BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

By combining the origin and research progress of the combination of disease and syndrome, the core pathogenesis, this article explored the research ideas and methods of the core pathogenesis of TCM. It is found that modern TCM is mostly guided by the idea of classification-staging-syndrome differentiation, the main prescription of the main disease, the special prescription of the special disease, and the idea of "dynamic-fixed sequential". The tongue image syndrome differentiation method, clustering analysis method, drug test syndrome method, compound pathogenesis method, "evidence-based pathogenesis-syndrome treatment system" research model, and the integration of traditional Chinese and Western medicine theory were used to explore the core pathogenesis of TCM under the condition of disease. Combined with the advantages of modern medical disease differentiation and TCM syndrome differentiation, the individualized diagnosis and treatment methods of integrated traditional Chinese and Western medicine have been continuously improved, in order to solve the stage contradictions of different clinical stages, effectively delay the progression of the disease and improve the prognosis of the disease.

Objective:To assess cognitive impairment in children with obstructive sleep-disordered breathing (OSDB) using event-related potentials (ERPs).Methods:This case-control study analyzed data from 143 OSDB children[94 males, 49 females, aged 9.0(7.0-11.0) years] scheduled for adenotonsillectomy at the Department of Otolaryngology-Head and Neck Surgery, Beijing Tsinghua Changgung Hospital, Tsinghua University, between June 2023 and September 2024, along with 17 healthy controls [control group: 10 males, 7 females, aged 10.0 (7.5-12.0) years]. Based on polysomnography results, OSDB children were divided into a mild group [obstructive apnea-hypopnea index (OAHI)≤5 events/hour, 49 males, 29 females, aged 9.0 (7.0-10.0) years] and a moderate-to-severe group [OAHI>5 events/hour, 45 males, 20 females, aged 9.0 (8.0-10.0) years]. All children completed a face perception integration task. The occipital P100 and parietal, central and frontal P300 components of incomplete face stimuli (S1) and complete face stimuli (S2) were recorded. Amplitude and latency differences across groups were analyzed. Intergroup comparisons were performed using ANOVA, while independent samples t-tests were used for pairwise comparisons. Non-normally distributed data were analyzed using the Mann-Whitney U test. Results:(1) P100: Both the mild group [occipital P100 amplitude: O1-S1(12.44±5.96) μV, O2-S1(14.19±6.39) μV, O2-S2(30.34±11.30) μV] and moderate-to-severe group [O1-S1 (12.12±5.58) μV, O2-S1 (14.08±5.48) μV, O2-S2(29.12±10.89) μV] showed significantly higher amplitudes than the control group [O1-S1(8.46±4.74) μV,O2-S1(9.68±3.70) μV,O2-S2(23.09±9.16) μV] ( F=3.501, 4.486, 3.072; all P<0.05). No significant differences were found between the two OSDB subgroups ( P>0.05), suggesting compensatory neuronal hyperactivity maintaining normal perceptual function. The moderate-to-severe group exhibited significantly prolonged P100 latency [O2-S1 (134.52±13.42) ms] compared to controls [O2-S1 (125.18±15.31) ms] ( F=3.156 , P<0.05), while no significant difference was observed between the mild group and either the control or moderate-to-severe groups ( P>0.05), indicating delayed visual processing in severely affected children. (2) P300: The mild group exhibited significantly higher P300 amplitudes in parietal regions [P4-S1(8.22±4.32) μV, P4-S2(17.67±9.42) μV] compared to controls [P4-S1 (4.84±2.89) μV, P4-S2 (13.19±7.23) μV] ( F=7.19, 4.771; both P<0.05), whereas no significant differences were observed between the moderate-to-severe group and either the control or mild groups ( P>0.05), indicating mild group reduced alertness. The latency of P300 in the central region showed an increase in the mild group, although not significantly ( P>0.05), indicating a potential decrease in attentional response speed. However, the moderate-to-severe group demonstrated significantly shorter P300 latencies [CZ-S1(394.18±89.12) ms] compared to the mild group [CZ-S1 (433.33±100.33) ms] ( F=3.145, P<0.05), possibly reflecting compensatory enhancement of attentional engagement in more severe cases. Conclusion:Children with OSDB exhibit impairments in primary visual processing and attentional regulation, as evidenced by altered ERP components such as P100 and P300. These findings suggest that OSDB may affect neural mechanisms underlying sensory integration and executive functioning.