ObjectiveTo investigate the role and mechanism of Lck/Yes-related novel protein tyrosine kinase （Lyn） on lipopolysaccharide （LPS）-induced M1-type polarization of macrophage. MethodsThe LentiCRISPR-V2 plasmid was digested with the restriction endonuclease BSMBI-V2， and the digested DNA fragments were recovered. The digested plasmid was ligated with Lyn-sgRNA using T4 ligase to generate the Lenti-Lyn-gRNA lentivirus. THP-1 cells were infected with the Lenti-Lyn-gRNA lentivirus to obtain a stable cell line with Lyn knockout， and a monoclonal THP-1 cell line with complete Lyn knockout （Lyn^⁻/⁻） was established subsequently. Wild-type Lyn （Lyn^WT） and Lyn^⁻/⁻ THP-1 cells were induced with 100 ng/mL phorbol myristate acetate （PMA） for 48 h to differentiate into M0 macrophages， which were further polarized into M1 macrophages by stimulation with 100 ng/mL LPS for 24 h. Quantitative real-time polymerase chain reaction （qPCR） was performed to detect the expression of M0 macrophage markers， including integrin αM （CD11b）， macrophage antigen （CD68）， and monocyte differentiation antigen （CD14）. The expression of Lyn in M1 macrophages differentiated from wild-type THP-1 cells （Lyn^WT-M1） was measured by qPCR， and the ratio of phosphorylated Lyn to total Lyn （P-Lyn/Lyn） in Lyn^WT-M1 cells was determined by Western blot. In M1 macrophages differentiated from Lyn-knockout THP-1 cells （Lyn^⁻/⁻-M1）， qPCR was used to detect the mRNA expression of inducible nitric oxide synthase （iNOS）， interleukin-6 （IL-6）， and chemokine （C-X-C motif） ligand 10 （CXCL-10）. Western blot was conducted to assess the protein expression of iNOS， as well as the protein levels of molecules related to the Janus kinase 1 （JAK1）-signal transducer and activator of transcription 1 （STAT1）signaling pathway， including JAK1， phosphorylated JAK1 （P-JAK1）， STAT1， and phosphorylated STAT1 （P-STAT1）. Additionally， the expression of the M1 macrophage marker cluster of differentiation 80 （CD80） was analyzed by flow cytometry. ResultsThe Lyn^-/- monoclonal cell line was successfully constructed. The expression of CD11b was significantly elevated in Lyn^-/- M0 macrophages， and the differentiation of M1 macrophages was successful. Knockdown of Lyn inhibited mRNA expression of iNOS， IL⁃6， CXCL⁃10， protein expression of iNOS and CD80 expression in M1 macrophages （P<0.05）. Western blot assay showed that Lyn knockdown inhibited protein expression of JAK1 and P-STAT1 （P<0.01）. ConclusionAfter CRISPR/Cas9-mediated Lyn knockout， the expression levels of JAK1 and P-STAT1， the key molecules in the JAK/STAT signaling pathway of M1 macrophages， are significantly downregulated； concomitantly， the expression of M1 macrophage-specific secretory factors （iNOS， IL⁃6， CXCL⁃10 mRNA） and CD80 is also downregulated， which may be achieved via targeted regulation of the JAK1/P-STAT1-mediated JAK/STAT signaling pathway.

Objective: To investigate the availability and use of child safety seats among children aged 0-3 years, so as to provide the basis for improving riding safety for children. Methods: Parents of children aged 0-3 years in Huangpu District, Shanghai Municipality, were recruited using the stratified multistage random sampling method from May to July 2024. Demographic information, family travel patterns, the use of child safety seat and related health beliefs were collected using questionnaire surveys. Factors affecting the use of child safety seats were identified using a multivariable logistic regression model. Results: Totally 514 valid questionnaires were recovered, with an effective rate of 96.98%. The respondents included 122 fathers (23.74%) and 392 mothers (76.26%), with a median age of 34.00 (interquartile range, 5.00) years. There were 446 families equipping with child safety seats, accounting for 86.77%; and 169 families using child safety seats, accounting for 32.88%. Multivariable logistic regression analysis showed that the parents who had children aged >1-2 years (OR=0.597, 95%CI: 0.366-0.973), travelled 2-4 times per month (OR=0.359, 95%CI: 0.213-0.607) or once per month or less (OR=0.384, 95%CI: 0.202-0.729), and scored high in perceived barrier (OR=0.634, 95%CI: 0.486-0.827) were less likely to use child safety seats; the parents who had children with local household registration (OR=2.506, 95%CI: 1.356-4.633), travelled 5-<10 km (OR=1.887, 95%CI: 1.148-3.101) or ≥10 km (OR=2.319, 95%CI: 1.355-3.967), always wore seat belts (OR=2.342, 95%CI: 1.212-4.524), scored high in perceived susceptibility (OR=1.392, 95%CI: 1.091-1.778) and self-efficacy (OR=1.413, 95%CI: 1.156-1.727) were more likely to use child safety seats. Conclusions Equipping family cars with child safety seats and using them can prevent and reduce traffic injuries among children aged 0-3 years. It is recommended to strengthen publicity to promote the use of child safety seats.

