Association between the composite dietary antioxidant index and metabolic syndrome: evidence from NHANES 2003-2018.

OBJECTIVE: A healthy and nutritional diet has been considered a promising approach to improve many adverse clinical outcomes. However, current evidence of the association of the intake of composite dietary antioxidants with metabolic syndrome (MetS) is limited. The current study was performed to explore the effect of the composite dietary antioxidant index (CDAI) on MetS and its components based on the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2018. MATERIALS AND METHODS: The dietary consumption was evaluated using the 24-hour diet recall method, and a previously validated approach that included six antioxidants was used to calculate CDAI. The National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATP III) was applied to evaluate MetS. ORs and 95%CIs were computed by logistic regression. The association between CDAI and MetS was determined by subgroup analyses and restricted cubic spline (RCS) regressions. RESULTS: This study included 24,705 individuals; approximately 18,378 (74.39%) participants were determined to be without MetS and 6,327 (25.61%) with MetS. After considering all confounders, compared to individuals of the lowest quartile of CDAI, those of the highest quartile showed a 31% lower risk of MetS (OR, 0.69, 95% CI: 0.57-0.82). RCS revealed a non-linear relationship between CDAI and MetS risk. CONCLUSIONS: A non-linear association was found between CDAI and decreased MetS risk, which indicated that selective combined intake of antioxidants could be a promising and effective approach to preventing MetS for the public.

[Survival analysis of malignant tumors in cancer registration areas of Hubei province in China, 2013 to 2015].

Objective: To analyze the survival of newly diagnosed malignant tumors in cancer registration areas of Hubei Province from 2013 to 2015. Methods: From January 1, 2013 to December 31, 2015, all newly diagnosed malignant tumors were collected from cancer registration areas in Hubei Province, and patients were followed up using a combination of active and passive methods. Cancer survival was analyzed using the strs package in Stata software. Observed and expected survival were calculated using the life table and Ederer Ⅱ methods, and the difference in survival rate of patients with different sex, age, urban and rural areas and different cancer species was compared. Results: From 2013 to 2015, 83 987 new malignant tumors were diagnosed in cancer registration areas in Hubei Province, including 45 742 males (54.46%) and 38245 females (45.54%). The overall 5-year relative survival rate was 41.46%, 34.43% for men and 49.63% for women. With the increase of age, the observed survival rate and relative survival rate of patients of different genders showed a decreasing trend. The 5-year relative survival rate of patients with malignant tumors was 47.58% in urban areas and 26.58% in rural areas. The observed survival rate and relative survival rate in rural areas were significantly lower than those in urban areas. The overall 5-year relative survival rates for common malignancies were 20.61% for lung cancer, 15.36% for liver cancer, 22.89% for esophageal cancer, 34.92% for gastric cancer, and 54.87% for colorectal cancer. In addition, the 5-year relative survival rates of common malignant tumors in women were 78.65% for breast cancer and 52.55% for cervical cancer. Conclusions: In Hubei Province, the survival rate of malignant tumors is different among different genders, regions, age groups and cancer species. Prevention and treatment and health education should be strengthened for malignant tumor patients in rural areas and those with high incidence and low survival rate such as liver cancer and lung cancer, and relevant strategies should be formulated according to the gender and age distribution characteristics of different cancer species.

[Inhibition of GAS5 promoted invasion, migration and epithelial-mesenchymal transition of colorectal cancer cells via miR-21/PTEN/Akt axis].

Objective: To explore the effect of growth arrest-specific5 (GAS5) inhibition on the proliferation, colony formation, invasion, migration andepithelial-mesenchymal transition(EMT), cancer cell stem of HCT-116 and its mechanism. Methods: The colorectal carcinoma (CRC) cell HCT116 was divided into blank control, negative control (NC), si-GAS5 and si-GAS5+ miR-21 inhibitor groups. The quantitative real-time polymerase chain reaction (qRT-PCR) was used to test the expressions of miR-21 and GAS5 at 48 h after transfection. The binding site of GAS5 and miR-21 was determined by luciferase reporter array. Cell proliferation ability was detected by CCK-8 assay. Cell colony ability was detected by colony formation assay. Cell invasion and migration abilities were detected by Transwell assay. Cell cycle and apoptosis were examined by flow cytometer (FCM). The protein levels of EMT associated factors including Snail, N-cadherin, vimentin, E-cadherin, stem cell related factors including CD44, SOX2, Oct2, and PTEN/Akt signal pathway associated factors were examined by western blotting. Results: The expression levels of miR-21 in blank, NC, si-GAS5 group were 1.00±0.10, 1.00±0.10, 1.80±0.20, the absorbance values were 0.51±0.02, 0.50±0.01 and 0.65±0.01, the cell clones were 90±4, 91±5, 200±8, the invaded cells were 118±3, 119±3, 150±4, the migrated cells were 110±2, 108±2, 127±2, the cell ratios in G(1) phase were (49.3±2.1)%, (50.1±2.0)% and (42.2±1.1)%, the cell ratios in S phase were (19.2±1.2)%, (20.2±1.1)% and (28.3±2.2)%, the cell apoptotic ratios were (14.4±2.2)%, (14.5±2.1)% and (7.2±1.3)%. These results indicated that inhibition of GAS5 up regulated the expression level of miR-21, promoted cell proliferation, invasion and migration, decreased G(1)-phase cells and increased S-phase cells, and suppressed cell apoptosis (P<0.05). Moreover, inhibition of GAS5 up regulated the expressions of Snail, N-cadherin, vimentin, Sox2, CD44, Oct2 and p-Akt in HCT-116 cells (P<0.05), while down regulated the expressions of E-cadherin and PTEN (P<0.05). Inhibition of miR-21 reversed the impact of GAS5 knockdown on PTEN/Akt signaling pathway (P<0.05). Conclusion: GAS5 can act as a competing endogenous RNA for miR-21, and down regulation of GAS5 can promote the development of CRC by activating the miR-21/PTEN/Akt signaling pathway and promoting the acquisition of EMT and tumor cell stemness.

