Objective: To examine the reciprocal relationships of anxiety and depressive symptoms,uncertainty stress with academic buoyancy among college students, providing evidence for mental health promotion and academic resilience enhancement. Methods: A multi stage cluster random sampling method was used to selected 741 undergraduates from grade 1 to 2 of a university in Xuzhou, Jiangsu Province. Participants completed two waves of surveys (T1: October 2022; T2: October 2023) using the Uncertainty Stress Scale, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Academic Buoyancy Scale. Cross lagged models analyzed bidirectional relationships between three mental health variables and academic buoyancy, followed by latent variable modeling integrating all mental health dimensions. Results: Cross lagged model results revealed that T1 uncertainty stress negatively predicted T2 academic buoyancy ( β =-0.14), while T1 academic buoyancy negatively predicted T2 uncertainty stress ( β =-0.11); T1 depressive symptom negatively predicted T2 academic buoyancy ( β =-0.08), while T1 academic buoyancy negatively predicted T2 depressive symptom ( β =-0.09); furthermore, T1 academic buoyancy negatively predicted T2 anxiety symptom( β =-0.10) ( P <0.05). Results from the latent variable cross lagged model of psychological problems (constructed from the three mental health variables) indicated that T1 psychological problems negatively predicted T2 academic buoyancy ( β =-0.09), while T1 academic buoyancy negatively predicted T2 psychological problems ( β =-0.09) ( P <0.05). Conclusions Longitudinal bidirectional relationships exist between mental health status and academic buoyancy in college students. Better mental health facilitates higher academic buoyancy.

Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis. However, mechanisms associated with stem cell senescence require further investigation. In this study, we conducted a proteomic analysis of human dental pulp stem cells (HDPSCs) obtained from individuals of various ages. Our findings showed that the expression of NUP62 was decreased in aged HDPSCs. We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo. Conversely, the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs. Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression, we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1. This, in turn, stimulates the transcription of the epigenetic enzyme NSD2. Finally, the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes (HMGA1, HMGA2, and SIRT6). Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
Humans ; Dental Pulp/cytology* ; Nuclear Pore Complex Proteins/genetics* ; Cellular Senescence/genetics* ; Stem Cells/metabolism* ; Epigenesis, Genetic ; Cell Proliferation ; Cell Differentiation ; Histone-Lysine N-Methyltransferase/metabolism* ; Cells, Cultured ; Cellular Reprogramming ; Cell Movement ; Proteomics

Large cell neuroendocrine carcinoma(LCNEC)of lung is a rare neuroendocrine carcinoma subtype with difficulty in early diagnosis and poor prognosis which is treated with standard strategies of small cell lung cancer and non-small cell lung cancer.In recent years,the precise types of LCNEC and its response to therapy have been identified by next-generation sequencing.Some researches have also found the correlation between different subtypes of LCNEC and the efficacy of chemotherapy regimens.However,there is no consensual agreement of its therapy.Recently,immune checkpoint inhibitors(ICIs)has provided a new option for LCNEC patients based on some retrospective research data and case reports.In this review,we aimed to summarize the epidemiological characteristics,standard therapy,the advances of molecular subtypes and clinical applications of ICIs of LCNEC,so as to provide optimal systemic clinical decision-making for LCNEC patients.