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective To develop and validate a"quick self-assessment questionnaire for cochlear implant out-come(QSACI)".Methods A research team,composed of audiologists,otolaryngologists,data analysis experts,and cochlear implant(CI)recipients,was formed to establish objectives,research subject criteria,and framework of the QSACI.An item pool was creaed through literature review and brainstorming.Question items were evaluated and screened,and the framework and answer options of the questionnaire were established.The comprehensibility,etc.,was analyzed and refined through pilot test,interviews,and expert consultation,leading to the development of the final version.A total of 39 post-lingually deafened adults with known stable outcomes completed the question-naire.The split-half and test-retest reliabilty of the questionnaire was analyzed,and the validity was quantitatively analyzed by comparing scores with the categories of auditory performance(CAP)scores.Results The initial item pool of the questionnaire had 18 items,and the final questionnaire consisted of 12 questions in four dimensions:com-munication status,audiological status,medical factors,and other factors.The average score of 39 recipients was 88.81±6.17 and CAP was 6.19±0.94.The questionnaire showed good reliability and validity,with a Cronbach's alpha coefficient of 0.71 and a test-retest reliability of 0.824(P＜0.05).The criterion-related validity,assessed by the correlation between the self-assessment questionnaire scores and CAP scores,showed a significant moderate pos-itive correlation(r=0.512,P＜0.05).The correlation coefficient between self-assessment and professional assess-ment was 0.720(P＜0.05),indicating a significant correlation.The area under the receiver operating characterstic(ROC)curve was 0.82(P＜0.05),the cutoff values corresponding to the maximal Youden index were 82.5 and 88.6,therefore score of 85 was taken as the median threshold score of judgement.Conclusion The QSACI reflects the post-imlplant outcomes,and it can serve as a tool for people with postlingually deafness and their families to un-derstand the eligbility of CI and the expected outcomes,helping to establish realistic expectations before CI surgery.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective To develop and validate a"quick self-assessment questionnaire for cochlear implant out-come(QSACI)".Methods A research team,composed of audiologists,otolaryngologists,data analysis experts,and cochlear implant(CI)recipients,was formed to establish objectives,research subject criteria,and framework of the QSACI.An item pool was creaed through literature review and brainstorming.Question items were evaluated and screened,and the framework and answer options of the questionnaire were established.The comprehensibility,etc.,was analyzed and refined through pilot test,interviews,and expert consultation,leading to the development of the final version.A total of 39 post-lingually deafened adults with known stable outcomes completed the question-naire.The split-half and test-retest reliabilty of the questionnaire was analyzed,and the validity was quantitatively analyzed by comparing scores with the categories of auditory performance(CAP)scores.Results The initial item pool of the questionnaire had 18 items,and the final questionnaire consisted of 12 questions in four dimensions:com-munication status,audiological status,medical factors,and other factors.The average score of 39 recipients was 88.81±6.17 and CAP was 6.19±0.94.The questionnaire showed good reliability and validity,with a Cronbach's alpha coefficient of 0.71 and a test-retest reliability of 0.824(P＜0.05).The criterion-related validity,assessed by the correlation between the self-assessment questionnaire scores and CAP scores,showed a significant moderate pos-itive correlation(r=0.512,P＜0.05).The correlation coefficient between self-assessment and professional assess-ment was 0.720(P＜0.05),indicating a significant correlation.The area under the receiver operating characterstic(ROC)curve was 0.82(P＜0.05),the cutoff values corresponding to the maximal Youden index were 82.5 and 88.6,therefore score of 85 was taken as the median threshold score of judgement.Conclusion The QSACI reflects the post-imlplant outcomes,and it can serve as a tool for people with postlingually deafness and their families to un-derstand the eligbility of CI and the expected outcomes,helping to establish realistic expectations before CI surgery.