[Long noncoding RNA ZEB1-AS1 aggravates cerebral ischemia/reperfusion injury in rats through the HMGB1/TLR-4 signaling axis].

OBJECTIVE: To investigate the role of long non-coding RNA ZEB1-AS1 in cerebral ischemia/reperfusion injury (CI/RI). METHODS: We detected the temporal changes of ZEB1-AS1 and HMGB1 expression using qPCR and Western blotting in SD rats following CI/RI induced by middle cerebral artery occlusion (MCAO). The rat models of CI/RI were subjected to injections of vectors for ZEB1-AS1 overexpression or knockdown into the lateral ventricle, and the changes in cognitive function, brain water content, blood-brain barrier integrity, and IL-1ß and TNF-α levels in the cerebrospinal fluid (CSF) and serum were observed. Neuronal loss and cell apoptosis in the cortex of the rat models were detected by FJC and TUNEL methods, and HMGB1 and TLR-4 expressions were analyzed with Western blotting. We also examined the effects of ZEB1-AS1 knockdown on apoptosis and expressions of HMGB1 and TLR-4 in SH-SY5Y cells with oxygen-glucose deprivation/reoxygenation (OGD/R). RESULTS: In CI/RI rats, the expressions of ZEB1-AS1 and HMGB1 in the brain tissue increased progressively with the extension of reperfusion time, reaching the peak levels at 24 h followed by a gradual decline. ZEB1-AS1 overexpression significantly aggravated icognitive impairment and increased brain water content, albumin content in the CSF, and IL-1ß and TNF-α levels in the CSF and serum in CI/RI rats (P < 0.05), while ZEB1-AS1 knockdown produced the opposite effects (P < 0.05 or 0.01). ZEB1-AS1 overexpression obviously increased the number of FJC-positive neurons in the cortex and enhanced the expressions of HMGB1 and TLR-4 in the rat models (P < 0.01); ZEB1-AS1 knockdown significantly reduced the number of FJC-positive neurons and lowered HMGB1 and TLR-4 expressions (P < 0.01). In SH-SY5Y cells with OGD/R, ZEB1-AS1 knockdown significantly suppressed cell apoptosis and lowered the expressions of HMGB1 and TLR-4 (P < 0.01). CONCLUSION: ZEB1-AS1 overexpression aggravates CI/RI in rats through the HMGB1/TLR-4 signaling axis.

Cosmetic approach selection in parotidectomy for benign parotid gland tumour according to its location.

OBJECTIVE: The aim of this study is to evaluate the feasibility and aesthetic results when comparing two cosmetic approaches that were employed in parotidectomy according to the tumour location with the traditional Blair approach. DESIGN: Retrospective study. SETTING: Tertiary Referral Centre. PATIENTS: Seventy-six patients were included in the study. RESULTS: The degree of satisfaction with the cosmetic incision approach was significantly higher than that with the traditional Blair approach. The incidence of transient facial paralysis and salivary fistula were not statistically significant when compared with those in the traditional incision in 6-month follow-up post-operatively. DISCUSSION: Conventional parotidectomy using the traditional Blair incision (or its modification) usually leaves a visible scar in this region, which can have major adverse impacts on the social or psychological well-being of an individual. To achieve better aesthetic results, according to the location of the benign parotid tumour, two formal cosmetic approach incisions could be performed in parotidectomy, which was superior to the traditional Blair incision. The authors propose that these two cosmetic approaches for parotidectomy can be both technically feasible and safe.

Identification of prognostic immune-related signature predicting the overall survival for colorectal cancer.

