Objective To investigate the effect of chemokine CXC ligand 9(CXCL9)on cognitive function impairment in patients with breast cancer brain metastases undergoing whole-brain radiotherapy(WBRT)using bioinformatics methods.Methods The mRNA of breast cancer brain metastases datasets GSE43837 and GSE12276 and Alzheimer's disease(AD)dataset GSE161199 were screened and downloaded from GEO database.Limma method and Venn diagrams were used to identify common differentially expressed genes(DEGs),and protein-protein interaction and functional prediction through GeneMANIA website assays were performed.A total of 42 patients with breast cancer brain metastases who first visited the Department of Radiotherapy at the First Affiliated Hospital of Hebei North University from January 2021 to January 2023 were selected.Patients were divided into normal cognitive function group and cognitive function impairment group based on cognitive status.Enzyme-linked immunosorbent assay(ELISA)was employed to detect serum CXCL9 levels one week before and three months after radiotherapy.The mini-mental state examination(MMSE)was used to assess patients'cognitive function.Results The DEGs from datasets GSE43837 and GSE12276 included PKP1,POLDIP2,SPAG5,ALDOC,PTPRZ1,PKIA,TLCD1,CPE,PMP22 and CXCL9.The DEGs from GSE161199 included RPS16,CD79A,LYPD3,RPL28,HBG2,RPL23AP7,TRNR,CXCL9.Venn diagram showed that CXCL9 was a common DEG between breast cancer brain metastasis and AD.Functional enrichment analysis indicated that CXCL9 was involved in cellular responses to chemokines,negative regulation of immune system processes,negative regulation of vascular morphogenesis,Toll-like receptor signaling pathway,nucleotide oligomerization domain(NOD)-like receptor signaling pathway,and JAK-STAT signaling pathway.Before radiotherapy,patients with cognitive function impairment and normal cognitive function accounted for 61.9%and 38.1%,respectively,with a statistically significant difference in MMSE scores[(24.53±2.19)vs.(28.89±1.36),P＜0.01].Compared with normal cognitive function group,patients with cognitive function impairment had a significantly increased number of brain metastases and significantly lower Karnofsky performance status(KPS)scores and serum CXCL9 levels(P＜0.05).Three months after radiotherapy,patients with cognitive function impairment and normal cognitive function accounted for 47.6%and 52.4%,respectively,with a statistically significant difference in MMSE scores[(25.16±1.98)vs.(28.18±1.08),P＜0.01].Compared with normal cognitive function group,patients with cognitive function impairment had significantly lower CXCL9 levels(P=0.003).In patients with normal cognitive function,CXCL9 levels were remarkably lower after radiotherapy compared to those before radiotherapy(P=0.009).Conclusions Patients with cognitive function impairment had significantly lower CXCL9 levels than those with normal cognitive function,and whole-brain radiotherapy may be related to a certain degree of reduction in CXCL9 levels.

Objective:To study the effects of metformin on marginal bone resorption of implants in patients with type 2 diabetes melli-tus(T2DM)and exercise habit.Methods:63 cases with 73 implants were included.Among them,there were 41 cases(47 implants)without T2DM in group N,10 cases(13 implants)with T2DM and without exercise habit in group M,12 cases(12 implants)with T2DM and exercise habit in the MR group.The patients were followed up at 6 months,1 and 2 years after implantation.The marginal bone loss(MBL).Implantation success rate and peri-implantitis incidence rate were compared among the groups.Results:The bone resorption of the proximal and median margins of the long-term bone level of the implants in the N and MR groups were significantly lower than that in the M group(P=0.001 and P=0.000 5,respectively).The implant success rates of group N,MR and M were 95.74％,100％and 76.92％,respectively.The incidence of peri-implantitis of the three groups was 2.13％,0 and 15.38％,respec-tively.Conclusion:Metformin is more effective in the improvement of the long-term marginal bone resorption of implants,increase the success rate of implants,and reduce the incidence of peri-implantitis in patients with T2DM and exercise habit in the mandibular first molar area.

