OBJECTIVE To investigate the immunotoxicity and potential mechanism of Carthamus tinctorius extract on RBL-2H3 cells via direct induction and induction by sensitized serum prepared with an overdose of the extract. METHODS For direct induction by C. tinctorius extract， RBL-2H3 cells were divided into normal control group （no treatment） and C. tinctorius extract group （10 mg/mL）. For induction by sensitized serum prepared with an overdose of C. tinctorius extract， rats were divided into normal control group （no treatment）， adjuvant-treated group （1 mL adjuvant）， C. tinctorius extract-induced sensitization group （2.04 g/mL）， and ovalbumin （OVA）-induced sensitization group （50 mg/mL）. Sensitization was performed once every other day for a total of 3 times. Morphological changes of RBL-2H3 cells were observed， the degranulated rate of cells was counted， and histamine content was determined； the release rate of β -hexosaminidase （ β -Hex） was calculated， the levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） and intracellular Ca²⁺ concentration were detected. RESULTS Under direct induction by C. tinctorius extract， compared with the normal control group， the volume of cells in the C. tinctorius extract group was significantly reduced and cell density decreased； the degranulation rate of cells， histamine content， β -Hex release rate， IL-6 and TNF-α levels， as well as intracellular Ca²⁺ concentration were all significantly increased （ P ＜0.01）. Under i nduction by sensitized serum prepared with an overdose of C. tinctorius extract， compared with the adjuvant-treated group， the above indicators in the C. tinctorius extract-induced sensitization group and the OVA-induced sensitization group showed consistent changes with those in the C. tinctorius extract group under direct induction， all being significantly elevated （ P ＜0.01）. CONCLUSIONS C. tinctorius extract may affect degranulation of RBL-2H3 cells and promote Ca²⁺ influx accompanied by the release of pro-inflammatory cytokines through two approaches： direct induction and induction by sensitized serum prepared under overdose administration. Its mechanism may be related to the activation of the calcium signaling pathway and the regulation of inflammatory pathways under the synergistic effect of multiple components.

With the rapid development of network technology， live surgery has become the new way of surgery teaching. However， the issue of patient privacy protection caused by live surgery has received widespread attention. Based on the evolutionary game theory， this paper constructed an evolutionary game model from the three-party perspectives of doctors， patients， and government and analyzed the game behaviors of the three parties in the process of live surgery. Matlab software was utilized to conduct dynamic simulation and numerical simulation analysis. It was found that the factors affecting the choice of doctors’ strategies included protection costs， the cost of privacy leakage， the benefits of protection， high-traffic benefits， and other aspects； the factors affecting the choice of patient strategies encompassed surgical costs， the risk of privacy leakage， additional benefits， and other aspects； the factors affecting the choice of government strategies embodied regulatory costs and the improvement of credibility. To realize a win-win situation among doctors， patients， and the government， the three parties need to work together to ensure that patient privacy is not violated and find a balance between expanding the influence of medical education and protecting patient privacy.

Objective To analyze the characteristics of HIV-1 pretreatment drug resistance(PDR)and molecular transmission networks in Yubei District,Chongqing,providing evidence for targeted interventions.Methods Using a cross-sectional design,plasma samples were collected from HIV/AIDS patients receiving antiretroviral therapy(ART)in Yubei District from January 2022 to December 2023.Pol gene fragments were extracted and amplified for HIV-1 genotyping and drug resistance analysis.Molecular transmission networks were constructed based on genetic distance calculations.Results Among 478 HIV-1 pol sequences,eight geno-types were identified:with CRF07_BC(60.4%,289/478),CRF08_BC(15.5%,74/478),CRF01_AE(11.7%,56/478),and CRF85_BC(5.9%,28/478).The overall PDR rate was 6.3%(30/478),with resistance to nucleoside reverse transcriptase inhibitors(NRTIs)and non-nucleoside reverse transcriptase inhibitors(NNRTIs)at 1.7%(8/478)and 5.2%(25/478),respectively.No protease inhibitor(PI)resistance was de-tected.The molecular network included 177 cases(37.0%network entry rate),forming 53 clusters with 198 connections.Cluster sizes ranged from 2 to 17 nodes,and 75.3%(149/198)of connections were associated with five subdistricts/towns:Shuanglonghu Street,Huixing Street,Luoqi Town,Gulu Town,and Baoshenghu Street.Conclusion HIV-1 genotypes in Yubei District exhibit diversity and complexity,with moderate PDR prevalence.Regional clustering of transmission networks suggests the need for enhanced molecular surveil-lance and targeted interventions based on analytical findings.