Activity cliffs (ACs) are generally defined as pairs of similar compounds that only differ by a minor structural modification but exhibit a large difference in their binding affinity for a given target. ACs offer crucial insights that aid medicinal chemists in optimizing molecular structures. Nonetheless, they also form a major source of prediction error in structure-activity relationship (SAR) models. To date, several studies have demonstrated that deep neural networks based on molecular images or graphs might need to be improved further in predicting the potency of ACs. In this paper, we integrated the triplet loss in face recognition with pre-training strategy to develop a prediction model ACtriplet, tailored for ACs. Through extensive comparison with multiple baseline models on 30 benchmark datasets, the results showed that ACtriplet was significantly better than those deep learning (DL) models without pre-training. In addition, we explored the effect of pre-training on data representation. Finally, the case study demonstrated that our model's interpretability module could explain the prediction results reasonably. In the dilemma that the amount of data could not be increased rapidly, this innovative framework would better make use of the existing data, which would propel the potential of DL in the early stage of drug discovery and optimization.

ObjectiveTo analyze the detected results of CD4⁺T lymphocytes and viral load in newly identified human immunodeficiency virus (HIV) infected patients in Huangpu District of Shanghai in 2023, to explore the correlation between them, so as to provide a scientific basis for the development of targeted prevention and control measures and antiviral treatment programs. MethodsThe data of CD4 cell count, viral load and demographic characteristics of the newly infected patients living with HIV in Huangpu District, Shanghai in 2023 were collected and analyzed by using descriptive epidemiological method. ResultsThe mean CD4 cell count of the 67 newly identified HIV infected patients in Huangpu District was (301.22±235.19) cells·µL^-1, with a mean viral load of (5.15±1.28) ×10⁵ copies·mL^-1.There were statistically significant differences in CD4 cell count and viral load among different age groups (P<0.05), but there were no statistically significant differences by gender and marital status (both P>0.05). The CD4 cell count and CD4/CD8 ratio both were negatively correlated with the lg value of viral load (r=-0.290, -0.378; P=0.027, 0.002). ConclusionThe CD4 cell counts of the newly identified HIV infected patients in Huangpu District in 2023 were generally low, the proportion of patients with high viral load was high, but the risk for elderly infected with HIV was high. The elderly have gradually become the key population for AIDS prevention and control in Huangpu District. It is recommended to expand HIV screening in the elderly to reduce the risk of HIV transmission and increase the rate of early detection and treatment.

OBJECTIVE: To assess the osteogenesis height in maxillary sinus segment one year after zygomatic implantation by imaging methods, and evaluate the influence of patient factors, maxillary sinus anatomical factors and surgical factors on postoperative osteogenesis height. METHODS: This study is a retrospective study, including patients who underwent zygomatic implantation and whose zygomatic implants passed through the maxillary sinus at the Department of Implantology, Peking University School and Hospital of Stomatology from July 2017 to January 2022. Preoperative and postoperative cone beam CT (CBCT)was taken to measure and calculate the average osteogenesis height (AOH) in maxillary sinus segment of the zygomatic implants, then the residual bone height, the width and morphology of the maxillary sinus floor in the buccal and palatal directions were measured. Besides, the integrity of Schneiderian membrane during implant surgery, and the general information of the patients and zygomatic implants were recorded. By comparing anatomical situations and surgical characteristics, the differences of AOH under different conditions were analyzed. Then AOH was divided into two groups (obvious osteogenesis group and non-obvious osteogenesis group) using the median as the threshold, and the influencing factors of osteogenesis were evaluated using mixed effect generalized linear model univariable and multivariable analysis. RESULTS: A total of 47 zygomatic implants were implanted in 24 patients. During the average follow-up period of 12.1 months, there was no implant failure, and the implant survival rate was 100%. Postoperative CBCT showed that 43 zygomatic implants had osteogenic images in the maxillary sinus segment, most of which originated from the floor of the maxillary sinus, and the median AOH was 3.1 mm [interquartile range (IQR): 4.0 mm]. In terms of maxillary sinus width, there were 31 cases (66.0%) of wide type and 16 cases (34.0%) of narrow type. In the aspect of buccal and palatal morphology, 17 cases were taper (36.2%), 20 cases were round (42.6%), and 10 cases were flat (21.3%). The median of residual bone height was 2.8 mm (IQR: 2.2 mm) before operation. Univa-riate analysis of mixed effect generalized linear model showed that postoperative obvious osteogenic rate was related to the residual bone height (OR=2.09, P=0.006). Multivariate analysis showed that the resi-dual bone height (OR=2.55, P=0.022) and the shape of a taper maxillary sinus (OR=11.44, P=0.040) had a significant impact on the postoperative obvious osteogenic rate. CONCLUSION The maxillary sinus floor showed osteogenic images 1 year after the zygomatic implantation surgery. Larger residual bone height and the shape of a taper maxillary sinus may be favorable factors for osteogenesis.
Humans ; Maxillary Sinus/surgery* ; Cone-Beam Computed Tomography ; Retrospective Studies ; Zygoma/diagnostic imaging* ; Male ; Female ; Osteogenesis/physiology* ; Middle Aged ; Adult ; Dental Implants ; Aged ; Dental Implantation, Endosseous/methods*

