Objective:To investigate the differential effects of proton FLASH irradiation and conventional dose rate (CONV) irradiation on human normal liver cells WRL68 and human hepatocellular carcinoma cells HepG2.Methods:Using a 100 MeV high-current proton cyclotron accelerator, WRL68 and HepG2 cells were subjected to CONV (0.8 Gy/min) and FLASH (40 Gy/s) irradiation with 4 Gy protons. After irradiation, changes in cell proliferation, apoptosis, and cell cycle arrest were detected at different time points. Additionally, transcriptome sequencing was employed to analyze alterations in the gene expression profiles of the two cell lines.Results:For WRL68 cells, compared with CONV irradiation, proton FLASH irradiation enhanced cell proliferative activity ( t=10.18-16.67, P<0.05), reduced the apoptotic rate ( t=3.21-8.30, P<0.05), and decreased the proportion of cells arrested in the G 2 phase at the same time points ( t=34.08-65.16, P<0.05). In contrast, for HepG2 cells, proton FLASH irradiation significantly inhibited cell proliferation ( t=2.57-9.39, P<0.05), increased the apoptotic rate ( t=3.25-66.70, P<0.05), and similarly induced cell cycle arrest predominantly in the G 2 phase ( t=10.87-27.47, P<0.05). Transcriptome sequencing identified 906 differentially expressed genes (DEGs) between the FLASH group and the CONV group in WRL68 cells, and 1 243 DEGs were detected in HepG2 cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these DEGs suggested that cellular adhesion and oxygen effect may serve as crucial microscopic mechanisms underlying FLASH radiotherapy. Conclusions:Under proton FLASH irradiation, the radiation-induced damage to human normal liver cells was significantly alleviated, whereas the damage to hepatocellular carcinoma cells was aggravated. The identified DEGs are involved in multiple radiobiological functional pathways.

Objective: To develop the Adolescent Peer Bullying Knowledge-Attitude-Practice (KAP) Questionnaire and to evaluate its reliability and validity, so as to provide an effective tool for evaluating the KAP level regarding peer bullying among adolescents. Methods: A preliminary framework was developed through literature review, expert consultation, and group discussions. In September 2024, 2 203 students in grades 7 to 9 from two regular junior high schools in Anhui Province were selected using cluster sampling for a preliminary survey aimed at questionnaire development, including item screening and reliability and validity testing. Results: The initial KAP questionnaire on adolescent peer bullying consisted of 25 items: two items, "Behavior 6" and "Behavior 7", were excluded as their correlation coefficients with the total KAP score being only 0.08 and 0.05, respectively, falling below the preset criteria(0.4). The final questionnaire comprised 23 items, divided into three dimensions: knowledge, attitude, and behavior. Reliability testing showed that the overall Cronbach α coefficient of the questionnaire was 0.89, with Cronbach α coefficients for the knowledge, attitude, and behavior dimensions being 0.91, 0.67 and 0.79, respectively. The overall splithalf reliability of the questionnaire was 0.87, with split half reliabilities for the knowledge, attitude, and behavior dimensions being 0.82, 0.64 , and 0.66, respectively. Testretest reliability ranged from 0.82 to 0.97. Confirmatory factor analysis results indicated that the questionnaire had RMSEA=0.062, NFI=0.924, CFI =0.931, with good discriminant validity. Conclusion The developed KAP questionnaire on adolescent peer bullying demonstrates good reliability and validity and can be used as an assessment tool for evaluating the KAP level regarding peer bullying among adolescents.

