Objective: To examine the causal relationship between inflammatory factors and breast cancer using two-sample Mendelian randomization (MR) approach, so as to provide the basis for the prevention and treatment of breast cancer. Methods: Data of 91 inflammatory cytokines (n=14 824) and 5 subtypes of breast cancer (n=247 173) were collected from genome-wide association studies (GWAS). Single nucleotide polymorphism (SNP) associated with 91 inflammatory factors were selected as instrumental variables. MR analyses were performed using the inverse-variance weighted (IVW) method with inflammatory factors as exposure factors and breast cancer as outcome variables. The risk of type I error and the effect of multiple testing were reduced using the FDR correction method. The stability and reliability of the results were verified using Steiger test of directionality, MR-Egger regression, MR-PRESSO test and leave-one out method. Results: Twenty-three inflammatory factors, including β nerve growth factor, interleukin-5, cystatin D and C-X-C chemokine ligand 1 were statistically associated with breast cancer (all P<0.05). After FDR adjustment, only evaluated abundance of oncostatin-M was found to be statistically associated with an increased risk of Basal-like (triple-negative) breast cancer (OR=1.186, 95%CI: 1.081-1.302, P=0.001, q=0.029), and the other 22 inflammatory factors had a high risk of type I error (all q>0.1). The sensitivity analysis indicated that the results were robust. No instrumental variables were found to have a significant impact on the results, which could exclude the influence of heterogeneity, horizontal pleiotropy, and reverse causality on the outcome. Conclusion The increased abundance of oncostatin-M may increase the risk of Basal-like (triple-negative) breast cancer.

Objective:To discuss the effect of Wnt/β-catenin signaling pathway inhibitor methyl 3-｛[(4-methyl-phenyl)sulfonyl]amino ｝ benzoate(MS AB)on the fibrogenic response of the human endometrial stromal cells(HESCs),and to provide the foundation for the application of MSAB in the target therapy of intrauteriue adhesion(JUA).Methods:The normal HESCs were cultured in vitro and divided into two groups:control group and transforming growth factor β1(TGF-β1)group;the HESCs from the adhesion part of the IUA patients were cultured in vitro,regarded as IUA group.Western blotting method was used to detect the expression levels of fibrotic marker protein type Ⅰ collagen α1(COL1A1)in the cells in various groups at different time points(0,12,24,48,and 60 h)after treated with TGF-β1.MTT assay was used to detect the proliferation activities of the cells in various groups.Western blotting method was used to detect the expression levels of the fibrotic marker protein COL1A1,stromal marker proteins such as N-cadherin and α-smooth muscle actin(α-SMA),and Wnt/β-catenin signaling pathway-related protein β-catenin in the cells in control and IUA groups.Based on the MSAB concentrations,the normal HESCs were divided into 0(control),0.25,0.50,0.75,and 1.00 μmol·L-1 MSAB groups,and MTT assay was used to detect the survival rates of the cells in various groups.After treated with MSAB,the normal HESCs were divided into control group(normal HESCs),TGF-β1 group(10 μg·L-1 TGF-β1 induced normal HESCs for 24 h then the drug was withdrawn,replaced with complete culture medium,and the cells continued to be cultured for 24 h),and MSAB group(10 μg·L-1 TGF-β1 induced normal HESCs for 24 h then the drug was withdrawn,replaced with a complete medium containing 0.75 μmol·L-1 MSAB and the cells continued to be cultured for 24 h).Real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of epithelial-mesenchymal transition(EMT)-related transcription factors Snail,Slug,Smuc,ZEB1,and ZEB2,and COL1A1 mRNA in the cells in various groups.Western blotting method was used to detect the expression levels of COL1A1,N-cadherin,α-SMA,β-catenin,and c-myc proteins in the cells in various groups.Results:Compared with control group(after treated with TGF-β1 for 0 h),the expression levels of COL1A1 proteins in the HESCs after treated with TGF-β1 for 12,24,48,and 60 h in TGF-β1 group were increased(P＜0.05 or P＜0.01).Compared with control group,there was no significant difference in the proliferation activity of the HESCs in IUA and TGF-β1 groups(P＞0.05).Compared with control group,the expression levels of COL1A1,β-catenin,N-cadherin,and α-SMA proteins in the cells in IUA group were increased(P＜0.05 or P＜0.01).Compared with control group,the survival rates of the cells in 0.75 and 1.00 μmol·L-1 MSAB groups were decreased(P＜0.05 or P＜0.01).Compared with control group,the expression levels of Snail,Slug,and COL1A1 mRNA in the cells in TGF-β1 group were increased(P＜0.05 or P＜0.01);compared with TGF-β1 group,the expression levels of Snail,Slug,and COL1A1 mRNA in the cells in MSAB group were decreased(P＜0.05 or P＜0.01).Compared with control group,after treated with TGF-β1 for 24 h,the expression levels of COL1A1,N-cadherin,α-SMA,β-catenin,and c-myc proteins in the cells in TGF-β1 group were increased(P＜0.01);compared with TGF-β1 group,the expression levels of COL1A1,N-cadherin,α-SMA,β-catenin,and c-myc proteins in the cells in MSAB group were decreased(P＜0.05 or P＜0.01).Conclusion:MSAB can inhibit the fibrogenic responses of the HESCs in vitro,and the results provide the theoretical basis for the application of MSAB in the target therapy of IUA.

