Purpose To investigate the sex differences of white matter damage in Alzheimer's disease(AD)and their association with cognitive impairment.Materials and Methods This retrospective study included 88 AD patients(48 females),71 amnestic mild cognitive impairment(aMCI)patients(39 females),and 95 healthy controls(63 females)recruited from the Memory Disorder Clinic at the First Affiliated Hospital of Anhui Medical University from September 2017 to July 2024.High-resolution three-dimensional T1 structure images and diffusion tensor imaging images were all obtained from each participant.The mean diffusivity(MD)and fractional anisotropy(FA)values of each white matter region were obtained,and the two-way ANOVA analysis was conducted to investigate brain regions with interaction effects between groups and sexes,those brain regions were then chosen as regions of interest for further correlation analysis with a series of cognitive scale scores.Results In terms of FA values,the right posterior corona radiata,right anterior limb of the internal capsule and left corticospinal tract showed interaction between sexes and cognitive groups(F=4.764,3.812,5.937,all P<0.05).The FA value of AD group was significantly lower than that of healthy control and aMCI group(all P<0.05),but there was no significant difference between healthy control and aMCI group(except the right anterior limb of the internal capsule,P=0.018).In AD group,FA values were significantly higher in women than in men in the previously described brain regions(all P<0.05),while there was no significant difference in FA values between male and female in healthy control and aMCI groups(except the left corticospinal tract,P<0.001).In terms of MD values,the right anterior limb of the internal capsule,right superior corona radiata and left external capsule showed interaction effect between sexes and cognitive groups(F=8.581,3.680,7.218,all P<0.05).The MD value of AD group was significantly higher than that of aMCI group(P<0.001),and aMCI group was higher than that of healthy control group(all P<0.05).In AD group,the MD values in the above brain regions were significantly higher in males than those in females(all P<0.01),while no significant difference was found between males and females in healthy control and aMCI groups(except for the left external capsule,P<0.05).For correlation analysis,the AD group was dimidiated into two groups by sex,the scores of the Montreal cognitive assessment,the Mini Mental state examination and the verbal fluency test of the female patient group were positively correlated with the FA values of the right posterior corona radiate(r=0.372,P=0.009;r=0.345,P=0.016;r=0.383,P=0.007),while the Mini Mental state examination and the verbal fluency test scores of female AD patient group were negatively correlated with the MD values of the right superior corona radiata(r=-0.360,P=0.012;r=-0.360,P=0.003).Conclusion Compared to the healthy control and MCI groups,white matter damage in AD patients shows sex differences and is associated with general cognitive and language functions impairment in female AD patients.

Purpose To investigate the sex differences of white matter damage in Alzheimer's disease(AD)and their association with cognitive impairment.Materials and Methods This retrospective study included 88 AD patients(48 females),71 amnestic mild cognitive impairment(aMCI)patients(39 females),and 95 healthy controls(63 females)recruited from the Memory Disorder Clinic at the First Affiliated Hospital of Anhui Medical University from September 2017 to July 2024.High-resolution three-dimensional T1 structure images and diffusion tensor imaging images were all obtained from each participant.The mean diffusivity(MD)and fractional anisotropy(FA)values of each white matter region were obtained,and the two-way ANOVA analysis was conducted to investigate brain regions with interaction effects between groups and sexes,those brain regions were then chosen as regions of interest for further correlation analysis with a series of cognitive scale scores.Results In terms of FA values,the right posterior corona radiata,right anterior limb of the internal capsule and left corticospinal tract showed interaction between sexes and cognitive groups(F=4.764,3.812,5.937,all P<0.05).The FA value of AD group was significantly lower than that of healthy control and aMCI group(all P<0.05),but there was no significant difference between healthy control and aMCI group(except the right anterior limb of the internal capsule,P=0.018).In AD group,FA values were significantly higher in women than in men in the previously described brain regions(all P<0.05),while there was no significant difference in FA values between male and female in healthy control and aMCI groups(except the left corticospinal tract,P<0.001).In terms of MD values,the right anterior limb of the internal capsule,right superior corona radiata and left external capsule showed interaction effect between sexes and cognitive groups(F=8.581,3.680,7.218,all P<0.05).The MD value of AD group was significantly higher than that of aMCI group(P<0.001),and aMCI group was higher than that of healthy control group(all P<0.05).In AD group,the MD values in the above brain regions were significantly higher in males than those in females(all P<0.01),while no significant difference was found between males and females in healthy control and aMCI groups(except for the left external capsule,P<0.05).For correlation analysis,the AD group was dimidiated into two groups by sex,the scores of the Montreal cognitive assessment,the Mini Mental state examination and the verbal fluency test of the female patient group were positively correlated with the FA values of the right posterior corona radiate(r=0.372,P=0.009;r=0.345,P=0.016;r=0.383,P=0.007),while the Mini Mental state examination and the verbal fluency test scores of female AD patient group were negatively correlated with the MD values of the right superior corona radiata(r=-0.360,P=0.012;r=-0.360,P=0.003).Conclusion Compared to the healthy control and MCI groups,white matter damage in AD patients shows sex differences and is associated with general cognitive and language functions impairment in female AD patients.