Objective: To evaluate the effectiveness of a family-school-community integrated intervention based on the microsystem theory in reducing peer bullying among junior high school students, so as to provide empirical evidence and feasible pathways for junior high school students bullying prevention and control in China. Methods: A combining convenience with clustering method was employed to select 6 268 students from three regular junior high schools in Fuyang and Anqing cities, Anhui Province, as the study subjects in October 2024, and randomly assigned by drawing lots to three groups: family-school-community integrated intervention ( n =2 063), school only intervention ( n =1 864), and control group ( n =2 341). From October 10, 2024, to January 10, 2025, the intervention was implemented for three months using posters, brochures, and videos, with one session every half month, each lasting 40 minutes. The family-school-community integrated intervention group received multi level interventions involving families, schools, and communities, while the school only intervention group received only school based interventions. The control group received routine school health education but no other interventions. Before and after the intervention, data on peer bullying among junior high school students were collected using the Peer Bullying Scale, and comparison of detection rate of peer bullying by Chi square test. Results: After the intervention,group comparison results showed that the incidence rates of various types of peer bullying in the family-school-community integrated intervention group, the school only intervention group, and the control group all showed statistically significant differences ( χ 2=28.61-66.85, all P <0.05). The detection rates of verbal bullying ( 7.51 %), relational bullying (5.62%), physical bullying (3.34%), cyberbullying (1.75%), being bullied (10.81%), verbal bullying others (2.67%), relational bullying others (1.55%), physical bullying others (1.36%), cyberbullying others (1.41%), and overall peer bullying (3.64%) in the family-school-community integrated intervention group were all lower than those in the control group (12.52%, 11.58%, 6.24%, 5.00%, 19.14%, 7.56%, 4.49%, 4.53%, 3.80%, 9.40%); additionally, the detection rates of verbal bullying others, overall peer bullying , verbal bullying, and being bullied , in the family-school-community integrated intervention group were all lower than those in the school only intervention group (4.67%, 6.65%, 13.14%, 16.42%), with statistically significant differences ( χ 2=30.04, 48.49, 19.75, 34.60, 58.89, 52.65, 31.32, 37.37, 24.14, 58.26; 11.25, 18.53, 33.93, 26.41, all P <0.016 7). Group comparison showed that in both intervention groups, the majority of peer bullying behaviors decreased after the intervention ( χ 2=4.86-171.01, all P <0.05). Conclusions The family-school-community integrated intervention based on the microsystem can effectively reduce peer bullying among junior high school students, with better efficacy than the single school intervention. The model can serve as a practical reference for establishing a multi level prevention and intervention system for junior high school students bullying in China.

This study analyzed the clinical characteristics,diagnosis,treatment,and outcomes of disseminated Tsalaromycosis marneffei(DTSM)in non-HIV-infected patients.A retrospective analysis was conducted on 20 cases of non-HIV-infected DTSM treated at Guangzhou Chest Hospital between January 2015 and December 2021.Clinical data,including demographic characteris-tics,time to diagnosis,clinical manifestations,comorbidities,treatment details,and outcomes,were collected and analyzed.Among the 20 cases,9 were in males,and 11 were in females;the median age was 46(range:1-70)years.The median time from symptom onset to definitive diagnosis was 12(range:1-24)months,and 16 cases were initially misdiagnosed with mycobacterial disease.More than half the patients exhibited four major clinical features:fever,lymphadenopathy,skin lesions,and bone lesions.Pulmonary imag-ing abnormalities were observed in 19 cases,and an average of(3.6±1.6)lung lobes were involved.The positive detection rate of multi-sample cultures(70%,14/20)was significantly higher than that identified through histopathological examination(25%,5/20)(χ2=8.120,P=0.004).Findings for all five patients with positive next-generation sequencing(NGS)results were further confirmed through pathogen culture or histopathology.After antifungal treatment,14 patients showed clinical improvement and were discharged.In conclusion,non-HIV-infected DTSM is characterized by complex clinical manifestations and extensive pulmonary involvement,thus leading to frequent misdiagnosis and diagnostic delays.Pathogen detection methods,such as multi-sample cultures and NGS,demonstrate superior diagnostic accuracy to histopathological examination.Early identification and standardized antifungal therapy are critical factors in determining patient outcomes.

