[LncRNA SNHG11 promotes malignant progression of colorectal cancer cells through the PI3K/Akt/mTOR signaling pathway].

Objective: To investigate the effects of lncRNA SNHG11 on proliferation, migration, invasion and apoptosis of colorectal cancer cancer cells and possible mechanisms. Methods: qRT-PCR was performed to detect the expression level of lncRNA SNHG11 in colorectal cancer tissues and its related cell lines. The correlation between SNHG11 expression and clinical prognosis of patients was assessed by bioinformatics techniques. Cultured CRC cell lines were transfected with shCtrl (shCtrl group), shSNHG11#1 (shSNHG11#1 group), shSNHG11#2 (shSNHG11#2 group), Control cDNA (Control cDNA group), and SNHG11 cDNA (SNHG11 cDNA), respectively. Thiazolyl blue (MTT), clone formation assay, Transwell assay, cell scratch assay, and flow cytometry were used to detect the proliferation, migration, invasion, and apoptosis of CRC cells in each group. Western protein blotting was used to detect the expression of relevant proteins in each group, and the effect of lncRNA SNHG11 knockdown on the growth of tumour cells in vivo was analysed by nude mice tumouring assay. Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signalling pathway inhibitor LY294002 was used for rescue experiments. Results: The expression of lncRNA SNHG11 was significantly higher in colorectal cancer cells and tissues than in normal tissues (P<0.05). Survival analysis showed that the expression level of SNHG11 was not statistically associated with CRC survival (P>0.05). shSNHG11#2 group compared with shCtrl group. MTT OD490/570 values decreased, the number of CRC cell clones decreased, the number of Transwell cells decreased, the area of cell scratch decreased, and the apoptosis rate increased (P<0.05). The mesenchymal markers matrix metalloproteinase (MMP9), N-cadherin and vimentin were significantly reduced, and the expression of the epithelial marker E-cadherin was upregulated. The expression of anti-apoptotic proteins Bcl-2 and Bcl-xl was decreased, and the expression of pro-apoptotic protein Bax was increased (P<0.05).In vivo experiments showed that lncRNA SNHG11 knockdown inhibited the growth of colorectal cancer cells, and the expression of Ki67 was reduced in tumours (P<0.05). LncRNA SNHG11 knockdown inhibited the expression of p-PI3K, p-Akt and p-mTOR.The PI3K/Akt/mTOR signaling pathway inhibitor LY294002 was able to restore the malignant cytological progression of colorectal cancer cells induced by the overexpression of lncRNA SNHG11. Conclusions: LncRNA SNHG11 is highly expressed in colorectal cancer. lncRNA SNHG11 can promote the malignant progression of colorectal cancer cells by regulating the PI3K/Akt/mTOR signaling pathway, and this finding provides a new theoretical basis for targeted therapy of colorectal cancer.

[Study the involvement of Langerin in mediating epicutaneous sensitization of atopic dermatitis-like mouse model].

Objective: To explore the role of Langerin in mediating epicutaneous sensitization of atopic dermatitis (AD) in mouse model. Methods: Mice were topically treated with calcipotriol (MC903) plus ovalbumin (OVA) on the ears to establish AD mouse models, and mice were divided into wild-type control group, wild-type AD group, Langerin knockout control group, and Langerin knockout AD group. Changes of lesion were daily observed. Infiltration of inflammatory cells, mRNA expression of Tslp, Il4, Il13, Il17a, and Il22, levels of serum total IgE, OVA-specific IgE (sIgE), OVA sIgG1 and OVA sIgG2a, proportion of regulatory T (Treg) cells in cervical draining lymph nodes were evaluated at the end of model preparation. Results: Skin tumidness and thickness, dermal inflammatory cells infiltration, the mRNA expression levels of Tslp, Il4, Il13, Il17a and Il22 in wild-type AD groups were higher than those in wild-type control groups, with (1.80±0.66, 1.64±0.25, 1.71±0.54, 2.41±0.23, 2.49±0.32) and (0.53±0.45, 0.85±0.29, 0.73±0.50, 0.72±0.25, 0.56±0.29), respectively (all P<0.05). In addition, the levels of serum total IgE, OVA sIgE and OVA sIgG1 in wild-type AD groups were higher than those in wild-type control groups, with [(1 216.00±572.70) ng/ml, (597.00±538.30) ng/ml, 1.59±0.09] and [(24.22±35.04) ng/ml, (20.01±41.71) ng/ml, 1.16±0.03], respectively (all P<0.05). In Langerin knockout mice, compared to wild-type mice, skin erythema, skin tumidness, epidermal thickening, inflammatory cell infiltration were more obvious; the mRNA expression levels of Tslp, Il4, Il13, Il17a and Il22 were upregulated with (8.19±6.44, 2.53±0.69, 2.82±0.73, 3.94±1.32, 3.80±1.43) (all P<0.05); the levels of serum total IgE, OVA sIgE and OVA sIgG1 were significantly increased with (2 508.00±657.10) ng/ml, (1 808.00±470.70) ng/ml, (1.73±0.09) (all P<0.05); the number of CD4+CD25+CD127-Treg cells were decreased significantly with (13.25±0.96)% and (15.31±1.47)%, respectively (P<0.05). Conclusion: Langerin is involved in mediating epicutaneous sensitization of the AD mouse model and plays a negative immunoregulatory role.

