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 assess the clinical efficacy and safety of image-guided γ-ray stereotactic body radiation therapy(IG γ-SBRT)in treating advanced pancreatic cancer.Methods:A total of fifty-six patients with advanced pancreatic cancer admitted to Senior Department of Oncology Medicine of the Fifth Medical Center of Chinese PLA General Hospital(Department of Oncology of the Sixth Medical Center)from February 2017 to September 2020 were selected.All patients were treated with IG γ-SBRT,and the 50%-60%of isodose curve covered the planned target volume(PTV).The peripheral dose of each time was 3.0-4.5 Gy,and there were 10-11 times of treatment.The therapeutic effect was observed and was evaluated by follow-up.The visual analog scale(VAS)score was adopted to assess the situation of the pain of patients before and 3 months after treatment,and the adverse reaction of them.Results:In the 56 patients,52 cases occurred epigastric pain with VAS ranging from 3 to 10 points,among which 32 patients accompanied by symptoms such as lower back pain and abdominal distension.After 3 months of treatment,the results of reexamination and follow-up indicated that there were 48 patients whose VAS scores decreased 3 scores and above 3 scores on the basis of original scores,and the efficiency of treating pain was 92.3%.In addition,the VAS scores of 3 patients decreased 1-2 scores on the basis of original scores,which ratio was 5.85%of the total number of people.All 56 patients were reexamined at the 3rd month after treatment,and 13 cases of them obtained complete response(CR),and 37 cases obtained partial response(PR),and 1 case obtained progressive disease(PD),and 5 cases obtained stable disease(SD),and the objectively response rate(ORR)was 89.3%,and the locally control rate was 98.2%.In addition,median progression-free survival(PFS)was 6.5 months,and 1-year survival rate was 62.5%(35/56),and 2-year survival rate was 23.2%(13/56).The adverse reactions of 56 patients were the adverse reactions of digestive system and blood system,among which 47 patients occurred upper digestive tract reaction,and the incidence of adverse reactions was 83.9%(47/56).A total of 43 patients occurred myelosuppression,and the incidence of myelosuppression was 76.8%(43/56).Conclusion:IG γ-SBRT can effectively relieve the symptoms of metastatic pancreatic cancer,and improve the effectiveness of treatment,the local control rate and survival rate.The tolerance of adverse reaction of that is favorable,and the safety of that is higher.

Objective:To investigate the clinical and molecular features of patients with CD7 +relapsed or refractory acute myeloid leukemia(r/rAML)and the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods:172 r/rAML patients who underwent allo-HSCT in department of hematology, Aerospace Center Hospital between January 1st 2017 and December 31st 2020 were retrospectively analyzed The patients were were divided into CD7 + group( n=75) and CD7 - group( n=97) according to the expression CD7 in the initial immunophenotype. Mann-Whitney U and Chi-square test were used to compare the clinical data, molecular and cytogenetic characteristics of the two groups of patients. Kaplan-Meier method was used to analyze the median progression-free survival (PFS) and median overall survival (OS) of the two groups of patients, and Cox regression screenthe prognostic factors of the patients. Results:The median follow-up time was 19 months. The recurrence rates were 23.71% and 50.67%, respectively in CD7 - and CD7 + group (χ 2=13.428 P<0.001). In relapsed patients, 86.96 percentage of CD7 - group did not express CD7 while 86.84 percentage of CD7 + group expressed CD7. The median PFS was 25 and 5 months in CD7 - and CD7 + group (χ 2=8.695, P=0.003), and the medianOS was 34 and 15 months in CD7 - and CD7 + group (χ 2=2.579, P=0.108). Univariate analysis showed that the CD7 +group, had the lower rates of morphological remission (χ 2=10.014, P=0.002), molecular remission (χ 2=22.809, P<0.001), and more male patients (χ 2=5.281, P=0.022). The incidence of CEBPA double-site mutation was higher (23.4% vs 8.2%, χ 2=8.180, P=0.004) and the rearrangement of RUNX1::RUNX1T1 was lower(4.0% vs18.6%, χ 2=8.362, P=0.004)in CD7 +group than in CD7 -group. Multivariate analysis showed that pre-transplant tumor load was the only prognostic factor for PFS (HR, 1.600; 95% CI, 1.203 to 2.127; P=0.001) and OS (HR, 1.737; 95% CI, 1.273 to 2.369; P<0.001) in r/r AML patients. Conclusion:CD7 expression is a risk factor for poor prognosis in r/r AML patients, and CD7 expression is stable after relapse. Positive CD7 can be used as a target for immune targeted therapy.