Objective The study aimed to compare the efficacy and safety of tislelizumab combined with chemotherapy versus pembrolizumab combined with chemotherapy as first-line treatments for advanced lung squa-mous cell carcinoma.Methods We retrospectively reviewed and analyzed the medical records of 116 patients with advanced lung squamous cell carcinoma treated with first-line chemotherapy plus tislelizumab or pembrolizumab in Guangzhou Chest Hospital from September 2020 to April 2024.We focused on analysis of time to treatment failure(TTF)and objective response rate(ORR)as well as disease control rate(DCR)and treatment-related adverse events(TRAEs).Results At a median follow up of 19.7 monyhs,the median TTF was 9.7 months in the tislelizumab group and 7.7 months in the pembrolizumab group(P<0.05).In addition,the ORR in the tislelizumab group was significantly higher than that in the pembrolizumab group(77.6%vs.60.3%,P<0.05),with DCRs of 93.1%and 87.9%,respectively(P=0.342).Regarding safety,the proportions of grade 3 or higher TRAEs and any-grade TRAEs were comparable between the two groups:29.3%and 81.0%in the tislelizumab group,and 32.8%and 87.9%in the pembrolizumab group,respectively.The most common TRAEs in both groups were hematological toxicities.Conclusions Tislelizumab plus chemotherapy demonstrated better efficacy and safety compared to pembrolizumab with chemotherapy as first-line treatment for Chinese patients with advanced lung squamous cell carcinoma.

Objective:To investigate the differential effects of proton FLASH irradiation and conventional dose rate (CONV) irradiation on human normal liver cells WRL68 and human hepatocellular carcinoma cells HepG2.Methods:Using a 100 MeV high-current proton cyclotron accelerator, WRL68 and HepG2 cells were subjected to CONV (0.8 Gy/min) and FLASH (40 Gy/s) irradiation with 4 Gy protons. After irradiation, changes in cell proliferation, apoptosis, and cell cycle arrest were detected at different time points. Additionally, transcriptome sequencing was employed to analyze alterations in the gene expression profiles of the two cell lines.Results:For WRL68 cells, compared with CONV irradiation, proton FLASH irradiation enhanced cell proliferative activity ( t=10.18-16.67, P<0.05), reduced the apoptotic rate ( t=3.21-8.30, P<0.05), and decreased the proportion of cells arrested in the G 2 phase at the same time points ( t=34.08-65.16, P<0.05). In contrast, for HepG2 cells, proton FLASH irradiation significantly inhibited cell proliferation ( t=2.57-9.39, P<0.05), increased the apoptotic rate ( t=3.25-66.70, P<0.05), and similarly induced cell cycle arrest predominantly in the G 2 phase ( t=10.87-27.47, P<0.05). Transcriptome sequencing identified 906 differentially expressed genes (DEGs) between the FLASH group and the CONV group in WRL68 cells, and 1 243 DEGs were detected in HepG2 cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these DEGs suggested that cellular adhesion and oxygen effect may serve as crucial microscopic mechanisms underlying FLASH radiotherapy. Conclusions:Under proton FLASH irradiation, the radiation-induced damage to human normal liver cells was significantly alleviated, whereas the damage to hepatocellular carcinoma cells was aggravated. The identified DEGs are involved in multiple radiobiological functional pathways.

This study analyzed the clinical characteristics,diagnosis,treatment,and outcomes of disseminated Tsalaromycosis marneffei(DTSM)in non-HIV-infected patients.A retrospective analysis was conducted on 20 cases of non-HIV-infected DTSM treated at Guangzhou Chest Hospital between January 2015 and December 2021.Clinical data,including demographic characteris-tics,time to diagnosis,clinical manifestations,comorbidities,treatment details,and outcomes,were collected and analyzed.Among the 20 cases,9 were in males,and 11 were in females;the median age was 46(range:1-70)years.The median time from symptom onset to definitive diagnosis was 12(range:1-24)months,and 16 cases were initially misdiagnosed with mycobacterial disease.More than half the patients exhibited four major clinical features:fever,lymphadenopathy,skin lesions,and bone lesions.Pulmonary imag-ing abnormalities were observed in 19 cases,and an average of(3.6±1.6)lung lobes were involved.The positive detection rate of multi-sample cultures(70%,14/20)was significantly higher than that identified through histopathological examination(25%,5/20)(χ2=8.120,P=0.004).Findings for all five patients with positive next-generation sequencing(NGS)results were further confirmed through pathogen culture or histopathology.After antifungal treatment,14 patients showed clinical improvement and were discharged.In conclusion,non-HIV-infected DTSM is characterized by complex clinical manifestations and extensive pulmonary involvement,thus leading to frequent misdiagnosis and diagnostic delays.Pathogen detection methods,such as multi-sample cultures and NGS,demonstrate superior diagnostic accuracy to histopathological examination.Early identification and standardized antifungal therapy are critical factors in determining patient outcomes.