[Effect of human Wharton's Jelly or adipose derived mesenchymal stem cells culture supernatant on endothelial cells angiogenesis].

Objective: To compare the curative effect of mesenchymal stem cells derived from human Wharton's Jelly(WJ-MSC) or adipose(AD-MSC) culture supernatant on endothelial cells angiogenesis. Methods: WJ-MSC and AD-MSC were isolated, identified, and the culture supernatant of stem cells was collected.The WJ-MSC or AD-MSC supernatant co-cultured with the endothelial cells. The expression levels of pro-angiogenic and anti-angiogenic genes of endothelial cells were assessed using qRT-PCR analysis, and the effects of stem cell culture supernatant on angiogenesis were evaluated by performing a tube formation assay in vitro. Results: After adding WJ-MSC and AD-MSC culture supernatant, the expression levels of pro-angiogenic genes in endothelial cells were upregulated, and the expression levels of anti-angiogenic genes were downregulated significantly in both experimental groups compared to the control group (P<0.01), and tube formation of endothelial cells was also significantly increased in both experimental groups as determined by the increase of the tube length ((43.2±9.2) mm vs (94.3±13.2)mm, (86.1±7.2)mm, P<0.01). Conclusion: The results showed that AD-MSC culture supernatant can promote endothelial cells angiogenesis and its curative effect is similar to that of WJ-MSC.

Characterization of three regulatory genes involved in enduracidin biosynthesis and improvement of enduracidin production in Streptomyces fungicidicus.

AIMS: To increase enduracidin production in Streptomyces fungicidicus ATCC 31731 by overexpressing positive regulators in enduracidin biosynthesis. METHODS AND RESULTS: Genes orf22 and orf42 were knocked out by in-frame deletion based on CRISPR/Cas9 strategy, while the orf41 gene was inactivated by replacing it with the apramycin resistance gene cassette aac(3)IV using a fast screening blue/white system. The integrative plasmid pSET152ermE was used for the overexpression of orf22, orf41 and orf42 individually. The constructed plasmids were transformed into wild-type strain Streptomyces fungicidicus ATCC 31731. Three gene inactivation mutants Δorf22, Δorf41 and Δorf42 and three recombinant strains overexpressing orf22, orf41 and orf42 were all fermented and the enduracidin production of each strain was detected and compared by HPLC analysis. Two resulting engineered strains were generated through overexpression of gene orf22 and orf42 in Streptomyces fungicidicus, respectively, and in these strains the enduracidins titres were increased by approximately 4·0-fold and 2·3-fold higher than that of the wild-type strain. CONCLUSIONS: The functions of three regulatory genes orf22, orf41 and orf42 in the enduracidin gene cluster in Streptomyces fungicidicus ATCC 31731 were examined. The orf22 gene, encoding a SARP family protein, was proposed to act in a positive manner. The proteins encoded by genes orf41 and orf42 were proposed to compose a two-component regulation system, in which the response protein Orf41 was characterized as a repressor, and the kinase Orf42 was shown to be an activator. The production of enduracidins was improved considerably by overexpression of the two positive regulatory genes orf22 and orf42 respectively. SIGNIFICANCE AND IMPACT OF THE STUDY: The production of enduracidins was successfully improved by manipulating the regulatory genes involving in enduracidin biosynthesis, providing an efficient approach to improve enduracidin production further for fermentation industry and synthetic biological research.

let-7i inhibits proliferation and migration of bladder cancer cells by targeting HMGA1.