Objective To explore the correlation between the change of the serum levels of thyroid hormone and the severity of anxiety symptoms in patients with generalized anxiety disorder after treatment with paroxetine hydrochloride.Methods 76 patients with generalized anxiety disorder treated in the Third People's Hospital of Huzhou from January to August 2023 were collected as study group,and they were divided into mild group(n=23),moderate group(n=30),and severe group(n=23),according to degree of anxiety by Hamilton anxiety scale(HAMA),69 healthy examination subjects in the same period were selected as control group.Patients in study group were treated with paroxetine hydrochloride tablets for 8 weeks,patients were evaluated anxiety symptoms,the serum levels of thyroid hormone were measured at baseline and 8 weekend,including triiodothyronine(T3),thyroxine(T4),free triiodothyronine(FT3),free thyroxine(FT4),thyroid stimulating hormone(TSH),antithyroglobulin antibody(TG),anti-thyroid peroxidase antibody(TPO).Results After 8 weeks of paroxetine hydrochloride treatment,the significant efficacy rates of mild group,moderate group,and severe group were 73.9％,76.7％,and 73.9％,with no statistically significant difference in efficacy among three groups(x2=0.073,P＞0.05).In the baseline period,FT4 levels of patients in moderate group and severe group were significantly higher than those in mild group and control group,and the difference was statistically significant(P＜0.05).The severity of anxiety symptoms in the baseline period of patients in moderate group and severe group showed a low positive correlation and a significant positive correlation with FT4 levels(r=0.382、0.610,P＜0.05).After 8 weeks treatment,the FT4 levels of patients in moderate group and severe group decreased significantly compared to the baseline period,and the difference was statistically significant(t=2.847,3.042,P＜0.05).The reduction rate of HAMA score in severe group was positively correlated with the change in FT4 level during the baseline period and at the end of 8 weeks of treatment(r=0.517,P＜0.05).By a binary Logistic regression analysis showed that the higher levels of FT4 in the baseline period with the worse efficacy in moderate group and severe group.Conclusion The improvement of anxiety symptoms could be affected by high baseline levels of FT4 in generalized anxiety disorder patients with moderate to severe anxiety.

