Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Purpose: This Phase II trial was objected to evaluate the efficacy and safety of adding fulvestrant to neoadjuvant chemotherapy in patients with estrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)– locally advanced breast cancer (LABC). Additionally, the study aimed to investigate the association of 16α-18F-fluoro-17β-fluoroestradiol (18F-FES) positron emission tomography (PET)–computed tomography (CT) and metabolites with efficacy. Materials and Methods: Fulvestrant and EC-T regimen were given to ER+/HER2– LABC patients before surgery. At baseline, patients received 18F-FES PET-CT scan, and plasma samples were taken for liquid chromatography–mass spectrometry analysis. The primary endpoint was objective response rate (ORR). Secondary endpoints included total pathologic complete response (tpCR) and safety. Results: Among the 36 patients enrolled, the ORR was 86.1%, the tpCR rate was 8.3%. The incidence of grade ≥ 3 treatment-emergent adverse events was 22%. The decrease in ER value in sensitive patients was larger than that in non-sensitive patients, as was Ki-67 (p < 0.05). The maximum standardized uptake value, mean standardized uptake values, total lesion ER expression of 18F-FES PET-CT in sensitive patients were significantly higher than those in non-sensitive patients (p < 0.05). Moreover, these parameters were significantly correlated with Miller and Payne grade and the change in ER expression before and after treatment (p < 0.05). Thirteen differential expressed metabolites were identified, which were markedly enriched in 19 metabolic pathways. Conclusion This regimen demonstrated acceptable toxicity and encouraging antitumor efficacy. 18F-FES PET-CT might serve as a tool to predict the effectiveness of this therapy. Altered metabolites or metabolic pathways might be associated with treatment response.

Objective:To explore the hematological phenotype and genotypic characteristics of five Chinese individuals with a rare thalassemia mutation HBB: c. 93-21G>A. Methods:A retrospective study was carried out on five individuals identified by the People′s Hospital of Yangjiang and Guangzhou Hybribio Co., Ltd. from May 2018 to September 2022. Routine blood test and hemoglobin electrophoresis were performed, and the genotypes of five subjects were determined by using PCR combined with reverse dot blotting (RDB), nested PCR, Gap-PCR and Sanger sequencing. This study was approved by Medical Ethics Cornmittee of the People′s Hospital of Yangjiang (Ethics No. 20240001).Results:Among the five individuals, hematological data of one was unavailable, and the remaining four had presented with microcytosis and hypochromia. The results of hemoglobin electrophoresis indicated that all of them had a HbA 2 level of ≥4.7%. Genetic analysis showed that one case had harbored compound heterozygous mutations of ααα anti3.7 triplet and HBB: c. 93-21G>A, one had compound heterozygous mutations of -α 3.7 and HBB: c. 93-21G>A, whilst the remaining three were heterozygous for the HBB: c. 93-21G>A mutation. Conclusion:The hematological phenotype of β-thalassemia carriers ( HBB: c. 93-21G>A) is similar to that of other β + thalassemia heterozygotes with mild β-thalassemia characteristics.

Objective:To explore the application value and surgical experience of neuroendoscopic resection for pediatric patients with cerebellar tumors.Methods:This was a case series study.The clinical data and outcomes of 30 pediatric patients with cerebellar tumors treated through neuroendoscopic surgery in the Department of Neurosurgery, the Guizhou Hospital of Shanghai Children′s Medical Center and Guizhou Provincial People′s Hospital from January 2021 to January 2024 were retrospectively analyzed.Results:Twenty-six patients underwent total resection, 3 patients underwent subtotal resection, and 1 patient underwent biopsy.Postoperative pathological findings showed 9 cases of medulloblastoma, 3 cases of ependymoma, 17 cases of astrocytoma (5 cases of World Health Organization Grade Ⅰ, 3 cases of Grade Ⅱ, and 9 cases of Grade Ⅲ), and 1 case of cerebellar benign lesion.During the perioperative period, malignant arrhythmia occurred and induced death in 1 case, cerebellar mutism occurred in 12 cases, and ataxia occurred in 22 cases.During the 1-36 months of follow-up, 2 cases developed communicating hydrocephalus at the 2 nd and the 6 th month, respectively, and improved after ventriculoperitoneal shunt; cerebellar mutism was relieved to varying degrees after an average postoperative follow-up period of (115±23) days(46-194 days), and ataxia was alleviated after an average postoperative follow-up period of (127±42) days(27-173 days).Tumors relapsed in 5 cases during the last follow-up. Conclusions:Neuroendoscopy provides an alternative to the microscope for experienced operators to achieve the surgical exposure requirements during the resection of pediatric cerebellar vermis tumors.