Objective:To study the impact of number and location of metastatic lymph nodes on prognosis of patients after radical resection for intrahepatic cholangiocarcinoma (ICC).Methods:A retrospective study was conducted on 105 patients who underwent radical resection and lymphadenectomy for ICC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2010 to December 2020. There were 49 males and 56 females, with age of (58±10) years old. These patients were divided into 2 groups using the TNM staging (8th edition) into the N0 stage group ( n=62) and N1 stage group ( n=43). Using the NMLN staging, those with 0, 1-2, and >3 number of metastatic lymph nodes (NMLN) were divided into 3 groups: the stage 0 group ( n=62), stage 1 group ( n=24), and stage 2 group ( n=19). Of the 43 patients with lymph node metastasis, they were divided into 2 groups according to whether the lymph node metastasis was limited to the first lymph node station: the first station metastasis group ( n=11) and the non-first station metastasis group ( n=32). The general data, extent of lymph node dissection, pathological examinations, and postoperative survival outcomes of these patients were collected. Determination of risk factors for prognosis of ICC after radical resection was carried out. Results:The median number of lymph node harvested, or the detection of N0 and N1 staging were 6 (3, 8) and 6 (3, 10), respectively. There were no significant differences between the two groups ( Z=-1.10, P>0.05). Overall survival of patients in the N0 stage group was better than the N1 stage group (32.0 vs. 9.0 months, χ 2=23.99, P<0.001). The median survival times of patients in the stage 0, stage 1 and stage 2 groups were 32.0, 14.0 and 6.0 months, respectively. There was a significant difference in overall survival among the 3 groups (χ 2=32.18, P<0.001). The time-dependent receiver operating characteristic curves showed that NMLN staging had better prognostic predictive ability than the N staging. The median survival times of the first station metastasis group and the non-first station metastasis group were 18.0 and 7.0 months, respectively. There was no significant difference between the two groups (χ 2=2.21, P>0.05). Multivariate analysis showed that tumor carbohydrate antigen 125>35.0 U/ml ( HR=4.297, 95% CI:2.418-7.634), hepatolithiasis ( HR=2.713, 95% CI:1.499-4.911), T4 staging ( HR=2.934, 95% CI:1.478-5.825), NMLN stage 1 ( HR=2.759, 95% CI:1.500-5.077) and NMLN stage 2 ( HR=7.376, 95% CI:3.553-15.312) were independent risk factors affecting prognosis of ICC after radical resection ( P<0.05). Conclusion:Lymph node metastasis was an important poor prognostic risk factor after radical resection of intrahepatic cholangiocarcinoma. The prognosis of ICC patients was related to the NMLN, but it was not related to the location of metastatic lymph nodes.

Objective:To examine the correlation between perineural invasion and clinicopathological factors and the role of perineural invasion on the prognosis of patients with curatively resected gallbladder carcinoma.Methods:The clinicopathological and follow-up data of 548 patients with gallbladder carcinoma who underwent radical surgery from the First Affiliated Hospital of Xi′an Jiaotong University from January 2013 to December 2020 were analyzed retrospectively. There were 173 males and 375 females,with age( M(IQR)) of 62(14)years(range:30 to 88 years). The correlations between perineural invasion and the clinicopathological features were analyzed. The relationship between prognosis and clinicopathological factors were further analyzed. The survival curve was drawn using the Kaplan-Meier method. The univariate analysis and multivariate analysis were done using the Log-rank test and Cox proportional hazard model respectively. Results:Radical resection was performed in 548 cases,including 59 cases(10.8%) with perineural invasion. The results of univariate analysis showed that perineural invasion was related to serum bilirubin level,serum carcinoembryonic antigen(CEA) level,CA19-9 level,T stage,lymph node metastasis,liver invasion,vessel invasion and tumor location(all P<0.05).The results of multivariate analysis showed that jaundice,high-level serum CA19-9,high-level serum CEA,T4 stage,vessel invasion and tumor located in the neck or cystic duct of the gallbladder were independent risk factors of perineural invasion in gallbladder carcinoma. Survival of 367 patients in T3-T4 stages were analyzed. The prognosis of gallbladder carcinoma patients with perineural invasion was significantly worse than that of patients without perineural invasion(median survival time:12.0 months vs. 34.7 months, P<0.01). Univariate analysis showed that perineural invasion,gallbladder stones,gallbladder polyps,CA125,CEA,CA19-9,serum bilirubin level,tumor location,N stage,liver invasion and pathological differentiation were independent risk factors affecting prognosis of patients with gallbladder carcinoma(all P<0.05). The results of Cox proportional hazard model showed that perineural invasion,N stage,liver invasion,gallbladder stones,pathological differentiation were independent risk factors affecting prognosis of patients with gallbladder carcinoma(all P<0.05). Conclusions:Jaundice,high-level serum CA19-9,high-level serum CEA,T4 stage,vessel invasion and tumor located in the neck or cystic duct of the gallbladder are independent risk factors for perineural invasion of gallbladder carcinoma. Perineural invasion is one of the independent risk factors affecting the prognosis of T3-T4 stage gallbladder carcinoma.