BACKGROUND: Let-7 is one of the earliest discovered microRNAs(miRNAs) and has been reported to be down-regulated in multiple malignant tumors. The effects and molecular mechanisms of let-7i in bladder cancer are still unclear. This study was to investigate the effects and potential mechanisms of let-7i on bladder cancer cells. METHODS: Total RNA was extracted from bladder cancer cell lines. The expression levels of let-7i and HMGA1 were examined by quantitative real-time PCR. Cell viability was detected using the CCK-8 and colony formation assays, while transwell and wound healing assays were used to evaluate migration ability. Luciferase reporter assay and western blot were used to confirm the target gene of let-7i. RESULTS: Compared with the SV-40 immortalized human uroepithelial cell line (SV-HUC-1), bladder cancer cell lines T24 and 5637 had low levels of let-7i expression, but high levels of high mobility group protein A1 (HMGA1) expression. Transfection of cell lines T24 and 5637 with let-7i mimic suppressed cell proliferation and migration. Luciferase reporter assay confirmed HMGA1 may be one of the target genes of let-7i-5p. Protein and mRNA expression of HMGA1 was significantly downregulated in let-7i mimic transfected cell lines T24 and 5637. CONCLUSIONS: Up-regulation of let-7i suppressed proliferation and migration of the human bladder cancer cell lines T24 and 5637 by targeting HMGA1. These findings suggest that let-7i might be considered as a novel therapeutic target for bladder cancer.

[Application of radial artery in arterialized coronary artery bypass grafting in Chinese patients].

Objective: To summarize the application of radial artery (RA) as the second arterial graft in coronary artery bypass grafting (CABG). Methods: From January 1, 2015 to June 11, 2019, the clinical data of all patients undergoing CABG in TEDA International Cardiovascular Hospital was retrospectively reviewed. The patients who underwent RA grafting were included. The application of RA, internal mammary artery (IMA) and the saphenous vein, their target vessels, and the operative results were analyzed. Results: A total of 2 901 patients underwent CABG. Of those, 208 patients (7.2%) had RA grafting, with 197 males and 11 females. The average age was (53±8) years old and the average grafts per patient was 3.79. The target vessel for RA was first obtuse marginal (OM, 102 cases), first diagonal (50 cases), right coronary artery (RCA) or posterior descending artery (PDA) (40 cases), intermediate (22 cases), respectively. Among those, 172 were single distal anastomosis with the proximal end anastomosed to the ascending aorta (168 cases), saphenous vein (SV) graft (3 cases) and IMA (1 case). Seventy-two patients accept sequential grafting with the proximal to the ascending aorta (58 cases), SV graft (13 cases) and IMA (1 case). The left IMA was mainly anastomosed to left descending artery (LAD) (188 cases) and diagonal (10 cases). The target vessels for SV were remaining coronary arteries when the IMA and RA were used. The operative time was (5.0±1.5) h. The hospital stay was (17.4±6.4) d. There were 6 cases undergoing exploratory thoracotomy for bleeding (5 cases) or hemodynamic instability due to ventricular arrhythmia (1 case). There was no death. All patients were successfully discharged. Conclusions: Use of the RA and IMA with additional SV for CABG exhibits good results in the Chinese patients. Currently available clinical protocols are effective and safe.

[Regulatory effect of exosomes secreted by vaginal wall fibroblasts on angiogenesis in patients with stress urinary incontinence].