OBJECTIVE: The morbidity and mortality of patients with colorectal cancer, one of the most common malignant tumors worldwide, is steadily increasing. The aim of this study was to investigate the association between prognostic immune-related gene profile and the outcome of colorectal cancer in patients by analyzing datasets from The Cancer Genome Atlas (TCGA). MATERIALS AND METHODS: Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) further demonstrated that these genes were enriched in many immune-related biological processes. Univariate Cox regression analysis was applied to examine the association of immune-related genes with the prognosis in patients with colorectal cancer. The least absolute shrinkage and selection operation (LASSO) Cox regression model was then used to establish the immune-related signature for the prognostic evaluation of colorectal cancer in patients. Survival differences were assessed by the Kaplan-Meier method along with the log-rank test. RESULTS: A total of 133 prognostic immune-related signatures were identified by using the univariate Cox proportional hazards regression analysis. A 14-gene signature-based risk score was constructed using the LASSO Cox regression. According to the cut-off of the risk-score, patients were assigned to the low-risk and high-risk groups. The log-rank test suggested that the survival time of the low-risk group was significantly higher than that of the high-risk group. In the time-dependent ROC curve analysis, the AUC for 1-year, 3-year, and 5-year overall survival (OS) were 0.781, 0.742, and 0.791, respectively. GO and KEGG analysis further revealed that the gene sets were actively involved in immune and inflammatory response, as well as the cytokine-cytokine receptor interaction pathway. CONCLUSIONS: To summarize, we identified a novel 14-gene immune-related signature that may potentially serve as a prognostic predictor for colorectal cancer, thereby contributing to patient personalized treatment decisions. Further research needs to be conducted to validate the prognostic value of the selected genes.

Nanoscale bubble delivered YCD-TK/Cx26 gene therapeutic system suppresses tumor growth by inducing necrosis of tumor tissues in mouse Xenograft bladder cancer models.

OBJECTIVE: Bladder cancer is considered as the fifth most common cancer in the whole world. This study aimed to investigate the anti-tumor effects of Nanoscale bubbles delivered yeast cytosine deaminase thymidine kinase/connexin 26 (YCD-TK/Cx26) on tumor cell proliferation and tumor growth. MATERIALS AND METHODS: Nanoscale bubble was prepared using thin-film hydration-sonication method. Nanoscale bubble-LV5-YCD-TK+PCD-Cx26 was generated and transfected into BIU-87 cells. MTT assay was employed to detect cell viability. Apoptosis was determined using a flow cytometry assay. YCD-TK and Cx26 expressions were detected using Western blot and Real Time-PCR (RT-PCR). BIU-87 cells were transplanted into mice to establish Xenograft models. The tumor volume was recorded. HE staining was used to examine necrosis areas in tumor tissues. RESULTS: Nanoscale bubble (Nanoscale bubble-LV5-YCD-TK+PCD-Cx26) successfully mediated YCD-TK and Cx26 gene expression in BIU-87 cells. Nanoscale bubble delivered YCD-TK/Cx26 expression significantly inhibited cell viability and induced apoptosis compared to Nanoscale bubble-LV5-YCD-TK and Nanoscale bubble group (p<0.05). Nanoscale bubble delivered YCD-TK/Cx26 expression triggered significantly higher levels of bystander effect compared to single YCD-TK or single Cx26 gene (p<0.05). Nanoscale bubble delivered YCD-TK/Cx26 expression significantly reduced tumor volume in mouse Xenograft bladder cancer model compared to LV5-YCD-TK and 5-FC+GCV group (p<0.05). Nanoscale bubble delivered YCD-TK/Cx26 expression significantly reduced the necrosis of tumor tissues in mouse Xenograft bladder cancer model compared to LV5-YCD-TK group and 5-FC+GCV group (p<0.05). CONCLUSIONS: Nanoscale bubble delivered YCD-TK/Cx26 gene therapeutic system efficiently reduced BIU-87 cell proliferation in vitro, and suppressed tumor growth by inducing necrosis of tumor tissues in mouse Xenograft bladder cancer models.

MiR-182-5p inhibited proliferation and metastasis of colorectal cancer by targeting MTDH.

OBJECTIVE: To investigate the role and molecular mechanism of miR-182-5p in the development of colorectal cancer (CRC), thereby providing a theoretical basis for new CRC therapeutic targets. PATIENTS AND METHODS: The expression of miR-182-5p in CRC clinical cases and biological cell lines was detected. On-line target gene prediction and Luciferase reporter gene assay were performed to screen and verify the target of miR-182-5p, respectively. The role of miR-182-5p in CRC cell function was further analyzed. RESULTS: MiR-182-5p expression was significantly decreased in both CRC tissues and cell lines. Metadherin (MTDH) was screened and verified as a functional target of miR-182-5p. The cell proliferation, invasion and migration ability of CRC cells were significantly inhibited after the up-regulation of miR-182-5p. However, MTDH limited the anti-cancer effects of miR-182-5p in CRC cells. CONCLUSIONS: Our research demonstrated the inhibitory function of miR-182-5p in CRC. Therefore, the miR-182-5p/MTDH axis was expected to be one of the targets of CRC targeted therapy.

[The clinical characteristics of the evoked nystagmus in the non-affected side during Dix-Hallpike test in the unilateral posterior semicircular canal benign paroxysmal positional vertigo].

