Objective To explore the relationship between circadian rhythm genes and the occurrence, development, prognosis, and tumor microenvironment (TME) of lung adenocarcinoma (LUAD). Methods The Cancer Genome Atlas data were used to evaluate the expression, copy number variation, and somatic mutation frequency of circadian gene sets in LUAD. Gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis were used to explore the potential mechanisms by which circadian rhythm genes affected LUAD progression. Cox regression, least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and random forest screened circadian genes and established prognostic models, and on this basis constructed nomogram to predict patients’ 1-, 3-, and 5-year survival rates. Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model, and the external dataset of GEO further verified the prognostic value of the prediction model. In addition, we evaluated the association of the prognostic model with immune cells and immune checkpoint genes. Single cell RNA sequencing (scRNA-seq) analysis was used to explore the molecular characteristics between prognostically relevant circadian genes and different immune cell populations in TME. Results Differentially expressed circadian rhythm genes were mainly enriched in biological processes related to cGMP-PKG signaling pathway, lipid and atherosclerosis, and JAK-STAT signaling pathway. Seven circadian rhythm genes: LGR4, CDK1, KLF10, ARNTL2, RORA, NPAS2, PTGDS were screened out, and a RiskScore model was established. According to the median RiskScore, samples were divided into a high-risk group and a low-risk group. Compared with patients in the low-risk group, patients in the high-risk group showed a poorer prognosis (P<0.001). Immunological characterization analysis showed that there were differences in the infiltration of multiple immune cells between the low-risk group and high-risk group. Most immune checkpoint genes had higher expression levels in the high-risk group than those in the low-risk group, and RiskScore was positively correlated with the expression of CD276, TNFSF4, PDCD1LG2, CD274, and TNFRSF9, and negatively correlated with the expression of CD40LG and TNFSF15. The scRNA-seq analysis showed that RORA and KLF10 were mainly expressed in natural killer cells. Conclusion The prognostic model based on seven feature circadian rhythm genes has certain predictive value for predicting survival of LUAD patients. Dysregulated expression of circadian genes may regulate the occurrence, progression as well as prognosis of LUAD through affecting TME, which provides a possible direction for finding potential strategies for treating LUAD from the perspective of mechanism by which circadian disorder affects immune cells.

Background The air quality index (AQI), which is based on the concentration of a dominant pollutant, and the air quality health index (AQHI), which is constructed using excess risk estimates for individual pollutants, may not fully capture the health risks associated with combined exposure to air pollutants. These approaches also provide limited information on the relative contributions of different pollutants. Given the geographical heterogeneity in the composition and health effects of air pollutant mixtures, it is necessary to develop region- and disease-specific AQHIs for different population groups. Objective To develop and evaluate a health risk-based AQHI for respiratory disease mortality associated with air pollutant mixtures using the weighted quantile sum (WQS) regression model and to quantify the relative weight contributions of selected pollutants. Methods Daily data on six air pollutants, the AQI, meteorological factors, and deaths from respiratory diseases in the central urban districts of Tianjin from 2014 to 2019 were collected and integrated into a time-series database. First, generalized additive models (GAMs) were applied to identify indicator pollutants associated with respiratory disease mortality. Second, the WQS regression model was then applied to estimate the relative weight contributions of selected pollutants and to establish the exposure-response relationship between air pollutant mixtures and respiratory disease mortality for AQHI development. Finally, the exposure-response relationships of the AQHI and AQI with respiratory disease mortality were evaluated and compared across population subgroups and seasons. Results Fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), and ozone (O₃) were identified as indicator pollutants for combined air pollution exposure. Particulate matter, including PM_2.5 and PM₁₀, and O₃ contributed the most to the mixture index, followed by SO₂. Each interquartile range (IQR) increase in the WQS-based AQHI was significantly associated with respiratory disease mortality in the total population, males, elderly individuals, non-elderly individuals, and during the warm season. The corresponding excess risks (ER) were 3.79% (95%CI: 1.24%, 6.27%), 4.37% (95%CI: 0.96%, 7.67%), 3.16% (95%CI: 0.47%, 5.77%), 9.36% (95%CI: 2.01%, 16.15%), and 7.13% (95%CI: 1.31%, 13.30%), respectively. Compared with the AQI, the AQHI showed stronger associations with respiratory disease mortality across different population subgroups and seasons. Conclusion PM_2.5, PM₁₀, and O₃ contribute substantially to the association between air pollutant mixtures and respiratory disease mortality in Tianjin. Compared with the AQI, the WQS-based AQHI better characterizes the association between air quality and respiratory disease mortality across population subgroups.

