ObjectiveTo explore the potential mechanism of moxibustion at Guanyuan （CV 4） in delaying skin photoaging. MethodsThirty-two male Wistar rats were randomly divided into four groups， namely blank group， model group， vitamin E group， and moxibustion group， with 8 rats in each group. Except for the blank group， dorsal skin of rats were exposed to ultraviolet （UV） radiation to establish a skin photoaging model. One week after modeling， the moxibustion group received moxibustion at "Guanyuan （CV 4）" once a day， five days per week； the vitamin E group received vitamin E （25 mg/kg·d） once a day by gavage， five days per week； the blank group， model group， and moxibustion group received an equivalent volume of normal saline via gavage； the intervention lasted for 7 weeks. After 7 weeks， dorsal skin tissues were collected to analyze the following indicators， such as skin tissue moisture content， histomorphological changes using hematoxylin-eosin （HE） staining， Collagen Ⅰ and collagen Ⅲ content using ELISA. Malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， superoxide dismutase （SOD）， hydrogen peroxide （H₂O₂）， and catalase （CAT） activity in skin tissue were dectected. Western Blot was used to determin autophagy-related proteins， including microtubule-associated protein 1A/1B-light chain 3 （LC3）， polyubiquitin-binding protein （p62）， and autophagy-specific gene （Beclin-1）； LC3， p62， and Beclin-1 mRNA expression was detected via qRT-PCR， and autophagosome formation was observed using transmission electron microscopy （TEM）. ResultsHE staining showed that the epidermal structure in the blank group was orderly and evenly thick， while the model group exhibited uneven epidermal thickness. In the moxibustion group， the epidermis was well-structured， smooth， and uniform， with densely arranged dermal layers； the epidermis in the vitamin E group was thicker than that in the model group. Compared with the blank group， the model group exhibited decreased skin moisture content and reduced level of Collagen Ⅰ and collagen Ⅲ， reduced SOD， CAT， and GSH-Px activity in skin tissue， increased H₂O₂ and MDA activity， elevated p62 protein and mRNA expression， reduced LC3 and Beclin-1 protein and mRNA expression （P＜0.05 or P＜0.01）. Compared with the model group， the moxibustion group showed significant improvement in all these indicators （P＜0.05 or P＜0.01）； whereas the vitamin E group did not show a statistically significant difference in Collagen Ⅰ and collagen Ⅲ levels （P＞0.05）. TEM results showed that， compared with the blank group， the model group had atrophic skin cells， extensive mitochondrial vacuolization， and degraded cellular structures； the moxibustion group exhibited crescent- or cup-shaped autophagosomes with a significantly increased number of autophagosomes per unit area， whereas the vitamin E group showed less improvement than the moxibustion group. ConclusionMoxibustion at "Guanyuan （CV 4）" may alleviate skin photoaging by regulating oxidative stress imba-lance， modulating cellular autophagy， and promoting collagen synthesis， thereby slowing the aging process of the skin.

Objective: To investigate the current status of refractive errors and insufficient hyperopia reserve in preschool children aged 3-6 years in Hefei and to analyze influencing factors, so as to provide a scientific basis for formulating targeted myopia prevention policies and comprehensive interventions. Methods: In May 2022, a stratified cluster random sampling method was used to select 897 preschool children from 8 kindergartens across four districts (Baohe, Yaohai, Shushan, and Economic and Technological Development Zone) in Hefei, and Children’s Visual Health related Behavior Assessment Scale was used to collect personal information and environmental factors. Pre and post cycloplegic refraction tests were conducted to assess insufficient hyperopic reserve and refractive development levels. Group comparisons were conducted using 2 test, t-test or analysis of variance. Multivariate regression analysis was performed to identify key factors influencing hyperopic reserve, axial length and spherical equivalent in preschool children. Results: The detection rates of refractive errors among preschool children were 6.8% for hyperopia, 1.6% for myopia, and 11.1% for astigmatism. Notably, the prevalence of myopia was significantly higher in boys (2.3%) than in girls (0.7%) ( χ 2=3.88, P <0.05). Additionally, 8.8% of the children exhibited insufficient hyperopic reserve. The results of multiple regression analysis showed that preschool children with high myopia in the father, high myopia in the mother, longer daily duration of near work, and longer daily electronic product use time had increased risks of axial growth ( β =0.12, 0.09, 0.15, 0.11), SE reduction ( β =-0.10, -0.07, -0.18, -0.13), and insufficient hyperopic reserve ( OR=1.87, 2.22, 1.40, 1.28) (P <0.05). While, preschool children with longer sleep time and daily outdoor activity duration had lower risks of axial growth ( β =-0.11, -0.10 ), SE reduction ( β =0.39, 0.51), and insufficient hyperopia reserve ( OR =0.54, 0.51) in preschool children ( P <0.05). Conclusions The rates of refractive errors and insufficient hyperopia reserve in preschool children in Hefei are relatively low, which are influenced by many factors. Parents, kindergartens and relevant departments should implement early vision monitoring and intervention for preschool children, and cultivate their scientific eye use habits.

