With the advent of an aging society,Alzheimer's disease(AD)has gradually become a major ailment affecting the elderly.AD is a neurodegenerative disorder associated with cognitive impairments.In AD patients,brain network connections are disrupted,and their topological properties are also affected,leading to the disintegration of anatomical and functional connections.Anatomical connections can be tracked and evaluated using structural magnetic imaging(MRI)and diffusion tensor imaging(DTI),while functional connections are detected through functional MRI to assess their connectivity status.This review incorporates the findings of previous scholars and summarizes the current research of AD.It mainly discusses the imaging characteristics of large-scale brain network changes in AD patients,so as to provide researchers with scientific and objective imaging markers for AD prediction and early diagnosis,as well as future research.

Objective:To establish an antibody expression system to reduce the antibody-dependent enhancement (ADE) effect of target antibody.Methods:Site-directed mutagenesis was used to mutate the 234 and 235 sites of the Fc region of the mammalian cell antibody expression vector-L234A and L235A to establish the antibody expression vector pFRT-IgG1κ-FcM. An antibody Wt-WNV with significant ADE effect obtained in previous work was selected and expressed by the pFRT-IgG1κ-FcM system to obtain mutant antibody FcM-WNV. The binding ability of FcM-WNV to target antigen West Nile virus envelope protein-DⅢ (WNV E-DⅢ) was detected by ELISA, and the its binding ability to human high-affinity IgG Fc receptor hFcγRⅠ (hCD64 ) was analyzed by flow cytometry. The neutralizing activity of FcM-WNV in vitro was detected by pseudovirus infection of host cells (BHK21 and K562). Results:The expression levels of FcM-WNV and Wt-WNV were comparable, and FcM-WNV could recognize and bind to WNVE-DIII in a concentration-dependent manner. Compared with Wt-WNV, the binding ability of FcM-WNV to hCD64 was significantly weakened, showing a significant decrease in fluorescence intensity. Consistent with the previous experimental results, Wt-WNV at a concentration of 5 μg/ml significantly enhanced the infection of K562 by WNV pseudovirus, while FcM-WNV at a concentration of 5 μg/ml could effectively block pseudovirus infection in both K562 and BHK21 cells.Conclusions:The established antibody expression system can effectively reduce the ADE effect of the target antibody.

Objective:To establish an in vivo infection model of West Nile virus (WNV) pseudovirus and evaluate the neutralizing activity of antibody WNV-XH1.Methods:A stable cell line that can package the WNV pseudovirus was established in the early stage to prepare the pseudovirus supernatant. The supernatant was concentrated and infected BHK21 cells to detect the titer of the pseudovirus. After intraperitoneal injection of the pseudovirus into C57BL/J mice, bioluminescence imaging was performed to observe the infection status of the pseudovirus in the mice. After simultaneous infection, blood was collected and ELISA was used to detect NS1 levels in mouse serum. The in vivo functional activity of antibody WNV-XH1 was evaluated using the established mouse infection model.Results:Fluorescence was detected in C57BL/J mice infected with WNV pseudovirus, and the NS1 levels in the peripheral blood serum of mice infected with pseudovirus were significantly higher than those of non infected mice (1.453±0.09vs0.305±0.018). After intravenous administration of WNV-XH1 antibody before the attack, the fluorescence signal in the mice decreased and the serum NS1 level decreased (0.384±0.015).Conclusions:A successful in vivo infection model of WNV pseudovirus was established, and it was confirmed that the antibody WNV-XH1 had a protective effect against WNV pseudovirus infection in vivo.

Objective:To compare the short-term efficacy of Kamikawa anastomosis and double-tract reconstruction (DTR) after proximal gastrectomy.Methods:This was a propensity score matched, retrospective, cohort study. Inclusion criteria comprised age 20–70 years, diagnosis of gastric cancer by pathological examination of preoperative endoscopic biopsies, tumor diameter ≤4 cm, and location in the upper 1/3 of the stomach (including the gastroesophageal junction), and TNM stage IA, IB, or IIA. The study cohort comprised 73 patients who had undergone laparoscopic proximal gastric cancer radical surgery in the Department of Gastroenterology, Tangdu Hospital, Air Force Medical University between June 2020 and February 2023, 19 of whom were in the Kamikawa group and 54 in the DTR group. After using R language to match the baseline characteristics of patients in a ratio of 1:2, there were 17 patients in the Kamikawa group and 34 in the DTR group. Surgery-related conditions, postoperative quality of life, and postoperative complications were compared between the two groups.Results:After propensity score matching, there were no statistically significant differences in baseline data between the two groups ( P>0.05). Compared with the DTR group, the Kamikawa group had longer operative times (321.5±15.7 minutes vs. 296.8±26.1 minutes, t=32.056, P<0.001), longer anastomosis times (93.0±6.8 minutes vs. 45.3±7.7 minutes, t=56.303, P<0.001), and less bleeding (76 [54~103] mL vs.112 [82~148) mL, Z=71.536, P<0.001); these differences are statistically significant. There were no statistically significant differences between the two groups in tumor size, time to first postoperative passage of gas, postoperative hospital stay, number of lymph nodes removed, duration of lymph node dissection, or total hospitalization cost (all P>0.05). The median follow-up time was 6.1 ± 1.8 months. As to postoperative quality of life, the Kamikawa group had a lower rate of upper gastrointestinal contrast reflux than did the DTR group (0 vs. 29.4% [10/34], χ 2=6.220, P=0.013); this difference is statistically significant. However, differences between the two groups in quality of life score on follow-up of 3 months and 6 months on the Gastroesophageal Reflux Disease (GERD) scale were not statistically significant (all P>0.05). The incidence of postoperative complications was 2/17 in the Kamikawa group, which is significantly lower than the 41.2% (14/34) in the DTR group (χ 2=4.554, P=0.033). Conclusion:Kamikawa anastomosis and DTR are equally safe and effective procedures for reconstructing the digestive tract after proximal gastric surgery. Although Kamikawa anastomosis takes slightly longer and places higher demands on the surgical team, it is more effective at preventing postoperative reflux.