Objective To determine the prognostic biomarkers and new therapeutic targets of the lung adenocarcinoma (LUAD), based on which to establish a prediction model for the survival of LUAD patients. Methods An integrative analysis was conducted on gene expression and clinicopathologic data of LUAD, which were obtained from the UCSC database. Subsequently, various methods, including screening of differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA), were employed to analyze the data. Cox regression and least absolute shrinkage and selection operator (LASSO) regression were used to establish an assessment model. Based on this model, we constructed a nomogram to predict the probable survival of LUAD patients at different time points (1-year, 2-year, 3-year, 5-year, and 10-year). Finally, we evaluated the predictive ability of our model using Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves. The validation group further verified the prognostic value of the model. Results The different-grade pathological subtypes' DEGs were mainly enriched in biological processes such as metabolism of xenobiotics by cytochrome P450, natural killer cell-mediated cytotoxicity, antigen processing and presentation, and regulation of enzyme activity, which were closely related to tumor development. Through Cox regression and LASSO regression, we constructed a reliable prediction model consisting of a five-gene panel (MELTF, MAGEA1, FGF19, DKK4, C14ORF105). The model demonstrated excellent specificity and sensitivity in ROC curves, with an area under the curve (AUC) of 0.675. The time-dependent ROC analysis revealed AUC values of 0.893, 0.713, and 0.632 for 1-year, 3-year, and 5-year survival, respectively. The advantage of the model was also verified in the validation group. Additionally, we developed a nomogram that accurately predicted survival, as demonstrated by calibration curves and C-index. Conclusion We have developed a prognostic prediction model for LUAD consisting of five genes. This novel approach offers clinical practitioners a personalized tool for making informed decisions regarding the prognosis of their patients.

After being treated with acupuncture, some patients with idiopathic tinnitus may experience a short-term aggravation of tinnitus symptoms on the original basis. These symptoms can be gradually relieved and the overall condition fluctuates towards recovery. This phenomenon has brought some difficulties to patients and clinicians. Based on the academic view of TCM, "destroying pathogens and re-building balance", and in association with the existing understanding of acupuncture in modern medicine for tinnitus, this paper briefly discusses the mechanism and influencing factors of symptom fluctuation in patients with idiopathic tinnitus after acupuncture treatment in terms of both TCM and modern medicine, and proposes the future direction in the research of symptom fluctuation, so as to promote the recognition of clinicians and patients on symptom fluctuation and make rational use of its positive effects. Besides, it is hoped that more researchers will pay attention to symptom fluctuation and advance the exploration of it in academic field.
Humans ; Tinnitus/physiopathology* ; Acupuncture Therapy ; Male ; Female

[Objective]To explore the origin and evolution of the unnamed prescriptions in Handbook of Prescriptions for Emergency in order to clarify the development context of the unnamed prescriptions in this book and provide some ideas for exploring the origins of other unnamed prescriptions in medical formulary.[Methods]By using methods of cataloging,bibliology and historical research,this article briefly describes the version of the Handbook of Prescriptions for Emergency and its unnamed prescriptions.Besides,it compares and analyzes the unnamed prescriptions in the Handbook of Prescriptions for Emergency with those in related medical books to investigate the origin and evolution of the unnamed prescriptions in this book.[Results]Apart from the accompanying prescriptions,Handbook of Prescriptions for Emergency contains a total of 1 130 unnamed prescriptions.There are 14 unnamed prescriptions in Handbook of Prescriptions for Emergency that can be traced back to the medical prescriptions on the wooden slips unearthed in Liye and Zhoujiatai,and the Formulas for Fifty-two Diseases written on silk from the Mawangdui Han Tomb,were particularly closely related to the latter formulas.Besides,there are 22 unnamed prescriptions in Handbook of Prescriptions for Emergency derived from Treatise on Febrile Diseases and Synopsis of the Golden Chamber.Although there are 26 unnamed prescriptions for treating sudden death and poisoning caused by drugs and food,which are similar to the content of"miscellaneous treatment prescriptions""taboos for poultry,animals,fish,insects"and"taboos for fruits,vegetables and grains"in the current edition of Synopsis of the Golden Chamber,they are suspected to be written by GE Hong and were confused by Song officials and added to Synopsis of the Golden Chamber.In addition,there are 255 unnamed prescriptions in Handbook of Prescriptions for Emergency that gradually evolved into named prescriptions in later generations,were mainly recorded in five books including Important Formulas Worth a Thousand Gold Pieces for Emergency,Arcane Essentials from the Imperial Library,Taiping Royal Prescriptions,Comprehensive Recording of Divine Assistance and Formulas for Universal Relief.Finally,it is speculated that Huanglian Jiedu Decoction in Cuishi Fang and Xiaodingzhi Pill in Sanyin Jiyi Bingzheng Fanglun are all originated from unnamed prescriptions in Handbook of Prescriptions for Emergency.[Conclusion]The emergence of prescriptions is not static,which has gone through a process from simple to complex,from unnamed prescriptions to named prescriptions.Taking the famous prescription book Handbook of Prescriptions for Emergency from the Jin Dynasty as an example,the unnamed prescriptions recorded in the book can be dated back to the medical records inscribed wooden slips of the Qin and Han Dynasties,and have inspired later famous prescriptions,revealing to some extent the laws of the origin and evolution of prescriptions.