The p21-activated kinase 4 (PAK4), a key regulator of malignancy, is negatively correlated with immune infiltration and has become an emergent drug target of cancer therapy. Given the lack of high efficacy PAK4 inhibitors, we herein reported the identification of a novel inhibitor 13 bearing a tetrahydrobenzofuro[2,3-c]pyridine tricyclic core and possessing high potency against MIA PaCa-2 and Pan02 cell lines with IC₅₀ values of 0.38 and 0.50 μmol/L, respectively. This compound directly binds to PAK4 in a non-ATP competitive manner. In the mouse Pan02 model, compound 13 exhibited significant tumor growth inhibition at a dose of 100 mg/kg, accompanied by reduced levels of PAK4 and its phosphorylation together with immune infiltration in mice tumor tissue. Overall, compound 13 is a novel allosteric PAK4 inhibitor with a unique tricyclic structural feature and high potency both in vitro and in vivo, thus making it worthy of further exploration.

Alzheimer's disease (AD), characterized by β-amyloid (Aβ) aggregation and neuroinflammation, remains a formidable clinical challenge. Herein, we present an innovative nose-to-brain delivery platform utilizing lactoferrin (Lf)-functionalized lipid nanoparticles (LNPs) co-encapsulating α-mangostin (α-M) and β-site APP cleaving enzyme 1 (BACE1) siRNA (siB). This dual-modal therapeutic system synergistically combines the neuroprotective and microglia-reprogramming capabilities of α-M with the transcriptional silencing of BACE1 via siB, thereby simultaneously inhibiting Aβ production and enhancing its clearance. Fabricated via a microfluidic approach, the LNPs exhibited uniform particle size distribution, great encapsulation efficiency, and robust colloidal stability. Upon intranasal administration, Lf-functionalization enabled superior brain-targeting efficacy through receptor-mediated transcytosis. In vitro studies demonstrated that α-M reversed Aβ-induced low-density lipoprotein receptor downregulation, promoting microglial phagocytosis and autophagic degradation of Aβ, while siB effectively suppressed BACE1 expression, abrogating Aβ synthesis. In vivo investigations in APP/PS1 transgenic mice revealed remarkable cognitive recovery, substantial Aβ plaque reduction, and alleviation of neuroinflammation and oxidative stress. This intricately designed LNP system, exploiting a non-invasive and efficient nose-to-brain delivery route, provides a biocompatible, synergistic, and transformative therapeutic strategy for the multifaceted management of AD.