Objective: To investigate the clinical characteristics of the evoked nystagmus in the non-affected side during Dix-Hallpike test(D-H test)in unilateral posterior semicircular canal benign paroxysmal positional vertigo(PC-BPPV). Method: Two hundred and thirty-six patients were diagnosed with unilateral PC-BPPV in the Tinnitus and Dizziness clinic.Among them,14 patients exhibited positive nystagmus when the non-affected side was stimulated by D-H test. The clinical data from this subgroup of patients were retrospectively analyzed. Result: The upbeat and torsional nystagmus of 14 patients were all evoked by D-H test in the affected side. 11 cases were right PC-BPPV and 3 cases were left PC-BPPV. Among these 14 patients, 5 patients exhibited the upbeat and torsional nystagmus during D-H test in the non-affected side, which was in the same direction as that evoked in the affected side. Among them, 4 cases were right PC-BPPV and 1 case was left PC-BPPV. However, the downbeat nystagmus of the remaining 9 patients were evoked by D-H test in the non-affected side, in which 7 cases were right PC-BPPV and 2 cases were left PC-BPPV.The nystagmus and vertigo of all patients completely disappeared after performing the Epley or Semont repositioning maneuvers on the affected side. Conclusion: The bilateral positive nystagmus of unilateral PC-BPPV can be evoked by D-H test. The form of nystagmus on the non-affected side is related with the initial position of otoconia in affected semicircular canal and the moving direction of otoconia during the positional test. It is effective to perform Epley or Semont repositioning maneuvers on the affected side. Meanwhile, both the effect of maneuvers and the type of nystagmus evoked by D-H test can verify which side is affected.

[Preliminary analysis of the effects of individualized sound therapy on chronic subjective tinnitus].

Objective:To explore the effect of individualized multi-compound sound therapy on chronic subjective tinnitus and the relationship between tinnitus frequency," notch " hearing loss and the treatment effect of sound therapy.Method: Seventy-eight cases of chronic subjective tinnitus with the pure tone test threshold (PTA)in normal range (≤25 dB HL)were enrolled in this study. Their hearing threshold were re-evaluated using the precise pure-tone audiogram (P-PTA).Tinnitus was evaluated on pitch and loudness matching, and the effectiveness of tinnitus was measured using Tinnitus Handicap Inventory (THI) before they received the individualized customized multi-compound sound therapy for 3 months. THI were re-evaluated on the 30th day and 90th day after treatment.Result: ①The averaged THI score of these patients before the sound treatment was 24.62±15.65 (n=78). The score dropped significantly to 15.82±13.02 and 13.62 ±10.98 on the 30th day and 90th day after treatment, respectively (P<0.01). ②Patient' s gender, age, and the side of tinnitus has no effect on the sound treatment of tinnitus. ③Of these 78 tinnitus patients, 31 patients who showed "notch " hearing loss and 47 patients without "notch " hearing loss in the P-PTA. The averaged THI score between the patients with and without "notch " showed no statistical difference after the treatment (P>0.05).These data suggested that "notch " hearing loss in P-PTA has no effect on the sound therapy.④Of 31 tinnitus patients with "notch " hearing loss, the tinnitus frequency of 22 cases was at the "notch " hearing loss and that of 9 cases was not at the "notch " hearing loss. Sound treatment showed significant between the former and the latter(P<0.05). After 30 days of treatment, tinnitus frequency of four patients whose tinnitus was not at the notch hearing loss drifted to the "notch " hearing loss frequency. Conclusion: Customized multi-compound sound therapy can reduce the THI score of chronic subjective tinnitus patients.The treatment reduced patient's anxiety and improved their quality of life.Sound treatment showed a better improvement in the patients whose tinnitus frequency was located at their notch hearing loss.

Effect of tea saponins on milk performance, milk fatty acids, and immune function in dairy cow.

This study investigated the effects of tea saponins (TSP) on milk performance, milk fatty acids, and blood immune function in dairy cows. A total of 20 early-lactation Holstein cows (days in milk = 66.4 ± 16.8 d; parity = 1.75 ± 0.91; and milk yield = 36.3 ± 7.32 kg/d; mean ± standard deviation) were randomly divided into 4 homogeneous treatment groups, with TSP added at 0, 20, 30, and 40 g/d per head, respectively. All cows had 2 wk of adaptation and 6 wk of treatments. Feed, milk, and blood were sampled and analyzed weekly. At the end of the experimental period (wk 6), the dry matter intake and yields of energy-corrected milk, milk, and milk protein, fat, and lactose in the cows fed TSP showed a quadratic response, with the lowest values in cows fed TSP at 40 g/d. The milk fat content of cows fed TSP increased linearly. Significant interactions for treatment by week were found in milk C16:1 cis-9 and C18:1 cis-9, with the highest values at wk 2, 3, and 4 in the cows fed TSP at 40 g/d. The levels declined quickly after 4 wk of feeding to values similar to those for other TSP treatments and the control at wk 5 and 6. Plasma malondialdehyde concentration decreased as the supplement level of TSP increased. The concentration of superoxide dismutase increased as the supplement level of TSP increased. The plasma concentration of tumor necrosis factor-α increased as the supplement level of TSP increased. In summary, this study showed that an intermediate dose of TSP (20 and 30 g/d) had no significant effect on feed intake, but the supplementation of 40 g/d TSP decreased feed intake, resulting in a lower milk yield. The energy-corrected milk of cows fed 40 g/d TSP declined at first but increased after 3 wk of feeding, indicating the potential adaptation to high doses of TSP supplements in dairy cows. The supplementation of TSP could reduce oxidative stress in cows and improve the immunity of dairy cows during 6 wk of feeding.