Objective: To explore sex differences in 3D T1texture features in the progression of Alzheimer's disease (AD) and to predict the diagnosis of AD patients of different sex． Methods: Seventy-seven AD patients (34 males and 42 females) ，74 amnestic mild cognitive impairment ( aMCI) patients ( 35 males and 39 females) and 75 healthy controls (HC) (35 males and 40 females) were recruited and high-resolution 3-dimensional T1 structural images were collected． Brain regions closely related to AD brain damage were selected as regions of interest ( ROIs) ，texture feature extraction and feature screening were performed．Analyses were performed by sex，and the support vector machine (SVM) was used for classification and prediction. Results : In the AD vs HC，AD vs aMCI and aMCI VS HC groups by different sex，we obtained some brain regions with relatively high recognition index in different subgroups，and found that there were significant differences between female patients and male patients with high recognition index，and the recognition index of female patients ( area under the curve，accuracy，sensitivity and specificity were generally higher than that of male． Conclusion There are significant sex differences in texture features in AD process，and the classification and prediction ability of texture features in female patients is better， suggesting the importance of sex differences in AD research．This study provides some reliable biomarkers for early sex-specific identification of AD，which may be helpful for the early diagnosis and treatment of AD in the future.

Objective:To explore the research hotspots of early enteral nutrition and analyze its development trend.Methods:The Web of Science core database was retrieved. HistCite and CiteSpace were used to conduct quantitative analysis and co-word clustering analysis of early enteral nutrition.Results:A total of 823 articles were retrieved, and the number of articles was increasing. The research hotspots of early enteral nutrition mainly included severe disease, esophageal cancer, acute pancreatitis, sepsis, malnourished patients and premature infants. At the same time, the selection of early enteral nutrition nutrients was also a research hotspot.Conclusions:Early enteral nutrition research in critically ill patients is mature, and other specialized fields can carry out specialized early enteral nutrition support based on the research on critically ill patients. In the future, comparative studies on the effects of different nutrients in early enteral nutrition can also be carried out.

Objective:To explore the clinical characteristics and risk factors of the severe delayed encephalopathy after acute carbon monoxide poisoning (s-DEACMP).Methods:A retrospective analysis of 170 acute carbon monoxide poisoning (ACMP) patients treated in the Hyperbaric Oxygen (HBO) Department of Beijing Chao-yang Hospital, Capital Medical University from January 1st, 2017 to December 31st, 2020 was conducted. According to the occurrence of delayed encephalopathy, the ACMP patients were divided into DEACMP group and non-DEACMP (n-DEACMP) group. The DEACMP patients were stratified by the activities of daily living scale when they were most severely ill. The patients with total score≤60 were classified as s-DEACMP and the patients with total score >60 were classified as mild to moderate DEACMP (m-DEACMP). Their clinical characteristics were compared and the risk factors of s-DEACMP were analyzed.Results:There were 70 s-DEACMP patients, 49 m-DEACMP patients, and 51 n-DEACMP patients. Compared with the n-DEACMP group, the s-DEACMP group was older (average age: 59.0 vs. 49.0, P=0.005), had a higher proportion of patients over 40 years old (97.1% vs. 66.7%, P<0.001), lower Glasgow coma scale scores [(4.0±3.0) vs.(6.0±5.0), P=0.024] on admission to the hospital, longer consciousness disturbance [(32.0±31.8) h vs.(20.5±26.4) h, P=0.017], a higher proportion of patients with consciousness disturbance over 48 hours (24.3% vs. 9.8%, P=0.041), a lower proportion of patients receiving HBO therapy (70.0% vs. 86.3%, P=0.036), a higher proportion of patients with hypertension (38.6% vs. 17.6%, P=0.013), a higher proportion of patients with hyperhomocysteinemia (40.0% vs. 19.6%, P=0.017), and a higher proportion of patients with smoking index over 400 (24.3% vs. 9.8%, P=0.041). Compared with the m-DEACMP group, the s-DEACMP group had a higher proportion of patients with hyperhomocysteinemia (40.0% vs. 20.4%, P=0.024). Multivariate Logistic regression showed that age over 40 years old, consciousness disturbance over 48 hours, hypertension, and hyperhomocysteinemia were independent risk factors of s-DEACMP( P<0.05). Conclusion:The clinical characteristics of s-DEACMP patients are that the patients are older, have a deeper and longer consciousness disturbance, a lower proportion of early HBO intervention, a higher proportion of hypertension, hyperhomocysteinemia, and smoking index over 400. Among them, the age over 40 years old, disturbance consciousness over 48 hours, and hypertension were the independent risk factors of the occurrence of s-DEACMP.In additon hyperhomocysteinemia was also an idependent risk factor for s-DEAMP, which special worth attention.

