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*

Cardiovascular disease (CVD) is the leading cause of death worldwide. As the key pathological basis of CVD, arteriosclerosis holds great significance for early screening. However, existing clinical and homecare detection devices have many shortcomings; for instance, the commonly used non-invasive indicator PWV (pulse wave velocity) is easily interfered by blood pressure.This study developed a homecare arteriosclerosis monitoring system, which integrates the measurement functions of cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI). The hardware design of the system includes an integrated structure of flexible silver ion electrodes and clip-type cuffs, a contact heart sound sensor, and a stepped deflation blood pressure measurement module. Meanwhile, a high-precision analog-to-digital conversion module and the STM32F405 main control chip are used to realize the synchronous acquisition of multiple signals.In terms of software, the underlying driver program was designed through MDK (Keil5), and a user interface was built on the Visual Studio platform to achieve functions such as data acquisition, display, and storage. At the algorithm level, the system adopted algorithms like the Pan-Tompkins algorithm to identify key feature points of physiological signals, and then calculate CAVI and ABI.System test results show that the ECG input noise of the system is less than 20 μV, the common-mode rejection ratio is 95 dB, and the blood pressure measurement error does not exceed 2 mmHg, which meets the design goals. Clinical data analysis indicates that CAVI is highly positively correlated with pulse wave velocity (PWV) ( r=0.85, P<0.001), but CAVI is less affected by blood pressure fluctuations. In addition, with the increase of risk factors (such as hypertension, hyperlipidemia, coronary heart disease, etc.) and age, arteriosclerosis indicators (CAVI, PWV, ABI) all show an upward trend.In conclusion, the homecare arteriosclerosis monitoring system proposed in this study not only overcomes the problems of traditional devices that rely on professional operation and are susceptible to blood pressure interference, but also provides a reliable tool for arteriosclerosis screening in home scenarios, and has important reference value for clinical diagnosis.
Humans ; Cardio Ankle Vascular Index ; Home Care Services ; Atherosclerosis/diagnosis* ; Ankle Brachial Index ; Algorithms ; Pulse Wave Analysis ; Arteriosclerosis/diagnosis* ; Monitoring, Physiologic/instrumentation*

This study aims to determine the therapeutic effect and then elucidate the molecular mechanism of Dietary Yangrong Decoction(DYRT)on blood deficiency syndrome based on net-work pharmacology and study its active compounds.The molecular mechanism of DYRT in the treatment of blood deficiency syndrome was predicted by network pharmacology.The blood defi-ciency of rats was established using cyclophosphamide and acetophenohydrazine jointly,which was divided into a blank control group,a model group,a Men's Yangrong Decoction group(MYRT)(positive control group),a medicinal group and food-based Yangrong Decoction group.The active components were analyzed by liquid chromatography-mass spectrometry(HPLC-MS),the periph-eral hemogram was detected by an automatic biochemical analyzer,the levels of hematopoietic regulatory factors in serum were determined by ELISA,and the relative expression of EPO in kid-ney and PI3K,AKT,GM-CSF in bone marrow were measured by RT-PCR.The results showed that DYRT had 57 active ingredients and 128 potential targets for the treatment of spleen deficien-cy syndrome.1 835 items were obtained by GO enrichment analysis,and 20 pathways were ob-tained by KEGG enrichment analysis;DYRT and MYRT were identified by HPLC-MS to contain 12 same blood active compounds.Animal experiments showed that,compared with the model group,the number of red blood cells,the number of platelets and the content of hemoglobin in the DYRT group were significantly increased,and the number of white blood cells was significantly decreased(P＜0.05).The contents of EPO,IL-3,IL-6 and GM-CSF in serum were significantly in-creased,and the content of TNF-α was significantly decreased(P＜0.05).The relative expression levels of EPO in kidney and PI3K,AKT and GM-CSF mRNA in bone marrow were significantly increased(P＜0.05).Compared with the MYRT group,the number of white blood cells in the DYRT group was significantly reduced,the content of GM-CSF in serum was significantly in-creased,and the content of EPO and GM-CSF mRNA was significantly increased(P＜0.05).In conclusion,DYRT contains the same active compounds as MYRT,which can regulate hematopoi-etic factors,thereby activating the PI3K/AKT pathway to restore hematopoietic function and im-prove the blood deficiency state of the body.

