Alzheimer's disease (AD) is regarded as a neurodegenerative disease, and it has been proposed that AD may be a systemic disease. Studies have reported associations between non-neurological diseases and AD. The correlations between AD pathology and systemic (non-neurological) pathological changes are intricate, and the mechanisms underlying these correlations and their causality are unclear. In this article, we review the association between AD and disorders of other systems. In addition, we summarize the possible mechanisms associated with AD and disorders of other systems, mainly from the perspective of AD pathology. Regarding the relationship between AD and systemic pathological changes, we aim to provide a new outlook on the early warning signs and treatment of AD, such as establishing a diagnostic and screening system based on more accessible peripheral samples.
Alzheimer Disease/therapy* ; Humans ; Brain/pathology*

Objective To identify the risk factors and investigate etiological spectrum of pulmonary fungal infections(PFIs)in patients with end-stage liver disease(ESLD).Methods A retrospective analysis was performed on the clinical data of 211 ESLD patients.Based on pulmonary imaging,clinical manifestations,and microbiological test results,patients were categorized into three groups,including the PFI group(or the case group),the non-fungal pneumonia group(or the control group 1),and the group without pneumonia(or the control group 2).The clinical characteristics of patients in the the case group were then compared with those of patients in the two control groups.Taking patients without pneumonia as the control,univariate and multivariate logistic regression analyses were performed to identify independent risk factors for PFI,and a nomogram prediction model was constructed based on these risk factors.Results Among the 211 patients,76(36.1%)had PFIs,46(21.8%)had non-fungal pneumonia,and 89(42.2%)did not have pneumonia.According to findings from the multivariate logistic regression,elevated white blood cell count upon admission(OR=1.211;95%CI,1.011-1.460),higher Model for End-Stage Liver Disease-Sodium(MELD-Na)score(OR=1.140;95%CI,1.021-1.282),concomitant hepatorenal syndrome(OR=4.150;95%CI,1.050-17.300),cumulative glucocorticoid use for more than seven days(OR=26.832;95%CI,6.361-113.221),and the administration of broad-spectrum antibiotics at the time of hospital admission(OR=6.601;95%CI,1.951-22.362)were identified as independent risk factors for PFI.A predictive nomogram model named TJLFPFI was constructed based on these risk factors.The area under the receiver operating characteristic(AUC)curve of the model was 0.899(95%CI,0.853-0.945).Etiologic analysis of the 76 PFI cases revealed that 36(47.4%)had positive results for culture,while 40(52.6%)had negative results for sputum culture but tested positive by the 1,3-β-D-glucan test and/or galactomannan test.Aspergillus was the most frequently identified pathogen,detected in 25 of the 36 cases(59.5%).Conclusion PFI in ESLD patients is closely associated with disease severity at admission,early use of broad-spectrum antibiotics,and prolonged glucocorticoid therapy.Aspergillus is the predominant pathogen.The TJLFPFI model shows potential value in identifying high-risk patients,but prospective validation is still warranted.

Mild cognitive impairment(MCI)is often regarded as a prodromal stage of dementia,primarily characterized by mild decline in cognitive function.Due to the mild nature of its symptoms,many MCI cases miss the opportunity for intervention.Research indicates that linguistic changes in MCI may precede other cognitive symptoms,providing an opportunity for early identification and intervention.These linguistic changes include abnormalities in speech rate,pronunciation,and intonation.Speech repetition tasks,such as the five-word test,delayed digit matching,and sentence repetition tests,are effective methods for assessing the speech characteristics of MCI patients.These tasks involve asking patients to repeat specific content,and analyzing the accuracy of their repetitions to assess their speech function.The application of machine learning and deep learning techniques enables automatic extraction of MCI-related features from speech data,improving diagnostic accuracy.The combined application of these techniques contributes to the early detection of MCI,providing a basis for timely intervention.