Objective:To investigate the effects of bisphenol A(BPA)on the proliferation activity and stemness characteristics of endometrial mesenchymal stem/stromal cells(eMSCs),and to elucidate the improvement effect of human umbilical cord mesenchymal stem cell-derived supernatant(hUCMSC-Sup)on the cell injury.Methods:The eMSCs were cultured in vitro and treated with different concentrations of BPA(0,200,250,300,350,and 400 μmol·L-1).The eMSCs were divided into control group(only cultured with culture solution),BPA group(cultured with isovolumetric culture solution including 200 μmol·L-1 BPA),BPA+hUCMSC-Sup group(cultured with isovolumetric culture solution including 200 μmol·L-1 BPA and 50%volumetric ratio of hUCMSC-Sup),and BPA+CHIR-99021 group(cultured with isovolumetric culture solution including 200 μmol·L-1 BPA and 10 μmol·L-1 CHIR-99021).The survival rates of eMSCs in various groups were detected by methyl thiazolyl tetrazolium(MTT)assay.The numbers and diameters of the spheroids in various groups were detected by spheroids formation assay,the proliferation activities of the cells in eMSCs stem cell spheroids in various groups were detected by CCK-8 assay;the percentage of CD73+cells in eMSCs in various groups were detected by flow cytometry;the expression levels of sex determining region Y-box 2(Sox2),octamer-binding transcription factor 4(Oct4),and Nanog mRNA in the eMSCs in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method,the expression levels of β-catenin protein in the eMSCs in various groups were detected by Western blotting method.Results:The MTT results showed that after treated with BPA for 24 and 48 h,compared with 0 μmol·L-1 BPA group,the survival rates of eMSCs in 200,250,300,350,and 400 μmol·L-1 BPA groups were significantly decreased(P<0.01).At 24 and 48 h after treatment,compared with control group,the survival rate of the eMSCs in BPA group was significantly decreased(P<0.01);at 48 h after treatment,compared with BPA group,the survival rate of the eMSCs in BPA+hUCMSC-Sup group was significantly inereased(P<0.05).The spheroids formation assay results showed that compared with culture 3 d group,the numbers and diameters of stem cell spheroids of the eMSCs in culture 4 d group and culture 5 d group were significantly increased(P<0.05 or P<0.01);compared with control group,after 48 h of culture,the number and diameter of the cells in eMSCs stem cell spheroids in BPA group were significantly decreased(P<0.05 or P<0.01).The CCK-8 results showed that after 24 and 48 h of treatment,compared with control group,the proliferation activity of the cells in eMSCs stem cell spheroids in BPA group was significantly decreased(P<0.01);compared with BPA group,the proliferation activity of the cells in eMSCs stem cell spheroids in BPA+hUCMSC-Sup group was significantly increased(P<0.01).The flow cytometry results showed that compared with control group,the percentage of the CD73+cells in the eMSCs in BPA group was significantly decreased(P<0.01);compared with BPA group,the percentage of the CD73+cells in eMSCs in BPA+hUCMSC-Sup group was significantly increased(P<0.01).The RT-qPCR results showed that compared with control group,the expression levels of Sox2,Oct4,and Nanog mRNA in the cells in BPA group were significantly decreased(P<0.01);compared with BPA group,the expression levels of Sox2,Oct4,and Nanog mRNA in the cells in BPA+hUCMSC-Sup group and BPA+CHIR-99021 group were significantly increased(P<0.01).The Western blotting results showed that compared with control group,the expression level of β-catenin protein in the eMSCs in BPA group was significantly decreased(P<0.01);compared with BPA group,the expression levels of β-catenin protein in the eMSCs in BPA+hUCMSC-Sup group and BPA+CHIR-99021 group were signifrcantly inereased(P<0.01).Conclusion:BPA can inhibit the stemness characteristics of the eMSCs,and injury the self-renewal and repair of endometrium;its mechanism may be related to down-regulating the activity of Wnt/β-catenin signal pathway in the cells.hUCMSC-Sup can promote the proliferation of injured eMSCs,and has improvement effect on the stemness injury induced by BPA.