Objective:To summarize the clinical manifestations and prognostic factors of patients with hepatic amyloidosis in a single center.Methods:The clinical data of 28 primary systemic light chain amyloidosis cases with liver involvement in our center from October 2012 to January 2023 were retrospectively analyzed. The main clinical manifestations and prognostic factors were studied. Statistical analysis were performed using the χ 2 test, Fisher's exact test, Wilcoxon rank test, or Kaplan-Meier survival curve log-rank test according to the different data. Results:The main clinical manifestations of patients with liver involvement were abdominal distension, hepatomegaly, and edema. CD56 and chemokine receptor 4 protein expression accounted for 52% (13/25) and 56% (14/25). 64.3% (9/14) patients were combined with t (11,14), and 21.4% (3/14) patients were positive for 1q21 (+), and no patients were detected with del(17p). Univariate analysis showed that Mayo 2004 and 2012 stages and total bilirubin (TBil) ≥34.2 μmol/L were associated with progression-free survival and overall survival. The median progression-free survival and overall survival were significantly inferior in patients with TBil≥34.2μmol/L group (0.178 years, 0.195 years) than with the TBil<34.2μmol/L group (0.750 years, 3.586 years) ( P ?

AIM To optimize the extraction process for uracil,hypoxanthine,xanthine,uridine,thymine,inosine,guanosine and 2'-deoxyguanosine from Pheretima guillelmi(Michaelsen),and to determine their contents.METHODS With solid-liquid ratio,ultrasonic time and ultrasonic temperature as influencing factors,contents of hypoxanthine and total nucleosides as evaluation indices,the extraction process was optimized by orthogonal test.HPLC was adopted in the content determination of varioud nucleosides,the analysis was performed on a 30℃thermostatic Agilent C18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of methanol-water flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 260 nm.RESULTS The optimal conditions were determined to be 1∶250 for solid-liquid ratio,60 min for ultrasonic time,and 60℃for ultrasonic temperature.Eight nucleosides showed good linear relationships within their own ranges(R2＞0.999 0),whose average recoveries were 99.11%-103.27%with the RSDs of 0.85%-2.89%.CONCLUSION This stable and reliable method can be used for the extraction and content determination of nucleosides from P.guillelmi.

Objective:To compare the short-term efficacy of Kamikawa anastomosis and double-tract reconstruction (DTR) after proximal gastrectomy.Methods:This was a propensity score matched, retrospective, cohort study. Inclusion criteria comprised age 20–70 years, diagnosis of gastric cancer by pathological examination of preoperative endoscopic biopsies, tumor diameter ≤4 cm, and location in the upper 1/3 of the stomach (including the gastroesophageal junction), and TNM stage IA, IB, or IIA. The study cohort comprised 73 patients who had undergone laparoscopic proximal gastric cancer radical surgery in the Department of Gastroenterology, Tangdu Hospital, Air Force Medical University between June 2020 and February 2023, 19 of whom were in the Kamikawa group and 54 in the DTR group. After using R language to match the baseline characteristics of patients in a ratio of 1:2, there were 17 patients in the Kamikawa group and 34 in the DTR group. Surgery-related conditions, postoperative quality of life, and postoperative complications were compared between the two groups.Results:After propensity score matching, there were no statistically significant differences in baseline data between the two groups ( P>0.05). Compared with the DTR group, the Kamikawa group had longer operative times (321.5±15.7 minutes vs. 296.8±26.1 minutes, t=32.056, P<0.001), longer anastomosis times (93.0±6.8 minutes vs. 45.3±7.7 minutes, t=56.303, P<0.001), and less bleeding (76 [54~103] mL vs.112 [82~148) mL, Z=71.536, P<0.001); these differences are statistically significant. There were no statistically significant differences between the two groups in tumor size, time to first postoperative passage of gas, postoperative hospital stay, number of lymph nodes removed, duration of lymph node dissection, or total hospitalization cost (all P>0.05). The median follow-up time was 6.1 ± 1.8 months. As to postoperative quality of life, the Kamikawa group had a lower rate of upper gastrointestinal contrast reflux than did the DTR group (0 vs. 29.4% [10/34], χ 2=6.220, P=0.013); this difference is statistically significant. However, differences between the two groups in quality of life score on follow-up of 3 months and 6 months on the Gastroesophageal Reflux Disease (GERD) scale were not statistically significant (all P>0.05). The incidence of postoperative complications was 2/17 in the Kamikawa group, which is significantly lower than the 41.2% (14/34) in the DTR group (χ 2=4.554, P=0.033). Conclusion:Kamikawa anastomosis and DTR are equally safe and effective procedures for reconstructing the digestive tract after proximal gastric surgery. Although Kamikawa anastomosis takes slightly longer and places higher demands on the surgical team, it is more effective at preventing postoperative reflux.