Objective:To evaluate the predictive efficacy of different comorbidity indices for hospitalization due to acute exacerbations in chronic obstructive pulmonary disease (COPD) patients with comorbidities (CO-COPD).Methods:This retrospective cohort study included 259 stable COPD patients with comorbidities from Beijing Tongren Hospital, Capital Medical University, between October 2021 and September 2023, all with ≥1-year follow-up. Patients were categorized into hospitalized ( n=75) and non-hospitalized ( n=184) groups based on acute exacerbation events. Clinical characteristics, comorbidities, and comorbidity indices, including Charlson Comorbidity Index (CCI), COPD-specific Comorbidity Test (COTE), and comorbidities in chronic obstructive lung disease index (COMCOLD) were compared between two goups. Risk facors of hospitalization due to acute exacerbations were analyzed by Cox regression. Modified indices were developed by incorporating additional respiratory comorbidities (asthma, bronchiectasis, lung cancer) weighted by hazard ratios (HRs) from Cox reguression. The predictive performance of different comorbidity indices for hospitalization was assessed by receiver operating characteristic (ROC) curves. Results:Hospitalized patients exhibited lower BMI, FEV 1% predicted, and FEV 1/FVC (all P<0.05), alongside higher modified British Medical Research Coucil (mMRC) scores and COPD assessment test (CAT) scores, eosinophil counts, and Global Initiative for Chronic Obstructive Lung Disease, (GOLD)severity ( t=3.73, Z=-3.43, Z=-2.43, Z=-11.10, Z=-11.32, Z=-1.80, χ2=17.62, all P<0.05); and also higher use rates of inhaled corticosteroid (ICS) and systemic oral corticosteroid (OCS) ( χ2=5.48, 7.15, all P<0.05). The comorbidities of asthma, bronchiectasis, lung cancer, hypertension, coronary atherosclerotic heart disease, anxiety and depression in hospitalized group were significantly higher ( χ2=22.49, 18.30, 15.63, 5.10, 4.68, 7.46, 5.16, all P<0.05), along with the increased CCI and COTE index ( P<0.05). Comorbid asthma, bronchiectasis, and lung cancer were independent risk factors for hospitalization ( HR=1.841, 2.924, and 2.076, respectively; all P<0.05). Original CCI and COTE showed moderate predictive value ( AUC=0.609 and 0.655), while modified CCI, COTE, and COMCOLD demonstrated improved performance ( AUC=0.730, 0.760, and 0.713, respectively). At optimal cutoffs (modified CCI>3.5, COTE>4.5, COMCOLD>6.5), sensitivities were 61.3%, 76.0%, and 58.7%, with specificities of 70.1%, 61.4%, and 72.3%. Age-stratified analysis revealed enhanced predictive utility of modified indices across age groups. Conclusions:CCI, COTE, and COMCOLD provide modest predictive value for hospitalization in CO-COPD. Modified indices incorporating respiratory comorbidities significantly improve risk stratification, offering clinical utility for identifying high-risk patients in primary care settings.

This study aims to determine the therapeutic effect and then elucidate the molecular mechanism of Dietary Yangrong Decoction(DYRT)on blood deficiency syndrome based on net-work pharmacology and study its active compounds.The molecular mechanism of DYRT in the treatment of blood deficiency syndrome was predicted by network pharmacology.The blood defi-ciency of rats was established using cyclophosphamide and acetophenohydrazine jointly,which was divided into a blank control group,a model group,a Men's Yangrong Decoction group(MYRT)(positive control group),a medicinal group and food-based Yangrong Decoction group.The active components were analyzed by liquid chromatography-mass spectrometry(HPLC-MS),the periph-eral hemogram was detected by an automatic biochemical analyzer,the levels of hematopoietic regulatory factors in serum were determined by ELISA,and the relative expression of EPO in kid-ney and PI3K,AKT,GM-CSF in bone marrow were measured by RT-PCR.The results showed that DYRT had 57 active ingredients and 128 potential targets for the treatment of spleen deficien-cy syndrome.1 835 items were obtained by GO enrichment analysis,and 20 pathways were ob-tained by KEGG enrichment analysis;DYRT and MYRT were identified by HPLC-MS to contain 12 same blood active compounds.Animal experiments showed that,compared with the model group,the number of red blood cells,the number of platelets and the content of hemoglobin in the DYRT group were significantly increased,and the number of white blood cells was significantly decreased(P＜0.05).The contents of EPO,IL-3,IL-6 and GM-CSF in serum were significantly in-creased,and the content of TNF-α was significantly decreased(P＜0.05).The relative expression levels of EPO in kidney and PI3K,AKT and GM-CSF mRNA in bone marrow were significantly increased(P＜0.05).Compared with the MYRT group,the number of white blood cells in the DYRT group was significantly reduced,the content of GM-CSF in serum was significantly in-creased,and the content of EPO and GM-CSF mRNA was significantly increased(P＜0.05).In conclusion,DYRT contains the same active compounds as MYRT,which can regulate hematopoi-etic factors,thereby activating the PI3K/AKT pathway to restore hematopoietic function and im-prove the blood deficiency state of the body.