Proteolysis targeting chimeria (PROTAC) degrades target proteins by utilizing the ubiquitin-proteasome pathway, subverting the concept of traditional small molecule inhibitors. Among the common mutation targets of non-small cell lung cancer (NSCLC), PROTAC technology has successfully achieved the effective degradation of kirsten rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK ) and other proteins in preclinical studies. PROTAC drugs with their unique event-driven advantages, are expected to overcome acquired drug resistance caused by small molecule inhibitors and show good therapeutic potential for undruggable targets, thereby providing a new strategy for the treatment of NSCLC.
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Carcinoma, Non-Small-Cell Lung/pathology* ; Humans ; Lung Neoplasms/pathology* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proteolysis ; Proto-Oncogene Proteins p21(ras)/genetics*

Objective:To examine the correlation between perineural invasion and clinicopathological factors and the role of perineural invasion on the prognosis of patients with curatively resected gallbladder carcinoma.Methods:The clinicopathological and follow-up data of 548 patients with gallbladder carcinoma who underwent radical surgery from the First Affiliated Hospital of Xi′an Jiaotong University from January 2013 to December 2020 were analyzed retrospectively. There were 173 males and 375 females,with age( M(IQR)) of 62(14)years(range:30 to 88 years). The correlations between perineural invasion and the clinicopathological features were analyzed. The relationship between prognosis and clinicopathological factors were further analyzed. The survival curve was drawn using the Kaplan-Meier method. The univariate analysis and multivariate analysis were done using the Log-rank test and Cox proportional hazard model respectively. Results:Radical resection was performed in 548 cases,including 59 cases(10.8%) with perineural invasion. The results of univariate analysis showed that perineural invasion was related to serum bilirubin level,serum carcinoembryonic antigen(CEA) level,CA19-9 level,T stage,lymph node metastasis,liver invasion,vessel invasion and tumor location(all P<0.05).The results of multivariate analysis showed that jaundice,high-level serum CA19-9,high-level serum CEA,T4 stage,vessel invasion and tumor located in the neck or cystic duct of the gallbladder were independent risk factors of perineural invasion in gallbladder carcinoma. Survival of 367 patients in T3-T4 stages were analyzed. The prognosis of gallbladder carcinoma patients with perineural invasion was significantly worse than that of patients without perineural invasion(median survival time:12.0 months vs. 34.7 months, P<0.01). Univariate analysis showed that perineural invasion,gallbladder stones,gallbladder polyps,CA125,CEA,CA19-9,serum bilirubin level,tumor location,N stage,liver invasion and pathological differentiation were independent risk factors affecting prognosis of patients with gallbladder carcinoma(all P<0.05). The results of Cox proportional hazard model showed that perineural invasion,N stage,liver invasion,gallbladder stones,pathological differentiation were independent risk factors affecting prognosis of patients with gallbladder carcinoma(all P<0.05). Conclusions:Jaundice,high-level serum CA19-9,high-level serum CEA,T4 stage,vessel invasion and tumor located in the neck or cystic duct of the gallbladder are independent risk factors for perineural invasion of gallbladder carcinoma. Perineural invasion is one of the independent risk factors affecting the prognosis of T3-T4 stage gallbladder carcinoma.

Objective:To evaluate the related factors of gallstones related gallbladder intraepithelial neoplasia(GBIN) and establish the prediction models for gallstones related GBIN.Methods:The clinicopathological data of 750 patients who underwent cholecystectomy for gallstones at Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi′an Jiaotong University from January 2013 to December 2018 and the postoperative pathological examination showed chronic cholecystitis or GBIN were analyzed retrospectively,including 150 cases of gallstones with GBIN and 600 cases of gallstones with chronic cholecystitis.There were 264 males and 486 females with age of (51.3±14.5) years (range: 18 to 90 years).The related factors for gallstones related GBIN were screened by χ 2 test and Logistic regression model,and the prediction models were established based on independent related factors and internal validation was conducted.The original data were randomly divided into a training cohort(526 cases) and a validation cohort(224 cases) at a ratio of 7∶3,and the nomogram and tree augmented na?ve Bayes were conducted to establish the prediction model for gallstones related GBIN.The consistency index(C-index),calibration chart,area under the receiver operating characteristic curve(AUC) and confusion matrix were used to evaluate the prediction performance of the two models. Results:Univariate analysis showed that age,gallstones history(years),gallbladder size,whether the gallbladder mucosa smooth or not,whether the gallbladder wall thickened or not,gallstones diameter,and number of gallstones were related factors for the occurrence of gallstones related GBIN (χ2=19.957,8.599,9.724,9.301,8.341,15.288,9.169,all P<0.05).Multivariate analysis showed that age ( OR=2.23,95% CI:1.50-3.31, P<0.01),gallbladder size ( OR=2.11,95% CI:1.17-3.80, P=0.013),whether the gallbladder mucosa smooth or not ( OR=1.80,95% CI:1.13-2.88, P=0.014),gallstones diameter( OR=2.98,95% CI:1.71-5.21, P<0.01),and number of gallstones ( OR=2.14,95% CI:1.34-3.42, P<0.01) were independent related factors for the occurrence of gallstones related GBIN; the C-index of the nomogram in training cohort and validation cohort were 0.708 and 0.696,respectively.The AUC of the two models in training cohort were 70.60% and 70.73%,and in validation cohort were 68.14% and 67.47%,respectively.The accuracy of the two models in training cohort were 69.96% and 70.72%,and in validation cohort were 66.96% and 67.41%,respectively. Conclusion:Age,gallbladder size,whether the gallbladder mucosa smooth or not,gallstones diameter and number of gallstones are independent related factors for the occurrence of gallstones related GBIN,and the nomogram and tree augmented na?ve Bayes prediction models based on the above factors can be used to predict the occurrence of GBIN.