Thiamine supplementation facilitates thiamine transporter expression in the rumen epithelium and attenuates high-grain-induced inflammation in low-yielding dairy cows.

An experiment was conducted to uncover the effects of increasing dietary grain levels on expression of thiamine transporters in ruminal epithelium, and to assess the protective effects of thiamine against high-grain-induced inflammation in dairy cows. Six rumen-fistulated, lactating Holstein dairy cows (627 ± 16.9 kg of body weight, 180 ± 6 d in milk; mean ± standard deviation) were randomly assigned to a replicated 3 × 3 Latin square design trial. Three treatments were control (20% dietary starch, dry matter basis), high-grain diet (HG, 33.2% dietary starch, DM basis), and HG diet supplemented with 180 mg of thiamine/kg of dry matter intake. On d 19 and 20 of each period, milk performance was measured. On d 21, ruminal pH, endotoxic lipopolysaccharide (LPS), and thiamine contents in rumen and blood, and plasma inflammatory cytokines were detected; a rumen papillae biopsy was taken on d 21 to determine the gene and protein expression of toll-like receptor 4 (TLR4) signaling pathways. The HG diet decreased ruminal pH (5.93 vs. 6.49), increased milk yield from 17.9 to 20.2 kg/d, and lowered milk fat and protein from 4.28 to 3.83%, and from 3.38 to 3.11%, respectively. The HG feeding reduced thiamine content in rumen (2.89 vs. 8.97 µg/L) and blood (11.66 vs. 17.63 µg/L), and the relative expression value of thiamine transporter-2 (0.37-fold) and mitochondrial thiamine pyrophosphate transporter (0.33-fold) was downregulated by HG feeding. The HG-fed cows exhibited higher endotoxin LPS in rumen fluid (134,380 vs. 11,815 endotoxin units/mL), and higher plasma concentrations of lipopolysaccharide binding protein and pro-inflammatory cytokines when compared with the control group. The gene and protein expression of tumor necrosis factor α (TNFα), IL1B, and IL6 in rumen epithelium increased when cows were fed the HG diet, indicating that local inflammation occurred. The depressions in ruminal pH, milk fat, and protein of HG-fed cows were reversed by thiamine supplementation. Thiamine supplementation increased thiamine contents in rumen and blood, and also upregulated the relative expression of thiamine transporters compared with the HG group. Thiamine supplementation decreased ruminal LPS (49,361 vs. 134,380 endotoxin units/mL) and attenuated the HG-induced inflammation response as indicated by a reduction in plasma IL6, and decreasing gene and protein expression of pro-inflammatory cytokines in rumen epithelium. Western bottling analysis showed that thiamine suppressed the protein expression of TLR4 and the phosphorylation of nuclear factor kappa B (NFκB) unit p65. In conclusion, HG feeding inhibits thiamine transporter expression in ruminal epithelium. Thiamine could attenuate the epithelial inflammation during high-grain feeding, and the protective effects may be due to its ability to suppress TLR4-mediated NFκB signaling pathways.

[Effects of allogeneic bone marrow mesenchymal stem cells on polarization of peritoneal macrophages in rats with sepsis].

Objective: To explore the effects of allogeneic bone marrow mesenchymal stem cells (BMSCs) on polarization of peritoneal macrophages isolated from rats with sepsis induced by endotoxin/lipopolysaccharide (LPS). Methods: (1) BMSCs were isolated, cultured and purified from 5 SD rats with whole bone marrow adherent method. The third passage of cells were collected for morphologic observation, detection of expressions of stem cell surface markers CD29, CD44, CD45, and CD90 with flow cytometer, and identification of osteogenic and adipogenic differentiation. (2) Another 45 SD rats were divided into sham injury group (SI, n=5), LPS control group (LC, n=20), and BMSCs-treated group (BT, n=20) according to the random number table. Rats in groups LC and BT were injected with LPS (5 mg/kg) via tail vein to induce sepsis; rats in group SI were injected with the same amount of normal saline to simulate the damage. At post injury hour (PIH) 1, rats in group BT were given 1 mL BMSCs (2×10(6)/mL) via tail vein injection; rats in another two groups were injected with equal volume of phosphate buffer saline. Five rats in group SI at PIH 24 and in groups LC and BT at PIH 6, 12, 24, and 48 were sacrificed to harvest lung tissue for pathological observation with HE staining. In addition, rats in group SI at PIH 24 and in groups LC and BT at PIH 24 and 48 were simultaneously performed with intraperitoneal injection of low-glucose DMEM. Then peritoneal fluid was harvested to culture peritoneal macrophages. Flow cytometer was used to assess the positive expression of cell makers of macrophages including CD68 (making gate), CD11c, and CD206 in group SI at PIH 24 and in groups LC and BT at PIH 24 and 48. Data were processed with one-way analysis of variance and LSD test. Results: (1) The third passage of cells showed uniform fiber-like shape similar to fibroblasts. These cells showed positive expressions of CD29, CD44, CD90 and weak positive expression of CD45. They were able to differentiate into osteoblasts and adipocytes. These cells were identified as BMSCs. (2) At PIH 24, the structure of pulmonary alveoli of rats in group SI was clear and complete with no congestion or inflammatory cell infiltration. At PIH 6, the structure of pulmonary alveoli of rats in groups LC and BT was clear with a small amount of inflammatory cell infiltration, slight congestion and pulmonary interstitial thickening. At PIH 12, the inflammatory responses in lung tissue of rats in group LC were more severe than those in group BT with a large amount of inflammatory cell infiltration, serious congestion, and obvious pulmonary interstitial thickening. The pathological results of rats in group BT at PIH 12 was consistent with the results at PIH 6. At PIH 24, the pathological results of rats in groups LC and BT were similar to the results at PIH 12. At PIH 48, the structure of pulmonary alveoli tissue of rats in group LC was still severely disrupted, with a large number of inflammatory cell infiltration and congestion in lung tissue, but pulmonary interstitial thickening was slightly alleviated than before. The condition of rats in group BT nearly recovered to that in group SI. (3) At PIH 24, the positive expression rate of CD11c in peritoneal macrophages of rats in group LC [(83±10)%] was close to that in group BT [(87±7)%, P>0.05], and they were both significantly higher than the rate in group SI [(55±12)%, with P values below 0.01]. The positive expression rate of CD11c in peritoneal macrophages of rats in group LC [(59±11)%] at PIH 48 was close to that in group SI at PIH 24 (P>0.05), and they were both significantly higher than the rate in group BT [(20±11)%] at PIH 48 (with P values below 0.01). At PIH 24, the positive expression percentages of CD206 in peritoneal macrophages of rats were similar among the three groups (with P values above 0.05). The positive expression percentage of CD206 in peritoneal macrophages of rats in group SI at PIH 24 was close to that in group BT at PIH 48 (P>0.05), and they were both significantly lower than the percentage in group LC at PIH 48 (with P values below 0.01). Conclusions: BMSCs can reduce the pathological inflammatory responses in the lung of rats with sepsis and inhibit peritoneal macrophages from polarizing into M1 phenotype, whereas they can not promote macrophages to polarize into M2 phenotype.