Objective:To evaluate the predictive efficacy of different comorbidity indices for hospitalization due to acute exacerbations in chronic obstructive pulmonary disease (COPD) patients with comorbidities (CO-COPD).Methods:This retrospective cohort study included 259 stable COPD patients with comorbidities from Beijing Tongren Hospital, Capital Medical University, between October 2021 and September 2023, all with ≥1-year follow-up. Patients were categorized into hospitalized ( n=75) and non-hospitalized ( n=184) groups based on acute exacerbation events. Clinical characteristics, comorbidities, and comorbidity indices, including Charlson Comorbidity Index (CCI), COPD-specific Comorbidity Test (COTE), and comorbidities in chronic obstructive lung disease index (COMCOLD) were compared between two goups. Risk facors of hospitalization due to acute exacerbations were analyzed by Cox regression. Modified indices were developed by incorporating additional respiratory comorbidities (asthma, bronchiectasis, lung cancer) weighted by hazard ratios (HRs) from Cox reguression. The predictive performance of different comorbidity indices for hospitalization was assessed by receiver operating characteristic (ROC) curves. Results:Hospitalized patients exhibited lower BMI, FEV 1% predicted, and FEV 1/FVC (all P<0.05), alongside higher modified British Medical Research Coucil (mMRC) scores and COPD assessment test (CAT) scores, eosinophil counts, and Global Initiative for Chronic Obstructive Lung Disease, (GOLD)severity ( t=3.73, Z=-3.43, Z=-2.43, Z=-11.10, Z=-11.32, Z=-1.80, χ2=17.62, all P<0.05); and also higher use rates of inhaled corticosteroid (ICS) and systemic oral corticosteroid (OCS) ( χ2=5.48, 7.15, all P<0.05). The comorbidities of asthma, bronchiectasis, lung cancer, hypertension, coronary atherosclerotic heart disease, anxiety and depression in hospitalized group were significantly higher ( χ2=22.49, 18.30, 15.63, 5.10, 4.68, 7.46, 5.16, all P<0.05), along with the increased CCI and COTE index ( P<0.05). Comorbid asthma, bronchiectasis, and lung cancer were independent risk factors for hospitalization ( HR=1.841, 2.924, and 2.076, respectively; all P<0.05). Original CCI and COTE showed moderate predictive value ( AUC=0.609 and 0.655), while modified CCI, COTE, and COMCOLD demonstrated improved performance ( AUC=0.730, 0.760, and 0.713, respectively). At optimal cutoffs (modified CCI>3.5, COTE>4.5, COMCOLD>6.5), sensitivities were 61.3%, 76.0%, and 58.7%, with specificities of 70.1%, 61.4%, and 72.3%. Age-stratified analysis revealed enhanced predictive utility of modified indices across age groups. Conclusions:CCI, COTE, and COMCOLD provide modest predictive value for hospitalization in CO-COPD. Modified indices incorporating respiratory comorbidities significantly improve risk stratification, offering clinical utility for identifying high-risk patients in primary care settings.

