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 Investigating the impact of miR-15a-5p on autophagy in trophoblast cells of pre-eclamptic placenta.Methods Collect 20 cases of normal placental tissue and 20 cases of preeclamptic placental tissue from December 2020 to December 2022.Use fluorescence quantitative PCR to detect the expression of miR-15a-5p in placental tissue and trophoblast cells,and study its correlation with patient blood pressure.The HTR8-S/Vneo cells are divided into normal group(control)and hypoxia group,and the effect of hypoxia on the expression of miR-15a-5p is observed.Additionally,mimic-NC group,mimic-NC+hypoxia group,miR-15a-5p mimic group,miR-15a-5p mimic+hypoxia group,inhibitor-NC group,inhibitor-NC+hypoxia group,miR-15a-5p inhibitor group,and miR-15a-5p inhibitor+hypoxia groups are set up to observe the effect of miR-15a-5p on hypoxia-induced autophagy-related proteins LC3B and p62 protein in trophoblast cells.Western blot is used to detect the expression levels of autophagy-related proteins LC3B and p62 protein in each group;TargetScan website predicts the target genes of miR-15a-5p,and detects their expression levels in placental tissue and trophoblast cells.Results Compared with the control group,the expression levels of miR-15a-5p were significantly increased in the placentas and hypoxic trophoblasts of preeclampsia,and they were positively correlated with the blood pressure of the patients.Under hypoxic conditions,the overexpressed miR-15a-5p promoted the protein expression of LC3BII/I,while the relative expression of P62 was decreased.But after interference with miR-15a-5p,LC3BII/I expression was down-regulated and P62 expression was up-regulated.The results of quantitative PCR and Western blot showed that the expression levels of YAP1 in the preeclampsia placental tissues and hypoxic trophoblasts were significantly reduced.Conclusion The upregulation of miR-15a-5p in trophoblast cells of the placenta in individuals with preeclampsia could enhance autophagy in preeclampsia by forming a complex with YAP1.