Objective:To explore the clinical characteristics and risk factors of the severe delayed encephalopathy after acute carbon monoxide poisoning (s-DEACMP).Methods:A retrospective analysis of 170 acute carbon monoxide poisoning (ACMP) patients treated in the Hyperbaric Oxygen (HBO) Department of Beijing Chao-yang Hospital, Capital Medical University from January 1st, 2017 to December 31st, 2020 was conducted. According to the occurrence of delayed encephalopathy, the ACMP patients were divided into DEACMP group and non-DEACMP (n-DEACMP) group. The DEACMP patients were stratified by the activities of daily living scale when they were most severely ill. The patients with total score≤60 were classified as s-DEACMP and the patients with total score >60 were classified as mild to moderate DEACMP (m-DEACMP). Their clinical characteristics were compared and the risk factors of s-DEACMP were analyzed.Results:There were 70 s-DEACMP patients, 49 m-DEACMP patients, and 51 n-DEACMP patients. Compared with the n-DEACMP group, the s-DEACMP group was older (average age: 59.0 vs. 49.0, P=0.005), had a higher proportion of patients over 40 years old (97.1% vs. 66.7%, P<0.001), lower Glasgow coma scale scores [(4.0±3.0) vs.(6.0±5.0), P=0.024] on admission to the hospital, longer consciousness disturbance [(32.0±31.8) h vs.(20.5±26.4) h, P=0.017], a higher proportion of patients with consciousness disturbance over 48 hours (24.3% vs. 9.8%, P=0.041), a lower proportion of patients receiving HBO therapy (70.0% vs. 86.3%, P=0.036), a higher proportion of patients with hypertension (38.6% vs. 17.6%, P=0.013), a higher proportion of patients with hyperhomocysteinemia (40.0% vs. 19.6%, P=0.017), and a higher proportion of patients with smoking index over 400 (24.3% vs. 9.8%, P=0.041). Compared with the m-DEACMP group, the s-DEACMP group had a higher proportion of patients with hyperhomocysteinemia (40.0% vs. 20.4%, P=0.024). Multivariate Logistic regression showed that age over 40 years old, consciousness disturbance over 48 hours, hypertension, and hyperhomocysteinemia were independent risk factors of s-DEACMP( P<0.05). Conclusion:The clinical characteristics of s-DEACMP patients are that the patients are older, have a deeper and longer consciousness disturbance, a lower proportion of early HBO intervention, a higher proportion of hypertension, hyperhomocysteinemia, and smoking index over 400. Among them, the age over 40 years old, disturbance consciousness over 48 hours, and hypertension were the independent risk factors of the occurrence of s-DEACMP.In additon hyperhomocysteinemia was also an idependent risk factor for s-DEAMP, which special worth attention.