Objective:To investigate the role of Gasdermin E (GSDME) -mediated keratinocyte pyroptosis induced by Cutibacterium acnes ( C.acnes) in the pathogenesis of acne. Methods:The human immortalized keratinocyte HaCaT cells were stimulated with heat-inactived C.acnes for 15 minutes to 24 hours, and Western blot analysis was performed to determine the expression of cleaved GSDME (GSDME-NT) in HaCaT cells at different time points. Skin tissue samples were collected from 5 acne patients and 4 healthy controls, who visited the Hospital for Skin Diseases, Chinese Academy of Medical Sciences from January 2 to December 1, 2024; additionally, 3 samples of acne cyst contents and 3 samples of normal follicle contents were collected. Immunohistochemical study and Western blot analysis were conducted to determine GSDME-NT expression in the epidermis. Enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of interleukin (IL) -1β and tumor necrosis factor (TNF) -α in acne cyst or normal follicle contents. GSDME-knockdown HaCaT cells were constructed by transfection with lentivirus carrying GSDME-shRNA, and HaCaT cells transfected with lentivirus carrying the nonsense sequence control (NC) served as controls; ELISA was performed to detect the levels of IL-1β and TNF-α in GSDME-knockdown HaCaT cells after C. acnes stimulation ( C. acnes + GSDME knockdown group) , as well as in the phosphate-buffered saline (PBS) + NC group, C. acnes + NC group, and PBS + GSDME knockdown group. Western blot analysis was conducted to determine the GSDME-NT expression in HaCaT cells pretreated with or without retinol after C. acnes stimulation. Results:The cleavage of GSDME in HaCaT cells began at 1 hour after in vitro C. acnes stimulation, and GSDME-NT could be detected at this time. Compared with the control epidermis, the proportion of GSDME-NT-positive HaCaT cells (9.34% ± 2.92% vs. 3.05% ± 1.14%, t = -3.47, P = 0.026) and GSDME-NT protein expression levels ( t = -3.51, P = 0.025) significantly increased in the lesional epidermis of acne patients. The levels of IL-1β and TNF-α were significantly higher in the acne cyst contents than in the normal follicle contents (IL-1β: 1 337.24 [1 182.32, 2 230.61] pg/ml vs. 0.00 [0.00, 108.21] pg/ml, Z = 1.99, P = 0.046; TNF-α: 811.31 [438.26, 817.73] pg/ml vs. 46.67 [12.41, 53.21] pg/ml, Z = 1.96, P = 0.049) . ELISA showed that the levels of IL-1β and TNF-α were significantly higher in the C. acnes + NC group (12.12 ± 3.07 pg/ml, 26.06 ± 1.57 pg/ml, respectively) than in the PBS + NC group (3.73 ± 2.24 pg/ml, 10.14 ± 0.79 pg/ml, P = 0.003, < 0.001, respectively) ; compared with the C. acnes + NC group, the levels of IL-1β and TNF-α significantly decreased in the C. acnes + GSDME knockdown group (3.38 ± 0.93 pg/ml, 12.67 ± 2.10 pg/ml, P = 0.003, < 0.001, respectively) . The GSDME-NT expression was significantly lower in the retinol + C. acnes group than in the C. acnes group ( P = 0.029) . Conclusion:C. acnes may induce GSDME-mediated pyroptosis in keratinocytes, thereby promoting the release of inflammatory factors and aggravating the inflammatory response in acne, while retinol may be able to inhibit this process.