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

ObjectiveTo understand the current situation of medical damage liability disputes involving breach of the duty to inform in China， analyze the factors influencing the types of medical staff’s breach of the duty to inform， and explore the notification problems of medical staff in clinical practice. On these foundations， suggestions were proposed to improve the performance of the duty to inform and reduce medical disputes. MethodsUsing public cases from the China Judgements Online as the data source， the relationship between risk points and types of breach of duty to inform was analyzed using the Chi-square test. Logistic regression analysis was performed to explore the influencing factors of the types of breach of the duty to inform， and qualitative research summarized the specific contents of breach of the duty to inform. ResultsThere were differences in the effects of factors， including whether the patient was hospitalized， whether surgery was performed， whether Intensive Care Unit （ICU） treatment was required， the level of the medical institution， and whether a consultation occurred， on the types of breach of the duty to inform （P<0.05）. Whether surgery was performed was an influencing factor for the types of breach of the duty to inform. Qualitative research showed that the contents of breach of duty to inform primarily involve risk， treatment plan， and deficiencies in disease notification. ConclusionStrengthening the performance of the medical staff’s duty to inform should mainly focus on the medical side， coordinating with multiple parties and taking measures to improve the performance of the duty to inform， to reduce unnecessary medical disputes.

Objective:To explore the current status and influencing factors of quality of life in patients with thyroid-associated ophthalmopathy (TAO) .Methods:From January to July 2024, convenience sampling was used to select TAO patients of the Department of Ophthalmology of Peking University Third Hospital as research subjects. The patients were surveyed using the General Information Questionnaire, Graves' Ophthalmopathy Quality of Life Questionnaire (GO-QOL), Negative Physical Self Scale-Appearance (NPSS-A), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Perceived Social Support Scale (PSSS). Spearman correlation analysis was used to explore the correlation between GO-QOL scores and NPSS-A, SAS, SDS, and PSSS scores. Multiple linear regression was used to analyze the factors influencing the quality of life of TAO patients.Results:A total of 234 questionnaires were distributed, and 203 valid questionnaires were collected, with a valid response rate of 86.75%. The GO-QOL visual function and social function dimensions scores of 203 TAO patients were [78.57 (50.00, 100.00) ] and [43.75 (18.75, 62.50) ], respectively. Multiple linear regression analysis showed that age, eye movement disorders, eyelid retraction, and disease grading, were the influencing factors of the visual function dimension of GO-QOL ( P<0.05). Age, social support, and body image were the influencing factors on the social function dimension of GO-QOL ( P<0.05) . Conclusions:The quality of life of TAO patients is poor. Healthcare professionals should develop coping strategies based on factors affecting different dimensions of quality of life, so as to improve patients' quality of life.

Objective:To explore the current status and influencing factors of quality of life in patients with thyroid-associated ophthalmopathy (TAO) .Methods:From January to July 2024, convenience sampling was used to select TAO patients of the Department of Ophthalmology of Peking University Third Hospital as research subjects. The patients were surveyed using the General Information Questionnaire, Graves' Ophthalmopathy Quality of Life Questionnaire (GO-QOL), Negative Physical Self Scale-Appearance (NPSS-A), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Perceived Social Support Scale (PSSS). Spearman correlation analysis was used to explore the correlation between GO-QOL scores and NPSS-A, SAS, SDS, and PSSS scores. Multiple linear regression was used to analyze the factors influencing the quality of life of TAO patients.Results:A total of 234 questionnaires were distributed, and 203 valid questionnaires were collected, with a valid response rate of 86.75%. The GO-QOL visual function and social function dimensions scores of 203 TAO patients were [78.57 (50.00, 100.00) ] and [43.75 (18.75, 62.50) ], respectively. Multiple linear regression analysis showed that age, eye movement disorders, eyelid retraction, and disease grading, were the influencing factors of the visual function dimension of GO-QOL ( P<0.05). Age, social support, and body image were the influencing factors on the social function dimension of GO-QOL ( P<0.05) . Conclusions:The quality of life of TAO patients is poor. Healthcare professionals should develop coping strategies based on factors affecting different dimensions of quality of life, so as to improve patients' quality of life.