Objective To investigate the relationship between serum stem cell factor receptor(c-kit)and myocardial fibrosis,cardiac function and prognosis in patients with dilated cardiomyopathy(DCM)complicat-ed with heart failure.Methods A total of 77 patients with DCM complicated with heart failure who were trea-ted in 3201 Hospital from May 2020 to June 2022 were enrolled in the study as study group,and 70 DCM pa-tients without heart failure were enrolled as the control group.The levels of serum c-kit mRNA and three my-ocardial fibrosis markers[α-smooth muscle actin(α-SMA),collagen type Ⅰ and collagen type Ⅲ]were detec-ted in the two groups.Cardiac function parameters were obtained by echocardiography.The relationship be-tween serum c-kit mRNA level and myocardial fibrosis and cardiac function was analyzed.According to the oc-currence of major adverse cardiovascular events(MACE),the patients were divided into poor prognosis group and good prognosis group.Multivariate Logistic regression analysis was used to analyze the factors affecting the prognosis of DCM patients complicated with heart failure.Receiver operating characteristic(ROC)curve was used to analyze the efficacy of serum c-kit mRNA level in predicting the prognosis of DCM patients.Results The serum c-kit mRNA level in the study group was lower than that in the control group(P＜0.05).The levels of three myocardial fibrosis indicators in the study group were higher than those in the con-trol group(P＜0.05).The left ventricular ejection fraction(LVEF)in the study group was lower than that in the control group(P＜0.05),and the left ventricular end-diastolic volume(LVEDV)and left ventricular end-systolic volume(LVESV)in the study group were higher than those in the control group(P＜0.05).Pearson correlation analysis showed that serum c-kit mRNA level was positively correlated with LVEF(r=0.677,P＜0.05),while negatively correlated with α-SMA,collagen type Ⅰ,collagen type Ⅲ,LVEDV and LVESV(r=-0.725,-0.748,-0.744,-0.745,-0.662,P＜0.05).Multivariate Logistic regression analysis showed that serum c-kit mRNA level is an independent factor for the prognosis of DCM patients with heart failure.ROC curve analysis showed that serum c-kit mRNA level had a sensitivity of 82.80％,a specificity of 81.80％,and an area under the curve of 0.829(95％CI:0.745-0.912,P＜0.001)for evaluating the progno-sis of DCM patients complicated with heart failure.Conclusion The serum c-kit mRNA level is significantly decreased in patients with DCM complicated with heart failure,and the serum c-kit mRNA level is correlated with myocardial fibrosis and cardiac function.The detection of serum c-kit mRNA level has a high efficacy in evaluating the prognosis of patients with DCM complicated with heart failure.

Objective: To understand the pubertal development of primary and secondary school students in urban and rural areas of the Inner Mongolia Autonomous Region in 2021, so as to provide clues for further clarification of the health hazards of early pubertal initiation. Methods: From October to November 2021, primary and secondary school students in 12 provinces and cities of Inner Mongolia were selected by stratified cluster random sampling, including 21 662 girls who had reached menarche and 10 600 boys who had their first seminal emission, as well as 46 183 girls who had not reached menarche and 78 995 boys who had not experienced their first seminal emission. The height and weight of the primary and secondary school students were measured, and the time of first seminal emission or menarche was recorded. The study used the Mann-Whitney U test to analyze the differences between urban and rural students, Spearmans rank correlation to analyze the correlation between overweight and obesity and the age of pubertal initiation, and the Logistic regression model to analyze the correlation between pubertal initiation and age of pubertal initiation. Results: The age of menarche for urban girls [(12.31±1.29) years old] was earlier than that of suburban girls [(12.43±1.24) years old], and the age of first spermatozoa for urban boys [(13.85±1.20) years old] was statistically significant compared with that of suburban boys [(13.79±1.36) years old] (t=12.76, 10.58, P<0.05). There was a negative correlation between the age of menarche and overweight/obesity among girls aged 10-14 years (r=-0.169, P<0.05), and there was no statistically significant correlation between the age of spermarche and overweight/obesity in boys aged 5-9, 10-14, and 15-20 years (r=0.122, -0.022, -0.004, P>0.05). The occurrence of menarche in overweight girls was 1.06(95%CI=1.01-1.11) times higher than that in the normal group, and 1.13(95%CI=1.06-1.20) times higher among obese girls than normalweight girls. Compared to urban areas, primary and secondary school students in suburban counties observed the onset of puberty later [OR=0.88(95%CI=0.85-0.91) for menarche, OR=0.94(95%CI=0.89-0.99) for first spermatozoa] (P<0.05). Conclusions Obesity during childhood and adolescence is associated with earlier onset of puberty among female students in Inner Mongolia, and later onset of puberty among primary and secondary school students in suburban counties compared with those in urban areas.

