OBJECTIVE To investigate the expression characteristics and regulatory mechanisms of the circadian clock gene period circadian regulator 1(PER1)and the tumor suppressor gene serine peptidase inhibitor Kazal type 5(SPINK5)in head and neck squamous cell carcinoma(HNSCC),and to elucidate the molecular mechanism by which PER1 regulates SPINK5 transcription via the NF-κB signaling pathway.METHODS Differentially expressed genes in HNSCC were screened using The Cancer Genome Atlas(TCGA)and GSE205155 datasets.The association between SPINK5 expression and patient prognosis was assessed via the GEPIA database.mRNA and protein expression levels of SPINK5 and PER1 in 60 clinical samples were detected by RT-qPCR,immunohistochemistry,and Western blot.PER1 knockdown(using siRNA)and overexpression(via plasmid transfection)were performed in the AMC-HN-8 cell line.Wound healing and colony formation assays were applied to evaluate the effects of PER1,SPINK5,and their interaction on HNSCC cell migration and proliferation.Western blot was utilized to examine the regulatory effect of NF-κB on SPINK5.RESULTS SPINK5 and PER1 were significantly downregulated in HNSCC tissues(all P<0.01),and their low expression was correlated with poor patient prognosis(for SPINK5,HR=0.69,P=0.006 7).A significant positive correlation was observed between PER1 and SPINK5 expression(R2=0.719 2,P=0.001 0).Knockdown and overexpression of PER1 respectively resulted in synchronous alterations in SPINK5 mRNA levels(all P<0.05).PER1 knockdown enhanced cell migration and proliferation(P<0.05),whereas SPINK5 overexpression suppressed these capabilities(P<0.01).Importantly,SPINK5 overexpression reversed the phenotypic changes induced by PER1 knockdown.Mechanistically,PER1 overexpression led to concomitant changes in NF-κB expression,activating the NF-κB pathway and thereby promoting SPINK5 transcription.CONCLUSION PER1 positively regulates SPINK5 transcription via the NF-κB pathway,inhibiting HNSCC cell proliferation and migration.These findings suggest that PER1 and SPINK5 may serve as potential therapeutic targets for HNSCC.

Hypoxia-related diseases,such as altitude sickness,acute lung injury,and heart failure,have emerged as significant public health challenges worldwide and are strongly associated with increased mortality risks.These conditions tend to cause functional impairment and structural alterations in multiple organs,primarily due to inadequate oxygen supply or the inability of tissues to utilize oxygen effectively.To elucidate the pathophysiological mechanisms underlying hypoxia-associated diseases and to explore potential therapeutic strategies,researchers have employed animal models to conduct extensive mechanistic studies and drug development trials.In this review,we provide a comprehensive overview of the methods used to construct animal models for various hypoxia-related diseases.We made a thorough evaluation of the strengths,weaknesses,limitations,and applicability of each approach.In particular,we focus on modeling strategies for key pathologies such as altitude sickness,acute lung injury,pulmonary hypertension,and heart failure,discussing their respective advantages and restrains.Furthermore,we examined the potential application of gene editing technologies in optimizing animal models,especially its role in enhancing the accuracy and reproducibility of the models.The integration of these advanced technologies holds great promise for developing animal models with improved specificity and simulation of key features of diseases,which will serve as a solid foundation for basic research,drug screening,and preclinical trials concerning hypoxia-related diseases.Herein,we present a systematic summary and future outlook of animal models for hypoxia-related diseases,ultimately providing theoretical support for developing clinical treatment strategies and improving patient outcomes.

ObjectiveTo explore the relationships between internet gaming disorder (IGD), interpersonal needs, loneliness, and depression in adolescents through the construction of a chain mediation model, to clarify the underlying mechanisms of these associations, and to provid a theoretical basis for depression prevention and intervention. MethodsBased on the data of the 7th Population Census, using convenient sampling method 1 106 adolescents aged between 10‒19 years in South China (176), North China (147), Central China (332), and East China (451) were selected to conduct a cross-sectional survey, with a ratio of 1∶1∶1.5∶2.5. The survey was conducted with a questionnaire consisting of general information (sex, age, grade, parents’ education level), the Chinese version of the IGDS9-SF, the INQ-15, the short-form of the ULS-8 and the PHQ-9 were used to evaluate the depression status of adolescents. Spearman correlation analysis was used to explore the correlation between the variables. A multiple-mediator model was constructed using IBM SPSS Statistics 22.0 PROCESS to examine the mediating effects of interpersonal needs and loneliness on the relationship between IGD and depression. The significance of the chain mediating effect was tested using the Bootstrap method. ResultsOverall, 39.06% (432/1 106) adolescents experienced depression. The incidence of depression among adolescents with smoking and without smoking was 62.50% and 38.36%, respectively. Similarly, the incidence of depression among adolescents with alcohol consuming and without alcohol consuming was 61.94% and 35.94%, respectively. There were statistically significant differences between IGD, interpersonal needs, loneliness, and depression (P<0.01). The chain mediation model demonstrated a good fit, and the bootstrap test showed that the 95%CI of each mediation path did not include 0, indicating significant mediation effects. The overall effect was 0.337. The direct effect of IGD on depression was significant (effect value=0.138, 95%CI:0.102-0.173, P<0.001). The mediation effects included three paths: ① IGD →interpersonal needs → depression (effect value=0.073, P<0.05), accounting for 21.47% of the total effect;② IGD→ loneliness → depression (effect value=0.093, P<0.05), accounting for 27.35%; and ③ IGD → interpersonal needs → loneliness → depression (effect value=0.036, P<0.05), accounting for 10.59%. ConclusionInterpersonal needs and loneliness independently and jointly mediate the relationship between IGD and depression among adolescents. To reduce depression and improve mental health in this population, measures should be taken to prevent and intervene in IGD, address adolescents’ social and emotional needs, enhance satisfaction of interpersonal needs, and reduce loneliness.