Objective To investigate the mechanism of Fuzheng Huayu(FZHY) decoction in the treatment of liver cancer based on network pharmacology. Methods TCMSP, BATMAN, and Drugbank databases were searched for the main chemical components and corresponding targets of FZHY, and STRING database was used to perform a PPI network analysis. Cytoscape software was used to establish a drug-disease network model and perform a network analysis, and R language was used to perform GO and KEGG enrichment analysis of targets. Results A total of 192 intersection genes between FZHY and liver cancer and 95 potential compounds were screened out, among which quercetin and luteolin were the active components with an important regulatory role. INS, IL-6, and EGFR were the key targets for the potential effect of FZHY. The GO enrichment analysis showed the involvement in various biological processes such as response to drug and response to oxygen level, and the KEGG enrichment analysis showed the involvement in the signaling pathways including apoptosis and tumor necrosis factor signaling pathways. Conclusion Based on the method of network pharmacology, this study reveals the mechanism of action of multiple targets and targets of FZHY in the treatment of liver cancer, which provides a theoretical basis for clinical and basic scientific research.

Objective:To evaluate the related factors of gallstones related gallbladder intraepithelial neoplasia(GBIN) and establish the prediction models for gallstones related GBIN.Methods:The clinicopathological data of 750 patients who underwent cholecystectomy for gallstones at Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi′an Jiaotong University from January 2013 to December 2018 and the postoperative pathological examination showed chronic cholecystitis or GBIN were analyzed retrospectively,including 150 cases of gallstones with GBIN and 600 cases of gallstones with chronic cholecystitis.There were 264 males and 486 females with age of (51.3±14.5) years (range: 18 to 90 years).The related factors for gallstones related GBIN were screened by χ 2 test and Logistic regression model,and the prediction models were established based on independent related factors and internal validation was conducted.The original data were randomly divided into a training cohort(526 cases) and a validation cohort(224 cases) at a ratio of 7∶3,and the nomogram and tree augmented na?ve Bayes were conducted to establish the prediction model for gallstones related GBIN.The consistency index(C-index),calibration chart,area under the receiver operating characteristic curve(AUC) and confusion matrix were used to evaluate the prediction performance of the two models. Results:Univariate analysis showed that age,gallstones history(years),gallbladder size,whether the gallbladder mucosa smooth or not,whether the gallbladder wall thickened or not,gallstones diameter,and number of gallstones were related factors for the occurrence of gallstones related GBIN (χ2=19.957,8.599,9.724,9.301,8.341,15.288,9.169,all P<0.05).Multivariate analysis showed that age ( OR=2.23,95% CI:1.50-3.31, P<0.01),gallbladder size ( OR=2.11,95% CI:1.17-3.80, P=0.013),whether the gallbladder mucosa smooth or not ( OR=1.80,95% CI:1.13-2.88, P=0.014),gallstones diameter( OR=2.98,95% CI:1.71-5.21, P<0.01),and number of gallstones ( OR=2.14,95% CI:1.34-3.42, P<0.01) were independent related factors for the occurrence of gallstones related GBIN; the C-index of the nomogram in training cohort and validation cohort were 0.708 and 0.696,respectively.The AUC of the two models in training cohort were 70.60% and 70.73%,and in validation cohort were 68.14% and 67.47%,respectively.The accuracy of the two models in training cohort were 69.96% and 70.72%,and in validation cohort were 66.96% and 67.41%,respectively. Conclusion:Age,gallbladder size,whether the gallbladder mucosa smooth or not,gallstones diameter and number of gallstones are independent related factors for the occurrence of gallstones related GBIN,and the nomogram and tree augmented na?ve Bayes prediction models based on the above factors can be used to predict the occurrence of GBIN.