Objective:To investigate the role of ferroptosis in bone marrow mesenchymal stem cells (BMMSCs) combine with normothermic machine perfusion (NMP) in repairing steatotic liver donor after cardiac death (DCD) in SD rats.Methods:BMMSCs were derived from SD rats to establish the DCD model of rats steatotic liver. A total of 24 rats were randomly divided into four groups: simple steatotic liver model group (Sham), static cold storage group (SCS), NMP, BMMSCs combine with NMP preservation group (BNMP), and the preservation time was 4 hours. The donor liver function was evaluated by liver structure, liver enzymes and lactic acid content of perfusion fluid, bile secretion and inflammatory cytokines; furthermore, in order to evaluate the occurrence of liver ferroptosis, the content of Fe 2+, malondialdehyde and glutathione (GSH) in liver tissue, as well as the mRNA or protein expression changes of cyclooxygenase-2 (COX-2), prostaglandin-endoperoxide synthase 2 (Ptgs2), glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) were detected. Results:After DCD steatotic donor liver was preserved for 4 hours, the liver injury, pro-inflammatory and anti-inflammatory cytokines expression in the BNMP and NMP groups were better than those in the SCS group. During the machine perfusion preservation period, alanine aminotransferase [(189.0±12.5)U/L vs. (227.7±16.2)U/L], aspartate aminotransferase [(207.3±18.6)U/L vs. (247.0±11.8)U/L] and lactic acid [(2.3±0.3)mmol/L vs. (2.9±0.2)mmol/L] in the BNMP group is lower than those in NMP group, moreover, the amount of hepatic bile secretion in the BNMP group [(1 245.7±46.8) μl vs. (1 014.3±67.9) μl] was more than that in NMP group, the difference was statistically significant (all P<0.05). The content of Fe 2+ and malondialdehyde in the liver tissue of BNMP group was significantly lower than those of SCS and NMP groups, on the contrary, the content of GSH was significantly higher than those of SCS and NMP groups. In addition, in the BNMP group, the mRNA level of Ptgs2 and protein level of COX-2 in the liver were significantly reduced, and expression of GPX4 and FTH1 were significantly higher than those of NMP and SCS groups, the differences were statistically significant (all P<0.05). Conclusion:BMMSCs combine with normothermic machine perfusion can better repair SD rats DCD steatotic donor liver and its mechanism of action may be related to its regulation on liver ferroptosis.