Objective To investigate the correlation between KRAS gene mutations and their clinical,path-ological,and laboratory characteristics in patients with colorectal cancer.Methods KRAS gene mutation de-tection was performed using the Mutation Amplification System PCR(ARMS-PCR)method.297 colorectal cancer patients were divided into[KRAS wild-type(KRAS-WT)group and KRAS mutant type(KRAS-MT)group]based on their KRAS gene mutation status.Data on patient gender,age,primary site,metastatic infil-tration,TMN staging,pathological type,differentiation degree,immunohistochemistry,and serum tumor markers were collected.Statistical analysis was performed.Results Among 297 colorectal cancer patients,the total mutation rate of KRAS gene was 47.81％(142/297),with the highest mutation rate at the locus on exon 2,accounting for 35.69％(106/297).Compared with the KRAS-WT group,the KRAS-MT group had a higher proportion of patients with the primary site being the right colon and females(P＜0.05).There was a statis-tically significant difference in the proportion of Ki67 positive cells among the exon 2 mutation group,the exon 3 and 4 mutation group,and the KRAS-WT group(P＜0.05).There were statistically significant differences in serum CEA and CA199 levels among the exon 2 mutation group,exon 3 and 4 mutation groups,and KRAS-WT group(P＜0.05).Conclusion There is a certain correlation between KRAS gene mutation types in colorectal cancer and different clinical,pathological,and laboratory characteristics of patients,which could provide clues for the clinical diagnosis and treatment of colorectal cancer.

ObjectiveTo investigate the therapeutic effect of rhubarb decoction （RD） retention enema on a rat model of minimal hepatic encephalopathy （MHE） and its mechanism of action based on bile acid （BA） metabolomics. MethodsA total of 55 male Sprague－Dawley rats were randomly divided into blank group （NC group with 10 rats）， hepatic encephalopathy group （HE group with 15 rats）， MHE group with 15 rats， and MHE+rhubarb decoction treatment group （MHEY group with 15 rats）. Intraperitoneal injection of carbon tetrachloride （CCl₄） and thioacetamide （TAA） was performed to establish a rat model of MHE or HE， and the rats were sacrificed after 2 weeks of administration. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， alkaline phosphatase （ALP）， total bilirubin （TBil）， and total bile acid （TBA） and the concentration of blood ammonia were measured； the colonic contents were collected to measure pH value； liver and brain tissue samples were collected， and HE staining was used to observe the histopathological changes of the liver； the bile was collected， and liquid chromatography－mass spectrometry was used to perform BA－targeted metabolomics analysis. Continuous data were expressed as mean±standard deviation； a one－way analysis of variance was used for comparison between multiple groups， and the least significant difference t－test was used for further comparison between two groups. ResultsCompared with the NC group， the HE group and the MHE group had a significant increase in searching platform latency （after modelling and after administration） and a significant reduction in the number of platform crossings （all P<0.05）； compared with the MHE group， the MHEY group had a significant reduction in searching platform latency （after administration） and a significant increase in the number of platform crossings， and the HE group had a significant increase in searching platform latency and a significant reduction in the number of platform crossings （all P<0.05）. Compared with the NC group， the HE group and the MHE group had significant increases in AST， ALT， ALP， TBil， TBA， blood ammonia， and colon pH value （all P<0.05）； compared with the MHE group， the MHEY group had significant reductions in AST， ALT， ALP， TBil， TBA， blood ammonia， and colon pH value （all P<0.05）， and the HE group had significant increases in AST， ALT， ALP， TBil， TBA， blood ammonia， and colon pH value （all P<0.05）. The MHE group had significantly lower TBA， primary BA， and secondary BA than the NC group （all P<0.05）； compared with the MHE group， the HE group had significantly lower TBA and primary BA （all P<0.05）， and the MHEY group had significantly higher TBA and primary BA （all P<0.05）. Compared with the NC group， the MHE group had significant reductions in GCDCA， GUDCA， GHDCA， TCDCA， TUDCA， GLCA， and TLCA （all P<0.05） and significant increases in γ－MCA， THCA， 7－KDCA， AlloLCA， and α－MCA （all P<0.05）， and compared with the MHE group， the MHEY group had significant increases in THDCA， TMCA， TCDCA， TUDCA， and TLCA （all P<0.05）. ConclusionRD retention enema can improve liver injury and cognitive function in a rat model of MHE induced by CCl₄ and TAA by regulating the enterohepatic circulation of BA， possibly by increasing the synthesis of taurine－binding BA.

