Objective:Mild cognitive impairment(MCI)is characterized by its heterogeneity in pathology, clinical outcomes, and the degree of cognitive impairment.This study aims to identify distinct subtypes of MCI and examine their associated risk of progression to Alzheimer's disease(AD).Methods:Four cognitive domains—memory, language, attention/executive function, and visuospatial ability—were evaluated using seven neuropsychological tests.K-means cluster analysis was employed to categorize MCI into distinct subtypes.Kaplan-Meier survival analysis and Cox regression were utilized to estimate the median survival time and the risk of progression to AD for each subtype, with cognitively normal(CN)individuals at baseline serving as the control group.Only participants with a minimum of two follow-up visits were included in this analysis.Results:A total of 1, 020 subjects with baseline MCI were included in the study, with an age range of 60 to 90 years and a mean age of 73.6 years.Among these subjects, 40.5% were female, and the mean length of education was 16.0 years.The MCI subtypes were classified based on their characteristics as follows: amnestic(n=485), mixed(n=147), and derived normal(n=388).The mixed subtype performed poorly across all neuropsychological tests, particularly demonstrating significantly worse results than the other two subtypes in attention/executive ability and visuospatial functioning.The amnestic subtype primarily exhibited deficits in the memory cognition dimension, while the derived normal subtype scored poorly on the delayed recall aspect of memory cognition.For the survival analysis, a total of 1, 427 subjects were included, with a mean follow-up duration of 50 months.The proportions of subjects who progressed to AD during follow-up were 48.8% for amnestic MCI, 60.0% for mixed MCI, 16.0% for derived normal MCI, and 6.4% for CN individuals at baseline.The mean time to conversion to AD was 29.1 months for amnestic MCI, 19.6 months for mixed MCI, 53.6 months for derived normal MCI, and 85.9 months for CN subjects.There were statistically significant differences in survival time among the subtypes( P<0.001), with the mixed subtype exhibiting the shortest median survival time and the highest risk of progression to AD( HR=20.0, 95% CI: 13.0-30.8).In contrast, the derived normal subtype had the longest survival time and the lowest risk of progression to AD( HR=2.7, 95% CI: 1.7-4.1). Conclusions:MCI subtypes exhibit significant heterogeneity regarding cognitive impairment, progression risk, and time to AD.Individuals with mixed MCI demonstrate the shortest progression time and the highest risk of transitioning to AD.Consequently, early prevention and intervention strategies for AD should prioritize this particular subgroup.

Objective:Mild cognitive impairment(MCI)is characterized by its heterogeneity in pathology, clinical outcomes, and the degree of cognitive impairment.This study aims to identify distinct subtypes of MCI and examine their associated risk of progression to Alzheimer's disease(AD).Methods:Four cognitive domains—memory, language, attention/executive function, and visuospatial ability—were evaluated using seven neuropsychological tests.K-means cluster analysis was employed to categorize MCI into distinct subtypes.Kaplan-Meier survival analysis and Cox regression were utilized to estimate the median survival time and the risk of progression to AD for each subtype, with cognitively normal(CN)individuals at baseline serving as the control group.Only participants with a minimum of two follow-up visits were included in this analysis.Results:A total of 1, 020 subjects with baseline MCI were included in the study, with an age range of 60 to 90 years and a mean age of 73.6 years.Among these subjects, 40.5% were female, and the mean length of education was 16.0 years.The MCI subtypes were classified based on their characteristics as follows: amnestic(n=485), mixed(n=147), and derived normal(n=388).The mixed subtype performed poorly across all neuropsychological tests, particularly demonstrating significantly worse results than the other two subtypes in attention/executive ability and visuospatial functioning.The amnestic subtype primarily exhibited deficits in the memory cognition dimension, while the derived normal subtype scored poorly on the delayed recall aspect of memory cognition.For the survival analysis, a total of 1, 427 subjects were included, with a mean follow-up duration of 50 months.The proportions of subjects who progressed to AD during follow-up were 48.8% for amnestic MCI, 60.0% for mixed MCI, 16.0% for derived normal MCI, and 6.4% for CN individuals at baseline.The mean time to conversion to AD was 29.1 months for amnestic MCI, 19.6 months for mixed MCI, 53.6 months for derived normal MCI, and 85.9 months for CN subjects.There were statistically significant differences in survival time among the subtypes( P<0.001), with the mixed subtype exhibiting the shortest median survival time and the highest risk of progression to AD( HR=20.0, 95% CI: 13.0-30.8).In contrast, the derived normal subtype had the longest survival time and the lowest risk of progression to AD( HR=2.7, 95% CI: 1.7-4.1). Conclusions:MCI subtypes exhibit significant heterogeneity regarding cognitive impairment, progression risk, and time to AD.Individuals with mixed MCI demonstrate the shortest progression time and the highest risk of transitioning to AD.Consequently, early prevention and intervention strategies for AD should prioritize this particular subgroup.

