Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Glioma is the most common primary malignant tumor of the central nervous system in adults. Despite the standard treatment of surgery combined with radiotherapy and chemotherapy, the prognosis for high-grade glioma patients remains poor, highlighting the urgent need to further explore its pathogenesis and develop new therapeutic strategies. This article reviews the research progress in the field of glioma in China in 2024, covering tumorigenesis mechanisms, tumor immune microenvironment composition, advances in imaging techniques and novel imaging agents, improvements in surgical approaches, mechanisms of radio- and chemoresistance, and explorations of new therapeutic modalities. These studies provide a solid theoretical foundation for advancing clinical diagnosis and treatment of gliomas and may offer new opportunities to improve patient outcomes.

OBJECTIVE To establish a comprehensive evaluation system for lipid-lowering drugs aligned with the clinical reality of Liaoning province， and to assess the commonly used lipid-lowering drugs in medical institutions within Liaoning province. METHODS A comprehensive evaluation system for lipid-lowering drugs of Liaoning province was established using literature analysis and the Delphi expert consultation method. A calculation method of “indicator weighted score” to “step-by-step aggregation” to “percentile standardization” was employed to enable horizontal comparison of 49 commonly used lipid-lowering drugs. RESULTS This study successfully established a comprehensive clinical evaluation system for lipid-lowering drugs of Liaoning province， comprising 7 first-level indicators， 35 second-level indicators， and 116 scoring criteria. Among the first-level indicators， effectiveness （23%） had the highest weight， followed sequentially by safety （22%）， innovativeness （15%）， economy （13%）， suitability （13%）， accessibility （10%）， and other attributes （4%）. Among the 49 evaluated lipid-lowering drugs， the top 10 in overall score were all statins， with rosuvastatin calcium tablet B having the highest total score of 79.22. Inclisiran sodium injection had a total score of 57.14， performed outstandingly in safety （16.27） and innovativeness （11.27）. CONCLUSIONS This study established a relatively comprehensive and detailed clinical evaluation system for lipid-lowering drugs of Liaoning province. Statins remain the cornerstone of lipid management. Most patients can primarily choose drugs like rosuvastatin tablet B， while PCSK9 inhibitors and fixed-dose combinations can be considered for patients with conventional treatment failure or statin intolerance.

OBJECTIVE To mine the adverse drug event （ADE） signals of selinexor， and to provide reference for its clinical safety medication. METHODS ADE data for selinexor reported from July 3rd， 2019 to March 31st， 2023 were collected from the FDA adverse event reporting system （FAERS）. Data mining was performed by using the reporting odds ratio （ROR） and proportional reporting ratio （PRR） methods， and categorization statistics were performed by using the system organ class （SOC） and preferred term （PT） from drug ADE terminology set in the MedDRA （version 26.0）. RESULTS A total of 3 084 ADE reports were obtained for selinexor， with a total of 134 ADE-positive signals. Among the reported genders， there were 127 males and 124 females， with a predominant age of ≥65 years old （4.12%）； the United States had the highest number of reports （96.53%）， with consumers being the main reporters （77.27%）； severe ADR was mainly characterized by hospitalization/prolonged hospitalization （26.26%）， followed by death （17.15%）. The top 3 ADE in the list of frequency were nausea （1 162 times）， fatigue （790 times） and anorexia （610 times）， all of which were mentioned in the selinexor’s instructions. The top 3 signals in the list of strength were device-associated bacteremia （ROR＝115.07， PRR＝114.94）， blepharospasm dysfunction （ROR＝106.70， PRR＝106.54）， and salmonella sepsis （ROR＝99.90， PRR＝99.81）， all of which were not mentioned in the selinexor’s instructions. CONCLUSIONS In addition to the ADE of nausea mentioned in the instruction manual， attention should also paid to device-associated bacteremia， blepharospasm dysfunction， salmonella sepsis， and other ADE not mentioned in the instruction manual when using selinexor in clinical practice； weekly rechecking of the patient’s blood routine should be done to monitor the patient’s blood indexes， symptoms of infection， and so on， to ensure that the safety of 1661962346@qq.com drug use.

Objective:To study the clinical efficacy of digital design combined with three-dimensional (3D) printing model minimally invasive extraction of complex impacted mandibular third molars.Methods:Eight patients who visited the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology from April 2023 to March 2024 were included, including 3 males and 5 females, aged from 27 to 57 years old. The impacted mandibular third molars of all patients were closely related to the mandibular canal, and part of the dental tissue entered the mandibular canal. Preoperative digital design was used to simulate the intraoperative tooth segmentation and bone removal operation of the power system and the segmented tooth dislocation path, and analyze the tooth extraction resistance. The mandibular teeth, mandibular canal and mandibular model were three-dimensionally printed using light-curing resin inkjet. During the operation, an endoscope was used combined with the 3D printed model to minimally invasively extract the impacted mandibular third molar. Quantitative sensory testing of the patient′s lower lip skin on the operated side was performed before surgery, 2 days after surgery, and 7 days after surgery. Clinical data such as operation time were collected. A paired sample t test was performed on the 2 and 7 days postoperative data and the preoperative data to compare the data differences.Results:All 8 patients successfully completed preoperative design, model printing and minimally invasive surgery. The number of teeth segmented in the preoperative design was (4.4±1.3), and the number of teeth segmented in the actual operation was (4.0±1.1). The operation time was (33.3±13.0) min. None of the patients had postoperative numbness of the lower lip or other postoperative complication. It was observed endoscopically that the inferior alveolar neurovascular bundle was exposed in the extraction socket during the operation. The patient′s pressure pain threshold 2 days after surgery (0.601±1.170) was significantly lower than before surgery (1.251±1.109) ( t=2.83, P=0.025). Conclusions:For complicated impacted mandibular third molars, digital design combined with 3D printing model can be used to perform minimally invasive extraction with the assistance of an endoscope.