Allergic inflammation is closely related to the activation of mast cells (MCs), which is regulated by its intracellular Ca²⁺ level, but the intake and effects of the intracellular Ca²⁺ remain unclear. The Ca²⁺ influx is controlled by members of Ca²⁺ channels, among which calcium voltage-gated channel subunit alpha1 C (Ca_V1.2) is the most robust. This study aimed to reveal the role and underlying mechanism of MC Ca_V1.2 in allergic inflammation. We found that Ca_V1.2 participated in MC activation and allergic inflammation. Nimodipine (Nim), as a strong Ca_V1.2-specific antagonist, ameliorated allergic inflammation in mice. Further, Ca_V1.2 activation in MC was triggered by phosphatizing at its Ser1928 through protein kinase C (PKC), which calcium/calmodulin-dependent protein kinase II (CaMKII) catalyzed. Overexpression or knockdown of MC Ca_V1.2 influenced MC activation. Importantly, Ca_V1.2 expression in MC had detrimental effects, while its deficiency ameliorated allergic pulmonary inflammation. Results provide novel insights into Ca_V1.2 function and a potential drug target for controlling allergic inflammation.

Objective: To explore the possible mechanism of moxibustion in myocardial protection of rats undergoing long-term fatigue exercise based on observing the classical pyroptosis pathway mediated by nuclear factor kappa-B (NF-κB)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/cysteinyl aspartate specific proteinase 1 (Caspase-1).Methods: A total of 50 specific-pathogen-free male Sprague-Dawley rats were bought. Ten unqualified rats were excluded, and the remaining 40 rats were divided into a normal group, a normal + Shenque (CV8) group, a model group, a model + non-meridian non-point group, and a model + Shenque (CV8) group according to the random number table method, with 8 rats in each group. Except for rats in the normal group and the normal + Shenque (CV8) group, rats in the other three groups were trained with an incline running table exercise protocol to create a long-term fatigue exercise model, 1 h/time, once a day for 5 d with 2 d off, for a total of 8 weeks. Rats in the normal group received no modeling or intervention. Rats in the normal + Shenque (CV8) group were not modeled but received mild moxibustion at Shenque (CV8); those in the model group were modeled only without intervention; those in the model + non-meridian non-point group received moxibustion at non-meridian and non-point spots after the modeling; those in the model + Shenque (CV8) group received moxibustion at Shenque (CV8) after modeling. The above moxibustion interventions were performed for 15 min/time once daily, for 5 d with 2 d off per week and a total of 8 weeks. Blood was collected from the femoral artery 4 h after the last exercise, and the serum interleukin (IL)-1β and IL-18 levels were measured. The NF-κB, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, and gasdermin D (GSDMD) expression levels were detected by Western blotting. Myocardial morphology and pyroptosis were observed by hematoxylin-eosin (HE) staining and electron microscopy. Results: The HE staining results showed that the myocardial cells in the model group and the model + non-meridian non-point group were disorganized with blurred transverse lines, widened interstitial spaces, interstitial edema, and inflammatory cell infiltration. The structure of myocardial cells in the model + Shenque (CV8) group was clearly visible, with slightly widened interstitial spaces and occasional infiltration of inflammatory cells in the interstitium. Compared with the normal group, the serum IL-1β and IL-18 levels were increased, and myocardial NF-κB, NLRP3, ASC, Caspase-1, and GSDMD expression levels were elevated in the model group and the model + non-meridian non-point group (P<0.01). Compared with the model group, the above indicators did not change significantly in the model + non-meridian non-point group, while all the above indicators were decreased in the model + Shenque (CV8) group (P<0.01). Compared with the model + non-meridian non-point group, all the above biochemical indicators were decreased in the model + Shenque (CV8) group (P<0.01). Transmission electron microscopy showed that the mitochondria number was increased in the model group and the model + non-meridian non-point group, some of the mitochondrial lumen was irregularly enlarged, the cell membrane structure was unclear, and chromatin was aggregated. The mitochondria number was increased, the swelling was reduced, and the nuclear membrane structure was more intact in the model + Shenque (CV8) group. Conclusion: Moxibustion at Shenque (CV8) regulates the NF-κB/NLRP3/Caspase-1 pathway and reduces the pyroptosisin the myocardium of rats with long-term fatigue exercise, thus reducing the myocardial injury caused by long-term fatigue exercise.