Objective: To investigate the association of parental knowledge and skills in myopia prevention and control with healthy eye behavior in primary school children, so as to provide a basis for accurate family education. Methods: A total of 4 979 students in grades 1-5 from eight elementary schools in Pudong New Area were sampled between October and December in 2022 by using a stratified cluster sampling method. A self administered questionnaire was used to assess healthy eye behavior in primary school children and parental knowledge and skills in myopia prevention and control. The Chi squared test, independent samples t-test and Logistic regression were used to analyse the association between parental knowledge and skills in myopia prevention and control and healthy eye behaviour in primary school children. Results: Parents of primary school children with a high level of knowledge and skills in myopia prevention and control were 50.97% and 56.36%, respectively. The knowlegde entry scores for parents of lower and middle elementary school students were higher than those of parents of upper primary students with respect to their understanding, on the main causes of myopia in their children, the correct knowledge of myopia prevention and control, the role of family members in helping each other to manage and treat myopia in their children and the parents responsibility to teach their children to use their eyes correctly and scientifically (3.05±1.21, 2.97±1.20; 5.92±0.68, 5.83±0.86; 4.46±0.88, 4.40±0.93; 3.88±1.04, 3.72±1.07); all differences were statistically significant (t=2.04, 3.39, 2.00, 4.87, P<0.05). The differences in the scores of parents of primary school children in different grades for all items were statistically significant (t=2.93-7.31, P<0.05) in the skill entries. Parental knowledge levels were poor for items of full scores that assessed the following: knowing the main causes of their childrens myopia, awareness of the correct knowledge of myopia prevention and control measures, awareness of Comprehensive Prevention and Control Strategy for Children and Adolescents with Myopia, and concerning that their childrens future education and employment will be affected by myopia, understanding the responsibility of parents for guiding children to use their eyes scientifically and correctly, with 12.71%, 22.90%, 19.30%, 21.83% and 22.47% respectively. Parental skills were poor for items of full scores that assessed the following:reminding their children to rest their eyes when doing homework, reading or writing, deliberately avoiding mobile phone use when spending time with their children, the number of times which taking children to the hospital for refractive screening in the past year, and giving their children extra learning tasks, with 33.26%, 15.12%, 9.00% and 5.36% respectively. Compared to parental knowledge in myopia prevention and control, parental skills had a more pronounced effect on the four dimensions of healthy eye behavior (reading and writing, screen time, outdoor activities, and sleep duration) among students in different grades (OR=1.41-3.37, P<0.05). Conclusions Parental knowledge and skills in myopia prevention and control are still insafficient, associated with healthy eye behavior in primary school children. There is a need to strengthen accurate health education for parents on the prevention and control of myopia, to cultivate healthy eye behaviour among primary school students and reduce the incidence of myopia among them.

Objective:To evaluate insulin sensitivity(IS)and pancreatic β-cell secretion function in the elderly, analyze the influencing factors, and compare these parameters with those observed in adults.Methods:A total of 301 participants were selected from the health examination population at the Geriatrics Endocrinology Department of Jiangsu Provincial People's Hospital, all of whom had no history of diabetes, between December 2018 and June 2021.Participants were categorized into elderly and adult groups based on age.Personal and medical histories were recorded, and various measurements, including height, weight, waist circumference, hip circumference, blood lipids, and nutritional metabolic indicators, were obtained.Body composition was assessed using dual-emission X-ray absorptiometry(DXA).The oral minimal model(OMM)method was utilized to derive the insulin sensitivity index(ISI), dynamic insulin secretion(Φd), static insulin secretion(Φs), total insulin secretion(Φt), and disposition index(DI).Participants were grouped according to the results of oral glucose tolerance tests.Finally, the factors influencing IS and pancreatic β-cell function were analyzed in both elderly and adult populations, as well as to identify any differences between the two groups.Results:Following adjustments for gender and body mass index(BMI), partial correlation analysis indicated a decrease in Φd, DI-Φd, and DI-Φt with advancing age( r=-0.219, -0.210, -0.187; P=0.005, 0.015, 0.017).In contrast, ISI, Φs, Φt, and DI-Φs showed no significant correlation with age.Although ISI levels were comparable between the elderly and adult groups, individuals newly diagnosed with diabetes in the elderly cohort exhibited higher DI-Φd, DI-Φs, and DI-Φt compared to those in the adult group after ISI correction.When incorporating age, high-density lipoprotein cholesterol(HDL-C), total muscle mass, the android to gynoid ratio(A/G), and fat mass index(FMI)into a binary Logistic regression model, the findings underscored FMI as a common risk factor for both elderly and adult cohorts concerning the ISI( OR=2.324, 1.773; P=0.032, 0.005).The A/G ratio was identified as a risk factor for DI-Φd in both age groups( OR=69 252.464, 407.653; P=0.012, 0.001).Furthermore, HDL-C was recognized as a protective factor for ISI( OR=0.024, P=0.012)in the elderly, while advancing age( OR=1.454, P=0.039)was found to be a risk factor for DI-Φs in this demographic.Total muscle mass and the A/G ratio were also acknowledged as risk factors for ISI( OR=1.054, 15.725; P=0.021, 0.026), with FMI serving as a risk factor for DI-Φs in the adult cohort( OR=1.826, P=0.035). Conclusions:The secretion function of pancreatic β-cells declines with age, whereas ISI remains unchanged.The factors affecting ISI, DI-Φd, and DI-Φs in elderly and adult populations show notable differences.This indicates that implementing targeted lifestyle interventions for distinct age groups may be more effective in preserving both ISI and pancreatic β-cell function.