Objective: Exosomes are considered to mediate intercellular communication by delivering biomolecules like mRNA, miRNA into recipient cells. The purpose of this study was to evaluate the effects of exosomes secreted by fibroblasts from women with stress urinary incontinence (SUI-EXO) on endothelial cells angiogenesis. Methods: Primary fibroblasts were acquired from periurethral vaginal wall tissues and exosomes were prepared by ultracentrifugation of fibroblasts cells conditioned medium. The expression levels of pro-angiogenic and anti-angiogenic genes were assessed using qRT-PCR analysis. Migration of endothelial cells was measured by transwell assay, and the effects of SUI-EXO on angiogenesis were evaluated by performing a tube formation assay in vitro. Results: SUI-EXO was successfully isolated from fibroblasts cells conditional medium and transferred to endothelial cells efficiently. When the endothelial cells were treated with SUI-EXO, the expression levels of pro-angiogenic genes in fibroblasts were downregulated, and the expression levels of anti-angiogenic genes were upregulated significantly (P<0.01). Endothelial cells exhibited a decreased migratory capacity after treatment with SUI-EXO compared to exosomes from health women (64.6±8.7 vs 114.5±14.2,P<0.01), and tube formation of endothelial cells was also significantly inhibited in the SUI-EXO treated group as determined by the increase of the tube length (87.6±13.3 vs 168.5±28.3,P<0.01). Conclusion: This study suggests that SUI-EXO plays related roles in regulating endothelial cells angiogenesis and SUI-EXO maybe involve in the pathogenesis of SUI.

[The clinical safety and efficacy of low dose rituximab regimen on patients with Epstein-Barr virus infection after allogeneic hematopoietic stem cell transplantation].

To retrospectively analyze the safety and efficacy of low dose rituximab regimen in patients with Epstein-Barr virus (EBV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Among 12 cases, 11 achieved complete remission (CR), 1 with partial remission (PR). Patients received 15 infusions with a median of 2.5(1-4) in each. The EBV DNA negative transformation period was 5-25 days with median 12 days. Low dose rituximab could be an alternative choice in patients with EBV infection after allo-HSCT.

[Comparing the immunogenicity and safety of sequential inoculation of sIPV followed by bOPV (â +â ¢) in different dosage forms].

Objective: To compare the safety and immunogenicity of two different sequential schedules of inactivated poliomyelitis vaccine made from Sabin strain (sIPV) followed by typeⅠ+Ⅲ bivalent oral poliovirus vaccine (bOPV) in Drug Candy (DC) form or liquid dosage form). Methods: This randomized, blinded, single center, parallel-group controlled trial was done from September 2015 to June 2016 in Liuzhou, Guangxi province. Healthy infants aged ≥2 months were eligible for enrollment and divided into 1sIPV+2bOPV or 2sIPV+1bOPV sequential schedules. According to the bOPV dosage form each sequential schedules, the subjects again were divided into drug candy(DC) form or liquid dosage form group, being 1sIPV+bOPV (DC)/1sIPV+2bOPV(liquid)/2sIPV+1bOPV(DC)/2sIPV+1bOPV(liquid). According to 0, 28, 56 d immunization schedule, Each group were given 3 doses. We recorded adverse events during the clinical trial (399 participants who receive at least one dose). 28 days post-Dose 3, we receive a total of 350 blood samples (excluding the quitters or subjects against trial plan), using cell culture trace against polio virus neutralization test Ⅰ, Ⅱ, Ⅲ neutralizing antibody (GMT), calculating the antibody positive rate.PolioⅠ,Ⅱand Ⅲ antibody titers were assessed by virus-neutralizing antibody assay and the seroconversion (4-fold increase in titer) from pre-Dose 1 to 28 days post-Dose 3 was calculated (total 350 samples) . Results: During the vaccination, the incidence of AEs in 1sIPV+2bOPV(DC), 1sIPV+2bOPV (liquid), 2sIPV+1bOPV(DC), 2sIPV+1bOPV (liquid) group were 79%, 76%, 80% and 74% (χ(2)=1.23, P=0.747) , respectively. The severe AEs in groups were 6%, 5%, 6% and 4% (χ(2)=0.57, P=0.903) , respectively, and none was considered to be vaccination related. 28 days after 3(rd) vaccination, the seroconversion rates in 1sIPV+2bOPV (DC), 1sIPV+2bOPV (liquid), 2sIPV+1bOPV (DC), 2sIPV+1bOPV (liquid) group, were 99%, 100%, 99% and 99% (χ(2)=0.94, P=0.815) , respectively, for type Ⅰ poliovirus; and 47%, 57%, 80%, 79% (χ(2)=31.56, P<0.001) , respectively, for type Ⅱ; and were 100%, 99%, 100%, 99% (χ(2)=2.02, P=0.568) , respectively, for type Ⅲ. In each group, the GMT of antibody against poliovirus typeⅠ were 4 539.68, 6 243.43, 6 819.53 and 7 916.29 (F=25.87, P<0.001) , respectively; Type Ⅱ were 12.98, 10.54, 63.75 and 84.21 (F=8.68, P=0.034) , respectively; Type Ⅲ were 1 172.55, 1 416.03, 2 648.89 and 3 250.75 (F=14.50, P=0.002) , respectively. Conclusion: On the same sequential schedules, there was no significant difference between the dosage forms, all of them showed good safety and immunogenicity. In the same dosage forms with different sequential schedules, the seroconversion rate was higher in 2 dose sIPV group than the 1 dose sIPV group, especially at the neutralizing antibody GMT level against polio type Ⅱ and Ⅲ after vaccination.

