Objective This study examined the association between smoking and cognitive decline through a cohort in rural population in Xi'an.Methods Data were collected from the cognitive impairment cohort of middle-aged and elderly people in rural areas of Xi'an.The cohort selected the population aged 40 years and above in rural Xi'an.The baseline survey was completed between October 2014 and March 2015,and two follow-up visits were conducted in 2016 and 2018.This study took the baseline cognitively normal population of this cohort as the research subjects.According to the survey results in 2018,the population was divided into three groups according to smoking status:smoking,quitting and non-smoking.Cognitive function was assessed by Mini-Mental State Examination(MMSE).△MMSE(2014 rating-2018 rating)≥2 was defined as cognitive decline,and △MMSE＜2 was defined as cognitive stability.Binary Logistic regression model and stratified analysis were used to analyze the relationship between smoking and cognitive decline and the influence of age on the relationship.Results A total of 1 289 subjects were included in this study.According to smoking status in 2018,they were divided into non-smokers(910,70.6％),smokers(335,26.0％),and ex-smokers(44,3.4％).In the total population,there was no significant difference in the incidence of cognitive decline among non-smokers,smokers and ex-smokers(17.3％vs.16.1％vs.15.9％,P=0.880).When stratified by age,there was no significant difference in the incidence of cognitive decline among the three groups in the subgroup of age＜65 years(16.5％vs.13.2％vs.12.1％,P=0.365).In the subgroup of age≥65 years,no significant difference was found in the incidence of cognitive decline among non-smokers,smokers and ex-smokers(20.8％vs.30.9％vs.27.3％,P=0.306).After adjusting for confounding factors,smokers had a significantly higher risk of cognitive decline than non-smokers(OR=14.139;95％CI:1.541-129.705;P=0.019).There was a trend of cognitive decline in the ex-smokers group,but with no statistical significance(OR=8.252;95％CI:0.630-108.175;P=0.108).Conclusion Smoking is positively associated with cognitive decline in the elderly,suggesting that smoking may accelerate cognitive decline in this population.

Glaucoma is a blinding eye disease characterized by optic nerve damage and visual field defects,with a complex pathogenesis.Studies have shown that the abnormal activation of the cyclic GMP-AMP synthase-stimulator of in-terferon genes(cGAS-STING)signaling pathway may be closely related to the occurrence and development of glaucoma.New therapeutic strategies targeting this pathway,such as the cGAS small-molecule inhibitor RU.521 and the STING inhibi-tor H-151,have been shown to effectively alleviate pathological changes associated with glaucoma,and research into their mechanisms of action is becoming increasingly in-depth.This article aims to review the basic mechanisms of the cGAS-STING signaling pathway and its role in the pathogenesis of glaucoma,as well as the latest research progress of compounds targeting cGAS and STING in the treatment of glaucoma,in order to provide a new perspective for the immunotherapy of glaucoma.

Glaucoma is a blinding eye disease characterized by optic nerve damage and visual field defects,with a complex pathogenesis.Studies have shown that the abnormal activation of the cyclic GMP-AMP synthase-stimulator of in-terferon genes(cGAS-STING)signaling pathway may be closely related to the occurrence and development of glaucoma.New therapeutic strategies targeting this pathway,such as the cGAS small-molecule inhibitor RU.521 and the STING inhibi-tor H-151,have been shown to effectively alleviate pathological changes associated with glaucoma,and research into their mechanisms of action is becoming increasingly in-depth.This article aims to review the basic mechanisms of the cGAS-STING signaling pathway and its role in the pathogenesis of glaucoma,as well as the latest research progress of compounds targeting cGAS and STING in the treatment of glaucoma,in order to provide a new perspective for the immunotherapy of glaucoma.