Objective To analyze the clinical characteristics in children with digestive tract poison-ing in emergency department and discuss the measures of prevention and treatment. Methods Four hundred and seventy-three cases with digestive tract poisoning who visited the emergency department of Zhengzhou Children′s Hospital were retrospectively analyzed from January 2015 to December 2017. The ages,toxic poi-soning causes,types,clinical features, laboratory examinations, hospitalization expenses and outcomes were analyzed. They were divided into drug poisoning and non-drug poisoning group to compare. Results There were 317 (67. 0%) cases aged 6 days to 3 years old,133 (28. 1%) cases aged 3 to 6 years old,23 cases (4. 9%) >6 years old. The incidence rate was similar in each season but slightly lower in winter. There were 462 (97. 7%) cases of accidental poisoning,of which 377 (79. 7%) cases were mistreated and 85 (18. 0%) cases were mistakenly fed by parents,other 11 (2. 3%) cases were non-accidental poisoning. Three hundreds and thirty-six (71. 0%) cases were drug poisoning,and 137 (29. 0%) cases were non-drug poisoning. Drug poisonings were higher in urban children than in rural children, the difference was statistically significant (χ2 ＝7. 037,P＝0. 008). The percentage of digestive symptoms and blood system symptoms in non-drug poi-soning group were higher than those in drug poisoning group,and the differences were statistically significant (54. 0% vs. 8. 3%,χ2 ＝120. 067,P<0. 001;7. 3% vs. 3. 0%,χ2 ＝4. 491,P ＝0. 034). The percentage of cardiovascular system symptoms and respiratory symptoms in the non-drug poisoning group were lower than that in the drug poisoning group,and the differences were statistically significant (1. 5% vs. 14. 9%, χ2 ＝17. 915,P<0. 001;2. 9% vs. 11. 0%,χ2 ＝8. 050,P＝0. 005). Except for liver function and myocardial en-zyme,the percentage of abnormal laboratory indicators(white blood cells,platelets,blood glucose,lactic acid, electrolyte,coagulation) in non-drug poisoning group were higher than those in the drug poisoning group,and the differences were all statistically significant(all P<0. 05). The hospitalization cost of the non-drug poison-ing group was greater than that of the drug poisoning group,and the difference was statistically significant (Z＝ －12. 444,P<0. 001). Both in the drug-poisoning group and non-drug poisoning group,the cure or im-provement rate of the <6 h treating group were higher than that of the >6h treating group,and the difference was all statistically significant(all P<0. 05). Conclusion Children with acute gastrointestinal poisoning are mostly infants and preschoolers,mainly accidental poisoning,and often taken by mistake. Drug poisonings are mostly found in cities and non-drug poisonings in rural areas. Non-drug poisoning children have more serious damages and higher hospitalization costs than drug poisoning children. Early treatment after poisoning is an important factor to improve cure rate.

OBJECTIVETo use combined G-banding and array-comparative genomic hybridization (aCGH) for the prenatal diagnosis of a fetus with 5q35 deletion syndrome.

METHODSChromosomal karotypes of the fetus and parents were analyzed with G-banding analysis. aCGH was performed to detect minor chromosomal structural abnormalities.

RESULTSThe karyotype of the fetus was ascertained as 46, XY, t(5;10)(q35;p13), and the karyotypes of the parents were normal. aCGH has identified a de novo 1.68 Mb deletion at 5q35.2q35.3 and a 1.44 Mb duplication at 10p14p13.

CONCLUSIONaCGH has a higher resolution and greater accuracy for mapping chromosomal aberrations and is a useful supplement for G banding karyptyping analysis.

