Background Kurtosis reflecting noise's temporal structure is an effective metric for evaluating noise-induced hearing loss (NIHL), and its threshold is still unclear. Objective To explore the energy range of kurtosis and the threshold of NIHL induced by kurtosis in this energy rangeMethods Using cross-sectional design, 4631 noise-exposed workers in manufacturing industry were selected. The hearing loss and noise exposure data of each worker were collected. Logistic regression model was used to establish the dose-response relationship between noise exposure and hearing loss and estimate the range of energy effects. Restricted cubic spline model was utilized to analyze the dose-response relationship curves of kurtosis to noise-induced hearing loss (NIHI) and high-frequency noise-induced hearing loss (HFNIHL) under different 8 h equivalent sound levels (L_{EX,8 h}), as well as to estimate the kurtosis effect threshold. Results The logistic regression model analysis showed that the prevalence of NIHI and HFNIHL increased significantly with increase of L_{EX,8 h} for steady noise; when L_{EX,8 h} of non-steady noise was 80-100 dB(A), the risk of hearing loss increased with an increase in kurtosis (P<0.05). The restricted cubic spline model showed that when L_{EX,8 h} of non-steady noise was 0-80 dB(A) or >100 dB(A), there was no significant relationship between kurtosis and NIHI or HFNIHL. When L_{EX,8 h} was 80-100 dB(A), there was a significant nonlinear dose-response relationship between kurtosis and NIHL or HFNIHL (P <0.001), and kurtosis > 28.08 exerted effect in elevating NIHI or HFNIHL. Conclusion The effect threshold of kurtosis on NIHL is 28.08 when non-steady noise levels are in the range of 80-100 dB(A). The effect threshold of kurtosis needs further verification.

Oroxylin A (OA), a natural compound extracted from Scutellaria baicalensis, demonstrates preventive potential against ultraviolet B (UVB)-induced non-melanoma skin cancer (NMSC), the most prevalent cancer worldwide with increasing incidence. Utilizing SKH-1 hairless mice exposed to UVB, this study showed that OA delayed NMSC onset and alleviated acute skin damage. Mechanistic investigations revealed its dual action: inhibiting inflammation and enhancing nucleotide excision repair (NER) by stabilizing XPA, a crucial deoxyribonucleic acid (DNA) repair protein. This stabilization occurred through OA's interaction with glucose-regulated protein 94 (GRP94), which disrupted murine double minute 2 (MDM2)-mediated XPA ubiquitination and proteasomal degradation. By maintaining XPA levels, OA expedited photoproduct clearance and diminished genomic instability, ultimately impeding NMSC development. These findings suggest OA as a promising chemopreventive agent targeting the GRP94/MDM2-XPA axis to counteract UVB-induced carcinogenesis.
Animals ; Ultraviolet Rays/adverse effects* ; Skin Neoplasms/prevention & control* ; Flavonoids/pharmacology* ; Mice ; Xeroderma Pigmentosum Group A Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-mdm2/genetics* ; DNA Repair/drug effects* ; Scutellaria baicalensis/chemistry* ; Mice, Hairless ; Skin/radiation effects*

Objective To investigate the epidemiological trends,temporal and spatial distribution characteristics of pulmonary tuberculosis in Lanping County.Methods Based on tuberculosis management data and basic information systems from the"China Disease Prevention and Control Information System,"pulmonary tuberculosis data from Lanping County for 2018-2023 were obtained.Descriptive epidemiology,concentration method,circular distribution method,and spatial autocorrelation analysis were used to conduct epidemiological and spatial analyses of the pulmonary tuberculosis data.Results A total of 2836 TB cases were reported in Lanping County from 2018 to 2023,with an average annual incidence rate of 233.26 per 100000,showing a declining trend.The male-to-female ratio was 1.95∶1,with the highest incidence among individuals aged 60 and above(932 cases,32.86%).Cases were predominantly among farmers(91.01%)and the Lisu ethnic group(52.68%).TB incidence showed weak seasonality with a bimodal distribution,with primary peak occurring from October to March and secondary peak from June to August.Tu'e Township(324.74 per 100,000),Shideng Township(307.42 per 100000),and Jinding Town(260.98 per 100,000)had the highest incidence rates,accounting for 1,284 cases or 45.28%of the county's total cases.In 2020,the incidence of pulmonary tuberculosis in Lanping County showed a spatial clustering distribution(global Morans's I value<0,P value<0.05),with Shideng Township consistently showing high-low aggregation characteristics.Conclusion Between 2018-2023,while the tuberculosis incidence rate in Lanping County has declined,it still falls short of Yunnan Province's tuberculosis prevention and control targets,and the prevention and control work continues to face significant challenges.Strengthening screening of high-risk populations and providing medical support to remote areas will be key measures for future prevention and treatment.

Pharmacovigilance impact research(PIR),as an important application field of pharmacoepidemiology,has attracted continuous attention in recent years from drug regulatory authorities,pharmaceutical manufacturers,and the academic community both domestically and internationally.This paper provides an interpretation of PIR based on the Guide for Methodology in Pharmacoepidemiologic Research(2nd edition).First,an overview of the implications of PIR will be provided,focusing on the pathways of pharmacovigilance activities and the significant importance of conducting PIR.Second,it reviews commonly used study designs and presents illustrative case examples.Building on this,the specific statistical considerations relevant to PIR were discussed.Finally,the challenges and prospects of conducting pharmacovigilance impact studies in a scientific and standardized manner are summarized.Compared with the previous edition,the 2nd edition has expanded the application scenarios of pharmacoepidemiology to include new areas such as PIR.Drawing on the guideline content and practical experience,this paper provides a detailed introduction and case analysis of PIR,serving as a reference for researchers engaged in this field.

