Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To investigate the clinical characteristics and prognosis of patients with locally advanced or metastatic pulmonary neuroendocrine tumors(NETs).Methods:The clinical records of patients with locally advanced or metastatic pulmonary NETs in Peking Uni-versity Cancer Hospital&Institute were selected from January 2014 to June 2024.The clinical characteristics,treatment,and survival pro-gnosis were then analyzed.Results:There were 32 patients,of which 18 were male and 14 female.The median age was 56 years.Nine pa-tients had typical carcinoid and 23 had atypical carcinoid,with six in stage Ⅲ and 26 in stage Ⅳ.The common metastatic sites included the bones(18 cases),lungs(8 cases),pleura(7 cases),and liver(7 cases).The median length of the measurable primary tumor was 5.2 cm,which was mostly located centrally(22 cases).Five among the 16 patients who underwent somatostatin receptor(SSTR)imaging had high SSTR ex-pression.The initial symptoms mainly included respiratory symptoms,and none of them were combined with carcinoid syndrome.For the first-line treatment,19 patients were treated with chemotherapy,seven were treated with targeted therapy,four were treated with soma-tostatin analogs(SSAs),and two were treated with surgery.The best efficacy was evaluated as a partial response in one case(3.1%),stable disease in 23 cases(71.9%),and non-evaluable or unknown in eight cases(25%)in the first-line treatment.The median progression-free sur-vival(mPFS)of patients who received first-line treatment was 5.2 months(95%CI:0.0-13.9).The PFS of targeted therapy was the longest(11.0 months,95%CI:0.0-29.6),but there was no significant difference compared with the PFS of chemotherapy and SSA groups(P>0.05).The longest PFS(24.5 months,95%CI:0.0-58.7)was found in patients treated with chemotherapy combined with radiotherapy,but there was no significant difference compared to the PFS of the combined immunotherapy and combined anti-angiogenesis groups(P>0.05).The survival rates at 1,3,and 5 years were 79.1%,65.5%,and 58.9%,respectively.Cox regression analysis did not identify independent risk factors for prognosis.Conclusions:The initial symptoms of patients with locally advanced or metastatic NETs were mainly respiratory symp-toms but without specific manifestations.Some of them were accompanied by high SSTR expression,and there was generally no carcinoid syndrome.The first-line systemic therapy mainly included chemotherapy and target therapy,with relatively low objective response and high disease control rates.Targeted therapy and combined radiotherapy have longer PFS than that of chemotherapy.The overall survival of pa-tients with pulmonary NETs was good.

Aim To elucidate the underlying mecha-nism by which total triterpenoids extracted from Hove-nia dulcis(H-TP)enhance the sensitivity of A549/DDP cells to cisplatin.Methods The ARE-Nrf2 lu-ciferase reporter assay was applied to investigate the impact of H-TP on Nrf2 expression.Western blot was used to detect the protein levels of Keap-1/Nrf2/HO-1,Nrf2-GPX4 signaling pathway,apoptosis-related proteins of Bcl-2 and Bax.Further validation of its effects on Nrf2 was conducted by using Nrf2 activator/inhibitor.Results H-TP could enhance the sensitivi-ty of A549/DDP cells to cisplatin by modulating the expression of apoptosis-related proteins Bax and Bcl-2,inhibiting the Keap-1/Nrf2/HO-1/GPX4 signating pathway in A549/DDP cells,and inducing ferroptosis.Conclusion H-TP enhances the sensitivity of A549/DDP cells to cisplatin by inducing the Nrf2-mediated ferroptosis pathway.

The objective of this study was to evaluate the toxicity and safety of novel Mycobacterium tuberculosis fusion strain protein derivatives,referred to as B/R strain active proteins.In cellular experiments,RAW264.7 cells were treated with each vaccine preparation,and apoptosis rates were measured.In subsequent animal experiments,C57BL/6 mice were immunized via subcutaneous injection,and their survival and body weight changes were monitored and recorded at 2,4,8,12,and 16 weeks.The lungs and spleens were harvested to calculate organ coefficients,and pathological examinations were conducted.At the eighth week of immunization,the mice were infected with high concentrations of BCG,and pathological changes in the lungs and spleens were observed 4 weeks post-infection.The apoptosis rate at 6 hours was significantly higher in the experimental group than the PBS group(P<0.05).At 12 and 24 hours,the apoptosis rate in the experimental group remained higher than that in the PBS group,although this difference was not statistically significant.After immunization,mice in all four groups exhibited normal growth patterns,as indicated by stable body weight changes.At 4 and 12 weeks post-immunization,the lung coefficients in the protein group were significantly higher than those in the PBS group at the same time points.Additionally,the lung coefficients in the BCG group were significantly elevated across all time periods(P<0.05).The spleen coefficients in the protein and BCG groups were significantly higher than those in the PBS group at 2,4,8,12,and 16 weeks,whereas the ICD B/R group showed higher spleen coefficients than the PBS group only at week 8(P<0.05).Pathological examination revealed normal lung and spleen tissues in the PBS group.However,during the 2-8 weeks immunization period,lung and spleen tissues in all experimental groups exhibited varying degrees of damage,which gradually diminished by 12-16 weeks.Notably,no tuberculosis nodules were observed in any experimental group.After infection with high concentrations of BCG,no overt pathological changes were observed on the surfaces of the lungs and spleens in any group.Microscopic examination revealed less severe pathological changes in the lungs and spleens of mice in the experimental groups than the PBS group.Furthermore,no statistically significant differences were observed between the protein group and the BCG group.Our findings suggested that the B/R strain active proteins'toxicity and safety profiles were comparable to those of BCG,and showed immunoprotective effects.This study provides an experimental foundation for the development of a novel tuberculosis vaccine.

