Four novel β-galactoside prodrugs were designed and synthesized from anthraquinones HAQ-OH and AQ-OH in an attempt to use the prodrugs to selectively release superoxide anion (O2−) in cancer cells and to achieve selected anticancer activity by utilizing the Warburg effect and the elevated level of β-galactosidase in certain cancer cells. Cellular assays showed that the prodrugs Gal-HAQ and Gal-AQ selectively inhibited the proliferation and induced apoptosis of ovarian cancer OVCAR-3 cells overexpressing β-galactosidase. Using O2− fluorescent probe, it was found that in OVCAR-3 cells Gal-HAQ and Gal-AQ could time-dependently release O2−, which was essential for their anticancer activity. Furthermore, it was found that Gal-HAQ and Gal-AQ were effective senolytics toward senescent cells overexpressing β-galactosidase without affecting the viability of corresponding non-senescent cells, further confirming the β-galactosidase-dependent cytotoxicity of the prodrugs. In conclusion, Gal-HAQ and Gal-AQ, which release O2− in response to β-galactosidase, are expected to serve as candidate prodrugs targeting cancer cells.

Objective:To analyze the clinical characteristics and related factors of cognition disorders in elderly hypertensive patients.Methods:It was a cross-sectional study. A total of 612 hypertensive patients with the age of (69.06±6.58) years (median 68.00 years) admitted in the Department of Cardiology, General Hospital of Chinese People′s Liberation Army from October 2022 to April 2024 were enrolled. The demographic and clinical data were collected, the cognition status was assessed with Mini-Mental State Examination (MMSE) at admission. The related factors of cognition disorders were analyzed with univariate and multivariate logistic regression.Results:The results showed that female hypertensive patients and those with older age, lower education, higher fasting blood glucose (FBG) and diabetes mellitus, higher low-density lipoprotein cholesterol (LDL-C) level, higher systolic blood pressure (SBP) and more cardiovascular comorbidities were likely to have cognition disorders (all P<0.05). Multivariate logistic regression analysis showed that smoking history, elevated SBP, elevated heart rate, elevated FBG, and elevated LDL-C were independent risk factors for cognition disorders in elderly hypertensive patients,while higher education level was an independent protective factor (all P<0.05). Conclusion:Smoking, increased SBP, increased heart rate, increased FBG, increased LDL-C and lower education level are independently associated with cognition disorders in elderly hypertensive patients.

Objective:To investigate the association between estimated cumulative low-density lipoprotein cholesterol (LDL-C) exposure and the severity of coronary artery disease and long-term adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS).Methods:The subjects were from the PROMISE study. This study was a prospective cohort study led by Fuwai Hospital, Chinese Academy of Medical Sciences, with participation from eight regional tertiary hospitals as sub-centers, and enrolled 18 701 patients with confirmed coronary heart disease between January 2015 and May 2019. Among them, 8 429 patients with ACS were included in this study. The estimated cumulative LDL-C exposure was calculated by multiplying LDL-C by age. Participants were then divided into four groups based on quartiles. Baseline data and coronary angiography data were collected, and participants were followed for 2 years. The primary endpoint was MACCE, which was composed of all-cause death, cardiac death, myocardial infarction, revascularization, and stroke. Spearman correlation analysis was used to estimate the correlation between cumulative LDL-C exposure and the severity of coronary artery disease. The differences in MACCE among the four groups were compared, and multivariate Cox regression was used to divide the estimated cumulative exposure LDL-C into two groups, three groups, and four groups to analyze its relationship with MACCE.Results:The 8 429 ACS patients included in the study had an age of (60.9±11.4) years, with 1 951(23.1%) females. Spearman correlation analysis revealed that estimated cumulative LDL-C exposure was positively associated with the preoperative SYNTAX score, three-vessel lesions disease, left main disease, and the number of target lesions (correlation coefficients r=0.14, 0.10, 0.04 and 0.03, respectively, with all P<0.05). The 2-year follow-up results indicated that the incidence rates of MACCE, all-cause death, cardiac death, myocardial infarction, and stroke in ACS patients grouped by different levels of estimated cumulative LDL-C exposure were statistically significant (all P<0.05). The results of the Cox multivariate regression analysis showed that when the estimated cumulative LDL-C exposure was treated as a continuous variable and analyzed in two, three, and four groups, with the lowest group as the reference, the risk of MACCE occurrence in the high-value group increased by 21% (95% CI 1.08-1.37, P=0.002), 24% (95% CI 1.07-1.43, P=0.004), and 21% (95% CI 1.02-1.43, P=0.025) respectively. Conclusions:A positive correlation was found between estimated cumulative LDL-C exposure and severity of coronary artery disease. High estimated cumulative LDL-C exposure level is a risk factor for MACCE in ACS patients within 2 years.