ObjectiveTo explore the effect of Dingkundan on Qi stagnation and blood stasis syndrome in patients with chronic obstructive pulmonary disease （COPD） at a stable phase. MethodA randomized controlled clinical design method was adopted， and 60 patients who were diagnosed with Qi stagnation and blood stasis syndrome in COPD at a stable phase in the outpatient and inpatient departments of the respiratory department of Guang' anmen Hospital of China Academy of Chinese Medical Sciences from June 2019 to December 2019 were divided into observation group and control group according to 1∶1. During the study period， there was no dropout， loss of follow-up， or exclusion between the two groups. On the basis of both groups receiving traditional Chinese medicine （TCM） lung rehabilitation training， the observation group took Dingkundan 7 g/time orally， twice a day. The control group received oral administration of the same specification of Dingkundan starch simulator of 7 g/time， twice a day. Both groups have a treatment period of 12 weeks. The COPD Assessment Test （CAT）， modified Medical Research Council （mMRC）， fatigue scale-14 （FS-14）， self-rating anxiety scale （SAS）， self-rating depression scale （SDS）， 6-minute walk distance （6MWD）， and pulmonary function before and after treatment were evaluated. ResultAfter treatment， both groups showed improvements in CAT， mMRC， FS-14， SAS scores， and 6MWD （P<0.05）. The observation group also showed improvements in SDS scores and lung function indicators （P<0.05）. Compared with the control group after treatment， the observation group showed more significant improvement in CAT， FS-14， SAS， SDS scores， and 6MWD （P<0.05）. ConclusionDingkundan has a clear therapeutic effect on Qi stagnation and blood stasis syndrome in patients with COPD at a stable phase. It can reduce symptom burden， enhance exercise capacity， and improve psychological status and has the potential to improve lung function.

Objective: To analyze the epidemiological and molecular characteristics of norovirus outbreaks in schools in Xicheng District of Beijing from 2017 to 2022, so as to provide evidence for the prevention and control of norovirus outbreaks in schools. Methods: Data of norovirus outbreaks in schools in Xicheng District, Beijing during 2017 to 2022 were collected and analyzed by descriptive epidemiological methods. Realtime PCR was used to detect the nucleic acid of group GⅠand GⅡnorovirus, the positive norovirus nucleic acid samples were sent to Beijing Center for Disease Control and Prevention for molecular typing. Results: From 2017 to 2022, 185 norovirus outbreaks were reported in schools in Xicheng District, including 166 cluster outbreaks and 19 outbreaks. A total of 2 044 cases were reported, with a total attack rate of 13.92%. There were two peaks in the outbreak time, which were from March to June after the spring semester and from October to December after autumn semester. Primary schools were the most common place of occurrence (101 cases), followed by nursery institutions (68 cases) and secondary schools (16 cases). There were statistically significant differences in the incidence rates among different sites(12.37%, 22.78%, 8.47%, χ2=263.34, P<0.01). There were significant differences in the incidence of vomiting, diarrhea, nausea and stomachache among different students (χ2=263.33, 90.58, 20.42, 30.29, P<0.01). Vomiting was the main symptom in primary school and nursery school children (96.41%, 98.28%), and the diarrhea rate was higher in middle school students (68.22%). The outbreaks were mainly caused by type GⅡ norovirus. The genotype from 2017 to 2021 showed the characteristics of diversity, mainly GⅡ.2[P16], but there was no significant advantage for the GⅡ.2 [P16] during 2019 to 2021. Conclusions The norovirus outbreak in schools in Xicheng district of Beijing from 2017 to 2022 are mainly caused by GⅡ type genome. The main genotype is GⅡ.2[P16]. Norovirus infection mainly occurred in primary schools and kindergartens. For the vulnerable populations, it is necessary to improve the capacity to early identification, student infectious disease management, active infection control and prevention measures, and pathogen surveillance and sporadic case monitoring.