Inflammation-based indexes and clinicopathologic features are strong predictive values of preoperative circulating tumor cell detection in gastric cancer patients.

PURPOSE: Circulating tumor cell (CTC) count and the host inflammatory response are two independent predictors for patients with various malignant disease. Several inflammation-based indicators have been demonstrated to have prognostic value in many malignant solid tumors, including systemic immune-inflammation index (SII), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and prognostic nutrition index (PNI). The aim of this study was to evaluate the predictive value of the inflammation-based indexes including SII, NLR PLR, and PNI for CTC detection of gastric cancer patients before surgery. METHODS: CTCs were measured using the isolation method by size of epithelial tumor cells and Wright staining for 60 patients with gastric cancer who underwent surgery. The indicators of SII, NLR, PLR, and PNI were calculated based on clinical laboratory testing. RESULTS: The detected CTC number was correlated with extension of tumor invasion (p = 0.037), lymph node metastasis (p < 0.001), and TNM stage (p < 0.001). The CTC detection ratio was significantly correlated with T stage (p = 0.041), lymph node metastasis (p = 0.001), nerve fiber invasion of tumor outside the lymph nodes (p = 0.017), and TNM stage (p < 0.001). Statistical analysis showed that SII (p < 0.001), NLR (p < 0.001), PLR (p < 0.001), and PNI (p < 0.001) were significantly associated with positive CTC count and CTC detection rate. CONCLUSIONS: This study provides evidence that preoperative indicators consisting of SII, NLR, PLR, and PNI are robust predictors for CTC detection in gastric cancer patients undergoing tumor resection.

[Effect of specific immunotherapy on the psychological health level and quality of life in patients with allergic rhinitis].

Objective: To study the effect of specific immunotherapy on the psychological health level and quality of life in patients with allergic rhinitis(AR).Method:Selected 97 cases diagnosed as moderate to severe persistent AR patients, were treated with specific immunotherapy for one year. All patients received the evaluation with symptom check list 90(SCL-90) and rhinoconjunctivitis quality of life questionnaire(RQLQ) before specific immunotherapy, six, and 12 months after specific immunotherapy.Result:The total scores, scores of somatization, obsessive, anxiety, depression and phobia in SCL-90 of AR patients after 12 months treatment were significantly lower than that before treatment（P < 0.05）. Total score of quality of life and subitem score in RQLQ of AR patients after 12 months treatment were obviously lower than that before treatment (P < 0.05）.Conclusion:Specific immunotherapy can effectively alleviate the clinical symptoms and improve psychological health level and quality of life of AR patients.

Peri-operative chemotherapy for patients with resectable colorectal hepatic metastasis: A meta-analysis.