Objective: To examine the mediating effects of blood pressure, glucose, lipids, and serum uric acid on the association between childhood overweight/obesity and left ventricular hypertrophy (LVH), and to provide scientific evidence for the prevention and control of cardiovascular diseases during childhood. Methods: One public school in Huantai County, Zibo City was selected to conduct the baseline survey from November 2017 to January 2018 using a convenient cluster sampling method. A total of 1 400 children aged 6 to 11 were included in the study. According to the classification criteria based on body mass index (BMI), participants were divided into the non overweight/obese group ( n =787) and the overweight/obese group ( n =613). The mediating effects of metabolic variables on the association between childhood overweight/obesity and left ventricular hypertrophy (LVH) were analyzed using the "mediation" package in R software. Results: Children who were overweight/obese had higher levels of BMI- Z score (2.0±0.8), systolic blood pressure (SBP) (109.1±8.9 mmHg), diastolic blood pressure (DBP) (65.4±6.8 mmHg), fasting plasma glucose (FPG) (4.8±0.5 mmol/L), insulin (INS) (11.3±7.6 μU/mL), apolipoprotein B (ApoB) (0.7±0.2 g/L), lowdensity lipoprotein cholesterol (LDL-C) (2.4±0.7 mmol/L), total cholesterol (TC) (4.2±0.9 mmol/L), triglycerides (TG) (0.9±0.4 mmol/L), and serum uric acid (SUA) (321.2±91.4 μmol/L) compared to those who were non-overweight/obese [the corresponding values were (-0.2±0.7),(104.3±8.8) mmHg, (62.2±6.2) mmHg, (4.7±0.6) mmol/L, (6.1±4.2) μU/mL, (0.6±0.2) g/L, (2.2±0.6) mmol/L, (4.1±0.7) mmol/L, (0.7±0.2) mmol/L, and (278.6±74.7) μmol/L, respectively], whereas the levels of high density lipoprotein cholesterol (HDL-C) were lower in overweight/obese children (1.5±0.3 mmol/L) than in non-overweight/obese children (1.7±0.4 mmol/L). All differences were statistically significant ( t =53.66, 9.88, 9.19, 3.60, 16.32, 7.36, 5.11, 2.55, 11.08, 9.58, -10.31, P <0.05). After adjusting for potential covariates, overweight/obese children had 8.72 times increased risk of developing LVH compared to the non-overweight/obese children ( OR=8.72, 95%CI =5.45-14.66， P <0.01). Mediation analysis showed that INS, HDL-C, LDL-C, TG, ApoB, and SUA partially mediated the association between childhood overweight/obesity and LVH, and among these, INS and TG had relatively strong mediating effects, accounting for 28.05% and 13.71% of the total effects, respectively. Conclusions INS, HDL-C, LDL-C, TG, ApoB, and SUA are intermediate risk factors on the association between childhood overweight/obesity and LVH. Keeping metabolic indicators (especially INS and TG) at healthy levels is particularly important for reducing the burden of cardiovascular diseases in overweight/obese children.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Goniotomy (GT) is a safe and effective type of minimally invasive glaucoma surgery (MIGS) extensively utilized in China.It is particularly suited for treating primary open-angle glaucoma and advanced primary angle-closure glaucoma.Although GT is generally safe, hyphema and postoperative intraocular pressure (IOP) spikes remain common complications after GT.Currently, there is no standardized protocol for managing these issues, which can impact clinicians' assessment of surgical outcomes and potentially affect the prognosis.Therefore, it is crucial to establish comprehensive and detailed management protocols for perioperative hyphema and IOP spike following GT.This will guide clinical practitioners in managing complications appropriately and systematically, thereby promoting the further development and refinement of MIGS.To address these concerns, several domestic glaucoma treatment experts along with members of the Glaucoma Society of Ophthalmology, Guangdong Medical Association reviewed existing literature and held recommendation meetings to develop a guideline for managing perioperative hyphema and IOP spikes following GT.It includes defining perioperative hyphema in GT, discussing its high-risk factors and outcomes, exploring methods for prevention prior to surgery and techniques to reduce bleeding during the procedure, and managing postoperative hemorrhage.Additionally, it covers defining IOP spikes after GT, investigates their causes and contributing factors, and outlines management strategies and anticipated outcomes to provide a valuable resource for clinicians.

Objective To observe the value of multimodal imaging for diagnosis of cardiac space-occupying lesions.Methods Data of 70 patients with cardiac space-occupying lesions who underwent echocardiography and cardiac CT(CCT)were retrospectively analyzed,among them 35 also underwent cardiac MRI(CMRI).The value of multimodal imaging for diagnosis of cardiac space-occupying lesions were explored according to the results of surgical pathology or clinical diagnosis.Results Among 70 cases,benign tumors were confirmed by surgical pathology in 43 cases,while malignant tumors were confirmed by surgical pathology in 3 cases and clinically diagnosed in 1 case.Meanwhile,non-tumor-occupying lesions were clinically diagnosed in 23 cases,all obviously shrunken after treatments.Among 70 cases,echocardiography correctly diagnosed 57 cases,misdiagnosed 8 cases and unclearly diagnosed 5 cases,with diagnostic accuracy rate of 81.43%(57/70).CCT correctly diagnosed 63 cases,misdiagnosed 4 cases but missed 3 cases,with diagnostic accuracy rate of 90.00%(63/70).CMRI outcomes in all 35 cases were consistent with surgical pathologic results,with diagnostic accuracy rate of 100%(35/35).Conclusion Multimodal imaging might provide objective evidences for diagnosis and treatment of cardiac space-occupying lesions.