Objective:To study the distribution characteristics of natural killer(NK)cells and their subsets in normal peripheral blood in China,and to explore their normal value and significance.Methods:In this study,peripheral blood was collected from 200 healthy adults.Their age range was 18-87 years.All the subjects were divided into 6 age groups:18-30,31-40,41-50,51-60,61-70,and 71-87 years.With CD16,CD56,CD4,CD19,as surface markers,fluid cytology detection tech-niques were used to detect NK cells and the relative and absolute counts.SPSS 27.0 was used for system-atic analysis of the data,and the measurement data were expressed as mean±standard deviations.A t test,variance analysis or rank sum test were performed to compare the differences between the age groups and the sex groups.The significance level was set at α=0.05,and P＜0.05 was considered statistically significant.Results:The range of NK B cells in the 200 healthy adult subjects was(0.46±0.24)× 106/L,that of CD3-CD56+NK cells was(13.14±7.56)× 106/L,that of CD56dimCD16+NK cells was(5.23±3.12)×106/L,that of CD56bright NK cells was(85.61±7.40)× 106/L,and that of NK T cells was(4.16±3.34)×106/L.There were no statistically significant differences in CD3-CD56+NK cells and NK T cells with respect to age(P=0.417,P=0.217).However,there was a decreasing trend in the number of NK B cells and CD56dimCD16+NK cells with increasing age(r=0.234,P＜0.001;r=0.099,P＜0.001),particularly after the age of 50.Conversely,CD56bright NK cells showed an increasing trend with age(r=0.143,P＜0.001).Conclusion:The detection of NK cells and their subsets has significant reference value for the diagnosis,treatment,and prognosis of autoimmune diseases,infectious diseases,and tumors.This study provides a preliminary reference range for clinical detection of NK cell subsets,but further research with a larger sample size and multi-center trials are needed to confirm these findings.

ObjectiveTo explore the efficacy and predictive indicators of stellate ganglion block （SGB） as an adjunctive intervention for chronic subjective tinnitus and accumulate experience for the application of SGB in the clinical treatment of tinnitus. MethodsA retrospective review was conducted on the data of chronic subjective tinnitus patients who received SGB intervention， with unsatisfactory outcomes otherwise. Pure tone audiometry （PTA）， tinnitus loudness evaluation and Pittsburgh sleep quality index （PSQI） were used. The tinnitus handicap inventory （THI） scores were compared before and after SGB intervention. Correlation analysis and linear regression equations were employed to identify the potential indicators predicting the effectiveness of SGB intervention. Statistical analysis was performed by SPSS 24.0 software. ResultsBy April 2023， a total of 107 patients with chronic subjective tinnitus had undergone SGB intervention， including 67 male and 40 female， with a mean age of （45.32±11.40） years old and an average tinnitus history of （20.32±24.64） months ［16 （12~20）］. Only 7 patients （6.54%） quitted the intervention for personal reasons， which demonstrated good compliance with the intervention. No patients experienced adverse reactions such as infection at the injection site， hematoma， nerve injury， local anesthetic intoxication and so on， which revealed good safety. After SGB intervention， THI scores decreased to below 36 points in 77 patients and decrease by 10 points or more in 12 of the remaining patients， with a total effective rate of 89%. A paired sample t-test showed a significant difference in THI scores before and after SGB intervention （t=15.575， P<0.001）， indicating good improvement. Pearson correlation analysis suggested that pre-intervention THI scores and subjective tinnitus loudness were significantly positively correlated with the improvement level of THI scores （P<0.05）. Further stepwise linear regression analysis found that "pre-intervention THI scores" had statistical significance （P<0.001）， with a regression coefficient of 0.308， predicting a 17.4% improvement level in THI scores. ConclusionsDue to its good and safe short-term effects， SGB intervention can be used as a supplementary option for chronic subjective tinnitus when other interventions are not ideal， especially for patients with higher THI scores. However， further research is needed to clarify the long-term efficacy and underlying mechanisms， in order to establish a more solid theoretical basis for SGB intervention in the treatment of subjective tinnitus.

Aim To study whether genetically predicted serum testosterone level is causally associated with sys-temic multisite atherosclerosis.Methods Based on two pooled databases of genome-wide association studies on testos-terone and atherosclerosis in European populations from two separate foreign countries,the causal effect between testosterone and atherosclerosis was assessed using two-sample Mendelian randomization analysis with data on testosterone-associated genetic variants as instrumental variables(Ⅳ),and by using the inverse-variance weighted(IVW)method,MR-Egger regression,and weighted median estimation.Results IVW results showed that genetically predicted circu-lating testosterone levels were negatively associated with the risk of peripheral atherosclerosis(OR=0.93,95％CI:0.86～1.00,P=0.01),and that elevated testosterone level may reduce the risk of developing peripheral atherosclerosis,while no evidence of a potential causal association was found with cerebral atherosclerosis,coronary atherosclerosis and other athero-sclerosis type(P＞O.05).Conclusion The final analysis showed a causal relationship between genetically predicted testosterone level and the risk of developing peripheral atherosclerosis,and the role of testosterone therapy in the prevention and treatment of atherosclerosis deserves attention and further study.