Objectives:To compare the effects of manual and mechanical chest compression on patients receiving extracorporeal cardiopulmonary resuscitation (ECPR).Methods:Patients who underwent extracorporeal cardiopulmonary resuscitation admitted to Jinhua Municipal Central Hospital, Hangzhou First People's Hospital and the First Hospital of Jiaxing from September 2014 to July 2022 were enrolled in the study. The patients were divided into the manual group and mechanical group according to the compression method, and the clinical data of the two groups were compared. To explore the effects of the two compression method on the ECPR implementation, proportion of return of spontaneous circulation (ROSC) and hospital survival.Results:A total of 108 patients who underwent ECPR were included in the study, 50 patients in the manual group and 58 patients in the mechanical group. There were no significant differences in sex, age, laboratory tests before ECPR, ROSC proportion (90.0% vs. 86.2%) and survival (34.0% vs. 39.7%) between the two groups (all P>0.05). The puncture time in the mechanical group was shorter than that in the manual group [12 (9,15) min vs. 13 (11,16) min, P<0.05]. Conclusions:Compared with manual compression, mechanical compression during ECPR neither increase the probability of ROSC nor reduce in-hospital mortality in patients with cardiac arrest. However, mechanical compression may help to shorten the puncture time.

A simple, fast, and visual method for detecting antibodies against peste des petits ruminants virus (PPRV) using colloidal gold strips was developed. In this study, the pET-32a-N was transformed into Escherichia coli Rosetta (DE3) for expression. Hybridoma cell lines were generated by fusing SP2/0 myeloma cells with splenocytes from immunized mice with the expressed and purified N protein of PPRV. The PPRV N protein was labeled with colloidal gold particles as the gold-labeled antigen. The N protein served as the gold standard antigen and as the test (T) line-coated antigen, while the monoclonal antibody served as the quality control (C) line-coated antibody to assemble the colloidal gold immunochromatographic test strips for detecting antibodies against the N protein of PPRV. Hybridoma cell line designated as 1F1 was able to stably secrete the monoclonal antibody against the N protein of PPRV. The titer of 1F1 monoclonal antibody in ascites was 1:128 000 determined by indirect enzyme-linked immunosorbent assays (ELISA), and the immunoglobulin subtype of the monoclonal antibody was IgG1, with kappa chain. The obtained monoclonal antibody was able to specifically recognize the N protein of PPRV, as shown by Western blotting and indirect immunofluorescent assay (IFA). The developed colloidal gold test strip method was able to detect PPRV antibodies specifically, and there was no difference between different batches of the test strips. Testing of a total of 122 clinical sera showed that the compliance rate of the test strip with ELISA test was 97.6%.The test strip assay developed in this study has good specificity, reproducibility, and sensitivity, and it can be used for the rapid detection of PPRV antibodies.
Animals ; Mice ; Peste-des-Petits-Ruminants/prevention & control* ; Antibodies, Monoclonal ; Reproducibility of Results ; Peste-des-petits-ruminants virus ; Antibodies, Viral ; Enzyme-Linked Immunosorbent Assay ; Goats

Objective:To analyze long-term outcomes of inoperable non-metastatic pancreatic cancer patients treated with definitive radiotherapy-based comprehensive treatment.Methods:Clinical data of 168 patients with medically unfit, refusal to surgery or inoperable non-metastatic pancreatic cancer treated with radiotherapy-based comprehensive treatment in PLA General Hospital between January 2016 and December 2020 were retrospectively analyzed. Survival outcomes,prognostic factors and patterns of treatment failure were analyzed in the radiotherapy ( n=95) and combined chemoradiotherapy ( n=73) groups. The survival analysis was conducted by Kaplan-Meier method. The survival curve was compared by log-rank test. Independent prognostic factors were identified by Cox proportional harzard model. Results:With a median follow-up of 20.2 months in the entire group, the median overall survival (OS) and median progression-free survival (PFS) were 18.0 and 12.3 months. The corresponding median OS and median PFS after receiving radiotherapy were 14.3 and 7.7 months. The 1-, 2-and 3-year OS rates were 72.1%, 36.6% and 21.5%, and the 1- and 2-year local control rates were 82.6% and 64.3%, respectively. The median OS for stage Ⅰ, stage Ⅱ and stage III were 27.1, 18.0 and 17.0 months, respectively. There was no significant difference in the median OS of patients with localized disease (stage Ⅰ-Ⅱ) between the radiotherapy and combined chemoradiotherapy groups (21.1 vs. 20.4 months, P=0.470). In patients with locally advanced disease (stage Ⅲ), combined chemoradiotherapy group showed better median OS compared with radiotherapy group (19.2 vs. 13.8 months, P=0.004). Clinical stage, CA19-9 before radiotherapy, comprehensive treatment and biological effective dose (BED 10) were identified as the independent prognostic factors for OS ( P=0.032, 0.011, 0.003 and 0.014). The cumulative 1- and 2-year actuarial rates of treatment failure, local-regional recurrence and distant metastasis were 48% and 74.4%, 15.0% and 27.4%, 23.6% and 33.1%, respectively. Liver metastasis (16.1%, 27/168) and local recurrence (11.9%, 20/168) were the primary patterns of treatment failure. Conclusions:Definitive radiotherapy-based comprehensive treatment effectively prolongs long-term survival in patients with inoperable non-metastatic pancreatic cancer. Definitive radiotherapy can be an alternative treatment option with curative intent for patients with localized pancreatic cancer who are medically unfit or refuse to undergo surgery. The combination of radiotherapy and chemotherapy remains an effective treatment choice for locally advanced unresectable pancreatic cancer.