AIMS: The purpose of this meta-analysis is to assess the value of peri-operative chemotherapy for patients who have resectable colorectal cancer with liver metastases (CRCLM). The clinical effectiveness of peri-operative chemotherapy for CRCLM patients remains controversial. METHODS: A literature review was performed to compare CRCLM patients receiving peri-operative chemotherapy plus surgery with patients receiving surgery alone. The Hazard ratio (HR), odds ratio (OR) and 95% confidence intervals (95% CIs) were set as effect measures. RESULTS: There were 10 studies included in this meta-analysis, with a total of 1896 patients. There was no advantage in overall survival (OS) for patients receiving peri-operative chemotherapy compared with those who underwent surgery alone (HR, 0.88; 95% CI, [0.77, 1.01]; P = 0.07). However, there was significant benefit in disease-free survival (DFS) in patients who received chemotherapy compared with surgery alone (HR, 0.81; 95% CI, [0.72, 0.91]; P = 0.0007). In a subset analysis, the systemic chemotherapy group showed a DFS benefit (HR, 0.81; 95% CI, [0.69, 0.96]; P = 0.01) compared with different regional chemotherapy. The incidence of post-operative complications was significantly higher in patients who also received chemotherapy compared with the surgery alone group (OR, 1.42; 95% CI, [1.05, 1.92]; P = 0. 02). CONCLUSIONS: There was no significant improvement in OS in CRCLM patients who received peri-operative chemotherapy compared with surgery alone, and chemotherapy significantly increased the post-operative complications. However, this requires further clinical study.

Clinical effectiveness of neoadjuvant chemotherapy in advanced gastric cancer: an updated meta-analysis of randomized controlled trials.

AIMS: To assess the efficacy and safety of neoadjuvant chemotherapy (NAC) for advanced gastric cancer (AGC). METHODS: By searching electronic databases (PubMed, Embase, Cochrane Library) and ASCO proceedings from 1990 to 2012, all randomized controlled trials (RCTs) which compared the effect of NAC-combined surgery versus surgery alone in AGC were included. All calculations and statistical tests were performed using RevMan 5.0 software. RESULTS: 12 RCTs with a total of 1820 patients were included. All patients had locally advanced but resectable gastric cancer and received NAC. NAC can slightly improve the survival rate (OR = 1.32, 95% confidence interval (CI): 1.07-1.64, P = 0.01), with little or no significant benefits in subgroup analyses between either different population or regimens. NAC can significantly improve the 3-year progression-free survival (PFS) (OR: 1.85, 95% CI: 1.39-2.46, p < 0.0001), tumor down-staging rate (OR: 1.71, 95% CI: 1.26, 2.33, p = 0.0006) and R0 resection rate (OR: 1.38, 95% CI: 1.08-1.78, P = 0.01) of patients with AGC. There was no difference between the two arms, in terms of relapse rates (OR: 1.03, 95% CI: 0.60-1.78, p = 0.92), operative complications (OR: 1.20, 95% CI: 0.90-1.58, p = 0.21), perioperative mortality (OR: 1.14, 95% CI: 0.64-2.05, p = 0.65) and grade 3/4 adverse effects: gastrointestinal problem (OR: 0.57, 95% CI: 0.25-1.30, p = 0.18), leukopenia (OR: 0.88, 95% CI: 0.41-1.91, p = 0.75), thrombocytopenia (OR: 1.27, 95% CI: 0.27-5.93, p = 0.76). CONCLUSION: NAC is effective and safe. However, further prospective multi-national and multi-center RCTs are still needed in order to investigate the long-term oncological and functional outcomes to define the clinical benefits of NAC and the most effective strategies for AGC.

The B-Raf(V600E) inhibitor dabrafenib selectively inhibits RIP3 and alleviates acetaminophen-induced liver injury.

Receptor-interacting protein (RIP)3 is a critical regulator of necroptosis and has been demonstrated to be associated with various diseases, suggesting that its inhibitors are promising in the clinic. However, there have been few RIP3 inhibitors reported as yet. B-Raf(V600E) inhibitors are an important anticancer drug class for metastatic melanoma therapy. In this study, we found that 6 B-Raf inhibitors could inhibit RIP3 enzymatic activity in vitro. Among them, dabrafenib showed the most potent inhibition on RIP3, which was achieved by its ATP-competitive binding to the enzyme. Dabrafenib displayed highly selective inhibition on RIP3 over RIP1, RIP2 and RIP5. Moreover, only dabrafenib rescued cells from RIP3-mediated necroptosis induced by the necroptosis-induced combinations, that is, tumor necrosis factor (TNF)α, TNF-related apoptosis-inducing ligand or Fas ligand plus Smac mimetic and the caspase inhibitor z-VAD. Dabrafenib decreased the RIP3-mediated Ser358 phosphorylation of mixed lineage kinase domain-like protein (MLKL) and disrupted the interaction between RIP3 and MLKL. Notably, RIP3 inhibition of dabrafenib appeared to be independent of its B-Raf inhibition. Dabrafenib was further revealed to prevent acetaminophen-induced necrosis in normal human hepatocytes, which is considered to be mediated by RIP3. In acetaminophen-overdosed mouse models, dabrafenib was found to apparently ease the acetaminophen-caused liver damage. The results indicate that the anticancer B-Raf(V600E) inhibitor dabrafenib is a RIP3 inhibitor, which could serve as a sharp tool for probing the RIP3 biology and as a potential preventive or therapeutic agent for RIP3-involved necroptosis-related diseases such as acetaminophen-induced liver damage.

Using SNP array to identify aneuploidy and segmental imbalance in translocation carriers.