Objective:To assess cognitive impairment in children with obstructive sleep-disordered breathing (OSDB) using event-related potentials (ERPs).Methods:This case-control study analyzed data from 143 OSDB children[94 males, 49 females, aged 9.0(7.0-11.0) years] scheduled for adenotonsillectomy at the Department of Otolaryngology-Head and Neck Surgery, Beijing Tsinghua Changgung Hospital, Tsinghua University, between June 2023 and September 2024, along with 17 healthy controls [control group: 10 males, 7 females, aged 10.0 (7.5-12.0) years]. Based on polysomnography results, OSDB children were divided into a mild group [obstructive apnea-hypopnea index (OAHI)≤5 events/hour, 49 males, 29 females, aged 9.0 (7.0-10.0) years] and a moderate-to-severe group [OAHI>5 events/hour, 45 males, 20 females, aged 9.0 (8.0-10.0) years]. All children completed a face perception integration task. The occipital P100 and parietal, central and frontal P300 components of incomplete face stimuli (S1) and complete face stimuli (S2) were recorded. Amplitude and latency differences across groups were analyzed. Intergroup comparisons were performed using ANOVA, while independent samples t-tests were used for pairwise comparisons. Non-normally distributed data were analyzed using the Mann-Whitney U test. Results:(1) P100: Both the mild group [occipital P100 amplitude: O1-S1(12.44±5.96) μV, O2-S1(14.19±6.39) μV, O2-S2(30.34±11.30) μV] and moderate-to-severe group [O1-S1 (12.12±5.58) μV, O2-S1 (14.08±5.48) μV, O2-S2(29.12±10.89) μV] showed significantly higher amplitudes than the control group [O1-S1(8.46±4.74) μV,O2-S1(9.68±3.70) μV,O2-S2(23.09±9.16) μV] ( F=3.501, 4.486, 3.072; all P<0.05). No significant differences were found between the two OSDB subgroups ( P>0.05), suggesting compensatory neuronal hyperactivity maintaining normal perceptual function. The moderate-to-severe group exhibited significantly prolonged P100 latency [O2-S1 (134.52±13.42) ms] compared to controls [O2-S1 (125.18±15.31) ms] ( F=3.156 , P<0.05), while no significant difference was observed between the mild group and either the control or moderate-to-severe groups ( P>0.05), indicating delayed visual processing in severely affected children. (2) P300: The mild group exhibited significantly higher P300 amplitudes in parietal regions [P4-S1(8.22±4.32) μV, P4-S2(17.67±9.42) μV] compared to controls [P4-S1 (4.84±2.89) μV, P4-S2 (13.19±7.23) μV] ( F=7.19, 4.771; both P<0.05), whereas no significant differences were observed between the moderate-to-severe group and either the control or mild groups ( P>0.05), indicating mild group reduced alertness. The latency of P300 in the central region showed an increase in the mild group, although not significantly ( P>0.05), indicating a potential decrease in attentional response speed. However, the moderate-to-severe group demonstrated significantly shorter P300 latencies [CZ-S1(394.18±89.12) ms] compared to the mild group [CZ-S1 (433.33±100.33) ms] ( F=3.145, P<0.05), possibly reflecting compensatory enhancement of attentional engagement in more severe cases. Conclusion:Children with OSDB exhibit impairments in primary visual processing and attentional regulation, as evidenced by altered ERP components such as P100 and P300. These findings suggest that OSDB may affect neural mechanisms underlying sensory integration and executive functioning.