Objective The study aimed to compare the efficacy and safety of tislelizumab combined with chemotherapy versus pembrolizumab combined with chemotherapy as first-line treatments for advanced lung squa-mous cell carcinoma.Methods We retrospectively reviewed and analyzed the medical records of 116 patients with advanced lung squamous cell carcinoma treated with first-line chemotherapy plus tislelizumab or pembrolizumab in Guangzhou Chest Hospital from September 2020 to April 2024.We focused on analysis of time to treatment failure(TTF)and objective response rate(ORR)as well as disease control rate(DCR)and treatment-related adverse events(TRAEs).Results At a median follow up of 19.7 monyhs,the median TTF was 9.7 months in the tislelizumab group and 7.7 months in the pembrolizumab group(P<0.05).In addition,the ORR in the tislelizumab group was significantly higher than that in the pembrolizumab group(77.6%vs.60.3%,P<0.05),with DCRs of 93.1%and 87.9%,respectively(P=0.342).Regarding safety,the proportions of grade 3 or higher TRAEs and any-grade TRAEs were comparable between the two groups:29.3%and 81.0%in the tislelizumab group,and 32.8%and 87.9%in the pembrolizumab group,respectively.The most common TRAEs in both groups were hematological toxicities.Conclusions Tislelizumab plus chemotherapy demonstrated better efficacy and safety compared to pembrolizumab with chemotherapy as first-line treatment for Chinese patients with advanced lung squamous cell carcinoma.

Acute kidney injury (AKI) is an important factor for the occurrence and development of CKD. The protective effect of dihydroartemisinin on AKI and and reported mechanism have not been reported. In this study, we used two animal models including ischemia-reperfusion and UUO, as well as a high-glucose-stimulated HK-2 cell model, to evaluate the protective effect of dihydroartemisinin on premature senescence of renal tubular epithelial cells in vitro and in vivo. We demonstrated that dihydroartemisinin improved renal aging and renal injury by activating autophagy. In addition, we found that co-treatment with chloroquine, an autophagy inhibitor, abolished the anti-renal aging effect of dihydroartemisinin in vitro. These findings suggested that activation of autophagy/elimination of senescent cell might be a useful strategy to prevent AKI/UUO induced renal tubular senescence and fibrosis.
Animals ; Kidney ; Acute Kidney Injury/chemically induced* ; Ischemia ; Reperfusion Injury/drug therapy* ; Autophagy ; Reperfusion

Objective To investigate the relationship between lesion size of solitary bone cyst ( SBC) and pathological fracture of calcaneus, so as to provide references for the treatment of SBC. Methods The three dimensional (3D) finite element model of foot and ankle was established based on CT images. Four models with gradient spherical bone defects were constructed in the focal area to simulate different SBC lesion sizes, and the biomechanical characteristics of calcaneus in different gait phases were analyzed. Results With the increasement of SBC size, the kinematics of calcaneus did not change significantly, but the peak stress of calcaneus increased gradually. When the SBC size exceeded 75% of the calcaneal width, the stress in calcaneal sulcus and cortical bone below SBC increased by 1. 48 times and 7. 74 times, respectively. Conclusions The risk of pathological fracture increases when the SBC diameter exceeds 75% of the calcaneal width, and early surgical intervention should be recommended. The calcaneal sulcus and the cortex bone below SBC are stress concentration regions and can be used as important areas to evaluate pathological fractures.