Hormone receptor (HR)-positive/HER2-negative early breast cancer is the most common subtype of breast cancer, and endocrine therapy serves as the cornerstone of adjuvant treatment. In recent years, with the publication of key clinical trials such as SOFT, TEXT, and monarchE, and breakthroughs in novel agents studies like lidERA, the endocrine therapy strategy for HR-positive/HER2-negative early breast cancer has evolved toward increased precision and intensity. This article systematically reviews the latest advances in endocrine therapy, focusing on the consolidation of ovarian function suppression as a standard for high-risk premenopausal patients with updated follow-up evidence, the benefit-risk assessment of extended endocrine therapy, and the current application and interdrug differences of CDK4/6 inhibitors in the adjuvant setting. This manuscript also addresses existing challenges, including optimizing treatment-related quality of life and precisely identifying beneficiary populations, and briefly introduces the clinical trial progress of novel agents, such as oral selective estrogen receptor degraders. Furthermore, it outlines evidence-based strategies for ovarian protection during chemotherapy and fertility preservation for young patients. This review aims to provide clinicians with a comprehensive perspective, balancing the pursuit of maximal efficacy with patients′ long-term quality of life and individualized needs.

Objective: To explore the prevalence of bone defect and alveolar bone thickness changes in the mandibular incisors of untreated adults and post-orthodontic treatment adults, with the aim of providing strategies for preventing and managing alveolar bone defects during orthodontic treatment. Methods: This study was reviewed and approved by the Medical Ethics Committee. Clinical records, panoramic radiographs, cephalometric radiographs, and cone beam computed tomography (CBCT) images and informed consent were obtained for 150 untreated adults and 150 post-orthodontic adults. The untreated adults and post-orthodontic adults were respectively divided into three subgroups: skeletal ClassⅠ, Class Ⅱ and Class Ⅲ, with 50 cases per subgroup. Meanwhile, 60 cases with completeness of pre- and post-orthodontic data were enrolled from 150 post-orthodontic adults, including 20 cases each of skeletal ClassⅠ, Class Ⅱ, and Class Ⅲ. Cephalometric radiographs were imported into Dolphin software to measure skeletal parameters. CBCT images were imported into Mimics software to assess alveolar bone defects and to measure alveolar bone thickness of mandibular incisors among three groups: 150 untreated adult groups, 150 post-orthodontic groups and the pre- and post-treatment status of 60 patients selected from the latter group. Results: Untreated adult patients: the prevalence of labial dehiscence and fenestration in the mandibular incisors was higher than that on the lingual side among skeletal ClassⅠ, Ⅱ, and Ⅲ malocclusion patients, and there was a statistically significant difference in the alveolar bone thickness of the mandibular incisors among the three classes. Post-orthodontic treatment adults: for skeletal ClassⅠ and Ⅱ patients, the prevalence of lingual bone dehiscence in the mandibular incisors was significantly higher in the extraction groups than in the non-extraction groups; correspondingly, the lingual alveolar bone was also thinner in the extraction groups; Class Ⅱ non-extraction patients showed a higher prevalence of labial bone fenestration but a lower prevalence of lingual bone fenestration in mandibular incisors compared to Class Ⅱ extraction patients; the orthodontic-orthognathic combined treatment group showed significantly higher prevalence of labial/lingual bone dehiscence and thinner alveolar bone at multiple sites in the mandibular incisors compared to the camouflage group in skeletal Class Ⅲ patients. Comparison of mandibular incisor bone defects and thickness before and after orthodontic treatment in adult patients: in skeletal ClassⅠ and Ⅱ patients treated with premolar extraction and Class Ⅲ patients treated with orthodontic-orthognathic combined treatment, the lingual alveolar bone of mandibular incisors exhibited significant resorption and thinned after treatment, and this was accompanied by an increased prevalence of dehiscence; in non-extraction patients, ClassⅠ non-extraction patients showed thinning of the crestal-labial bone and apical-lingual bone, Class Ⅱ patients showed thinning of the crestal-labial bone and middle-labial bone of the mandibular incisors, along with an increased prevalence of dehiscence Conclusion In malocclusion adults, alveolar bone defects were already present in the mandibular incisors before orthodontic treatment. The alveolar bone defects and thickness in mandibular incisors among post-orthodontic adults were influenced by the treatment plan and Class of skeletal malocclusion.