Objective To explore pathogenic composition of hand,foot and mouth disease(HFMD),and the molecular typing of enterovirus in Tianjin Children′s Hospital in 2016.Methods Single center study.A total of 327 samples of HFMD cases which collected from Tianjin Children′s Hospital from March to November in 2016 were tested for nucleotide acid of enterovirus(EV),human enterovirus 71(EV71),Coxsackievirus A 16(CA16)by real-time reverse transcription polymerase chain reaction(RT-PCR),among which 104 sample of other EV positive were selected to amplify and sequence the whole VP1 region by using RT-PCR.Homology was analyzed and phylogenetic tree were constructed by comparison of the sequence with all subgenotype of EV by Chromas1.62 and MEGA6.06.EV positive rate in different age groups were compared by SPSS20.0.Results Of all the 327 HFMD cases tested,there were 272 EV positive cases,the constituent ratio of EV71,CA16 and other EV were 55.1％(150/272),6.6％(18/272)and 38.2％(104/272)respectively.The EV positive rates of different age groups(69.0％-90.9％)were different significantly(x2=15.897,P=0.044),the 3 years-old-group had the highest EV positive rate than that of the other age groups(90.9％,40/44).Of all 104 samples of other EV tested,34 were CA10(12.5％)and 14 were CA6(5.1％).Phylogenetic analysis of 11 EV71 VP1 and 20 CA10 VP1 showed that the EV71 and CA10 strains belonged to genotype C4a and genotype G,respectively.ConclusionsEV71 was still the predominant pathogen in spite of the constituent ratio of other EVs increased markedly in 2016 in Tianjin.It is important to enhance etiological monitoring for control and prevention of HFMD.

Objective To evaluate the effect of inhaling hydrogen (H2) on proteomics during acute lung injury in septic mice.Methods Sixty male ICR mice,aged 6 weeks,weighing 20-25 g,were divided into 4 groups (n=15 each) using a random number table:sham operation group (Sh group),sham operation plus H2 group (Sh+H2 group),sepsis group (S group) and sepsis plus H2 group (S+H2 group).Sepsis was produced by cecal ligation and puncture.The mice in Sh+H2 and S+H2 groups inhaled 2％ H2 for 1 h starting from 1 and 6 h after operation.At 24 h after operation,lungs were removed for identification of proteins by isobaric tags for relative and absolute quantification and liquid chromatography-tandem mass spectrometry analysis,and the differentially expressed proteins were screened.The differentially expressed proteins were used for KEGG pathway enrichment analysis and STRING protein-protein interaction networks analysis.Western blot was used to confirm the 4 differentially expressed proteins semaphorin 7A,transferrin,OTULIN and mitogen-activated protein kinase kinase kinase 1.Results A total of 4 472 quantifiable proteins were identified.A total of 192 proteins which were related to acute lung injury during H2 inhalationinduced reduction of sepsis were identified.The 192 proteins involved phosphatidylinositol 3-kinase/serine0threonine kinase signaling pathway,chemokine signaling pathway,hypoxia-inducible factor 1 signaling pathway,complement and coagulation cascades,peroxisome proliferator-activated receptor signaling pathway and proteins including ribosome proteins,myosin and troponin,collagen and adhesion-related proteins,coagulation-related proteins found in STRING protein-protein interaction networks.Conclusion Inhaling H2 can induce changes in the expression of 192 proteins,which may be the mechanism of lung protection in septic mice.