The reversal of the spontaneous exchange bias effect and zero-field-cooling magnetization in La1.5Sr0.5Co1-xFexMnO6: the effect of Fe doping.

The crystal structure, electronic structure and magnetic properties were systematically studied in a series of Fe-doped La1.5Sr0.5CoMnO6 double perovskites. The X-ray diffraction patterns of the samples are all refined with a rhombohedral (R3[combining macron]c) structure. The parameters a and c continuously increase with increasing Fe doping concentration x. X-ray photoelectron spectroscopy (XPS) spectra of the Mn, Co, and Fe 2p core levels, consistent with the soft X-ray absorption spectroscopy (XAS) spectra of Mn, Co, and Fe L2,3 edges, indicate that their valence states are Mn3+ and Mn4+, Co2+ and Co3+, and Fe3+, respectively. However, relative to samples with x ≤ 0.1, there is an abrupt change of photon energy in the Co- and Fe-2p XAS spectra for x ≥ 0.2, implying the spin state transition is from high to low. In addition, this is further confirmed by a comparison between the calculated effective spin moment from the paramagnetic data and the theoretical value. Interestingly, we demonstrate the reversal of both zero-field-cooling magnetization and the sign switching of the spontaneous exchange bias (SEB) with the doping concentration from magnetic measurements. The magnetization reverses from positive to negative with the temperature decreasing across the compensation temperature at the critical concentration x = 0.2. Meanwhile, the exchange bias field of the SEB reverses from large negative values to positive ones. Our findings allow us to propose that the spin state transition caused by inhomogeneity is considered to play an important role in the reversal of the magnetization and the SEB effect.

[A trend analysis of the incidence of occupational diseases in Chongqing, China, from 2006 to 2014].

Objective: To investigate the incidence of occupational diseases in Chongqing, China, from 2006 to 2014, and to analyze the harm, features, and trend of occupational diseases in Chongqing. Methods: The data of new cases of occupational diseases from 2006 to 2014 were collected, and the patients with a confirmed diagnosis of occupational diseases were selected as study subjects to analyze the incidence of occupational diseases in Chongqing. Results: There were 17499 cases of occupational diseases in total in Chongqing from 2006 to 2014. Among these patients, 17124 (97.86%) were male, most of whom (95.40%) had occupational pneumoconiosis, and 375 (2.14%) were female, most of whom (72.80%) had occupational chemical poisoning. There were 16400 cases (93.72%) of occupational pneumoconiosis in total, mainly coal workers' pneumoconiosis (55.87%) and silicosis (43.02%) , and the main industries involved were coal mining and washing, railway transport equipment manufacturing, and mining and washing of bituminous coal and anthracite. There were 724 cases of occupational poisoning in total; there were 281 cases of acute occupational poisoning, mainly gas poisoning (39.86%) and carbon monoxide poisoning (33.10%) ; there were 443 cases of chronic occupational poisoning, mainly poisoning caused by benzene (47.63%) , mercury and its inorganic compounds (32.74%) , and lead and its inorganic compounds (9.03%) . Conclusion: Occupational diseases in Chongqing are mainly occupational pneumoconiosis, and occupational health supervision should be enhanced in the industries of coal mining and washing and railway transport equipment manufacturing to protect workers' health.