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

ObjectiveTo explore the effect of Xianlian Jiedu prescription （XLJDP） on the proliferation and glycolysis of human colorectal cancer HCT-116 cells and the underlying mechanism. MethodHCT-116 cells were cultured with XLJDP and then the survival rate was examined by methyl thiazolyl tetrazolium （MTT） assay. The effect on the HCT116 cell proliferation was detected by colony formation assay and 5-ethynyl-2′-deoxyuridine （EDU） incorporation assay. The amount of glucose consumed by HCT-116 cells was measured by glucose test kit， and the amount of produced lactic acid was determined by lactic acid test kit 48 h after the treatment with XLJDP. The expression of glycolysis-related proteins mammalian target of rapamycin （mTOR）， phosphorylated mTOR （p-mTOR）， glucose transporter 1 （GLUT1）， and lactate dehydrogenase （LDHA） was detected by Western blot. ResultThe half-maximal inhibitory concentration （IC₅₀） of XLJDP against HCT-116 cells was 6.82 g·L^-1. Compared with the blank group， XLJDP （1.625， 3.25， 6.50 g·L^-1） inhibited the proliferation of HCT-116 cells （P<0.05， P<0.01）. Moreover， compared with the blank group， XLJDP （1.625， 3.25， 6.50 g·L^-1） suppressed glucose uptake and lactic acid production in a dose-dependent manner （P<0.05， P<0.01）. The expression of p-mTOR/mTOR， LDHA， and GLUT1 was down-regulated by XLJDP （P<0.05， P<0.01）. ConclusionXLJDP can significantly inhibit the proliferation and the Warburg effect of glycolysis in colorectal cancer cells by regulating the mTOR signaling pathway and the down-regulating the expression of LDHA， GLUT1， and other key proteins and enzymes in glycolysis.

Objective:To explore the effect of precision nursing based on evidence-based concept in the perioperative period of patients with total knee arthroplasty (TKA) .Methods:From January 2018 to December 2020, 200 TKA patients admitted to the First Affiliated Hospital of Zhengzhou University were selected as the study subject by convenience sampling. The patients were divided into the control group and the observation group according to simple random sampling with 100 cases in each group. The control group adopted routine nursing, while the observation group conducted precise nursing based on evidence-based concept on the basis of the control group. The incidence of postoperative complications and knee function between the two groups were compared.Results:The incidence of complications in the observation group was lower than that in the control group, with a statistically significant difference ( P<0.05) . At one, three and six months after operation, the knee function score of New York Hospital for Special Surgery (HSS) in both groups showed an upward trend. The HSS scores of the observation group at one, three, six months after operation were higher than those of the control group, and the difference was statistically significant ( P<0.01) . Conclusions:The precision nursing based on the evidence-based concept has a definite effect in the perioperative nursing of patients with TKA, which can reduce complications and improve the knee function.

【Objective】 To investigate the complaints of blood quality in Changsha, in order to continuously improve blood quality management. 【Methods】 The Handling Forms of Blood Quality Complaints of our center during 2014~2019, and the blood units issued, corresponded to the occurrence period of complaints, were collected from the SHINOW 9.0 system, and the overall blood supply and complaints of blood quality, including various components, were classified and analyzed by SPSS19.0. 【Results】 1 865 466 bags of blood were delivered from 2014 to 2019 in Changsha, coming down 435 complaints with 435 bags of blood involved, and the total ratio of blood quality complaints rated at 0.23‰(435/1 865 466), of which red blood cell complaint accounted for 45.06%(196/435), with a rise from 30.23%(26/86) in 2014 to 49.49%(49/99) in 2019. Meanwhile, the cryoprecipitate complaint increased from 10.47%(9/86) to 20.20%(20/99). The complaints were mainly broken blood bags 29.89%(130/435), positive serological testing results(irregular antibody screening+ or direct anti globulin test+ ) 34.48%(150/435), floccule or precipitates 18.39%(80/435), clot 5.52%(24/435), lipemia 3.45%(15/435), and blood type variant(ABO subgroups and variants of RhD) 2.07%(9/435). The complaints were different in blood components, each with a particular tilt as follows: positive serological testing results in red blood cell [72.45%(142/186)], broken blood bags in plasma [83.74%(103/123)], floccule or precipitates in platelet [54.17%(13/24)] and cryoprecipitate [64.13%(59/92)] . 【Conclusion】 Broken blood bags of plasma, floccule or precipitates of cryoprecipitate, and positive serological testing results of red blood cell were the main complaints of blood quality in Changsha. Blood banks should strengthen quality control, handle quality complains cautiously and strengthen community with hospitals before transfusion to improve blood satisfaction in clinical, and save blood resources.