The gut microbiota has been found to interact with the brain through the microbiota-gut-brain axis, regulating various physiological processes. In recent years, the impacts of the gut microbiota on neurodevelopment through this axis have been increasingly appreciated. The gut microbiota is commonly considered to regulate neurodevelopment through three pathways, the immune pathway, the neuronal pathway, and the endocrine/systemic pathway, with overlaps and crosstalks in between. Accumulating studies have identified the role of the microbiota-gut-brain axis in neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity disorder, and Rett Syndrome. Numerous researchers have examined the physiological and pathophysiological mechanisms influenced by the gut microbiota in neurodevelopmental disorders (NDDs). This review aims to provide a comprehensive overview of advancements in research pertaining to the microbiota-gut-brain axis in NDDs. Furthermore, we analyzed both the current state of research progress and discuss future perspectives in this field.
Humans ; Brain-Gut Axis ; Autism Spectrum Disorder/metabolism* ; Brain/metabolism* ; Gastrointestinal Microbiome ; Neurodevelopmental Disorders/metabolism*

Background The tobacco epidemic as one of the most serious public health problems in the world contributes great harm to human health. It is urgent to develop tobacco control strategy. Civil servants' behaviors as a role model for society have a great influence on the rest of society. Thus, it is important to promote tobacco control program on helping civil servants to quit smoking. Objective To understand the smoking and second-hand smoking exposures status, the awareness of knowledge of tobacco hazards, and the attitudes to tobacco control policies of civil servants in Minhang District, Shanghai. Furthermore, to explore the related strategies and measures for tobacco control, to provide a basis for the development and revision of relevant intervention measures and policies. Methods A total of 20 government agencies with newly installed smoking-free programs from 10 subdistricts and towns in Minhang District, including Xinzhuang, Wujing, Maqiao, Qibao, Meilong, Hongqiao, Zhuanqiao, Jiangchuan, Gumei, and Xinhong were selected as study sites.A questionnaire survey was conducted to investigate all civil servants (n=801) of selected agencies. The questionnaire included general characteristics, smoking and second-hand smoking exposure status, knowledge of tobacco hazard, and attitudes to tobacco control policies. Results A total of 794 civil servants returned valid questionnaires. The awareness rate of tobacco hazards in the smoking group was lower than that in the non-smoking group (P<0.05). Relatively high smoking rates were reported in those being male (17.08%), age ≥51 years old (25.61%), divorced or widowed (12.50%), technical secondary school or below education level (22.81%), having more than 10 years of working years (11.57%), being willing to dissuade indoor smoking (24.54%), having no punishment or warning measures for violation of smoking regulations in workplaces (18.37%), and having no dedicated smoking spot at home (15.38%). The results of multiple logistic regression analysis showed that age 31-40 years old (OR=3.446, 95%CI: 1.236-9.609) and to avoid confronting indoor smoking (OR=3.686, 95%CI: 1.041-13.049) were risk factors for smoking in civil servants. Conclusion Civil servants aged 31-40 years old who deliberately avoid confronting indoor smoking behaviors are the key intervention population of smoking control in Minhang District, Shanghai.