Objective To analyze the refractive prediction error(PE)in combined vitrectomy,phacoemulsification,and intraocular lens(IOL)implantation for patients with macular disease and cataract.Methods This study encom-passed 96 patients(96 eyes)diagnosed with macular disease and cataract,who underwent combined vitrectomy,phacoe-mulsification and IOL implantation at the Department of Ophthalmology in Xijing Hospital,Air Force Military Medical Uni-versity from May 2014 to November 2022.The best corrected visual acuity(BCVA)and actual spherical equivalent(SE)were studied,PE and absolute refractive error(ARE)were calculated,and the correlations between PE and axial length(AL),anterior chamber depth(ACD),lens thickness(LT),flat keratometry(Kf),steep keratometry(Ks),mean kera-tometry(Km),corneal astigmatism degree(cylinder,Cyl),intraocular pressure(IOP),BCVA,corneal astigmatism axis,the classification of macular diseases,and the type of intraoperative vitreous fillers were analyzed.Results In the early postoperative period(within 3 days after surgery),no statistically significant disparity in BCVA was observed compared to preoperative data among the 96 patients studied(P＞0.05).The ARE was determined to be(1.47±2.54)D,indicating a substantial deviation between the actual SE and preoperative predictive refraction of the 96 patients(P＜0.05).Among them,61 patients had a myopic shift,35 patients had a hyperopic shift,and the values of PE were(-1.81±3.07)D and(0.87±0.96)D,respectively.At the 1-month mark after surgery,there was no statistically significant difference in BCVA compared to the preoperative data of 12 follow-up patients(P＞0.05).Similarly,no statistically significant differences were found between every two of the three data,namely the actual SE one month after surgery,the preoperative predictive refraction,and the actual SE in the early postoperative period of the 12 follow-up patients(all P＞0.05).Also,no disparity was observed in BCVA at the last follow-up(P＞0.05)among the 6 patients who were followed up for over 1 year(long-term postoperative follow-up).The correlation analysis revealed that,in the early postoperative period,the PE of patients with myopic shift was negatively correlated with both preoperative AL and Cyl measurements(both P＜0.05).The early postoperative PE of patients with myopic shift was associated with the diagnostic classification of macular diseases(P＜0.05),and the degree of myopic shift was observed to be significantly greater in patients with pathological myopia macular holes compared to those with other macular diseases(P＜0.05).Additionally,the early postoperative PE of patients with myopic shift was uncorrelated with preoperative ACD,TL,Kf,Ks,Km,IOP,BCVA,the type of intraoperative vitreous fillers and the corneal astigmatism axis(all P＞0.05).In contrast,for patients exhibiting hyperopic shift,the PE observed in the early postoperative period exhibited a positive correlation with preoperative Cyl(P＜0.05).PE was also correlated with the type of intraoperative vitreous fillers(P＜0.05),and the degree of hyperopic shift was notably enhanced when the intraoperative vitreous cavity was filled with silicone oil(P＜0.05).The PE of patients with hyperopic shift observed in the early postoperative period exhibited no correlation with preoperative AL,ACD,TL,Kf,Ks,Km,IOP,BCVA,the diagnos-tic classification of macular diseases or the astigmatism axis(all P＞0.05).Conclusion Refractive prediction error may occur in patients with macular disease and cataract in the initial postoperative period after the vitrectomy combined with phacoemulsification and IOL implantation,predominantly caused by myopic shift.However,over time,there is a signifi-cant reduction in the magnitude of this refractive error.The direction and extent of diopter drift appear to be influenced by preoperative AL,Cyl,the specific diagnosis of macular disease,and the type of vitreous cavity filler utilized in the surgical procedure.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Objective: To elucidate the differences in manual acupuncture effectiveness at sensitized points by investigating the mechanisms of local skin action at different sensitization points in rats with knee osteoarthritis (KOA). Methods: Forty Sprague–Dawley rats were equally divided into control, model (1 mg of monoiodoacetate into the right knee joint cavity), sham operation, manual acupuncture at right Tianjing acupoint (MAR-SJ 10), and left SJ 10 groups. Safranine-O and fast green staining were used to assess the modeling. The morphological and functional changes in mast cells (MCs) were assessed during acupoint sensitization using toluidine blue and immunofluorescence staining. The levels of serotonin, histamine, substance P (SP), and tryptase at skin acupoints and serum levels of IL-β, IL-6, and TNF-α were detected using ELISA. Results: After 14 days of treatment, the number of MCs and their degranulation rates were statistically higher in the model group than in the control group (both P < .001). After applying acupuncture, the levels of 5-HT, HA, and SP at skin acupoints were lower than those in the model group (all P < .05), and tryptase level was higher (both P < .05). Tryptase level was higher on the skin at the MAL-SJ 10 acupoint than that on the MAR-SJ 10 acupoint (P = .004). Compared with the model group, the serum levels of IL-1β, IL-6, and TNF-α in the MAR-SJ 10 and MAL-SJ 10 groups were lower (all P < .05). Conclusion Acupuncture at KOA-sensitized acupoints mitigates joint injury in KOA rats and may bidirectionally regulate local MCs of these acupoints. This finding not only enhances the reference value of sensitizing points in clinical diagnosis and treatment, but also contributes to the understanding of the biological mechanisms underlying acupuncture intervention at sensitizing points.