Objective:To explore the mediating effect of self-rated health status between living space and social frailty of the elderly in community, and to provide reference for intervention strategies.Methods:From December 2023 to March 2024, 550 community elderly in Yandun Community, Yicheng Community and Binhu Community in Baohe District of Hefei City were selected as the research objects by convenient sampling method. The general information questionnaire, self-rated health questionnaire, social frailty index and living space assessment scale were used to investigate a cross-sectional survey. Spearman correlation analysis was used to explore the correlation between self-rated health, living space and social frailty of community elderly. Bootstrap method was used to test the mediating effect.Results:A total of 542 valid questionnaires were collected. Among the 542 elderly residents in the community, aged 65-94 (71.69 ± 6.54) years, there were 267 males and 275 females. Among the 542 community elderly, the self-rated health score, living space score and social frailty index were (2.52 ± 0.95), (73.39 ± 16.77) and 0.0 (0.0, 3.0), respectively. Spearman analysis showed that the total score of living space was negatively correlated with the scores of self-rated health and social frailty ( r=-0.477, -0.538, both P<0.01), and the score of self-rated health was positively correlated with the score of social frailty ( r=0.711, P<0.01).The mediating effect results showed that the living space could play a partial mediating effect on social frailty through the mediating variable of self-rated health (-0.028), accounting for 49.12% of the total effect. Conclusions:The self-rated health status of the elderly in the community has an indirect mediating effect between living space and social frailty. Medical workers should take the improvement of the living space mobility of the elderly as the starting point, and improve their self-rated health level through diversified intervention means, so as to reduce the occurrence of social frailty and promote active aging.

Objective:To explore the relationship between obesity indicators and DNA methylation clocks acceleration,and to analyze their temporal sequence.Methods:Data were obtained from two sur-veys conducted in 2013 and 2017-2018 by the Chinese National Twin Registry.Peripheral blood DNA methylation data were measured using the Illumina Infinium Human Methylation 450K BeadChip and EPIC BeadChip.DNA methylation clocks/acceleration metrics(GrimAA,PCGrimAA and Dunedin-PACE)were calculated using the DNA methylation online tool(https://dnamage.genetics.ucla.edu/)or R code provided by researchers.Obesity indicators included weight,body mass index(BMI),waist circumference,waist-hip ratio,and waist-height ratio.A total of 1 070 twin individuals were included in the cross-sectional analysis,comprising 378 monozygotic(MZ)twin pairs and 155 dizygotic(DZ)twin pairs for within-pair analysis.Mixed-effects models were used to examine the associations between obesity indicators and DNA methylation clocks,as well as their acceleration measures.The longitudinal analysis included 314 twin individuals,comprising 95 MZ twin pairs and 62 DZ twin pairs for within-pair analy-sis.Cross-lagged panel models were applied to further explore the temporal relationships between obesity and DNA methylation clock indicators.All analyses were conducted both in the full twin sample and separately within MZ and DZ twin pairs.Results:In the cross-sectional analysis population,monozygotic twins accounted for 71.0％,males for 68.0％,and the mean chronological age was(49.9±12.1)years.In the longitudinal analysis population,monozygotic twins accounted for 60.5％,males for 60.8％,with a mean baseline chronological age of(50.4±10.2)years and a mean follow-up duration of(4.6±0.6)years.Except for the waist-to-hip ratio,which was significantly higher at follow-up com-pared with baseline,no statistically significant differences were observed in the means of other obesity in-dicators between baseline and follow-up.Correlation analysis revealed that weight,BMI,waist circumfe-rence,waist-hip ratio(WHR),and waist-height ratio(WHtR)were positively correlated with Dunedin-PACE in all the twins,with WHtR showing the strongest association(β=0.21,95％CI:0.11 to 0.31).Weight and BMI were negatively associated with GrimAA(β=-0.03,95％CI:-0.05 to-0.01;β=-0.07,95％CI:-0.12 to-0.02),while weight was negatively associated with PCGrim-AA(β=-0.02,95％CI:-0.03 to 0.00).However,within-twin-pair analyses showed no statistically significant correlations.Cross-lagged panel model analysis indicated that higher baseline weight might lead to increased GrimAA at follow-up,while elevated baseline weight,BMI,and waist circumference might increase PCGrimAA.Higher baseline WHR was associated with increased DunedinPACE at follow-up.Conclusion:Obesity indicators correlate with DNA methylation clock acceleration metrics.Baseline obesity may influence changes in certain DNA methylation clock indicators over time,suggesting that obesity could exert long-term health effects by accelerating DNA methylation aging.However,these associations may be confounded by shared genetic or environmental factors among the twins.