Objective:To explore the effect of integrating open laboratories into Medical Microbiology experimental teaching for students majoring in Medical Laboratory Technology to enhance teaching quality.Methods:A total of 58 students from the grade 2020 majoring in Medical Laboratory Technology at a medical college were selected as the control group,receiving traditional teaching methods without open laboratory contents.A total of 58 students from the grade 2021 majoring in Medical Laboratory Technology were selected as the experimental group,integrating open laboratory contents into Medical Microbiology experimental teaching.The impact of open laboratories on teaching quality in Medical Microbiology experimental teaching was evaluated through analysis of final examination scores and questionnaire surveys.Results:Compared with the control group,the experimental group showed significant improvements in experimental report scores,experimental theory assessment scores,practical skill assessment scores,classroom performance scores,and overall scores(P＜0.01).The learning interest,multi-channel learning,mastery of key concepts,and ability to apply and expand knowledge of the experimental group also significantly improved(P＜0.01).The satisfaction rate of the experimental group in terms of participation level,acquired knowledge,mastered skills,and improved learning outcomes was all above 90%.Conclusion:Integrating open laboratory content into Medical Microbiology experimental teaching for students majoring in Medical Laboratory Technology can effectively stimulate students'engagement,enhance teaching quality,and help students better understand and master professional knowledge.

Objective:To investigate the clinical characteristics and prognosis of patients with locally advanced or metastatic pulmonary neuroendocrine tumors(NETs).Methods:The clinical records of patients with locally advanced or metastatic pulmonary NETs in Peking Uni-versity Cancer Hospital&Institute were selected from January 2014 to June 2024.The clinical characteristics,treatment,and survival pro-gnosis were then analyzed.Results:There were 32 patients,of which 18 were male and 14 female.The median age was 56 years.Nine pa-tients had typical carcinoid and 23 had atypical carcinoid,with six in stage Ⅲ and 26 in stage Ⅳ.The common metastatic sites included the bones(18 cases),lungs(8 cases),pleura(7 cases),and liver(7 cases).The median length of the measurable primary tumor was 5.2 cm,which was mostly located centrally(22 cases).Five among the 16 patients who underwent somatostatin receptor(SSTR)imaging had high SSTR ex-pression.The initial symptoms mainly included respiratory symptoms,and none of them were combined with carcinoid syndrome.For the first-line treatment,19 patients were treated with chemotherapy,seven were treated with targeted therapy,four were treated with soma-tostatin analogs(SSAs),and two were treated with surgery.The best efficacy was evaluated as a partial response in one case(3.1%),stable disease in 23 cases(71.9%),and non-evaluable or unknown in eight cases(25%)in the first-line treatment.The median progression-free sur-vival(mPFS)of patients who received first-line treatment was 5.2 months(95%CI:0.0-13.9).The PFS of targeted therapy was the longest(11.0 months,95%CI:0.0-29.6),but there was no significant difference compared with the PFS of chemotherapy and SSA groups(P>0.05).The longest PFS(24.5 months,95%CI:0.0-58.7)was found in patients treated with chemotherapy combined with radiotherapy,but there was no significant difference compared to the PFS of the combined immunotherapy and combined anti-angiogenesis groups(P>0.05).The survival rates at 1,3,and 5 years were 79.1%,65.5%,and 58.9%,respectively.Cox regression analysis did not identify independent risk factors for prognosis.Conclusions:The initial symptoms of patients with locally advanced or metastatic NETs were mainly respiratory symp-toms but without specific manifestations.Some of them were accompanied by high SSTR expression,and there was generally no carcinoid syndrome.The first-line systemic therapy mainly included chemotherapy and target therapy,with relatively low objective response and high disease control rates.Targeted therapy and combined radiotherapy have longer PFS than that of chemotherapy.The overall survival of pa-tients with pulmonary NETs was good.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.