Atmospheric fine particulate matter (particulate matter 2.5,PM_2.5) is a major component of haze, and its potential hazards to human reproductive health have garnered widespread attention. Establishing appropriate animal models is crucial for in-depth research into the reproductive toxicity of PM_2.5 exposure and its underlying mechanisms. This paper, based on recent literature, summarizes current methods for establishing PM_2.5-exposed animal models and the evaluation criteria for reproductive toxicity research. The primary modeling methods for PM_2.5 exposure include whole-body inhalation exposure and intratracheal instillation exposure. While whole-body inhalation exposure effectively simulates real-life human inhalation environments, it requires sophisticated experimental equipment. Conversely, intratracheal instillation exposure is more cost-effective and easier to operate but faces challenges in accurately mimicking the distribution and deposition of PM_2.5 during natural inhalation. Therefore, researchers must carefully weigh these exposure methods to enhance model rigor and achieve the most realistic simulation of human exposure conditions. When summarizing the application evaluation indicators of PM_2.5-induced reproductive toxicity, this review finds that the main indicators of male reproductive toxicity include reduced sperm quality, testicular tissue damage, and hormonal imbalances. For female reproductive toxicity, the primary indicators are reduced ovarian reserve, endocrine dysfunction, endometrial damage, and adverse perinatal reactions. Additionally, this review highlights the need for detailed chemical composition analysis of PM_2.5, exploring the reproductive toxic targets and mechanisms of particles containing different chemical components, such as heavy metals and polycyclic aromatic hydrocarbons. Long-term studies are also necessary to assess the effects of PM_2.5 exposure on reproductive health and transgenerational effects, to predict potential long-term risks for humans. Additionally, interdisciplinary collaboration should be encouraged, involving cooperation between environmental science, toxicology, reproductive medicine, and other disciplines, to comprehensively assess the environmental health risks of PM_2.5 and provide scientific support for the development of integrated prevention and control strategies. This review summarizes animal modeling methods, evaluation criteria, and their applications, providing valuable methodological references for future reproductive toxicity research on PM_2.5.