Objective To explore the efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in patients with locally advanced resectable non-small cell lung cancer (NSCLC). Methods The clinical data of patients with stage ⅡA-ⅢB NSCLC who underwent surgical treatment after receiving neoadjuvant immunotherapy combined with chemotherapy or chemotherapy alone at the First People’s Hospital of Jining between April 2021 and January 2024 were retrospectively analyzed. According to the preoperative neoadjuvant regimens, the patients were divided into a combined group and a chemotherapy group, and the clinical data of the two groups were compared. Results A total of 66 patients were included, including 61 males and 5 females. There were 53 patients in the combined group with a mean age of (63.40±6.80) years, and 13 patients in the chemotherapy group with a mean age of (58.62±8.30) years. There was a statistical difference in age between the two groups (P＜0.001), while no statistical difference was observed in other baseline data (P>0.05). The major pathological response rates in the combined group and the chemotherapy group were 54.7% and 23.1%, respectively (P=0.041), and the pathological complete response rates were 39.6% and 0.0%, respectively (P=0.006). The operative time in the combined group was shorter (P=0.039). There were no statistical differences between the two groups in intraoperative blood loss, duration of postoperative tube carrying, incidence of postoperative complications, overall survival, or event-free survival (P>0.05). Conclusion Surgical treatment following neoadjuvant immunotherapy combined with chemotherapy is safe and feasible, and its long-term efficacy requires further follow-up for confirmation.

Objective To observe the efficacy and safety of neoadjuvant sintilimab combined with chemotherapy in the treatment of patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC). Methods Clinical data were collected from patients with locally advanced resectable ESCC who received neoadjuvant immunotherapy combined with chemotherapy followed by surgical treatment at the Department of Thoracic Surgery of Jining No.1 People's Hospital from April 2020 to April 2022. The endpoints included major pathological response (MPR), pathological complete response (pCR), R0 resection rate, safety, and postoperative survival. Results A total of 43 patients with ESCC who received at least one cycle of neoadjuvant immunotherapy before surgery were included. Among them, there were 31 males and 12 females with a median age of 65 years (interquartile range: 58-69). All patients successfully completed the surgery without any surgical delays. The pCR rate was 14.0% (6/43), the MPR rate was 58.1% (25/43), and the R0 resection rate was 97.7% (42/43). Patients exhibited reliable safety during neoadjuvant therapy and postoperatively. The 2-year overall survival and disease-free survival rates were 90.7% and 81.4%, respectively. Kaplan-Meier survival analysis and log-rank test revealed lower recurrence rates and better survival in the MPR patients compared to the non-MPR patients. Conclusion The combination of neoadjuvant sintilimab and chemotherapy in the treatment of patients with locally advanced resectable ESCC has demonstrated significant clinical efficacy, while also being safe and reliable.

Objective: To explore the influencing factors of blood transfusion volume in obstetric patients based on the national health development strategy, and to provide evidence for clinical transfusion management and maternal and infant safety. Methods: A total of 1 203 obstetric patients who received blood transfusion in a tertiary hospital in Beijing from 2013 to 2023 were enrolled retrospectively. Seventeen indicators including age, body mass index (BMI), hemoglobin and prothrombin time were selected as research variables. Descriptive analysis was conducted firstly. Scatter plot matrix was used to analyze the correlation between continuous variables and transfusion volume, and box plots were used to analyze the relationship between categorical variables and transfusion volume. Linear regression, logistic regression and random forest models were established for empirical analysis, and ROC curves and AUC values were compared to evaluate model performance. Results: Descriptive analysis showed that the distribution of obstetric blood transfusion volume was right-skewed, and multiple indicators were significantly correlated with transfusion volume. Linear regression indicated that 9 variables such as age, BMI and hemoglobin had linear correlation with transfusion volume. Logistic regression confirmed that 7 variables including BMI and hemoglobin were statistically correlated with the probability of massive blood transfusion. Random forest model screened the core influencing factors, which were ranked by importance: hemoglobin, prothrombin time, hematocrit, BMI, activated partial thromboplastin time, platelet count and age. The AUC values of logistic regression and random forest were 0.78 and 0.81 respectively, and the latter had better predictive performance. Conclusion: Prenatal anemia, coagulation disorders, advanced age, obesity, gestational hypertension, placental abnormalities and organ damage can increase the risk of massive blood transfusion in obstetric patients. The random forest model has better analytical and predictive ability in this study. The results can provide reference for accurate blood transfusion and risk prediction in obstetrics.