In order to determine the causative agents responsible for the lethality of tumor disease in breeders,liver,spleen and other tissues of dead chickens were collected,and pathogen detection,se-quencing and genetic evolution analysis were carried out by PCR.The results showed that all three samples were negative for reticuloendotheliosis virus(REV),samples 1 and 2 wereavian leukosis virus subgroup J(ALV-J)positive,and sample 3 was positive for ALV-J and Marek's disease virus(MDV),which preliminarily determined that the breeder died of ALV-J infection or ALV-J and MDV mixed infection.Among them,the ALV-J gp85 gene had the highest nucleotide homology with the reference strain of ALV-J,ranging from 87.70％to 99.30％,and was in the same branch with the reference strain of subgroup J.Amino acid homology ranged from 78.00％to 96.20％,with some mutations.The nucleotide homology between the MDV meq gene and the vv+strain was the highest,which was 98.00％-99.00％,and they were in the same branch.The homology of amino acids was 95.90％-98.20％,and there were multiple mutation sites,among which the 176th amino acid destroyed the original Pro repeat of the virus MDV meq due to the mutation of Pro to Arg or Ala,which may lead to the enhancement of its virulence.This study will provide a reference for the prevention and control of neoplastic diseases in breeders in this region.

Objective:To investigate the association between estimated cumulative low-density lipoprotein cholesterol (LDL-C) exposure and the severity of coronary artery disease and long-term adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS).Methods:The subjects were from the PROMISE study. This study was a prospective cohort study led by Fuwai Hospital, Chinese Academy of Medical Sciences, with participation from eight regional tertiary hospitals as sub-centers, and enrolled 18 701 patients with confirmed coronary heart disease between January 2015 and May 2019. Among them, 8 429 patients with ACS were included in this study. The estimated cumulative LDL-C exposure was calculated by multiplying LDL-C by age. Participants were then divided into four groups based on quartiles. Baseline data and coronary angiography data were collected, and participants were followed for 2 years. The primary endpoint was MACCE, which was composed of all-cause death, cardiac death, myocardial infarction, revascularization, and stroke. Spearman correlation analysis was used to estimate the correlation between cumulative LDL-C exposure and the severity of coronary artery disease. The differences in MACCE among the four groups were compared, and multivariate Cox regression was used to divide the estimated cumulative exposure LDL-C into two groups, three groups, and four groups to analyze its relationship with MACCE.Results:The 8 429 ACS patients included in the study had an age of (60.9±11.4) years, with 1 951(23.1%) females. Spearman correlation analysis revealed that estimated cumulative LDL-C exposure was positively associated with the preoperative SYNTAX score, three-vessel lesions disease, left main disease, and the number of target lesions (correlation coefficients r=0.14, 0.10, 0.04 and 0.03, respectively, with all P<0.05). The 2-year follow-up results indicated that the incidence rates of MACCE, all-cause death, cardiac death, myocardial infarction, and stroke in ACS patients grouped by different levels of estimated cumulative LDL-C exposure were statistically significant (all P<0.05). The results of the Cox multivariate regression analysis showed that when the estimated cumulative LDL-C exposure was treated as a continuous variable and analyzed in two, three, and four groups, with the lowest group as the reference, the risk of MACCE occurrence in the high-value group increased by 21% (95% CI 1.08-1.37, P=0.002), 24% (95% CI 1.07-1.43, P=0.004), and 21% (95% CI 1.02-1.43, P=0.025) respectively. Conclusions:A positive correlation was found between estimated cumulative LDL-C exposure and severity of coronary artery disease. High estimated cumulative LDL-C exposure level is a risk factor for MACCE in ACS patients within 2 years.