As one of the pathogenic mechanisms contained in The Inner Canon of Yellow Emperor （《黄帝内经》）， “disease with latent pathogen induced by a new pathogen” means that the induced new pathogen resulted to a combination of the latent previous pathogen and the new pathogen， which caused the disease. Based on this， it is believed that the change of “nodule-cancer transformation” of pulmonary nodules is actually based on the deficiency of original qi， and the new pathogen induces the latent pathogens like phlegm coagulation， qi stagnation， blood stasis， toxicity， so healthy qi can not drive the pathogens out， and the long-time detention generated into cancerous turbidity， and deve-loped into cancerous tumour at the end. Therefore， based on the three-stage treatment of unformed cancer， dense cancerous toxin， and developed cancer， the clinical practice applied six methods of clearing， expelling， dissipating， tonifying， harmonizing， and transforming， taking into account both the manifestation and root cause， moving the treatment window of pulmonary nodules forward， attacking the pathogens when the toxin was not yet overbearing， supporting the healthy qi before declining， delaying the process of nodules-cancer transformation， and providing ideas for the prevention and treatment of pulmonary nodules “nodule-cancer transformation” in traditional Chinese medicine.

Objective:To investigate the real experience of patients returning to work after total hip and knee arthroplasty, in order to provide a reference for patients to return to work successfully.Methods:We searched for qualitative studies on the real experience of patients after total hip and knee arthroplasty in the returning to work process at home and abroad in the databases such as Cochrane Library, PubMed and Embase, etc, and the search period was from the establishment of the library to May 29, 2023, and the results were integrated by Meta-integration.Results:A total of 6 studies were included, 46 results were extracted, and 9 categories were formed and integrated into 4 themes, patients had different motivations for returning to work, there were many factors influencing patients′ return to work, and patients were eager to be helped in the process of returning to work, and learned from experience to improve their confidence in successfully returning to work.Conclusions:Patients with joint replacement have many obstacles and psychological burden in the process of regression, and hope to receive support from many aspects. Healthcare workers should pay attention to the needs of these populations, provide improved medical support, and actively promote the return of patients to work.

Objective:Based on data mining, the basic acupoint selection rules of allergic rhinitis were discussed, which provided a reference for the clinical treatment of allergic rhinitis.Methods:Computer search for literature on auriculo-sensitive rhinitis in VIP, China National Knowledge Infrastructure, Wanfang, China Biomedical Database, PubMed, Embase, Web of Science, the search period was from establishment of the database until August 29, 2023. The frequency, symptom type and distribution of ear point prescriptions were counted, and the association rules and cluster analysis of ear point prescriptions were carried out.Results:A total of 109 studies were included, and 127 prescriptions for ear points were extracted, involving 33 ear points. The association rules showed that the lungs, inner nose, adrenal glands and wind creek were the core ear points, and the cluster analysis formed six types of combinations: "spleen, kidney, lung, wind creek""subcortical, trachea, liver, throat, shenmen" "large intestine" "internal nose, adrenal gland" "endocrine" "sympathetic, external nose".Conclusions:Auricle therapy for allergic rhinitis mainly involves lungs, inner nose, adrenal glands and wind creeks, and dialectical acupoints are selected according to internal organs and symptoms, providing reference and reference for clinicians.

[ABSTRACT]OBJECTIVE To analyze the risk factors for relapse in patients with chronic rhinosinusitis with nasal polyps(CRSwNP)combined with asthm and provide favorable information for precise treatment and healthy prognosis of patients with CRSwNP combined with asthma.METHODS The clinical data of 161 patients with chronic rhinosinusitis with nasal polyps(CRSwNP)combined with asthm who underwent endoscopic surgery at the Department of Otolaryngology Head and Neck Surgery,Yantai Yuhuanding Hospital,affiliated to Qingdao University,from January 2016 to June 2021 were selected.Based on Lasso's Cox regression analysis and multifactorial Cox regression analysis,the associated risk factors were investigated,and the area under curve(AUC)was calculated to determine the performance of the model.Finally,the Kaplan-Meier(K-M)curves were plotted for the relevant influencing factors.RESULTS The Age[HR(95%CI):0.96(0.948-0.98),P<0.001],gender[HR(95%CI):1.94(1.21-3.14),P=0.006],tissue eosinophil percentage[HR(95%CI):1.01(1.01-1.02),P=0.004],and endoscopic nasal polyp score[HR(95%CI):0.86(0.78-0.96),P=0.005]were highly correlated with recurrence in patients with CRSwNP combined with asthma.Patients with CRSwNP combined with asthma had a higher likelihood of relapse after treatment when the tissue Eos%was>21.28%and the endoscopic nasal polyp score was>4.CONCLUSION The age,gender,tissue eosinophil percentage and endoscopic nasal polyp score are independent risk factors for disease recurrence in patients with CRSwNP combined with asthma.