BACKGROUND:Currently,numerous observational studies have frequently associated dietary antioxidant intake and circulating antioxidant levels with osteoarthritis.Nevertheless,the underlying causal mechanisms remain unclear.Therefore,this study employs publicly available genome-wide association data to investigate the causal associations between antioxidant intake,circulating levels,and osteoarthritis,offering evidence for the prevention and treatment of osteoarthritis.OBJECTIVE:To assess the potential causal associations between dietary antioxidants(including vitamins A,C,E,and carotenoids)and circulating antioxidants(such as Glutathione S-transferase,glutathione peroxidase,catalase,superoxide dismutase,ascorbic acid,α-tocopherol,γ-tocopherol,albumin,uric acid,bilirubin,zinc,and selenium)with osteoarthritis through Mendelian randomization.METHODS:Data from genome-wide association studies on four dietary antioxidants and twelve circulating antioxidants were employed as exposure variables.The outcome variable was the osteoarthritis consortium dataset,which comprised 77 052 osteoarthritis cases and 378 169 healthy controls.Causal effects were evaluated using the inverse variance-weighted method,MR-Egger regression,and the weighted median approach.Stability and reliability of the findings were assessed through horizontal pleiotropy tests and sensitivity analyses.RESULTS AND CONCLUSION:(1)These results demonstrated that dietary vitamin C intake was inversely associated with knee osteoarthritis risk(OR=0.83,95%CI:0.71-0.96,P=0.015).Conversely,vitamin E intake was positively associated with knee osteoarthritis(OR=1.20,95%CI:1.05-1.34,P=0.004)and both knee and hip osteoarthritis(OR=1.15,95%CI:1.03-1.27,P=0.008).(2)Circulating antioxidant albumin levels were negatively associated with knee(OR=0.94,95%CI:0.91-0.97,P=0.001),hip(OR=0.95,95%CI:0.91-0.99,P=0.03),and knee or hip osteoarthritis(OR=0.95,95%CI:0.92-0.98,P=0.01).Uric acid levels were positively associated with knee osteoarthritis(OR=1.10,95%CI:1.03-1.17,P=0.003).(3)Sensitivity analyses yielded consistent results without evidence of horizontal pleiotropy.(4)European genome-wide data indicated that vitamin C intake was associated with a decreased risk of knee osteoarthritis,and lower serum albumin levels were associated with reduced risks of knee and hip osteoarthritis.In contrast,vitamin E intake and higher serum uric acid were associated with an increased risk of knee osteoarthritis.These findings support public health education and osteoarthritis interventions,indicating that serum albumin could be a potential biomarker for risk assessment.(5)The study underscores the role of certain antioxidants in osteoarthritis prevention and provides evidence to inform nutritional guidelines and public health strategies for the Chinese population.Furthermore,it contributes to biomarker research in arthritis,facilitating the development of early diagnostic tools and risk assessment strategies for the Chinese population.