Objective:To investigate the effect of heme oxygenase-1 (HO-1) modified bone marrow mesenchymal stem cells (BMMSCs) combined with normothermic machine perfusion (NMP) on the intestinal barrier function in rats with acute rejection of liver transplantation.Methods:Specific pathogen free 2 male Brown Norway (BN) rats (4-5 weeks, 40-60 g) were used to isolat BMMSCs, and HO-1 was infected by adenovirus. Of 24 male Lewis rats (7-8 weeks old, 200-220g) were used as donors, 30 male BN rats (8-9 weeks old, 220-240 g) were used as recipients. Acute rejection models of orthotopic liver transplantation were established in rats using two cuff technique. BN recipient rats were randomly divided into five groups: sham group, abdomen of the mice was open and closed within 30 min; NMP livers were simply mechanically perfused for 4 h; the BMP group were perfused with BMMSCs through the portal vein; the HBP group were perfused with HO-1/BMMSCs through the portal vein; the FK506 livers were mechanically perfused for 4 h and administered intragastrically of tacrolimus daily following surgery, 6 per group, on days 14 after surgery, the relevant indicators were taken and the rejection activity index (RAI) changes were investigated. The changes of intestinal pathological were analyzed by HE staining and transmission electron microscope, the expression levels of zonula occludens-1 (ZO-1) and occludin protein in intestinal tissue were detected by Western blotting, the concentrations of lipopolysaccharide, D-lactic acid and diamine oxidase (DAO) in serum were detected by ELISA.Results:The RAI of HBP group (2.80±0.84) and FK506 group (2.20±0.84) were significantly lower than that of NMP group (7.60±1.14) and BMP group (6.00±1.58), the differences were statistically significant (all P<0.05). The intestinal villi in NMP group were significantly sparse, wrinkled and disorderly arranged while the degree of intestinal injury in BMP group, HBP group and FK506 group were more mitigated. Electron microscope observation showed that the microvilli of intestinal epithelial cells in HBP group were rich and orderly, and the tight junction structure between cells was complete. The protein expression levels of ZO-1 and Occludin in the intestinal tissues of HBP group [(0.87±0.06) (1.28±0.26)] were higher than those of NMP group [(0.41±0.12) (0.27±0.18)] and FK506 group [(0.52±0.15) (0.63±0.22)], the differences were statistically significant (all P<0.05). The concentration of lipopolysaccharide, D-lactic acid and DAO in serum of HBP group was lower than those of NMP group and FK506 group, the differences were statistically significant (all P<0.05). Conclusion:HO-1/BMMSCs combined with NMP protects the intestinal mucosal barrier function of BN rats with acute rejection after liver transplantation.

Objective:To analyze the safety and efficacy of left atrial appendage closure(LAAC)with Watchman in patients ≥85 years with atrial fibrillation(AF).Methods:515 elderly patients with atrial fibrillation, including 73 patients aged 85 years or older(85~91), who had undergone Watchman LAAC at Zhoupu Hospital affiliated to Shanghai Health Medical College from August 2016 to December 2020, were retrospectively analyzed.Of those ≥85 years, 44(60.3%)with transesophageal echocardiography records were assigned to the elderly group.Fifty-three patients aged 60 to 65 were selected as the control group.Differences in baseline data, intraoperative conditions, antithrombotic treatment plans and 1-year follow-up prognosis were compared between the two groups.Results:Compared with the control group, there was no difference in AF types, history of ischemic stroke/transient ischaemic attack(all P>0.05), but there were higher incidences of coronary heart disease and renal insufficiency, more severe heart failure, higher CHA 2DS 2-VASC(6.0±1.5 vs.3.6±1.5), HAS-BLED(3.2±1.2 vs.2.3±1.3)scores( t values were 7.682 and 3.871, respectively, P<0.05), and a lower one-stop surgery rate(6 cases or 13.6% vs. 27 cases or 50.9%, χ2=10.517, P<0.05)in the advanced age group.There was no difference in the diameter of the Watchman device, rate of device replacement, compression percentage and residual flow between the two groups during the perioperative period.The incidences of device-related thrombosis were 4.5%(2/44)and 3.8%(2/53)for the advanced age group and the control group, respectively, but the difference was not statistically significant( P>0.05). During the 12-month follow-up, there were no cases of ischemic stroke or intracerebral hemorrhage.Three died of heart failure and 1 died of cancer. Conclusions:LAAC with Watchman is safe and effective for patients over 85 years with AF, but the decision on the procedure should be based on careful assessment of patients' cardiac and renal function and general health.