Objective:To compare the clinical effective of clavicular hook plate with extra suture hole and traditional hook plate in the treatment of acute acromioclavicular dislocation.Methods:This study retrospectively analyzed the clinical data of traumatic acromioclavicular dislocation patients who were treated by operation from March 2017 to September 2020. The patients were included in traditional hook plate (THP) group and triangle stabilization technique hook plate (TSTHP) group according fracture fixations. TSTHP group adopted clavicular hook plate with extra suture hole. There were 27 patients in THP group with 18 male patients and 9 female patients; average age with 37.56±8.94 years old; 16 patients injured left side and 11 patients injured right side; crush injuries of 10 patients, traffic injuries of 9 patients and sports injuries of 8 patients; Rockwood classification of type III (9 patients), type IV (10 patients) and type V (8 patients). There were 20 patients in TSTHP group with 15 male patients and 5 female patients; average age with 38.95±9.91 years old; 13 patients injured left side and 7 patients injured right side; crush injuries of 9 patients, traffic injuries of 8 patients and sports injuries of 3 patients; Rockwood classification of type III (5 patients), type IV (9 patients) and type V (6 patients). The operation time, intraoperative bleeding, postoperative coracoclavicular space, visual analogue scale (VAS) and shoulder joint Constant-Murley score were compared between the two groups.Results:The operation time and blood loss of THP group and TSTHP group were 51.07±11.27 min, 87.41±15.34 ml and 55.65±8.59 min, 90.50±14.32 ml, respectively. The difference was not statistically significant ( t=1.52, 0.70, all P>0.05). Patients in both groups were followed up for 12 to 14 months after operations, with an average of 12.28 months. Six months after surgery, the coracoclavicular spaces of THP group and TSTHP group were 12.16±0.90 mm and 11.26±0.70 mm, respectively. The difference was statistically significant ( t=3.70, P<0.001). Postoperative VAS scores (2 days, 3 months, 6 months and 12 months) of TSTHP group [1.8±0.77, 0.00(0.00, 1.00), 0.00 (0.00, 0.00), 0.00(0.00, 0.00)] were significantly better than THP group [4.22±1.25, 2.00 (1.00, 3.00), 1.00 (0.00, 1.00), 0.00 (0.00, 1.00)]. The difference was statistically significant ( t=7.65, P<0.001; Z=4.85, P<0.001; Z=3.44, P=0.001; Z=2.96, P=0.003). Postoperative Constant-Murley scores (3 months, 6 months and 12 months) of TSTHP group (87.00±5.18, 91.25±2.75, 92.30±2.74) were significantly better than THP group (76.96±5.21, 83.22±3.86, 85.22±3.49). The difference was statistically significant ( t=6.54, 7.93, 7.51; P<0.001). The postoperative complication rates of THP group were higher than TSTHP group [70.4% (19/27) vs. 5.0% (1/20)]. Conclusion:In the treatment of acute acromioclavicular dislocation, the clavicular hook plate with extra suture hole can obtain satisfactory clinical effect compared with the THP, and clavicular hook plate with extra suture hole is more conducive to early recovery of shoulder function and reduce postoperative complications.

Objective:To preliminarily explore the association between single nucleotide polymorphisms (SNP) of five candidate genes (APH1B, PRNP, HMGCR, SIRT1, ApoE) and Alzheimer′s disease (AD), and to analyze the methylation levels of BAX and ApoE promoters on the pathogenesis of AD.Methods:Seventeen cases who were admitted to the Department of Geriatrics of the First Affiliated Hospital of Xinjiang Medical University from 2014 to 2015 and diagnosed as likely to be AD by geriatrician and neurologists according to the AD diagnostic criteria in 4th Revised Edition of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association served AD group, with an age of (75.65±5.86) years, and 34 non-AD patients with matching baseline data such as age, gender, ethnicity, and education status among patients hospitalized during the same period were selected as control group, with an age of (77.59±7.41) years. Sanger sequencing method was used for SNP typing of candidate genes. Methylation-specific polymerase chain reaction was used to determine the DNA methylation level.Results:The distribution of ApoE ε4 allele was statistically different between the AD group and the control group (χ 2=9.718, P=0.002). Candidate genes (SIRT1 rs7895833, APH1B rs1047552, PRNP rs1799990, HMGCR rs3846662) SNP locus genotypes and alleles had no statistically significant differences in the distribution between the AD group and the control group ( P>0.05). After stratification according to whether they carried ApoE ε4, no statistically significant difference was found between the two groups ( P>0.05). The BAX promoter methylation level of the AD group (0.045±0.025) was lower than that of the control group (0.061±0.028) ( t=-2.078, P=0.045). After gender stratification, the BAX methylation level of the female AD group (0.044±0.021) was lower than that of the control group (0.065±0.275) ( t=-2.230, P=0.045). There was no statistically significant difference in the methylation level of ApoE promoter between the AD group and the control group ( P>0.05). After stratification according to whether they carry ApoE ε4 or not, the methylation level of AD patients with ApoE ε4 allele (1.553±0.291) was higher than that of non-carriers (1.221±0.261) ( t=2.480, P=0.025). Conclusions:ApoE ε4 allele may be a risk factor for the onset of AD. BAX promoter hypomethylation contributes to AD in the elderly in Xinjiang, especially in female. ApoE ε4 allele may cause AD through the interaction with ApoE methylation.

Disulfiram, a drug that has been used for alcohol dependence. As an approved drug in clinical medicine, disulfiram can be used as the anticancer drug in the treatment of breast cancer, prostate cancer, glioblastoma, lung cancer, etc. This paper summarized the mechanism of disulfiram for anticancer treatment and the function for liver cancer therapy, and we also analyzed the potential mechanism of disulfiram for the treatment of liver cancer and its’ value in the clinical application.