BACKGROUND:Currently,numerous observational studies have frequently associated dietary antioxidant intake and circulating antioxidant levels with osteoarthritis.Nevertheless,the underlying causal mechanisms remain unclear.Therefore,this study employs publicly available genome-wide association data to investigate the causal associations between antioxidant intake,circulating levels,and osteoarthritis,offering evidence for the prevention and treatment of osteoarthritis.OBJECTIVE:To assess the potential causal associations between dietary antioxidants(including vitamins A,C,E,and carotenoids)and circulating antioxidants(such as Glutathione S-transferase,glutathione peroxidase,catalase,superoxide dismutase,ascorbic acid,α-tocopherol,γ-tocopherol,albumin,uric acid,bilirubin,zinc,and selenium)with osteoarthritis through Mendelian randomization.METHODS:Data from genome-wide association studies on four dietary antioxidants and twelve circulating antioxidants were employed as exposure variables.The outcome variable was the osteoarthritis consortium dataset,which comprised 77 052 osteoarthritis cases and 378 169 healthy controls.Causal effects were evaluated using the inverse variance-weighted method,MR-Egger regression,and the weighted median approach.Stability and reliability of the findings were assessed through horizontal pleiotropy tests and sensitivity analyses.RESULTS AND CONCLUSION:(1)These results demonstrated that dietary vitamin C intake was inversely associated with knee osteoarthritis risk(OR=0.83,95%CI:0.71-0.96,P=0.015).Conversely,vitamin E intake was positively associated with knee osteoarthritis(OR=1.20,95%CI:1.05-1.34,P=0.004)and both knee and hip osteoarthritis(OR=1.15,95%CI:1.03-1.27,P=0.008).(2)Circulating antioxidant albumin levels were negatively associated with knee(OR=0.94,95%CI:0.91-0.97,P=0.001),hip(OR=0.95,95%CI:0.91-0.99,P=0.03),and knee or hip osteoarthritis(OR=0.95,95%CI:0.92-0.98,P=0.01).Uric acid levels were positively associated with knee osteoarthritis(OR=1.10,95%CI:1.03-1.17,P=0.003).(3)Sensitivity analyses yielded consistent results without evidence of horizontal pleiotropy.(4)European genome-wide data indicated that vitamin C intake was associated with a decreased risk of knee osteoarthritis,and lower serum albumin levels were associated with reduced risks of knee and hip osteoarthritis.In contrast,vitamin E intake and higher serum uric acid were associated with an increased risk of knee osteoarthritis.These findings support public health education and osteoarthritis interventions,indicating that serum albumin could be a potential biomarker for risk assessment.(5)The study underscores the role of certain antioxidants in osteoarthritis prevention and provides evidence to inform nutritional guidelines and public health strategies for the Chinese population.Furthermore,it contributes to biomarker research in arthritis,facilitating the development of early diagnostic tools and risk assessment strategies for the Chinese population.

OBJECTIVE To explore the practicality of the pharmaceutical pathway for prophylactic use of antibiotics during the perioperative period of class Ⅰ neurosurgery incisions. METHODS The previously established pharmaceutical pathway for the prophylactic use of antibiotics in the perioperative period of class Ⅰ neurosurgery incisions was used to retrospectively evaluate the prophylactic use of antibiotics in 127 cases. The “antibiotics prophylactic use scoring system” in the pharmaceutical pathway was used to conduct preoperative scoring， and the patient’s actual antibiotics use was compared and analyzed in combination with existing Guiding Principles for Clinical Application of Antibiotics （2015 Edition） （hereinafter referred to as the Guiding Principles）. The pharmaceutical pathway also innovatively proposes key points for improvement in terms of the frequency of adding antibiotics during surgery and the duration of prophylactic use of antibiotics after surgery. By comparing with the actual medication situation of patients， the direction for updating the Guiding Principles was explored. RESULTS According to the retrospective analysis results， for neurosurgery class Ⅰ incision surgery， in addition to the preoperative prophylactic use of antibacterial drugs for skull mass resection and carotid endarterectomy recommended in the guidelines， endoscopic trigeminal microvascular decompression， arthroscopy and other specific joint examinations， spinal nerve Radical decompression， endoscopic lumbar nucleectomy， dural repair， and spinal canal decompression can also be further explored about the situation of not using antibacterial prophylaxis before surgery； at the same time， for the patients undergoing class Ⅰ neurosurgery incisions， the use of antibiotics during and after surgery may be considered for a second addition of antibiotics， taking into account the surgical time. If cerebrospinal fluid leakage occurred after surgery， it is recommended to extend the duration of prophylactic use of antibiotics appropriately. CONCLUSIONS The application of pharmaceutical pathways can provide more targeted analysis of key points in the prevention of antibiotic use， which promotes the transformation of perioperative antibiotics management for class Ⅰ incisions from “qualitative， empirical” management to “quantitative， scientific” management.