Repeated LPS Injection Induces Distinct Changes in the Kynurenine Pathway in Mice.

The immune system has been recognized as a potential contributor to psychiatric disorders. In animals, lipopolysaccharide (LPS) is used to induce inflammation and behaviors analogous to some of the symptoms in these disorders. Recent data indicate that the kynurenine pathway contributes to LPS-induced aberrant behaviors. However, data are inconclusive regarding optimal LPS dose and treatment strategy. Here, we therefore aimed to evaluate the effects of single versus repeated administration of LPS on the kynurenine pathway. Adult C57BL6 mice were given 0.83 mg/kg LPS as a single or a repeated injection (LPS + LPS) and sacrificed after 24, 48, 72, or 120 h. Mice receiving LPS + LPS had significantly elevated brain kynurenine levels at 24 and 48 h, and elevated serum kynurenine at 24, 48 and 72 h. Brain kynurenic acid and quinolinic acid were significantly increased at 24 and 48 h in mice receiving LPS + LPS, whereas serum kynurenic acid levels were significantly decreased at 24 h. The increase of brain kynurenic acid by LPS + LPS was likely unrelated to the higher total dose as a separate group of mice receiving 1.66 mg/kg LPS as single injection 24 h prior to sacrifice did not show increased brain kynurenic acid. Serum quinolinic acid levels were not affected by LPS + LPS compared to vehicle. Animals given repeated injections of LPS showed a more robust induction of the kynurenine pathway in contrast to animals receiving a single injection. These results may be valuable in light of data showing the importance of the kynurenine pathway in psychiatric disorders.

Co-suppression of vitamin C composite nano-drug carrier and its drug delivery to nidus in tumor cells.

This study aimed to discuss the co-suppression of vitamin C-contained composite nano-drug carrier and its drug delivery to nidus in tumor cells. Amphiphilic polymers PLA-block-PAAA and block polymer PLA-PEG4000-Maleimide, PLA-block-PAAA and PLA-PEG4000-Maleimide composite nano-micelles were prepared, and, PLA-block-PAAA polymer-coated Nile red nano-micelle, PLA-block-PAA and PLA-PEG4000-Maleimide composite nano-micelles as well as paclitaxel-carrying composite nano-micelle in different molar ratios were given stability tests. Lastly, PLA-block-PAAA and PLA-PEG4000-Maleimide composite nano-micelle cancer cells and paclitaxel-carrying composite nano-micelle cancer cells were given toxicity tests. Stability tests showed that self stability of PLA-block-PAAA (63/8) nano-micelle was not sufficient; the stability was good when the molar ratio of PLA-block-PAAA and PLA-PEG4000-Maleimide composite nano-micelle was 3:1; paclitaxel-carrying composite nano-micelle had good stability within 48 hours; PAAA segment had an inhibiting effect on C6 cancer cells and paclitaxel-carrying composite nano-micelle had a strong inhibiting effect also on tumors. After 24 hours, with the continuous release of paclitaxel, the tumor inhibiting effect of paclitaxel-carrying composite nano-micelle enhanced gradually, and the controlled-release of drugs had continuous inhibiting effect on tumor cells. Therefore, PAAA segment and paclitaxel had time-postponed synergistic effect. In conclusion, vitamin C-contained composite nanometer drug carrier materials can deliver anti-cancer drugs to nidus and thus inhibit tumor cells.

Role of GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms in the response to chemotherapy and overall survival of advanced non-small cell lung cancer.