To investigate the role of the DPP4-nestin axis in liver fibrosis induced by alveolar cyst infection,a murine model was established using C57BL/6 mice via hepatic portal vein injection.Liver histopathological changes were assessed using HE staining,while immunohistochemistry and immunofluorescence were employed to evaluate the expression levels of nestin and DPP4 in infected mouse livers.In vitro,J S1 cell line was stimulated with recombinant DPP4 protein to es-tablish a cellular model,and qPCR,Western blot,and shRNA lentivirus interference techniques were utilized to examine the involvement of the DPP4-nestin axis in hepatic stellate cell activation.The findings demonstrated that compared to the Sham group,liver tissue structure disruption and collagen deposition were evident along with significantly increased expressions of nestin and DPP4(P＜0.050 0),which colocalized with nesin and α-SMA.Furthermore,stimulation with recombi-nant DPP4 protein significantly enhanced JS1 cell activation(P＜0.050 0)as well as upregulated nestin expression(P＜0.050 0)when compared to control group cells.Notably,shRNA lentivirus-mediated inhibition of nestin expression effectively suppressed the activating effects exerted by re-combinant DPP4 protein on JS1 cells(P＜0.050 0).Collectively,these results highlight the crucial regulatory role played by the DPP4-nestin axis in hepatic stellate cell activation triggered by alveo-lar infection;thus,targeting this axis may represent a novel therapeutic strategy for treating alveo-lar infection-induced liver fibrosis.

Objective This study examined the association between smoking and cognitive decline through a cohort in rural population in Xi'an.Methods Data were collected from the cognitive impairment cohort of middle-aged and elderly people in rural areas of Xi'an.The cohort selected the population aged 40 years and above in rural Xi'an.The baseline survey was completed between October 2014 and March 2015,and two follow-up visits were conducted in 2016 and 2018.This study took the baseline cognitively normal population of this cohort as the research subjects.According to the survey results in 2018,the population was divided into three groups according to smoking status:smoking,quitting and non-smoking.Cognitive function was assessed by Mini-Mental State Examination(MMSE).△MMSE(2014 rating-2018 rating)≥2 was defined as cognitive decline,and △MMSE＜2 was defined as cognitive stability.Binary Logistic regression model and stratified analysis were used to analyze the relationship between smoking and cognitive decline and the influence of age on the relationship.Results A total of 1 289 subjects were included in this study.According to smoking status in 2018,they were divided into non-smokers(910,70.6％),smokers(335,26.0％),and ex-smokers(44,3.4％).In the total population,there was no significant difference in the incidence of cognitive decline among non-smokers,smokers and ex-smokers(17.3％vs.16.1％vs.15.9％,P=0.880).When stratified by age,there was no significant difference in the incidence of cognitive decline among the three groups in the subgroup of age＜65 years(16.5％vs.13.2％vs.12.1％,P=0.365).In the subgroup of age≥65 years,no significant difference was found in the incidence of cognitive decline among non-smokers,smokers and ex-smokers(20.8％vs.30.9％vs.27.3％,P=0.306).After adjusting for confounding factors,smokers had a significantly higher risk of cognitive decline than non-smokers(OR=14.139;95％CI:1.541-129.705;P=0.019).There was a trend of cognitive decline in the ex-smokers group,but with no statistical significance(OR=8.252;95％CI:0.630-108.175;P=0.108).Conclusion Smoking is positively associated with cognitive decline in the elderly,suggesting that smoking may accelerate cognitive decline in this population.