Translocation is one of the more common structural rearrangements of chromosomes, with a prevalence of 0.2%. The two most common types of chromosomal translocations, Robertsonian and reciprocal, usually result in no obvious phenotypic abnormalities when balanced. However, these are still associated with reproductive risks, such as infertility, spontaneous abortion and the delivery of babies with mental retardation or developmental delay. In recent years, array-based whole-genome amplification (WGA) technologies, including microarray comparative genomic hybridization (array CGH; aCGH) and single-nucleotide polymorphism (SNP) micro-arrays, have enabled the screening of every chromosome for whole-chromosome aneuploidy and segmental imbalance. These techniques have been shown to have clinical application for translocation carriers. Promising studies have indicated that array-based PGD of translocation carriers can lead to transfer pregnancy rates of 45-70% [2]. In addition to genetic testing techniques, the embryo biopsy stage (polar body, cleavage embryo or blastocyst) and the mode of embryo transfer (fresh or frozen embryos) can affect the outcome of PGD. It is now generally recommended that blastomere biopsy should be replaced by blastocyst biopsy to avoid a high mosaic rate and biopsy-related damage to cleavage-stage embryos, which might affect embryo development. However, more clinical data are required to confirm that the technique of SNP array-based PGD (SNP-PGD) combined with trophectoderm (TE) biopsy and frozen embryo transfer (FET) is superior to traditional FISH-PGD combined with Day 3 (D3) blastomere biopsy and fresh embryo transfer.

Single-nucleotide polymorphism microarray-based preimplantation genetic diagnosis is likely to improve the clinical outcome for translocation carriers.

STUDY QUESTION: Is preimplantation genetic diagnosis (PGD) for translocation carriers more effective when done with a single-nucleotide polymorphism (SNP) array using trophectoderm (TE) biopsy and frozen embryo transfer (FET) compared with traditional PGD based on fluorescence in situ hybridization (FISH-PGD) using blastomere biopsy and fresh embryo transfer? SUMMARY ANSWER: The procedure using the SNP array combined with TE biopsy and FET significantly improves the clinical pregnancy rate for translocation carriers. The miscarriage rate also slightly decreases. WHAT IS KNOWN ALREADY: FISH-PGD has been widely used in translocation carriers but the clinical outcomes have not been ideal. SNP arrays can detect both chromosome segmental imbalances and aneuploidy, and may overcome the limitations of FISH in PGD for translocation carriers. STUDY DESIGN, SIZE AND DURATION: This was a retrospective study of 575 couples with chromosomal translocations, including 169 couples treated by SNP-PGD between October 2011 and August 2012, and 406 couples treated by FISH-PGD between January 2005 and October 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study was set in an IVF center at the Reproductive and Genetic Hospital of CITIC-Xiangya, China. In total, 169 couples underwent SNP analysis, including 52 Robertsonian translocation carriers and 117 carriers of reciprocal translocations. Blastocysts (n = 773) were biopsied and FET was carried out on the balanced embryos. Four hundred and six couples underwent FISH-PGD, including 149 Robertsonian translocation carriers and 257 reciprocal translocation carriers. In total, 3968 embryos were biopsied and balanced embryos were transferred fresh. The SNP-PGD results and clinical outcomes were compared with those of FISH-PGD. MAIN RESULTS AND THE ROLE OF CHANCE: Reliable SNP-PGD results were obtained for 717 out of 773 (92.8%) biopsied blastocysts. The proportions of normal/balanced embryos, embryos with translocation-related and translocation-unrelated abnormalities, the median number of embryos per patient, the ongoing pregnancy rate per embryo transfer and the miscarriage rate were 58, 23, 19, 2, 69 and 12%, respectively, for Robertsonian translocation carriers and 36, 52, 12, 1, 74 and 11%, respectively, in reciprocal translocation carriers. Reliable FISH-PGD results were obtained for 3452 out of 3968 (87.0%) biopsied embryos. The proportions of normal/balanced embryos, unbalanced embryos, the median number of embryos per patient, the ongoing pregnancy rate per transfer and the miscarriage were 36, 64, 3, 38 and 17%, respectively, for Robertsonian translocation carriers and 20, 80, 1, 39 and 16%, respectively, for reciprocal translocation carriers. Thus, SNP-PGD achieved a higher pregnancy rate but a lower miscarriage rate than FISH-PGD. There were no significant differences in maternal age, basal endocrine level and the average number of retrieved oocytes and good-quality D3 embryos in the SNP-PGD group compared with the FISH-PGD group. LIMITATIONS, REASONS FOR CAUTION: This was a retrospective study with the two groups treated in different periods; therefore, there is a chance of sample bias and a possibility that the results were influenced by other factors that changed over time. Furthermore, the two treatment protocols differ in several respects and we cannot say which makes the greatest contribution to the difference in success. Complete pregnancy outcomes of SNP-PGD have not been obtained as some embryos have not been transferred yet. We cannot exclude differences between the final data and the data in the present manuscript. WIDER IMPLICATIONS OF THE FINDINGS: The adoption of SNP-PGD combined with TE biopsy and FET may significantly improve the clinical pregnancy rate, and decrease the miscarriage rate after PGD for translocation carriers.