Objective:To explore the effect and possible mechanism of normal temperature mechanical perfusion(NMP)plus bone marrow mesenchymal stem cells(BMMSCs)on early endoplasmic reticulum stress(ERs)and cellular apoptosis after donation after cardiac death(DCD)donor liver transplantation.Methods:BMMSCs were isolated and cultured by adherence method.Sixty Sprague-Dawley(SD)rats were randomly divided into five groups of sham operation(sham), static cold storage(SCS), NMP, BMMSC and NMP plus BMMSCs(BP)( n=12 each). Liver tissue and serum sample of each group were harvested at Day 1/7 post-operation.Hematoxylin-eosin(HE)staining was employed for observing pathological changes of liver tissue; TdT-mediated dUTP nick end labeling(TUNNEL)staining for detecting cellular apoptosis; immunohistochemistry for detecting the expression of hepatocyte transcription factor C/EBP homologous protein(CHOP); Western blot for detecting the expressions of GRP-78, p-PERK, ATF4, CHOP and cleaved caspase-3. Results:Compared with SCS group, hepatic injury and inflammation significantly declined in NMP, BMMSC and BP groups and improvement of hepatic injury was the most pronounced in BP group.Cellular apoptosis lessened markedly in BP group at Day 1/7 as compared with SCS group and the difference was statistically significant.The expressions of ERs-related proteins GRP-78, p-PERK and ATF4 spiked in SCS group and the expressions of pro-apoptotic proteins CHOP and cleaved caspase-3 were significantly elevated and declined markedly in BP group.And the difference was statistically significant.Conclusions:BMMSCs plus NMP can significantly improve hepatocyte apoptosis and inflammatory response after DCD donor liver transplantation.And its mechanism may be correlated with suppressing early endoplasmic reticulum stress of hepatocytes.

Objective: To explore the clinical manifestations and genetic characteristics of patients with epilepsy and episodic ataxia caused by SCN2A gene variation. Methods: The clinical data of seizure manifestation, imaging examination and genetic results of 5 patients with epilepsy and (or) episodic ataxia because of SCN2A gene variation admitted to the Department of Pediatrics, the Third Affiliated Hospital of Zhengzhou University from July 2017 to January 2021 were analyzed retrospectively. Results: Among 5 patients, 4 were female and 1 was male. The onset age of epilepsy ranged from 4 days to 8 months. There were 2 cases of benign neonatal or infantile epilepsy and 3 cases of epileptic encephalopathy, in whom 1 case had development retardation,1 case transformed from West syndrome to infantile spasm and another one transformed from infantile spasm to Lennox-Gastaut syndrome. One case of benign neonatal-infantile epilepsy was characterized by neonatal onset seizures and episodic ataxia developed at the age of 78 months. Electroencephalograms at first visit of 5 cases showed that 2 cases were normal, 1 case had focal epileptic discharge, and 2 cases had multi-focal abnormal discharge with peak arrhythmia. The brain magnetic resonance imaging (MRI) of 3 cases were nomal, 1 case was abnormal (brain atrophy with decreased white matter) and the results of 1 case was unknown. The follow-up time ranged from 17 months to 89 months. Four cases of epilepsy were controlled and 1 case died at 2 years of age. Two cases had normal intelligence and motor development, 2 had moderate to severe intelligence retardation and motor critical state, and 1 had moderate to severe intelligence and motor development retardation. SCN2A gene variations were identified in all cases. There were 4 missense variations and 1 frameshift variation. Three variations had not been reported so far, including c.4906A>G,c.3643G>T,c.638delT. Conclusions: Variations in SCN2A gene can cause benign neonatal or infantile epilepsy and epileptic encephalopathy. Some children develop episodic ataxia with growing age. The variation of SCN2A gene is mainly missense variation.