[Objective] To analyze the distribution of Rh blood group phenotype in some ethnic groups in China, so as to provide references for accurate blood transfusion. [Methods] The data of CNKI, Wanfang data and VIP were retrieved using "Rh blood group" and "nationality", and the search of PubMed database was conducted with the keywords "Rh blood group", "nationalities", "ethnic groups" and "China", with retrieval time until September 19, 2024 Data were extracted from eligible studies and the literature quality was evaluated using the criteria for cross-sectional studies in STROBE statement. Meta analysis was performed using Stata 11.0 software. [Results] A total of 350 relevant literature were retrieved, of which 26 were included. The total sample size for Rh phenotype distribution detection were 31 432, and the total population for RhD negative screening was 47 227, covering 26 ethnic groups. Meta-analysis revealed that the Rh blood groups phenotype distribution in certain ethnic populations in China was mainly CCDee 46.7% (95%CI=46.2%-47.2%), CcDEe 30.1% (95%CI=29.5%-30.6%), and CcDee 9.0% (95%CI=8.7%-9.3%). Analysis of the RhD-negative phenotype indicated an negative rate of RhD of 0.3% (95%CI=0.2%-0.3%), with the main phenotype distributions of ccdee at 0.2% (95%CI=0.1%-0.2%) and ccdEe at 0.2% (95%CI=0.0%-0.4%). The meta-analysis results of the distribution of common phenotypes among different ethnic groups showed that the CCDee phenotype was mainly distributed as Hani>Dong>Buyi>Miao>Tujia>Hui>Zang>Kazakh>Mongol>Uygur; the CcDEe phenotype: Zang>Mongol>Hui; the CcDee phenotype: Uygur>Kazakh>Mongol>Zang>Hui>Dong>Miao>Tujia>Buyi; the ccDEE phenotype: Zang>Hui=Mongol. The results of this study are similar to those of Qingdao population in China, but differ from studies conducted in North India, German individuals of European ancestry and Saudi Arabian populations. [Conclusion] The distribution of Rh blood group phenotypes in some ethnic groups in China shows no significant difference compared to the Han population, but there are differences when compared to populations in other countries and regions.

Objective:To analyze the perceptions, attitudes toward cognitive screening and associated factors in Chinese population.Methods:It was a cross-sectional study, a total of 1 246 Chinese residents who used smartphones and completed the cognitive screening survey in the Sojump application from February 22 to March 7, 2024 were consecutively selected as the study subjects. The questionnaire content included demographic data, physical examination information, perceptions of cognitive disorders, perceptions, attitudes and suggestions of cognitive screening. A total of 1 273 questionnaires were distributed, and 1 273 were retrieved, of which 1 246 were valid (97.9%). The logistic regression analysis was used to evaluate factors associated with the attitudes toward cognitive screening in the subjects.Results:Of the 1 246 respondents included in the study, 468 were male and 778 were female, with a mean age of (43.9±13.8) years. The respondents covered 26 provincial-level administrative regions in China, including 347 (27.8%) in the east, 429 (34.4%) in the middle and 470 (37.7%) in the west. While 943 respondents failed to comprehend the cognitive screening, 914 considered it necessary. Additionally, 447 respondents recommended initiating cognitive screening at age 50, 927 respondents recommended annual screening, and 924 respondents preferred scale assessment. Female ( OR=2.121, 95% CI: 1.599-2.815), middle-aged and elderly ( OR=1.681, 95% CI: 1.223-2.310), urban residents ( OR=1.426, 95% CI: 1.002-2.029), high per capita monthly household income ( OR=1.253, 95% CI: 1.063-1.477), had complete physical examination ( OR=1.404, 95% CI: 1.015-1.943), better understanding of cognitive disorders ( OR=2.202, 95% CI: 1.750-2.772), and better understanding of cognitive screening ( OR=3.313, 95% CI: 2.227-4.931) showed positive correlations with the attitude favoring cognitive screening (all P<0.05). Conclusion:The perception levels of cognitive screening among Chinese residents are relatively low, but their attitudes are positive. Socio-economic factors, behavioral experiences, and knowledge levels are associated with residents′ attitudes toward cognitive screening.