Objective:To diagnose and explore the genetic etiology of a neonate with Hereditary epidermolysis bullosa.Methods:A neonate who was admitted to Suqian Hospital Affiliated to Xuzhou Medical University on July 10, 2021 was selected as the study subject. Peripheral blood samples were collected from the child and his parents for the extraction of genomic DNA. And target gene capture and next-generation sequencing were carried out. Candidate variants were verified by Sanger sequencing and pathogenicity analysis.Results:The child was found to harbor compound heterozygous variants of the COL17A1 gene, namely c. 997C>T (p.Q333X) and c. 3481dupT (p.Y1161fs*2), which were respectively inherited from his father and mother. Both variants were predicted to be pathogenic. Conclusion:The child was diagnosed with Generalized atrophic benign epidermolysis bullosa due to the compound heterozygous variants of the COL17A1 gene.

Objective:To understand the etiology,clinical characteristics and prognosis of secondary hemophagocytic syndrome(HLH),so as to improve the understanding of HLH and reduce the rates of misdiagnosis and missed diagnosis of HLH.Methods:A retrospective study was conducted to analyze the cause,clinical characteristics,laboratory findings,therapy and outcomes of 75 adult patients with secondary HLH admitted to our hospital from January 2015 to December 2021.Follow-up continued until the last discharge time.Results:Among 75 patients,infection-related HLH was the most common(45.33％),followed by lymphoma-related HLH(17.33％).Fever was the most common clinical manifestation(97.67％).Laboratory indicators such as NK cell activity(98.31％low or absent),sCD25(93.22％increased),and serum ferritin(94.44％elevated)had higher sensitivity in diagnosis.By comparing the clinical manifestations and laboratory indicators of HLH patients with different causes,sex,lymph node enlargement and bone marrow morphology were more valuable for the diagnosis of primary disease(all P＜0.05).By comparing the treatment and clinical outcomes of HLH patients with different causes,the highest clinical remission rate(83.3％)was achieved in patients with autoimmune disease-related HLH treated with hormone+cyclosporine(P＜0.05).The overall 12-month survival rate of all patients was 26.7％,in which the infection-related HLH was the lowest(14.7％)while autoimmune disease-related HLH was the highest(63.6％).Conclusion:The causes and clinical characteristics of adult secondary HLH are varied,with poor prognosis and heterogeneity in disease severity.It is important to identify HLH cause early for diagnosis and needed to further understand HLH.

Objective:To explore the challenges in the implementation of drug centralized volume-based procurement policies in hospitals and propose corresponding optimization suggestions.Methods:From August to December 2023, a purposive sampling was conducted to select 11 pharmaceutical experts from tertiary hospitals in China for Delphi method. The survey content included " policy recommendations for promoting the acceleration and expansion of national drug centralized procurement and retaining surplus medical insurance funds for centralized procurement" .Results:Survey participants gave feedback on a set of existing problems found in the implementation of drug centralized procurement policies and proposed corresponding optimization methods. Kendall′s W coefficient of the specialist consultation was 0.332( P<0.05), demonstrating good consistency and concentration of the expert opinions. Among the problems, the score of drug supply guarantee was the highest(mean value of importance was 4.45). At the same time, the recommendation of strengthening monitoring and early warning, coordination and dispatch, and effectively ensuring the supply of centralized drug procurement had the highest score and concentration(mean value of importance was 4.91, coefficient of variation was 0.06). Conclusions:Through Delphi method, this study revealed issues and optimization methods in the implementation of drug centralized procurement policies in hospitals. The findings could provide valuable insights for improvements in the pharmaceutical sector and future policy adjustments.