunofluorescence and flow cytometry serological indicators, systemic and nasal mucosa. Result:Compared with the blank control group, allergic rhinitis group rats sneezing, flexible nose, runny nose, subcutaneous mass increases;The levels of IL-10, IFN-γ and Bregs in blood decreased, the levels of IL-4, CD23+ B cells and CD4+ T cells increased;Nasal mucosa CD23 fluorescence intensity increased, CD19 and IL-10 fluorescence intensity decreased. Compared with the allergic rhinitis group, the number of sneezing, the frequency of nasal flexion, the symptoms of runny nose and the subcutaneous mass in the antibody intervention group were significantly improved;The levels of IL-10 in the blood, IFN-γ, the percentage of Bregs cells in whole blood increased, the levels of IL-4, CD23+ B cells and CD4+ T cells decreased;Nasal mucosa CD23 fluorescence intensity decreased, CD19 and IL-10 fluorescence intensity increased. There is little difference between the two routes of administration. Conclusion:The enhanced expression of CD23 on B cells is involved in the development of allergic rhinitis. The anti-CD23 antibody may control the symptoms and signs of allergic rhinitis. There is no significant difference between subcutaneous administration and improved nasal-drip way. As the preferred method of anti-CD23 antibody application, anti-CD23 is expected to become a new method to control and treat allergic rhinitis. Anti-CD23 antibodies can exert a therapeutic effect by T cell activation,which rely on the Bregs-mediated secretion of IL-10.

[The efficacy and safety of testa triticum tricum purif in treatment of functional constipation in the late middle-aged and elderly patients: a multicenter randomized controlled clinical trial].

Objective: To evaluate the efficacy and safety of testa triticum tricum purif for the treatment of functional constipation(FC) in the late middle-aged and elderly patients. Methods: This study was designed as a multicenter randomized controlled trial. Patients who met Rome Ⅲ diagnostic criteria of FC were enrolled, with age between 55-85 years old. Those with organic diseases were excluded. The patients were randomly allocated to receive testa triticum tricum purif (3.5 g bid) or polyethylene glycol 4000 powder (PEG4000, 10g bid) for 8 weeks, followed by single dose of maintenance therapy for 4 weeks. Follow-up visits were at 4 and 12 weeks after treatment discontinuation. The independent investigators in each center evaluated the constipation symptoms scores. The primary endpoints included rates of significant improvement, improvement and overall improvement at the end of 2, 4 and 8 weeks of therapy, which were calculated by the reduction of symptom scores ≥75%, 50%-74%, ≥25% respectively. Results: A total of 127 FC subjects were enrolled from 3 centers, and 122 cases valid for final analysis. The mean age was (69.4±6.9) years old, including 62 cases in testa triticum tricum purif group and 60 cases in PEG4000 group. The demographic data, constipated symptoms scores and proportion of FC subtypes at baseline were comparable. The rates of significant improvement, improvement and overall improvement in testa triticum tricum purif and PEG4000 groups at the end of 2, 4 and 8 weeks were 37.70% (23/61) vs 59.32% (35/59) (P=0.018), 57.38% (35/61) vs 74.14% (43/58) (P=0.054), and 64.41% (38/59) vs 79.31% (46/58) (P=0.073) respectively. Testa triticum tricum purif therapy significantly improved the proportion of spontaneous bowel movement(SBM) ≥3 times/week from 43.55% (27/62) to 80.33% (49/61), 83.61% (51/61) and 93.22% (55/59) at 2, 4, and 8 weeks respectively (all P<0.01), which were comparable with PEG4000 group (all P>0.05). The proportion of normalized stool forms in study group was significant higher than that of control group at the end of 8 weeks [86.44% (51/59) vs 67.24% (39/58), P=0.014]. Only one patient complained mild abdominal distension during testa triticum tricum purif therapy. Conclusions: The efficacy of testa triticum tricum purif for the treatment of FC in late middle-aged and older patients is comparable with osmotic laxatives PEG4000, which has significant effect on normalization of fecal forms and reliable safety.

Prognostic significance of the T2 substage in patients with esophageal squamous cell carcinoma.

The invasion of the muscularis propria is defined as T2 stage in esophageal squamous cell carcinoma. Evidence is lacking regarding whether the T2 substage based on anatomy may serve as a prognostic indicator. This study aims to confirm the prognostic value of the T2 substage. The clinicopathological characteristics of 120 patients who had pathologically verified T2 tumors between 2006 and 2011 at the Tianjin Medical University Cancer Institute and Hospital were retrospectively studied. Based on the invasion depth, tumors that had penetrated the circular muscle layer were defined as T2a, while T2b disease referred to those that had invaded the longitudinal muscle layer. Factors potentially related to survival were analyzed with univariate and multivariate analyses. The logistic regression model was used to examine the factors associated with lymph node metastasis. To verify the prognostic value of the T2 substage further, patients with T1b and T3 stage disease during the same period were selected for comparisons. The univariate and multivariate analyses demonstrated that the T2 substage and N stage were independent prognostic factors. The T2 substage was highly relevant to lymph node metastasis in the logistic regression model (P = 0.044). When T1b and T3 was considered, the survival of T2a patients was closer to that of T1b patients, while the survival of T2b patients was closer to that of T3 disease (P = 0.000). The T2 substage was an independent prognostic factor. Patients with T2a tumors displayed a favorable survival, while the prognosis of T2b patients was closer to that of T3 patients.

[The expression and role of PLUNC, TLR2 and NF-κB in nasal polyps].

Objective:To investigate the expression of palate, lung, nasal epithelium clone (PLUNC), Tolllike receptor 2 (TLR-2) and nuclear factor-Kappa B (NF-κB) in nasal polyps tissues and normal inferior turbinate mucosa. To analysethe correlation of their expression and to provide a new treatment of nasal polyps.Method:The specimens were divided into two groups: nasal polyps tissues group (n = 46) and normal inferior turbinate mucosa group (n = 19). EOS and others inflammatory cells was detected by HE staining. performing immunohistochemistry, we investigated the expression and distribution of PLUNC, TLR2 and NF-κB. Meanwhile we evaluated the positive expression and correlation of PLUNC, TLR2 and NF-κB between experimental group and control group. All data were processed by using SPSS 21.0 software.Result:EOS infiltration was significantly higher than the control group (P< 0.05). The expression level of PLUNC in experimental group is significantly lower, there is a statistical significance (P< 0. 05). The expression of TLR2 and NF-κB in experimental group is obviously higher than the control group, with statistical significance (P< 0.05). Spearman correlation analysia showed that PLUNC in experimental group is negatively correlated with TLR2 and NF-κB (r= －0.675, r= －0.550, P< 0.05). TLR2 is positively correlated with NF-κB (r= 0.540, P< 0.05). EOS infiltration degree positive correlation with TLR2 and NF-κB exist (r= 0.417, r= 0.470, P< 0.05), degree negative correlation with PLUNC exist (r= －0.859, P< 0.05).Conclusion:PLUNC expression in nasal polyps is lower than the normal inferior turbinate group. TLR2 and NF-κB expression in nasal polyps are higher than the normal inferior turbinate group.suggesting that the formation of nasal nolyps may be associated with lower natural immunity and the existing of infectious agents.