Ataxia/genetics* ; Child ; Electroencephalography ; Epilepsy/genetics* ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Mutation ; NAV1.2 Voltage-Gated Sodium Channel/genetics* ; Retrospective Studies ; Spasms, Infantile/genetics*

Objective:To investigate the clinical characteristics and prognosis of coronavirus disease 2019 (COVID-19) patients with Omicron variant combined with atrial fibrillation (AF).Methods:From March 23, 2022 to May 15, 2022, 2 675 aged ≥ 50 years old COVID-19 patients with AF were admitted to Zhoupu Hospital, the designated hospital for COVID-19 in Shanghai. Patients were divided into mild symptoms group, normal group, and serious/critical group according to the symptoms. The clinical data, imaging examination and laboratory results and prognosis of the three group patients were compared.Results:The median age of 2 675 COVID-19 patients was 69.0 (60.0, 81.0) years old, the incidence of AF was 5.05% (135/2 675), the age range of AF patients were from 55 to 101 years old, with a median age of 84.0 (74.0, 89.0), and the number of mild symptoms, normal, serious/critical patients were 68, 30, 37, respectively, including 9 of serious and 28 of critical patients. In the serious/critical patients, aged 55-75 years old accounted for 43.2%, the rate of 2019 novel coronavirus vaccination was 32.4%. The identified new-onset AF was the highest among the three groups, but the rate of persistent AF was the highest in the mild symptoms group (58.8%). The severe/critical group complicated with fever (29.7%), hepatic insufficiency (13.5%), renal insufficiency (46.0%), type 2 diabetes (46.0%), and heart failure were higher in NYHA classification [compared with the mild symptoms and normal group (score): 1.8±1.1 vs. 1.1±0.8, 1.2±0.7, respectively, all P < 0.05]. In term of laboratory examinations, C-reactive protein (CRP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were significantly higher in serious/critical patients compared to the mild symptoms and normal groups [CRP (mg/L): 27.2 (6.0, 60.8) vs. 7.6 (3.1, 19.3), 12.8 (4.9, 26.3), ALT (U/L): 31.3±15.4 vs. 15.4±9.3, 19.3±11.7, AST (U/L): 78.0±21.7 vs. 34.7±15.6, 38.1±24.4, all P < 0.05]. The hemoglobin (Hb) and albumin (ALB) levels were significantly lower than those in the mild symptoms and normal groups [Hb (g/L): 105.3±22.5 vs. 125.8±25.4, 123.0±20.4, ALB (g/L): 33.7±6.0 vs. 39.0±5.5 and 39.6±13.1, all P < 0.05]. In addition, MB isoenzyme of creatine kinase (CK-MB) was significantly higher in the serious/critical group than that in the mild symptoms group [μg/L: 2.5 (1.5, 3.4) vs. 2.2 (1.2, 2.8), P < 0.05]. In terms of the treatment, the percentage of antiplatelet agents and low-molecular heparin ratio compared among the three groups were statistically significant, with the serious/critical group using the lowest percentage of antiplatelet agents (27.0%) and a higher percentage of low-molecular heparin usage than that in mild symptoms group [81.1% (30/37) vs. 51.5% (35/68), P < 0.05]. In terms of prognosis, the mortality of patients with AF was 18.5% (25/135), all of whom were critical ill, including 32.0% (8/25) with cerebral embolism, pulmonary embolism and cerebral hemorrhage. Among them, 40.0% (10/25) died of multiple organ failure (40.0% combined with gastrointestinal hemorrhage), 20.0% (5/25) died of heart failure, and 12.0% (3/25) died of respiratory failure; while there were no death cases recorded in the mild symptoms, normal group and 9 serious patients. Conclusions:The serious/critical patients infected with COVID-19 Omicron variant with AF, have a worse prognosis and high mortality. Multiple organ failure, heart failure, sudden cardiac death, respiratory failure and embolic disease are the major causes of death.