We evaluated the association between GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms and treatment outcomes of advanced non-small cell lung carcinoma. Between January 2010 and December 2012, a total of 244 patients with non-small cell lung carcinoma were recruited from Yiwu Central Hospital. The GSTM1, GSTT1, and GSTP1 IIe105Val gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism and the results were statistically analyzed. Conditional regression analysis, showed that individuals carrying the null GSTM1 were associated with an increased risk of response to chemotherapy when compared to the present GSTM1 (odds ratio = 1.88, 95% confidence interval (CI) = 1.01-3.47). Moreover, the GG genotype of GSTP1 IIe105Val was associated with a better response to chemotherapy compared to the AA genotype (odds ratio = 2.77, 95%CI = 1.14-6.64). The null GSTM1 genotype was associated with a lower risk of death from all causes when compared with the present GSTM1 genotype (hazard ratio = 2.16, 95%CI = 1.10-4.38). Moreover, the GG genotype of GSTP1 IIe105Val was correlated with a reduced risk of death from all causes compared with the AA genotype (hazard ratio = 2.94, 95%CI = 1.11-8.68). In conclusion, we found that the null GSTM1 and the GG genotype of GSTP1 IIe105Val were correlated with a good response to chemotherapy and improved overall survival of advanced non-small cell lung carcinoma patients.

Association of NF-κB1 gene polymorphisms with coronary artery disease in a Han Chinese population.

Nuclear factor (NF)-κB is a transcription factor that controls cell proliferation, differentiation, and immunity. Activated NF-κB1 is associated with the pathogenesis of coronary artery disease (CAD) and genetic polymorphisms in NF-κB1 have a plausible role in modulating the risk of CAD. To identify markers that contribute to the genetic susceptibility to CAD, we examined the potential association between CAD and single nucleotide polymorphisms (SNPs; rs28362491, rs230531, rs230528, rs1005819, rs4648055, rs3774964, and rs3774968) in the NF-κB1 gene using SNaPshot SNP genotyping assay. Participants included 361 patients with CAD and 385 healthy controls. The genotype and allele frequencies of the rs28362491 (promoter region) polymorphism in the CAD patients were significantly different from those in the healthy controls. The frequency of the D allele was significantly higher in CAD patients than in the healthy controls (P = 0.005 after Bonferroni correction). Strong linkage disequilibrium was observed in one block (D' > 0.9). Haplotype analysis revealed that haplotypes in block 1 of the NF-κB1 gene did not display a risk or protective effect (P > 0.05). These data suggest that NF-κB1 gene polymorphisms confer susceptibility to CAD and also support the notion that dysfunction of NF-κB1 is involved in the pathophysiological process of CAD.

Association between interleukin-17A polymorphism and coronary artery disease susceptibility in the Chinese Han population.

Coronary artery disease (CAD) is a major global health problem. In China, the incidence of CAD and the rate of mortality arising from it have increased every year. Interleukin-17A (IL-17A) is a proinflammatory cytokine produced by activated T cells, and it may be involved in the development of CAD. Genetic polymorphisms in functional regions of the IL17A gene have a plausible role in modulating the risk of CAD. To evaluate the role of IL17A polymorphisms as a risk factor for CAD, we performed a detailed analysis of possible functional single nucleotide polymorphisms (SNPs) in regulatory regions of IL17A. This study examined the potential association between CAD and five SNPs (rs8193037, rs8193036, rs3819024, rs2275913, and rs3748067) of the IL17A gene. The allelic or genotypic frequencies of the rs8193037 (promoter region) and rs8193036 (promoter region) polymorphisms in CAD were significantly different from those in healthy controls. The CAD subjects had a significantly lower frequency of the A allele of rs8193037 (P = 0.009, OR = 1.772, 95%CI = 1.146- 2.742) and the T allele of rs8193036 (P = 0.010, OR = 1.754, 95%CI = 1.139-2.701). Strong linkage disequilibrium was observed in one block (D' > 0.9). Significantly fewer T-G-G-A haplotypes (P = 0.045) were found in CAD subjects in block 1. These data suggest that IL17A gene polymorphisms confer susceptibility to CAD, and support the notion that dysfunction of IL-17A is involved in the pathophysiological process of CAD.

Modified radical vaginal hysterectomy for cervical cancer treatment.