[Objective] To compare the efficacy and safety of deglycerolized red blood cells (DRBC) and suspended red blood cells (SRBC) based on the propensity score matching (PSM) method, so as to provide evidence for the rational use of DRBC resources in clinical practice. [Methods] A total of 89 patients who received DRBC transfusion and 2 916 patients who received SRBC transfusion in our hospital from January 2023 to September 2024 were included. A 1∶1 nearest neighbor PSM was used to balance covariates such as gender, age, and body mass index (BMI). The changes of hemoglobin (Hb), red blood cell (RBC) count, hematocrit (HCT), and inflammatory markers such as white blood cell (WBC) count, neutrophil (NE) count, C-reactive protein (CRP), and Interleukin-6(IL-6) in the last 72 hours after transfusion were analyzed by SPSS 26.0 and R software to evaluate clinical efficacy and transfusion safety. [Results] The baseline of the two groups was balanced after PSM (P>0.05). There was no significant difference in the total effective rate between the DRBC group (80.9%) and the SRBC group (86.5%) (P>0.05). In the SRBC group, WBC (×10 /L) increased from 9.634±6.742 to 10.147±6.835, CRP (mg/dL) increased from 5.468±4.647 to 6.174±6.114, and IL-6(pg/mL) decreased from 213.733±587.191 to 157.255±552.626. In the DRBC group, WBC (×10 /L) decreased from 11.123±7.880 to 11.011±8.549, CRP (mg/dL) decreased from 5.729±4.761 to 5.326±4.466, and IL-6(pg/mL) decreased from 238.806±639.060 to 152.255±266.558. Compared with the before treatment, the differences between the SRBC group and DRBC group were not statistically significant (P>0.05). Among all patients included in the statistics, the overall incidence of transfusion adverse reactions was 0.205% (6/2 916) in the SRBC group, and no adverse reactions occurred in the DRBC group. The incidence in the SRBC group was higher than that in the DRBC group. [Conclusion] Based on PSM analysis, there was no significant difference in the efficacy and safety of DRBC transfusion compared with SRBC transfusion, which can provide evidence-based support for routine application.

The neonatal mammalian heart has a remarkable regenerative capacity, while the adult heart has difficulty to regenerate. A metabolic reprogramming from glycolysis to fatty acid oxidation occurs along with the loss of cardiomyocyte proliferative capacity shortly after birth. In this study, we sought to determine if and how metabolic reprogramming regulates cardiomyocyte proliferation. Reversing metabolic reprogramming by carnitine palmitoyltransferase 1 (CPT1) inhibition, using cardiac-specific Cpt1a and Cpt1b knockout mice promoted cardiomyocyte proliferation and improved cardiac function post-myocardial infarction. The inhibition of CPT1 is of pharmacological significance because those protective effects were replicated by etomoxir, a CPT1 inhibitor. CPT1 inhibition, by decreasing poly(ADP-ribose) polymerase 1 expression, reduced ADP-ribosylation of dual-specificity phosphatase 1 in cardiomyocytes, leading to decreased p38 MAPK phosphorylation, and stimulation of cardiomyocyte proliferation. Our present study indicates that reversing metabolic reprogramming is an effective strategy to stimulate adult cardiomyocyte proliferation. CPT1 is a potential therapeutic target for promoting heart regeneration and myocardial infarction treatment.

Colorectal cancer(CRC)is a prevalent malignancy of the digestive tract in China;it exhibits aggressive progression that is closely associated with tumor microenvironment(TME)modulation.Tumor-associated macrophages,which are pivotal immunomodulatory com-ponents of the TME,demonstrate remarkable functional heterogeneity.Among these,secreted phosphoprotein 1-positive tumor-associated macrophages(SPP1+TAMs)represent a distinct subset with well-characterized protumorigenic properties.Evidence indicates that SPP1+TAMs exhibit a unique spatial distribution pattern in CRC tissues,with pronounced enrichment at the invasive tumor front and metastatic niches.Through the secretion of SPP1 and other effector molecules,this subset orchestrates multifaceted oncogenic processes,including tumor cell adhesion,migration,angiogenesis,and metastatic dissemination.This review systematically elucidates the spatial distribution,molecular reg-ulatory mechanisms,and clinical implications of SPP1+TAMs in CRC,thereby providing a theoretical foundation for developingnovel diagnost-ic biomarkers and targeted therapeutic strategies.