To investigate the molecular mechanism of modified Yigong powder(MYG)in the treat-ment of spleen deficiency syndrome based on network pharmacology and analyzed the effect of MYG on gastrointestinal simulated intestinal flora of spleen deficiency dogs and mucosal barrier of Caco-2 cells,as well as the interaction between intestinal flora and mucosal barrier.The molecular mechanism of MYG in the treatment of spleen deficiency syndrome was predicted by network pharmacology.The fecal samples of three canines(12±1)years old with spleen deficiency were collected to establish an in vitro gastrointestinal simulation system,which was divided into the o-riginal fecal sample group,the gastrointestinal simulation group and the gastrointestinal simulation treated by MYG group.The structural changes of the flora in each group were detected by 16S rD-NA sequencing.The metabolites were extracted from the gastrointestinal simulation system trea-ted by MYG group to study its effect on LPS-induced Caco-2 cell mucosal barrier injury model.The cell experiments included the blank control group,LPS model group,modified Yigong metabolite group.The permeability of mucosal was determined by fluorescein sodium,and then relative ex-pression levels of Claudin-1,Occludin and ZO-1 mRNA were determined by qPCR.The correlation between intestinal flora and Caco-2 cell mucosal barrier index after MYG intervention was further analyzed.The results showed that MYG had 76 active ingredients and 45 potential targets for the treatment of spleen deficiency syndrome.Forty key targets were obtained through protein interac-tion analysis,34 items were obtained by GO enrichment analysis,and 16 pathways were obtained by KEGG enrichment analysis.In the gastrointestinal simulation system,compared with the gas-trointestinal simulation group,at the phylum level,the abundance of Firmicutes,Bacteroides and Actinobacteriota increased significantly(P＜0.05),and the abundance of Proteobacteria decreased significantly(P＜0.05).At the genus level,the abundance of Fusobacterium,[Ruminococcus]gna-vus group and Blautia increased significantly(P＜0.05),while the abundance of Escherichia-Shi-gella and Citrobacter decreased significantly(P＜0.05).The diversity index of intestinal flora in the gastrointestinal simulation treated by MYG group was significantly increased(P＜0.05).In cell experiments,compared with the LPS model group,the mucosal permeability of Caco-2 cells in the modified Yigong metabolite group was significantly reduced(P＜0.01),and the expression levels of Claudin-1,Occludin and ZO-1 mRNA were significantly increased(P＜0.01).Correlation analysis showed that there was a certain correlation between bacterial community structure and mucosal barrier indexes.In summary,MYG may act on 40 key targets such as TNF,IL6,IL18,CX-CL8 and AKT1 through 76 active ingredients such as quercetin,arachidonic acid and naringin,and treat spleen deficiency syndrome in dogs through 16 signaling pathways such as AGE-RAGE,FoxO and HIF-l.In addition,the gastrointestinal metabolites of MYG up-regulate tight junction protein mRNA expression,reduce mucosal permeability,and repair mucosal barrier,which may be related to MYG's regulation of flora structure.

Cancer of unknown primary(CUP)refers to a group of histopathologically confirmed malignancies that cannot be identified in terms of their primary origin despite thorough investigations.CUP accounts for approximately 3%-5%of all newly diagnosed cancers worldwide,with an overall survival(OS)ranging from 2.7 to 16.0 months.CUP has long been a significant scientific challenge due to the elusive nature and heterogeneity of the primary sites.In the era of immunohistochemistry(IHC),IHC has been applied to identify the primary site in approximately 70%of CUP cases.However,IHC also has limitations for undifferentiated cancers of unknown primary,and results can be influenced by experimental and human factors.In recent years,with the development of molecular tumor profiling(MTP),techniques such as cytology,histology,gene expression profiling(GEP),genomics and epigenomics have been able to accurately detect the primary site in 90%of cases.Currently,the 90-gene tumor tissue origin test has been proven to have an accuracy rate of 94.4%in diagnosing the primary site of CUP,laying the foundation for precision treatment.In the past,platinum and taxane-based empirical chemotherapy was commonly used for treating CUP.However,these treatments did not yield significant improvements in patient survival and prognosis.Since 2008,there has been a global emergence of clinical studies on MTP-guided first-line therapy for CUP.However,due to study design flaws and result controversies,there is no international consensus on the superiority of organ-specific treatment over empirical chemotherapy in terms of improving progression-free survival(PFS)and OS for CUP.Based on this,our center conducted the world's first phase Ⅲ clinical trial in 2017,and demonstrated improved PFS and favorable OS by GEP-guided site-specific therapy of CUP,which established the primacy of site-specific first-line therapy for CUP.In this review,we detailed the epidemiology,pathogenesis,clinical characteristics and the progression of CUP diagnosis from the era of IHC to MTP.Furthermore,we reviewed the advancements in CUP treatment from empirical chemotherapy to MTP-guided organ-specific treatment.Additionally,this review delved into the exploration of second-line treatment options and the establishment of a clinical stratified management model,which are two topics in future research of CUP.This review aimed to summarize the progress in the diagnosis and treatment of CUP,further explore future research directions for CUP,and improve the survival and prognosis of patients with CUP.