Objective:To explore the predictive value of very low frequency (VLF) for the efficacy of vitamin D treatment in children with postural orthostatic tachycardia syndrome (POTS).Methods:A retrospective case-control study was conducted. A total of 65 POTS children from the Department of Pediatrics of the Second Hospital of Lanzhou University from November 2023 to May 2024 were selected as the research subjects, while 102 healthy children from the same period were selected as the control group. The 25 (OH) D levels between POTS children and healthy children were compared. The frequency of eight main symptoms, including palpitations, headache, cold sweat, blurred vision, chest tightness, dizziness, fainting, and digestive discomfort in the POTS group were analyzed, the symptom scores of the orthostatic intolerance were calculated, and the parameters related to short-range heart rate variability (HRV) during the upright test, head-up tilt test (HUTT) were collected. The correlation between 25 (OH) D levels and symptom scores of orthostatic intolerance symptoms and HRV parameters in children with POTS were analyzed by Pearson correlation analysis. The total symptom scores of children with POTS were compared for 3 months before treatment and 2 months after treatment with vitamin D 800 U/d. The difference in score before and after treatment was ≥2 as responsive group, and the score difference before and after treatment was <2 as non-responsive group. The demographic characteristics including age, gender, height, weight, body mass index, as well as HRV parameters such as the standard deviation of nn intervals (SDNN), the standard deviation of the average NN intervals (SDANN), the root mean square of successive differences (rMSSD), low-frequency (LF), high-frequency (HF), very-low-frequency (VLF) were compared between the responsive group and non-responsive group. Multivariate Logistic regression was analyzed to screen independent influencing factors of vitamin D treatment efficacy for POTS. The marker molecules related to the efficacy of vitamin D treatment in children with POTS were analyzed through receiver operating characteristic (ROC) curve.Results:A total of 167 children were included in this study. There were 65 children in the POTS group, 38 males and 27 females, with the age of (10.6±2.2) years. There were 102 healthy children in the control group, 53 males and 49 females, with the age of (11.2±1.8) years.There was no statistically significant difference in gender and age between the two groups (both P>0.05). The serum 25 (OH) D level in children in the POTS group was (37±18)nmol/L, lower than that in the control group (61±17)nmol/L ( P<0.05).Pearson correlation analysis showed that serum 25(OH)D was positively correlated with VLF, SDNN and HF ( r=0.43, 0.65, 0.36, respectively, all P<0.05). Among the POTS children, there were 48 cases in responsive group and 17 cases in non-responsive group. Univariate analysis revealed that responsive group exhibited significantly lower values in age, SDNN, SDANN, and VLF compared to the non-responsive group (all P<0.05). Multivariate Logistic regression analysis showed that age ( OR=1.47, 95% CI 1.08-2.01), SDNN ( OR=1.01, 95% CI 1.00-1.22) and VLF ( OR=1.01, 95% CI 1.00-1.15) were independent influencing factors in the effect of vitamin D in POTS children (all P<0.05). ROC curve analysis showed that the area under the curve of VLF predicting response to vitamin D treatment for POTS was 0.72 (95% CI 0.58-0.85, P=0.008). When the cutoff value was 1 272 ms 2, the sensitivity and specificity were both 70%. Conclusion:VLF may help predict the efficacy of vitamin D treatment in children with POTS.

Objective:To prepare decellularized extracellular matrix (dECM)-gelatin methacryloyl (GelMA) composite hydrogels and to study their effects on hepatocyte proliferation.Methods:Hepatic dECM was prepared by elution, and GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels were prepared by pepsin solubilization. The morphology of normal liver and dECM liver was observed by eyes and scanning electron microscopy using hematoxylin-eosin, Sirius red and periodate-Schiff staining, respectively. The internal structure of the dECM-GelMA composite hydrogels was observed by scanning electron microscopy, and the pore diameter was measured. Liver HL-7702 cells were co-cultured with GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels, and the cell proliferation viability was determined by cell counting kit-8. The expression of proliferating cell nuclear antigen (PCNA), Wnt family protein 5a (Wnt5a), β-catenin, extracellular-regulated protein kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were detected by Western blotting. Comparisons were made using independent sample t-test or one-factor analysis of variance. Results:After decellularization, the hepatocyte morphology showed rounded depressions, and the extracellular matrix structure was intact. The GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels showed inernally porous structures. The pore diameter increased from (3.06±1.35) μm in the GelMA hydrogel to (16.01±4.02) μm in the 50% dECM-GelMA composite hydrogel. On the 3rd, 5th and 7th day, the relative cell proliferation was higher in the 50% dECM-GelMA composite hydrogel group than that in the GelMA hydrogel group (1.89±0.04 vs 1.53±0.01, 9.36±0.04 vs 3.89±0.09, 7.15±0.27 vs 4.89±0.15, all P<0.05). The relative expression levels of PCNA, Wnt5a, β-catenin, and p-ERK1/2/ERK1/2 proteins in the 50% dECM-GelMA composite hydrogel group were higher than those in the GelMA hydrogel group (2.14±0.04 vs 1.00±0.03, 2.36±0.09 vs 1.00±0.08, 1.45±0.03 vs 1.00±0.04, 1.43±0.04 vs 1.00±0.01, all P<0.05). Conclusions:A dECM-GelMA composite hydrogel can be prepared, which may promote hepatocyte proliferation by upregulating the phosphorylation of ERK1/2 and activating Wnt/β-catenin signaling pathway.