This study introduced the application of a log-linear model in the hybrid design of case-parents triad/control-mother dyad.Data related to the association between cleft lip with palate (CLP) and methylenetetrahydrofolate reductase (MTHFR) gene A1298C diversity was analyzed.Log-linear model based on likelihood ratio tests (LRTs) was used to analyze the relationships between mother,offspring genotypes and CLP.Data from our study noticed that children of mothers carrying the CC genotype presented a lower risk of CLP,comparing with the children of mothers carrying the AA genotype,with S2=0.45 (95％CI:0.26-0.79).Offspring that carrying the AC genotype presented a lower risk of CLP,comparing with the offspring that carrying the AA genotype,with R1 =0.69 (95％CI:0.48-0.97).However,no other types of relationships were found.The power of hybrid design was greater than the case-parents study (0.86＞0.78).MTHFR A1298C polymorphism seemed to have played an important role in the etiology on both cleft lip and palate.Data from the hybrid design and the log-linear model could help researchers to explore the effects of genotypes from both mothers and the offspring.This study design would present stronger power than the regular case-parents studies thus suitable for studies on the etiology of diseases in early lives,as birth defects.

Objective To compare the effects and significance of laparoscopic and open D2 gastrectomy on the expression of interleukin (IL)-6 and IL-10.Methods The clinical data of 146 patients with gastric cancer who were admitted to the Southwest Hospital from November 2010 to October 2011 were prospectively analyzed.All the patients were randomly divided into the laparoscopic group (75 patients) and open group (71 patients)according to the sealed envelope method.Laparoscopic or open D2 gastrectomy were performed according to the 14th edition of gastric cancer treatment guidelines of Japan Gastric Cancer Association.Peritoneal lavage fluid was collected at the beginning and the end of operation,and the concentrations of IL-6 and IL-10 in the peritoneal lavage fluid were detected by enzyme linked immunosorbent assay.The measurement data were analyzed using the t test,and the count data were analyzed using the chi-square test.Results The preoperative concentrations of IL-6 in the laparoscopic group and the open group were (34 ± 13)μg/L and (35 ± 12)μg/L,respectively,with no significant difference between the 2 groups (t =-5.110,P ＞ 0.05).The postoperative concentrations of IL-6 in the laparoscopic group and the open group were (4015 ± 1592)μg/L and (6724 ± 2112)μg/L,respectively.The postoperative concentration of IL-6 in the laparoscopic group was significantly lower than that of the open group (t =-8.367,P ＜ 0.05),and the postoperative concentrations of IL-6 were significantly higher than those before operation in the laparoscopic group and open group (t =-59.065,-87.123,P ＜0.05).The preoperative concentrations of IL-10 in the laparoscopic group and the open group were (43 ±9) μg/L and (42 ± 10) μL,respectively,with no significant difference between the 2 groups (t =1.190,P ＞0.05).The postoperative concentrations of IL-10 in the laparoscopic group and the open group were (92 ± 32)μg/L and (62 ± 23)μg/L,respectively.The postoperative concentration of IL-10 was significantly higher than that of the open group (t =6.408,P ＜ 0.05),and the postoperative concentrations of IL-10 were significantly higher than those before operation in the laparoscopic group and the open group (t =-12.680,-6.802,P ＜ 0.05).Conclusion Peritoneal inflammatory reaction is relatively lighter after laparoscopic D2 gastrectomy when compared with open D2 gastrectomy,which might prevent the peritoneal metastasis of gastric cancer mediated by IL-6.