Efferocytosis refers to the process that phagocytes recognize and remove the apoptotic cells, which is essential for maintaining tissue homeostasis both in physiological and pathological conditions. Numerous studies have demonstrated that efferocytosis can prevent secondary necrosis and proinflammatory factor release, leading to the resolution of inflammation and tissue immunological tolerance in numerous diseases such as stroke. Stroke is a leading cause of death and morbidity for adults worldwide. Persistent inflammation triggered by the dead cells or cell debris is a major contributor to post-stroke brain damage. Effective efferocytosis might be an efficient strategy to minimize inflammation and restore brain homeostasis for neuronal regeneration and function recovery. In this review, we will discuss the phagocytes in the brain, the molecular mechanisms underlying efferocytosis, the role of efferocytosis in inflammation resolution, and the potential therapeutic applications targeting efferocytosis in stroke.
Humans ; Stroke ; Phagocytosis/physiology* ; Inflammation ; Apoptosis/physiology* ; Animals ; Phagocytes/physiology* ; Brain/metabolism* ; Efferocytosis

Objective:To investigate the distribution of iron deposition in the substantia nigral (SN) subregions on quantitative susceptibility mapping (QSM) and the change of swallow tail sign (STS) in patients with relapsing-remitting multiple sclerosis (RRMS) of different disease stages.Methods:The clinical and imaging data of 53 patients with RRMS (case group) diagnosed at the First Hospital of Chongqing Medical University from November 2019 to December 2021 were retrospectively analyzed. The case group was divided into 0-5 years subgroup, 6-10 years subgroup, and >10 years subgroup according to the disease duration; another 37 age-and gender-matched healthy volunteers were recruited as the control group during the same period. All subjects underwent MRI and QSM reconstruction. First, the SN was divided into four subregions: rostral anterior-SN (aSNr), rostral posterior-SN (pSNr), caudal anterior-SN (aSNc), and caudal posterior-SN (pSNc) on the QSM, and the quantitative susceptibility value (QSV) of each subregion was measured, and then the STS of the SN was observed and scored on the susceptibility weighted imaging (SWI) generated by post-processing. ANOVA was used to compare the differences in the QSV of each subregion of SN among the groups, and the probability of abnormal STS was compared using the χ 2 test. Spearman′s test was used to analyze the correlation between the QSV of each subregion of SN and the STS score. Results:The differences in QSV of aSNr, pSNr, aSNc, and pSNc were statistically significant among the 0-5 years subgroup, 6-10 years subgroup,>10 years subgroup of RRMS patients and the control group ( P<0.05). The QSV of aSNr, pSNr, and aSNc in 0-5 years subgroup was higher than those in the control group ( P was 0.039, 0.008, 0.039, respectively). The QSV of aSNr, aSNc, and pSNc in the 6-10 years subgroup were higher than those in the 0-5 years subgroup ( P was <0.001, 0.020, 0.015, respectively). The QSV of the aSNc, pSNc in >10 years subgroup were lower than those in the 6-10 years subgroup ( P=0.037, 0.006). The QSV of aSNr, pSNr in >10 years subgroup were higher than those in the control group ( P was <0.001, 0.001). There were 7 cases of abnormal STS in the 0-5 years subgroup, 11 cases in the 6-10 years subgroup, 12 cases in >10 years subgroup, and 9 cases in the control subgroup, and there was a statistically significant difference in the probability of abnormal STS among the subgroups of the RRMS patients and the control subgroup (χ 2=16.20, P=0.011). Both the scores of STS in the 6-10 years subgroup and >10 years group were positively correlated with the QSV in pSNc ( r s=0.65, P=0.006; r s=0.48, P=0.045). Conclusions:In RRMS patients, SN iron deposition is concentrated on aSNr, pSNr, and aSNc in the 0-5 years subgroup and on aSNr, aSNc and pSNc in the 6-10 years subgroup. The QSVs of all SN subregions have a downward trend in >10 years subgroup compared with that in the 6-10 years subgroup. Both the QSVs of the pSNc in the 6-10 years group and >10 years group are positively related to STS scores. These help explore the potential progression pattern of SN iron deposition in RRMS patients and the cause of abnormal STS in RRMS patients.

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).

Breast cancer is the most commonly diagnosed cancer and the main cause of cancer deaths among women worldwide. HER2 positive breast cancer accounts for 15% of all breast cancer. This subtype of breast cancer is highly invasive and has a very poor prognosis. With the development of anti - HER2 targeted therapy, the prognosis of these patients has been improved. However, some patients have poor response to the anti-HER2 therapy. Therefore, it is necessary to select biomarkers that can predict the therapeutic effect for improving the efficacy of these patients. This article describes the research progress of HER2 positive biomarkers for breast cancer, focusing on biomarkers related to the efficacy of targeted therapy, in order to provide some reference for future clinical optimization of targeted therapy.

Objective:To understand the prevalence of human parechovirus (HPeV) in neonates of Hunan Provincial People’s Hospital, and analyze genetic evolutionary characteristics.Methods:From June to September 2021, fecal samples of inpatient neonates were collected in Hunan Provincial People′s Hospital. TaqMan real-time qPCR and RT-PCR were used for HPeV screening and genotyping. High-throughput sequencing and PCR were used to obtain whole genomes. Phylogenetic analysis was performed after sequencing.Results:A total of 123 fecal samples of neonates were collected, of which 22 were HPeV positive, with 17.89% positive rate. All the strains belonged to the HPeV-1 genotype. One full-length genomic sequence of 7 269 bp were obtained, and provisionally named Hunan/HPeV/2021, which has the highest nucleotide identity with known HPeV-1 genotype, with 86.6%-91.9% nucleotide identity. The nucleotide and amino acid identity of open reading frame (ORF) with known similar sequences were 90.3%-92.6% and 97.3%-98.3%, respectively. The phylogenetic analysis showed that Hunan/HPeV/2021 belongs to the HPeV-1 genotype, which is clustered into the same clade as the popular HPeV-1 strains in China.Conclusions:HPeV has a high prevalence in inpatient neonates of Hunan Provincial People’s Hospital and belong to the HPeV-1 genotype.