In order to determine the causative agents responsible for the lethality of tumor disease in breeders,liver,spleen and other tissues of dead chickens were collected,and pathogen detection,se-quencing and genetic evolution analysis were carried out by PCR.The results showed that all three samples were negative for reticuloendotheliosis virus(REV),samples 1 and 2 wereavian leukosis virus subgroup J(ALV-J)positive,and sample 3 was positive for ALV-J and Marek's disease virus(MDV),which preliminarily determined that the breeder died of ALV-J infection or ALV-J and MDV mixed infection.Among them,the ALV-J gp85 gene had the highest nucleotide homology with the reference strain of ALV-J,ranging from 87.70％to 99.30％,and was in the same branch with the reference strain of subgroup J.Amino acid homology ranged from 78.00％to 96.20％,with some mutations.The nucleotide homology between the MDV meq gene and the vv+strain was the highest,which was 98.00％-99.00％,and they were in the same branch.The homology of amino acids was 95.90％-98.20％,and there were multiple mutation sites,among which the 176th amino acid destroyed the original Pro repeat of the virus MDV meq due to the mutation of Pro to Arg or Ala,which may lead to the enhancement of its virulence.This study will provide a reference for the prevention and control of neoplastic diseases in breeders in this region.

Objective:To analyze the clinical characteristics and related factors of cognition disorders in elderly hypertensive patients.Methods:It was a cross-sectional study. A total of 612 hypertensive patients with the age of (69.06±6.58) years (median 68.00 years) admitted in the Department of Cardiology, General Hospital of Chinese People′s Liberation Army from October 2022 to April 2024 were enrolled. The demographic and clinical data were collected, the cognition status was assessed with Mini-Mental State Examination (MMSE) at admission. The related factors of cognition disorders were analyzed with univariate and multivariate logistic regression.Results:The results showed that female hypertensive patients and those with older age, lower education, higher fasting blood glucose (FBG) and diabetes mellitus, higher low-density lipoprotein cholesterol (LDL-C) level, higher systolic blood pressure (SBP) and more cardiovascular comorbidities were likely to have cognition disorders (all P<0.05). Multivariate logistic regression analysis showed that smoking history, elevated SBP, elevated heart rate, elevated FBG, and elevated LDL-C were independent risk factors for cognition disorders in elderly hypertensive patients,while higher education level was an independent protective factor (all P<0.05). Conclusion:Smoking, increased SBP, increased heart rate, increased FBG, increased LDL-C and lower education level are independently associated with cognition disorders in elderly hypertensive patients.

Objective To explore the effect of sling exercise with Tuina therapy on kinesiophobia in old patients with lumbar disc herniation,and analyze the mechanism based on brain-bone axis. Methods A total of 56 old patients with chronic lumbar disc herniation and kinesiophobia were selected from the Reha-bilitation Hospital of the Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine from September,2022 to December,2023;and randomly divided into control group(n=28)and experimental group(n=28).The control group accepted conventional exercise therapy,while the experimental group accepted sling exercise with Tuina therapy,for four weeks.They were assessed with simplified Chinese version of Tampa Scale of Kinesiophobia(TSK),Japanese Orthopaedic Association score(JOA)and Visual Analogue Scale for pain(VAS)before and after treatment,while the bone mineral density(BMD)was tested,the levels of osteoprote-gerin(OPG),norepinephrine(NE)and corticosteroids(Cor)in serum were measured,and the median frequency(MF)of weak-link erector spinae was detected with surface electromyography. Results Two cases dropped off in the control group,and one in the experimental group.The scores of all the assessment improved in both groups after treatment(|t|>14.168,P<0.001),as well as the serum levels of OPG,NE and Cor(|t|>2.103,P<0.05),BMD(|t|>2.726,P<0.05),and MF of erector spinae(|t|>14.736,P<0.001);all of them were better in the experimental group than in the control group(|t|>2.154,P<0.05). Conclusion Sling exercise with Tuina therapy can improve the pain and kinesiophobia of lumbar disc herniation in the old adults,which may promote the recovery of physical and mental function through regulating the levels of hor-mones and neurotransmitters related to the brain-bone axis.