Objective:To prepare heparin (Hep)-modified gelatin methacryloyl (GelMA) microspheres and to investigate their application in liver-targeted delivery of adipose-derived mesenchymal stem cells (ADSCs).Methods:GelMA microspheres were modified with Hep to obtain GelMA-Hep microspheres. The surface morphology of the GelMA-Hep microspheres was observed by scanning electron microscopy. The changes of carbon atoms, nitrogen atoms and sulfur atoms on the surface of the GelMA-Hep microspheres were detected by X-ray photoelectron spectroscopy. The surface chemical group composition of the GelMA-Hep microspheres was analyzed by Fourier transform infrared spectrometer. The swelling properties of the GelMA-Hep microspheres were detected by water absorption swelling experiment. Human liver HL-7702 cells transfected with lentivirus were co-cultured with GelMA, GelMA-dopamine (GelMA-dop) and GelMA-Hep microspheres. The effects of microspheres on cell proliferation activity were evaluated by cell counting kit-8 method and live/dead cell staining experiment. The adhesion of microspheres to cells was observed by confocal microscopy. The GelMA-Hep microspheres loaded with ADSCs were injected into C57BL/6 mice through the tail vein, and its efficiency of liver-targeted delivery of ADSCs was observed by a small animal in vivo imaging system. The data were compared by independent sample t test or one-way analysis of variance. Results:The GelMA-Hep microspheres were prepared by modifying the GelMA microspheres with Hep. Compared with the GelMA microspheres, the size of the GelMA-Hep microspheres did not change significantly, and the surface did not collapse and showed some crystalline particles. The binding energy of sulfur atoms on the surface of the GelMA-Hep microspheres increased from 166 eV to 168 eV. On the surface of the GelMA-Hep microspheres, the characteristic peaks of sulfonic acid and sulfate groups of Hep were detected at 1 490 cm ?1 and from 1 135 cm ?1 to 1 050 cm ?1, respectively. The swelling rate of the GelMA-dop microspheres was uniform, while the swelling rate of the GelMA microspheres and the GelMA-Hep microsphere was quite different, but the final swelling mass of the three microspheres tended to be consistent at 5 min. After 12, 24, 36 and 48 h of culture, the relative proliferation of cells in the GelMA-Hep group (1.61±0.29, 1.78±0.05, 2.27±0.08, 2.26±0.33) were higher than those in the negative control group (1.00±0.00, 1.28±0.06, 1.39±0.02, 1.41±0.04) (all P<0.05). After 36 h of culture, the relative proliferation of cells in the GelMA-Hep group was higher than that in the GelMA-dop group (1.63±0.21), with significant difference ( P<0.05). Live/dead cell staining experiment showed that after 12 h of cell culture in the GelMA-Hep group, only a few microspheres had cell adhesion; at 24 h, the cells were densely distributed on the surface of the microspheres. After 36 h, the number of cells increased further. At 48 h, live cells were distributed throughout the microspheres. Confocal microscopy showed that after 24 h of culture, cells adhered to the surface of the microspheres in the GelMA-Hep group and showed a stretched morphology. The liver of the GelMA-Hep+ADSCs group showed strong fluorescence at 0.5 h, and the fluorescence brightness continued to 48.0 h. The number of ADSCs reaching the liver was more than that of ADSCs group and GelMA+ADSCs group. Conclusions:GelMA-Hep microspheres were successfully prepared, which can improve the efficiency of liver-targeted delivery of ADSCs.