Objective:To investigate the correlation of peripheral blood relative mitochondrial DNA copy number(mtDNAcn)with intrinsic capacity and body composition, and to identify potential biomarkers for healthy aging.Methods:Clinical data of 416 patients admitted to our hospital from September 2019 to June 2021 were consecutively collected.MtDNA was extracted from peripheral blood of these subjects, and mtDNAcn was determined by a real-time fluoresence quantitative reverse transcription-polymerase chain reaction(qRT-PCR). Intrinsic capacity assessment included 5 aspects that were exercise[Morse Fall Scale(MFS), Physiological Frailty Phenotype(PFP), Sarcopenia Questionnaire(SARC-CALF), Short Physical Performance Battery(SPPB), Time Up and Go Test(TUG)]; vitality[Mini Nutritional Assessment(MNA), Multidimensional Prognostic Index(MPI)]; cognition[Mini-Mental State Examination(MMSE)scale]; psychology[Geriatric Depression Scale(GDS), Self-rating Anxiety Scale(SAS)]; sensory capacities[Cumulative Illness Rating Scale-the Comorbidity Index(CIRS-CI)]. To assess body composition, dual-energy X-ray absorptiometry was used to measure body fat, including trunk fat, total body fat, fat in the abdominal region, fat in the buttock region, and then to calculate fat index(FMI)and limb skeletal muscle mass index(ASMI).Results:Spearman correlation analysis showed that mtDNAcn had a negatively correlation with age( r=-0.176, P<0.05). After adjustment for gender and body mass index, partial correlation analysis showed mtDNAcn were still negatively correlated with age( r=-0.144, P<0.05). Furthermore, mtDNAcn was significantly correlated with 4 m gait speed, the scores of SARC-CalF, MFS, MNA, MMSE, MPI and its sub-scale's Activities of Daily Living(ADL)and Short Portable Mental Status Questionnaire(SPMSQ)( r=0.171, -0.207, -0.163, 0.221, 0.184, -0.210, 0.241, -0.269, all P<0.05). After adjustment for age, gender and body mass index, partial correlation analysis showed mtDNAcn still had a significant correlation with gait speed, the scores of MFS, MNA, MPI and SPMSQ( r=0.170, -0.170, 0.148, -0.242, -0.188, all P<0.05). In addition, the Spearman correlation analysis showed that mtDNAcn was positively correlated with FMI, trunk fat, total body fat, abdominal fat and fat in the buttock region( r=0.168, 0.143, 0.175, 0.116, 0.199, all P<0.05). However, after adjustment for age and gender, mtDNAcn was only correlated with FMI, total body fat, fat in the buttock region( r=0.126, 0.131, 0.127, all P<0.05). On the other hand, multiple linear regression analysis showed that mtDNAcn was significantly correlated with age, gait speed, FMI, total body fat, fat in the buttock region, the scores of MFS, PFP, MNA and MPI( β=-0.191, 0.156, 0.126, 0.131, 0.125, -0.119, -0.145, 0.151, -0.171, all P<0.05). Conclusions:MtDNAcn is correlated with physical function, frailty, nutrition, falling, cognition and body composition, and may be considered as a biomarker for the evaluation of the locomotion and vitality of human intrinsic capacity.