To investigate the presence of integrated Epstein-Barr virus (EBV) DNA in the NK/T cell lymphoma (NKTCL) ge-nome and analyze the integration information in the genome of NKTCL cell lines. Methods: PCR and in situ hybridization were used to detect EBV infection in five EBV (+) NK/T samples and four EBV (-) NK/T samples provided by the biobanks of the First Affiliated Hospi-tal of Zhengzhou University. Whole-genome DNA of the samples was sequenced and subjected to bioinformatics analysis. Whole-ge-nome sequence alignment was used to identify the EBV integration sequence. BLAST analysis was used to compare EBV fasta files of the samples and EBV fasta library. CREST software was used to extract softclip reads, filter all paired reads, and enumerate their distri-bution on chromosomes. The integrated genomics viewer (IGV) was used to compare the distribution of reads in partial regions of chromosome. PCR was used to amplify the high-frequency integration region of the EBV DNA. The amplified fragments were sanger se-quenced. Results: EBV DNA and EBER expression were detected in five EBV (+) NK/T samples but not in the four EBV (-) NK/T samples. Sequencing depth, coverage depth, proportion of coverage, and proportion of alignment all met the requirements for subsequent re-search. Sequence alignment revealed that the captured sequences were viral sequences. Filtered reads were most numerous in EBV (+) NKTCL cell line SNK, YTS, and EBV (+) nasal NKTCL tissue. The reads were non-randomly enriched in chromosome 2. EBV DNA inte-gration in the 400 bp region of chr2:30234084-30234483 caused insertion or deletion in the chr2p23.1 site. Conclusions: EBV DNA is highly integrated in the chr2p23.1 site of EBV (+) NKTCL cells and may affect the expression of related genes.

Objective: To investigate the expression and clinical significance of programmed death-ligand 1 (PD-L1), programmed death-ligand 2 (PD-L2), and their receptor programmed cell death protein 1 (PD-1) in EBV-positive T/NK lymphoproliferative disease [Epstein-Barr virus-positive T/natural killer (NK)-cell lymphoproliferative disease, EBV(+)-T/NK-LPD]. Methods: The pathological paraffin-embedded tissues of 17 patients with EBV(+)-T/NK-LPD from the First Affiliated Hospital of Zhengzhou University from January 2013 to December 2017 were collected. These patients include 12 males and 5 females, aged 10-82 years old, the average age being 29 years, 4 people in gradeⅠ, 7 in gradeⅡ, 3 in gradeⅢ, and 3 people with hydroa vacciniforme-like lymphoproliferative disorders. Immunohistochemical SP method was used to detect the expression of PD-1, PD-L1, and PD-L2 in human EBV(+)-T/NK-LPD tissues. The relationship between PD-1, PD-L1, PD-L2 expression, and clinicopathological parameters, pathological grades and prognosis were analyzed by Fisher's exact probabilities and Spearman rank correlation. Result: After statistical analysis, the results showed that in 17 cases of tissue samples, there were 12 cases with positive PD-1 expression, 6 cases with positive PD-L1 expression and 5 cases with positive PD-L2 expression. There was no significant correlation between PD-1 and PD-L2 expression and prognosis (P>0.05). PD-L1 expression showed a positive correlation with prognosis (P<0.05). There was no significant correlation between the expression of PD-L1 and PD-L2 with age, sex, as well as LDH and Ki-67 levels (P>0.05). Moreover, there was no significant correlation of PD-1 and PD-L2 expression with pathological grade (r=0.141, r=-0.149, both P>0.05). However, there was a negative correlation between the PD-L1 expression and pathological grade (r=-0.563), and the correlation between the PD-L1 ex-pression and pathological grade was statistically significant (P<0.05). Conclusions: PD-1, PD-L1, and PD-L2 are abnormally expressed in the pathological tissues of EBV(+)-T/NK-LPD. Although there was no significant correlation between the expression of PD-1 and prognosis or pathological grade, it was significantly higher in EBV+T/NK-LPD. PD-1/PD-Ls associated signaling pathway is expected to be a potential new target for EBV(+)-T/NK-LPD immunotherapy.

With the application of novel agents and high-dose chemotherapy with autologous stem cell transplantation(ASCT),the survival time of multiple myeloma(MM) has been significantly prolonged.However,due to the biological characteristics of myeloma and minimal residual disease after initial treatment,the disease courses of most MM patients show a series of remissions and relapses.Hence,it is necessary to apply consolidation and maintenance therapy after ASCT and continuous therapy for transplant-ineligible patients.This paper reviews the advances in consolidation,maintenance and continuous therapy for MM in the era of novel agents.