Trastuzumab deruxtecan(T-DXd)has demonstrated significant efficacy in clinical trials for human epidermal growth factor receptor 2(HER2)-expressing breast cancer,gastric cancer,lung cancer and other solid tumors.Its overall safety profile is manageable and tolerable,including the clinically concerning interstitial lung disease(ILD).The etiology of ILD is varied,among which drug-induced ILD is an exclusionary diagnosis.The incidence of ILD caused by different antitumor drugs varies with different symptoms,and the pathogenesis remains unclear.T-DXd-induced ILD is mostly Grades 1-2,and implementing a standardized clinical management protocol can reduce the incidence of severe ILD events,improve patient prognosis,and help maximize the clinical benefits of T-DXd.This article summarized the epidemiology,etiology,risk factors,and potential mechanisms of drug-induced ILD,with a focus on the incidence,time to onset,and outcomes of T-DXd-induced ILD after standardized clinical management.It aimed to help readers understand the importance of standardized clinical management before and during T-DXd treatment.Regarding specific clinical management strategies,the article reviewed comprehensive management approaches for T-DXd-induced ILD based on clinical trial protocols and real-world experiences from both domestic and international perspectives,covering patient screening,patient education,ILD monitoring,diagnosis,and treatment.Before initiating T-DXd treatment,patient screening helps identify those at high risk for ILD,and T-DXd should be used cautiously in these high-risk patients.Effective patient education can enhance patient initiative,encouraging them to promptly report suspected symptoms,which contributes to early identification of ILD.During T-DXd treatment,it is important to regularly monitor symptoms and signs related to ILD,implement regular imaging monitoring and leverage multidisciplinary team collaboration to diagnose ILD as early as possible,thereby minimizing the risk of severe ILD.If symptoms or imaging suggest ILD,T-DXd treatment must be immediately interrupted,and relevant examinations should be completed to rule out other possible causes while considering corticosteroid treatment.Upon ILD diagnosis,subsequent T-DXd dose adjustments,corticosteroid therapy,and supportive treatments should be guided by severity.The article also explored whether patients with T-DXd-induced ILD can be re-treated,concluding that Grade 1 ILD patients might be eligible for re-treatment under specific conditions.In conclusion,the article reviewed the epidemiology,characteristics,clinical trial-recommended management strategies,and real-world management measures of T-DXd-induced ILD,integrating clinical expert experiences to summarize and discuss comprehensive management strategies for it.This aimed to enhance clinicians'understanding of T-DXd-induced ILD and provide valuable insights for early identification,timely diagnosis,and proper management of it.

Objective:To explore the clinical features, treatment methods, and prognosis of testicular tumors in children with undescended testicle.Methods:A retrospective analysis was conducted on the clinical data of 13 children with undescended testicle and testicular tumors treated at the First Affiliated Hospital of Zhengzhou University from March 2013 to May 2022. The ages ranged from 7 months to 13 years, with an average age of (4.5±4.5) years. The main complaint was scrotal emptiness in 11 cases (with tumors on the cryptorchid side in 4 cases, and on the contralateral side in 7 cases), and testicular enlargement in 2 cases (both with contralateral tumors). Preoperative ultrasound examinations revealed testicular tumors in all cases. Preoperative serum alpha-fetoprotein (AFP) was significantly elevated in 2 cases, while the remaining 11 cases had normal AFP levels. All patients had normal human chorionic gonadotropin (β-HCG) levels. All patients underwent surgical treatment, with intraoperative frozen pathology performed. Based on frozen pathology results, 2 cases with malignant tumors and 2 cases with benign tumors (with no normal testicular tissue seen intraoperatively) underwent radical orchiectomy, while the remaining 9 cases with benign tumors underwent testicular preservation surgery and cryptorchidism fixation.Results:Postoperative pathology results were consistent with intraoperative frozen pathology results. The pathological diagnoses were 10 cases of mature teratomas, 2 cases of yolk sac tumors, and 1 case of epidermoid cysts. All pathological stages were classified as stage Ⅰ. One case of yolk sac tumor received chemotherapy with bleomycin, cisplatin, and etoposide (BEP regimen). One case was lost to follow-up 6 months after surgery. Twelve cases were followed up for 1 to 9 years. Follow-up included chest X-rays and ultrasounds every 3 to 6 months, and abdominal CT or MRI scans every 6 months, with no local recurrence or distant metastasis observed.Conclusions:Testicular tumors in children with undescended testicle are rare. The most common presenting symptom is scrotal emptiness, with contralateral testicular tumors being frequent in cryptorchid patients. The majority of testicular tumors in these patients are benign, with mature teratomas being the most common pathological type. Early diagnosis and timely surgical intervention result in a good prognosis.