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

Objective:To analyze the differences in pediatric CT radiation dose and scanning parameter Settings between children's specialized hospitals and general hospitals, and to provide reference for the optimization strategy of pediatric CT radiation dose.Methods:From July to August 2022, a stratified sampling method was used to select 7 comprehensive hospitals and 2 children's hospitals in Tianjin, and on-site survey was conducted to collect the dose data of children's head, chest, and abdomen and pelvic CT examinations in these hospitals. The Wilcoxon rank sum test was used to analyze the differences in CTDI vol and DLP of the same age group and examination site among different types of hospitals, and the stepwise regression analysis method was used to analyze the effects of age, examination site, and scanning parameters on radiation dose CTDI vol and DLP. Results:The CTDI vol and DLP of head (1-<5, 5-<10, 10-<15 years old group), chest (5-<10, 10-<15 years old group) and abdomen (1-<5, 5-<10, 10-<15 years old group) in children's specialized hospitals were lower than those in general hospitals (head, 1-<5, 5-<10, 10-<15 years old group, CTDI vol: Z=-9.32, -6.17, -9.86, P<0.001, DLP, Z=-4.41, -4.14, -5.76, P<0.001; chest, 5-<10, 10-<15 years old group, CTDI vol: Z=-3.84, -5.35, P<0.001, DLP, Z=-3.59, -4.63, P<0.001; abdomen, 1-<5、5-<10 and 10-<15 years old group, CTDI vol: Z=-7.88, -7.78, -8.53, P<0.001, DLP, Z=-7.24, -5.92, -3.44, P<0.001). The CT radiation dose in children was positively correlated with age, tube voltage, tube current time product and scan length, and negatively correlated with pitch and hospital type (general hospital and children's hospital) . Conclusion:There are some differences in the CT radiation dose and scanning parameters between children's hospitals and general hospitals. The results indicate that there is still much room for improvement in the optimization of radiation dose in pediatric CT examination.

The elimination of biofilms is a crucial step in controlling hospital-acquired infections.Once biofilms colonize luminal instruments,it is difficult to remove them using traditional disinfection methods.Conventional disinfection approaches now face a series of challenges,including microbial resistance,corrosiveness,cytotoxicity,residual disinfection byproducts,and environmental pollution.Therefore,developing novel disinfection technologies specifically targeting biofilm removal is vitally important.New disinfection technologies,such as slightly acidic electrolyzed water,plasma technology,surface modification techniques,nanomaterial-based disinfection,bacteriophage disinfection,and enzymatic disinfection,are constantly emerging.These technologies exhibit excellent performance against biofilms by leveraging the synergistic effects of multiple mechanisms,including the reactive oxygen species(ROS)burst,photocatalytic oxidation,physical disruption,and biological targeting.This review summarizes the characteristics,underlying mechanisms,and potential application scenarios of these novel disinfection technologies,with a particular focus on their effects against biofilms formed by common pathogenic bacteria on surfaces in hospital settings.It aims to provide a reference basis for the practical application and translation of these disinfection technologies and the development of new disinfection strategies.

Objective To explore the role and underlying mechanism of the transcriptional coactivator with PDZ-binding motif(TAZ)and a histone variant of acute histone H2A(H2A.Z)in the repair of hypoxia-induced lung injury.Methods A mouse model of hypoxic lung injury was established by being placed in a hypoxia chamber(simulating an altitude of 5 800 m)for 4 d.HE staining was used to observe the severity of lung injury.A hypoxia model of murine alveolar epithelial cells(murine lung epithelial-12,MLE12)was constructed by treating the cells in a hypoxia workstation(1%O2 concentration)for 24 h.Western blotting was employed to detect TAZ expression.The proliferation of alveolar epithelial cells(AECs)was evaluated by CCK-8 assay.Co-immunoprecipitation(Co-IP)assay was utilized to verify the interaction between TAZ and H2A.Z.CUT&Tag sequencing was performed to determine the effect of TAZ on the chromatin deposition of H2A.Z.Results Hypoxia significantly induced alveolar atrophy and inflammatory infiltration in mouse lung tissues(P＜0.01).Hypoxia significantly up-regulated the protein level of TAZ in MLE12 cells(P＜0.05).CCK-8 assay showed that knockdown of TAZ significantly reduced the proliferative capacity of AECs(P＜0.01).Co-IP assay confirmed the physical interaction between TAZ and H2A.Z.CUT&Tag sequencing revealed that hypoxia promoted the deposition of H2A.Z on chromatin(31 817 peaks under normoxia,44 078 peaks under hypoxia),which was partially reversed by TAZ knockdown(37 840 peaks).Conclusion Hypoxia significantly up-regulates the expression of TAZ,which combines with H2A.Z and promotes the deposition of H2A.Z on chromatin,thus enhancing the proliferation of AECs in response to hypoxic injury.