Objective To observe the effects of Yifei Jianpi Prescription on airway mucus hypersecretion and protein expressions of EGFR/PKC/NF-κB pathway in lipopolysaccharide(LPS)-induced acute lung injury(ALI)model rats;To explore its mechanism in the treatment of ALI.Methods Ten of 60 SPF SD rats were randomly selected as blank group,and the other rats were intratracheal instilled with LPS to establish ALI model.The model rats were randomly divided into model group,dexamethasone group and Yifei Jianpi Prescription high-,medium-and low-dosage groups,with 8 rats in each group.Each treatment group was given corresponding drug solution by gavage,and the blank group and model group were given equal volume of normal saline by gavage,once a day for 14 days.The pulmonary functions of rats were measured[peak expiratory flow(PEF),tidal volume(TV),expiratory volume(EV),50%expiratory flow rate(EF50)],HE staining was used to observe the morphology of lung tissue,AB-PAS staining was used to evaluate the proliferation and mucus secretion of goblet cells,the expressions of epidermal growth factor receptor(EGFR),protein kinase C(PKC),nuclear factor-κB(NF-κB)p65 and MUC5AC in lung tissue were detected by immunofluorescence staining,the mRNA expressions of EGFR and MUC5AC in lung tissue were detected by fluorescent quantitative PCR,and the content of MUC5AC in lung tissue was detected by ELISA.Results Compared with the blank group,PEF,TV,EV and EF50 of the model group rats significantly decreased(P<0.01);the bronchial wall was significantly thickened,the lumen narrowed,pulmonary interstitial edema and hyperemia,the thickness of alveolar wall increased,accompanied by a large number of inflammatory cells infiltration,and the lung tissue injury score increased significantly(P<0.01);goblet cells proliferated significantly,mucus secretion increased significantly(P<0.01);the protein expressions of EGFR,PKC,NF-κB p65,MUC5AC and mRNA expressions of EGFR and MUC5AC in lung tissue increased significantly(P<0.01),and the content of MUC5AC in lung tissue increased significantly(P<0.01).Compared with the model group,PEF,TV,EV and EF50 in dexamethasone group and Yifei Jianpi Prescription each dosage groups increased in varying degrees;the pathological injury of lung tissue was alleviated to varying degrees,the score of lung tissue injury was reduced;the proliferation of goblet cells was reduced,and the secretion of mucus was reduced,the expressions of EGFR,PKC,NF-κB p65,MUC5AC protein and EGFR,MUC5AC mRNA in lung tissue decreased,and the content of MUC5AC in lung tissue decreased.There was statistical significance in dexamethasone group and Yifei Jianpi Prescription high-and medium-dosage groups(P<0.01).Conclusion Yifei Jianpi Prescription can inhibit the hypersecretion of airway mucus and the high expression of EGFR/PKC/NF-κB pathway protein in rats with ALI induced by LPS.

Objective:To evaluate the efficacy and safety of the CLAE (cladribine + cytarabine + etoposide) regimen in refractory/relapsed T cell acute lymphoblastic leukemia/lymphoma (R/R T-ALL/LBL) .Methods:Patients with R/R T-ALL/LBL received the CLAE regimen in a prospective, multicenter, single-arm clinical study or compassionate use. From March 2019 to August 2024, data from 25 patients (18 in the study across five centers and 7 receiving compassionate treatment in Peking University Third Hospital) were collected. Outcomes included objective response rate, complete response (CR) rate, partial response (PR) rate after 1–2 cycles, bridging to allo-HSCT, progression-free survival (PFS), overall survival (OS), and treatment-related adverse effects.Results:Median age was 29 years (range, 13–63) ; 17 were male. Among the 24 evaluable patients, CR rate was 33.3% overall and 41.2% among enrolled patients. Median OS and PFS time were 199 (46–1 310) and 49 (28–1 310) days, respectively. Cumulative OS rate at 6 months, 1 year, and 2 years was (52.1±10.2) %, (29.7±9.3) %, and (27.1±9.1) %, respectively; cumulative PFS rate was (32.6±9.6) %, (24.9±8.9) %, and (23.8±8.7) %, respectively. Among patients achieving CR or PR (8 cases), median OS and PFS were not reached. Cumulative OS rate at 6 months, 1 year, and 2 years was (86.8±12.0) %, (78.3±14.6) %, and (72.9±15.7) %, respectively, and the cumulative PFS rate was (86.4±12.1) %, (74.8±15.3) %, and (72.9±15.7) %, respectively. Adverse events were mainly hematologic; no treatment-related mortality occurred. Seven patients achieving CR were bridged to allo-HSCT, with 5 remaining in continuous remission.Conclusion:The CLAE regimen is safe and effective for R/R T-ALL/LBL, facilitating CR as a bridge to allo-HSCT and potentially improving patient prognosis.