Objective:To study the trinucleotide repeats of GCN (GCA, GCT, GCC, GCG) encoding Alanine in exon 3 of the PHOX2B gene among healthy individuals from southwest China and two patients with Congenital central hypoventilation syndrome (CCHS). Methods:The number and sequence of the GCN repeats of the PHOX2B gene were analyzed by capillary electrophoresis, Sanger sequencing and cloning sequencing of 518 healthy individuals and two newborns with CCHS, respectively. Results:Among the 1036 alleles of the 518 healthy individuals, five alleles were identified, including (GCN) 7, (GCN) 13, (GCN) 14, (GCN) 15 and (GCN) 20. The frequency of the (GCN) 20 allele was the highest (94.79%). And five genotypes were identified, which included (GCN) 7/(GCN) 20, (GCN) 13/(GCN) 20, (GCN) 14/(GCN) 20, (GCN) 15/(GCN) 20, (GCN) 20/(GCN) 20. The homozygous genotypes were all (GCN) 20/(GCN) 20, and the carrier rate was 89.58%. Four GCN sequences of the (GCN) 20 homozygous genotypes were identified among the 464 healthy individuals. The GCN repeat numbers in the exon 3 of the PHOX2B gene showed no significant difference between the expected and observed values, and had fulfilled the, Hardy-Weinberg equilibrium. The genotypes of the two CCHS patients were (GCN) 20/(GCN) 25 and (GCN) 20/(GCN) 30, respectively. Conclusion:It is important to determine the GCN repeats and genotypic data of the exon 3 of the PHOX2B gene among the healthy individuals. The number of GCN repeats in 518 healthy individuals was all below 20. The selection of appropriate methods can accurately detect the polyalanine repeat mutations (PARMs) of the PHOX2B gene, which is conducive to the early diagnosis, intervention and treatment of CCHS.

Objective To identify factors associated with gastrointestinal heat retention in preschool children,and to provide a foundational understanding for future clinical investigations. Methods A case-control study was performed,which involved children from kindergartens in the Longgang District of Shenzhen City,Guangdong Province,from May to July 2021. Using the Children's Gastrointestinal Heat Retention Diagnostic Self-assessment Scale,subjects were allocated into a case group (children diagnosed with gastrointestinal heat retention) and a control group (children without this condition). An online survey was used to collect data on dietary behaviors,caregivers' feeding behaviors,early antibiotic use,daily routines,and birth conditions. SPSS 27.0 software was used to facilitate precise sociodemographic matching and paired logistic regression analysis to explore the association between gastrointestinal heat retention and the above factors. Results From the analysis of 51,252 matched cases,the study found that several factors contributed to an increased risk of gastrointestinal heat retention. These factors included reduced food intake compared to peers,reports of picky eating by caregivers,distractions during meals,pronounced dietary preferences,disinterest in food,meal durations ≥ 25 min,reluctance to sample new foods,consistent refusal of specific food types for over one month,irregular meal locations,coercive feeding practices,use of micronutrient supplements,allowing children too much freedom in food choice,persuading children to eat,infrequent encouragement to experiment with new foods,early antibiotic introduction,inadequate sleep,and premature birth (P<0.05). In contrast,exclusive breastfeeding in the first six months,engagement in moderate to massive physical activity,and regular napping patterns were associated with a reduced risk of gastrointestinal heat retention (P<0.05). Conclusion The suboptimal dietary habits,improper feeding practices,insufficient physical activity,inadequate sleep,and premature antibiotic exposure may be significant risk factors for gastrointestinal heat retention. Future research dedicated to unraveling the cause of gastrointestinal heat retention should prioritize these elements.