Objective:To describe the distribution characteristics of alcohol consumption in adult twins in the Chinese National Twin Registry (CNTR), and further explore the influence of genetic factors on alcohol consumption in adult twins.Methods:The subjects of the study were twins registered by CNTR in 11 project areas across China from 2010 to 2018. A total of 56 966 twins (28 483 pairs) aged 18 years and above who answered questions about drinking behavior were included, and the random effect model was used to describe the population and regional distribution characteristics of alcohol consumption. Intra-pair analysis was performed to calculate the concordance rate and heritability of their alcohol consumption.Results:The age of all subjects was (36.6±12.0) years, and current drinkers accounted for 16.6% (9 461/56 966) of all subjects. In men, those aged 50-59 years, those in northern China, those living in rural area, those with low education level and those with high BMI, the proportions of current drinkers were higher. After excluding 468 pairs of twins who had stopped alcohol use and 21 764 pairs of twins who had no drink or had small amount drink, an intra-pair analysis was conducted in 4 929 pairs of same-sex twins, and found that the concordance rate of alcohol consumption was 64.0% (2 059/3 215) in monozygotic twins, and 52.6% (902/1 714) in dizygotic twins, the difference was significant ( P<0.001), and the heritability of alcohol consumption was 24.1% (95% CI: 18.9%- 29.3%). The further stratified analysis found that in southern men, the heritability was highest in those aged 40-49 years (36.1%, 95% CI: 21.6%-50.7%), while in northern men, the heritability was highest in those aged 50-59 years (34.2%, 95% CI: 18.1%-50.3%). Conclusions:In adult twins in China, there were population and regional differences in the distribution of alcohol consumption behavior, and alcohol consumption was influenced by genetic factors, and gender, age and region had potential modifying effects.

Ferroptosis is an iron-dependent cell death modality triggered by the accumulation of lipid peroxides and is closely linked to tumor pathogenesis. Ferritinophagy refers to the selective autophagic degradation of ferritin, releasing intracellular stored iron to maintain iron metabolic homeostasis. This process is also significantly associated with tumor-targeted interventions. This review systematically elucidates the mechanisms of ferroptosis and ferritinophagy, their roles in tumor progression, and the therapeutic potential of pharmacologically induced ferritinophagy in anticancer strategies.

Objective To evaluate the efficacy of narrow-band ultraviolet B(NB-UVB)phototherapy combined with enteric-coated thymopeptide in treatment of pityriasis rosea and its impacts on vascular cell adhesion molecule-1(VCAM-1)and intercellular adhesion molecule-1(ICAM-1).Methods Eighty patients with pityriasis rosea who were admitted to Haimen District People's Hospital from September 2022 to February 2024 were selected as research objects.They were divided into treatment group(n=41)and control group(n=39)according to random number table method.The control group was treated with NB-UVB phototherapy for one month,and the treatment group received NB-UVB phototherapy and enteric-coated thymopeptide for one month.The efficacy,rash-related time changes,symptom improvement,Pityriasis Rosea Severity Score(PRSS),VCAM-1 and ICAM-1 levels,and adverse events were compared between the two groups.Results The total effective rate of the treatment group was higher than that of the control group.The skin rash came to a halt and disappeared in a shorter time in the treatment group than in the control group,while the time to itch cessation in the treatment group was significantly longer than that in the control group(all P<0.05).The PRSS scores and levels of VCAM-1 and ICAM-1 in the treatment group were lower than those in the control group after treatment(all P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion NB-UVB phototherapy combined with enteric-coated thymopeptide can enhance the therapeutic effects on pityriasis rosea and reduce VCAM-1 and ICAM-1 levels.