OBJECTIVES: The aim of this study was to modify vaginal radical hysterectomy (VRH), design a series of surgical instruments specialised for this procedure, and to study the feasibility, morbidity, and outcome of cervical cancer patients treated with modified laparoscopic-assisted radical vaginal hysterectomy (LARVH). MATERIALS AND METHODS: A total of 86 patients with early-stage cervical cancer (IB 1-IAl) underwent modified VRH and laparoscopic pelvic lymphadenectomy and para-aortic lymphadenectomy. Special instruments and modified procedures were used in VRH. Data were collected on operating time, blood loss, ureter separation time, nodal count, hospital stay, and complication recurrence and survival rates. RESULTS: All patients successfully completed LARVH. Median operating time was 238 minutes, mean blood loss was 283 ml, median time for ureter separation was 18.5 minutes, median time to post-operative exhaustion was 23 hours, urine recovery was 10.3 days, and median hospital stay was 9.2 days. On average, 23.2 lymph nodes were harvested. Except for one case of left internal iliac vein with intraoperative and postoperative complications, no other major complications occurred, particularly no bladder and ureter injury. Surgical margins were negative in all cases. After median follow-up of 46 months, recurrence rate and overall survival for 84 patients were 3.57% and 97.62%, respectively. DISCUSSION: Modified VRH with laparoscopic pelvic lymphadenectomy is an oncologically valid alternative for early stage cervical cancer treatment with minimal intraoperative and postoperative complications. The modification of this procedure and special instruments can enhance the feasibility and the safety of treatment.

China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI) to Prevent Cognitive Decline: Study Design and Progress.

BACKGROUND: Alzheimer's disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately. MEDTODS: We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60-80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application. RESULTS: Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025. CONCLUSIONS: This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China.

KLK1 A1789G gene polymorphism and the risk of coronary artery stenosis in the Chinese population.

Previous reports have shown that polymorphism of the human tissue kallikrein 1 (KLK1) A1789G gene is associated with susceptibility to hypertension. The current study aimed to confirm the association between the polymorphism in KLK1 and coronary artery stenosis (CAS). A total of 458 patients with CAS and 482 controls were used in a case-control study carried out between January 2008 and January 2011 at the Qilu Hospital (Jinan, China). Analyses of the KLK1 A1789G genotype were performed, and the logistic regression model was used to assess the odds ratio related to CAS. The results showed that the frequencies of the AA, AG, and GG genotypes were 11.4, 50.2, and 38.4%, respectively, in patients with CAS, and 21.2, 47.7, and 31.1%, respectively, in controls. Compared with the AA genotype, the GG and AG/GG genotypes were associated with a significantly increased risk of CAS. Furthermore, the AG and GG genotypes combined with smoking showed a remarkable increase in the risk for CAS. In conclusion, polymorphism of the KLK1 A1789G gene is associated with CAS, and smoking combined with the KLK1 GG genotype was significantly associated with an increased risk of CAS. This information is extremely important to prevention strategies for CAS.

Soluble interleukin-1 receptor, a potential negative regulator of orange-spotted grouper Epinephelus coioides interleukin-1 system.

In this study, the cDNA sequence encoding interleukin-1 (Il-1) receptor-like protein of orange-spotted grouper Epinephelus coioides was obtained. The newly identified sequence was named soluble type I Il-1 receptor (sIl-1rI) owing to its structural composition, which had two Ig-like domains, lack of transmembrane region and the Toll/interleukin-1 receptor (TIR) domain, similar to the brown rat Rattus norvegicus soluble Il-1rI. In addition, sequence comparison and phylogenetic analysis indicated that E. coioides sequence had a closer relationship with Il-1rI than Il-1rII. Real-time PCR revealed that sil-1rI mRNA expression presented a process of decrease, restoration and increase in Cryptocaryon irritans-infected E. coioides. The negative correlation between Il-1ß and sil-1rI mRNA in C. irritans-infected head-kidney implied the potential negative regulatory role of sil-1rI in E. coioides Il-1 system. The leucocytes incubated with lipopolysaccharide or polyriboinosinic polyribocytidylic acid exhibited different expression profiles of sil-1rI. Recombinant Il-1ß (rIl-1ß) protein was capable of inducing sil-1rI mRNA under the concentration of 100 ng ml(-1) , suggesting that high dosage or excess Il-1ß would stimulate the expression of sil-1rI to maintain the homoeostasis of E. coioides Il-1 system. For the first time, the role of teleost Il-1rI in parasite infection has been identified, and soluble Il-1r was found in fish.