Adult ; Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, Pair 5 ; genetics ; Comparative Genomic Hybridization ; Cri-du-Chat Syndrome ; diagnosis ; embryology ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Karyotyping ; Male ; Prenatal Diagnosis ; Trisomy ; diagnosis ; genetics

Objectives To examine the clinical effects of α-lipoic acid(ALA)combined with epalrestat in elderly patients with diabetic peripheral neuropathy(DPN)and its influence on plasma levels of high-sensitivity C-reactive protein(hs-CRP)and homocysteine(Hcy).Methods A total of 120 DPN patients aged over sixty years were randomly divided into the control group and the treatment group with 60 cases in each group.The control group received 0.6 g ALA in 250 ml saline given by an intravenous drip once a day and the treatment group was additionally given 50 mg epalrestat orally three times a day.Both groups were treated for two weeks.Improvement in clinical symptoms,nerve conduction velocity,and peripheral blood levels of hs-CRP and Hcy were compared between the two groups before and after treatment.Results TSS scores of all items and the total scores of the two groups decreased after treatment,with greater margins seen in the treatment group than in the control group(each P＜0.05).NCV increased in both groups after treatment (each P＜ 0.05),with greater increase in the treatment group(each P＜0.05).Levels of hs-CRP and Hcy were significantly reduced (each P＜0.05).A statistically significant difference was observed in hs-CRP(t =2.620,P=0.010) but not in Hcy(t =0.380,P =0.700)between the two groups.Conclusions ALA combined with epalrestat can significantly improve the symptoms of patients with DPN,with better outcomes than ALA alone,and effectively decrease the peripheral blood level of hs-CRP.

Objective:To explore the values of fat saturation sequence in MRI for juvenile arthritis.Methods:A total of 1 131 cases with juvenile arthritis and 1 601 with symptomatic arthritis were examined by MRI normal T1 weighted imaging (T1WI) and T2 weighted imaging (T2WI)sequence and spectral presaturation attenuatedinversion recovery (SPAIR) T2 fat saturation sequence.All the images were independently evaluated by two senior doctors from the Department of Radiology and the Department of Pediatric Rheumatology and Immunology respectively to confirm the types and degree of pathological changes of joint tissues.Results:Among the subjects,847 patients demonstrated positive in MRI,accounting for 52.9％;409 patients showed positive in normal sequence,accounting for 48.3％;816 patients showed positive in fat saturation sequence,accounting for 96.3％.Joint hydrops accounted for 59.5％.Bone marrow edema accounted for 39.7％.The relevant ratio of bone marrow edema,joint hydrops,thickening of synovium and cartilage injuries in fat saturation sequence were higher than that in normal sequence (P＜0.05).The relevant ratio of bone erosion in normal sequence was higher than that in fat saturation sequence (P＜0.05).However,no significant difference of joint cysts was found between the fat saturation sequence and normal sequence (P＜0.05).Conclusion:Application of fat saturation sequence by MRI to check juvenile arthritis could obviously improve the positive MRI relevant ratio.In addition,the relevant ratio of the early pathological changes of juvenile arthritis (such as bone marrow edema and joint hydrops) was high,which might provide references for the early diagnosis of juvenile arthritis.

Objective To understand the mental health status between left‐behind children and un‐left‐behind children during primary school period in Yongchuan district of Chongqing city ,and to provide the theoretical basis for the study of the left‐behind children children′s mental problems and formulating the strategy and measures for preventing their psychological problems .Methods The Mental Health Rate Scale for Pupil (M HRSP) was used to evaluate the mental health condition in 4 987 primary school pu‐pils from 4 primary schools in Yongcuan discrict ,including 3 482 un‐left‐behind children(69 .82% ) and 1 505 left‐behind children (30 .18% ) .Results Totally 4 753 effective questionnaires were taken back with the effective rate of 95 .31% .The detection rate of total score deviation in left‐behind children was 13 .98% ,which was significantly higher than in un‐left‐behind children(6 .33% ) . The deviation detection rate of learning disabilities in left‐behind children was 14 .90% ,emotional disorder was 16 .81% ,character flaw was 12 .36% ,social adjustment disorder was 13 .91% ,moral defect was 14 .27% ,bad habits was 15 .61% ,behavior disorder rate was 16 .53% and the special obstacles was 11 .72% .Compared with un‐left‐behind children ,excluding the character flaw ,social adjustment and moral defect ,the deviation detection rate and scores of other 5 items in left‐behind children were higher than those in un‐left‐behind children .The scores of learning disabilities ,emotional disorder and bad habits in male pupils were higher than those in female pupils with statistical difference(P< 0 .05) .The scores of learning disabilities ,emotional disorder ,character flaw and behavior disorder in the high grade pupils were higher than those in the low grade pupils ,the differences were statistically sig‐nificant(P<0 .05) .Conclusion The mental health level of rural left‐behind children in Yongchuan district is low ,the problems are more serious compared with un‐left‐behind children .In carrying out the mental health education work in primary school pupils ,es‐pecially the mental health education should be paid attention to rural left‐behind children ,moreover the mental health education should be carried out aiming at different ages and different genders .