Standardized research reporting is crucial for the translation of pharmacoepidemiology research findings,and visual reporting can significantly enhance the clarity,understandability,and transparency of research results.Based on the Guide on Methodological Standards in Pharmacoepidemiology(2nd edition),this article systematically explains the key points for writing each component of a research report(including title,abstract,introduction,research methods,research results,discussion and conclusions,acknowledgments,conflict of interest statement,and references).This article also summarizes recognized international and domestic standards for pharmacoepidemiology research reporting,providing a reference for researchers.Furthermore,real-world cases will be used to demonstrate common forms of visualized reports and their interpretation methods.Finally,it further explores strategies for communicating research results.This study aims to provide pharmacoepidemiology researchers with detailed guidance on visually presenting research results and writing high-quality research reports,thereby enhancing the integrity and impact of their research.

Objective To retrospectively analyze the distribution and differences of oral behavior among patients with acute and chro-nic painassociated with temporomandibular disorders(TMD).Methods A total of 212 patients with pain TMD in West China Hospital of Stomatology completed oral behaviors checklist(OBC).SPSS statistical software was used to analyze all the data.Results The pa-tients with pain-related TMD had specific oral behaviors,such as"pressure on the jaw during sleep"(49.5%),"unilateral chewing"(49.5%),"upper and lower teeth contact when not eating"(37.7%),etc.Scores of"upper and lower teeth contact when not eating"and"muscle tension when teeth are not clenched or teeth are not in contact"in patients with chronic pain TMD were higher than those of acute patients,and the difference was statistically significant(P＜0.05).The total OBC scores and daytime OBC scores of chronic pain TMD patients were higher than those of acute pain patients,and the difference was statistically significant(P＜0.05).There was no significant difference in OBC scores of patients with acute and chronic pain TMD during sleep(P＞0.05).Conclusion Pain-related TMD patients had specific oral behaviors,and patients with chronic pain TMD exhibited higher levels of total OBC,daytime OBC,"upper and lower teeth contact when not eating"and"muscle tension when teeth do not bite or teeth are not in contact"oral behavior than acute pain TMD patients.In the treatment of patients with painful TMD,correcting the patient's bad oral behavior can help the treatment of pain-related TMD.

Standardized research reporting is crucial for the translation of pharmacoepidemiology research findings,and visual reporting can significantly enhance the clarity,understandability,and transparency of research results.Based on the Guide on Methodological Standards in Pharmacoepidemiology(2nd edition),this article systematically explains the key points for writing each component of a research report(including title,abstract,introduction,research methods,research results,discussion and conclusions,acknowledgments,conflict of interest statement,and references).This article also summarizes recognized international and domestic standards for pharmacoepidemiology research reporting,providing a reference for researchers.Furthermore,real-world cases will be used to demonstrate common forms of visualized reports and their interpretation methods.Finally,it further explores strategies for communicating research results.This study aims to provide pharmacoepidemiology researchers with detailed guidance on visually presenting research results and writing high-quality research reports,thereby enhancing the integrity and impact of their research.

Pharmacovigilance impact research(PIR),as an important application field of pharmacoepidemiology,has attracted continuous attention in recent years from drug regulatory authorities,pharmaceutical manufacturers,and the academic community both domestically and internationally.This paper provides an interpretation of PIR based on the Guide for Methodology in Pharmacoepidemiologic Research(2nd edition).First,an overview of the implications of PIR will be provided,focusing on the pathways of pharmacovigilance activities and the significant importance of conducting PIR.Second,it reviews commonly used study designs and presents illustrative case examples.Building on this,the specific statistical considerations relevant to PIR were discussed.Finally,the challenges and prospects of conducting pharmacovigilance impact studies in a scientific and standardized manner are summarized.Compared with the previous edition,the 2nd edition has expanded the application scenarios of pharmacoepidemiology to include new areas such as PIR.Drawing on the guideline content and practical experience,this paper provides a detailed introduction and case analysis of PIR,serving as a reference for researchers engaged in this field.

Objective To retrospectively analyze the distribution and differences of oral behavior among patients with acute and chro-nic painassociated with temporomandibular disorders(TMD).Methods A total of 212 patients with pain TMD in West China Hospital of Stomatology completed oral behaviors checklist(OBC).SPSS statistical software was used to analyze all the data.Results The pa-tients with pain-related TMD had specific oral behaviors,such as"pressure on the jaw during sleep"(49.5%),"unilateral chewing"(49.5%),"upper and lower teeth contact when not eating"(37.7%),etc.Scores of"upper and lower teeth contact when not eating"and"muscle tension when teeth are not clenched or teeth are not in contact"in patients with chronic pain TMD were higher than those of acute patients,and the difference was statistically significant(P＜0.05).The total OBC scores and daytime OBC scores of chronic pain TMD patients were higher than those of acute pain patients,and the difference was statistically significant(P＜0.05).There was no significant difference in OBC scores of patients with acute and chronic pain TMD during sleep(P＞0.05).Conclusion Pain-related TMD patients had specific oral behaviors,and patients with chronic pain TMD exhibited higher levels of total OBC,daytime OBC,"upper and lower teeth contact when not eating"and"muscle tension when teeth do not bite or teeth are not in contact"oral behavior than acute pain TMD patients.In the treatment of patients with painful TMD,correcting the patient's bad oral behavior can help the treatment of pain-related TMD.

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.