Objective:To investigate the effect of subacute exposure of Di(2-ethylhexyl)phthalate(DEHP)on endometrial decidualization and early pregnancy miscarriage in mice.Methods:CD1 mice were orally administrated with 300(low-dose group),1000(medium-dose group),or 3000 mg·kg-1·d-1 DEHP(1/10 LD50,high-dose group)for 28 days,respectively.An early natural pregnancy model and an artificially induced decidualization model were established.The uterine tissues were collected on D7 of natural pregnancy and D8 of artificially induced decidualization,respectively.The effects of a subacute exposure to DEHP on the decidualization of mice were detected by HE staining,Masson staining,TUNEL assay,and Western blotting.A model of spontaneous abortion was constructed in mice after subacute exposure to 300 mg·kg-1·d-1 DEHP,and the effect of impaired decidualization on pregnancy was investigated by observing the pregnancy outcome on the 10th day of gestation.Results:Compared with the control group,the conception rate was significantly decreased in the high-dose DEHP subacute exposure group(P＜0.05).HE staining showed that,compared with the control group,the decidual stromal cells in the low-and medium-dose exposure groups were disorganized,the nuclei of the cells were irregular,the cytoplasmic staining was uneven,and the number of polymorphonuclear cells was significantly reduced.Masson staining showed that compared with the control group,the collagen fibers in the decidua region of the DEHP low-dose group and the medium-dose group were more distributed,more abundant and more disorderly.TUNEL assay showed increased apoptosis in the decidua area compared to the control group.Western blotting showed that the expression of BMP2,a marker molecule for endometrial decidualization,was significantly reduced(P＜0.05 or P＜0.01).The abortion rate and embryo resorption rate were increased,and the number of embryos,uterine wet weight,uterine area and placenta wet weight were decreased in DEHP low-dose group compared to the control group stimulated by mifepristone,an abortifacient drug(P＜0.05 or P＜0.01).Conclusion:Subacute exposure to DEHP leads to impaired endometrial decidualization during early pregnancy and exacerbates the risk of adverse pregnancy outcomes in mice.

Objective:To prospectively observe the changes of tumor-related symptoms in patients with nasopharyngeal carcinoma following the administration of nimotuzumab one week before radiotherapy.Methods:Non-metastatic nasopharyngeal carcinoma patients with positive epidermal growth factor receptor (EGFR) expression and symptoms caused by the primary lesion or metastatic cervical lymph nodes admitted to Cancer Hospital of Chinese Academy of Medical Sciences were prospectively recruited. Investigators recorded tumor-related symptoms in recruited patients one day before the first administration of nimotuzumab (D0) and conducted follow-up visits from day 2 to day 7 after the first administration (D2-D7) to document symptom changes. All recruited patients were asked to assess tumor-related symptoms on D0 and D7 by visual analogue scale (VAS) scores. VAS scores were analyzed by paired t-test. Results:From June 2020 to April 2023, a total of 21 patients met the inclusion criteria. The median age was 49 years (range: 27-69 years), with a male-to-female ratio of 1.3:1. Among the patients, 17 patients (81%) received concurrent nimotuzumab for 8 cycles, 7 cycles for 3 cases (14%), and 6 cycles for 1 case (5%), respectively. All patients completed symptom assessments as required. The overall response rate of symptoms after the first administration of nimotuzumab was 62%, with response rates of 4/6、5/8、4/10、4/10、4/11、3/11 for tinnitus, headache, aural fullness, secondary pain caused by neck mass, nasal bleeding, and nasal obstruction, respectively. The VAS scores for overall symptoms were significantly decreased after the administration of nimotuzumab one week before radiotherapy ( P<0.001), with the most significant decrease in VAS scores for tinnitus, aural fullness, and headache. Conclusion:The administration of nimotuzumab one week before radiotherapy significantly alleviates tumor-related symptoms in patients with nasopharyngeal carcinoma, particularly in alleviating tinnitus, aural fullness, and headache.

Objective·To investigate the current situation and distribution characteristics of chronic comorbidities,and to provide reference for further improving the self-management of comorbidities and implementing the whole course and all-round management of comorbidity.Methods·Two thousand and forty-five inpatients in the Department of Geriatrics,Renji Hospital,Shanghai Jiao Tong University School of Medicine were enrolled in this study from December 2020 to February 2023.The general vital signs,routine laboratory examination and disease status were collected.The epidemiological distribution characteristics of chronic diseases and comorbidities were analyzed.Results·The incidence of chronic diseases in the surveyed population was 99.6％,and the incidence of comorbidities was 94.2％.The top 5 chronic diseases were hypertension(43.68％),diabetes mellitus(24.81％),malignant tumor(21.48％),hyperlipidemia(18.38％)and coronary heart disease(11.99％).The detection rates of hypertension,diabetes mellitus,coronary heart disease,chronic obstructive pulmonary disease,stoke and chronic kidney disease in males were significantly higher than those in females(P＜0.05).The proportion of patients with 5 chronic diseases was the highest(11.99％),followed by 7 chronic diseases(10.26％)and 6 chronic diseases(10.04％).Among the patients of different ages,the comorbidity rate was the highest in the patients aged 50-59 years(27.78％).In different age groups,patients aged 50 to 59 with 2 chronic diseases had the highest incidence of comorbidity,which was as high as 40.82％.Although the overall proportion of comorbidities among male patients(95.37％)was higher than that among females(93.77％),there was no statistically significant difference(P=0.125).However,the proportions of male patients with 2 and 5 chronic diseases were 70.41％and 60.63％,respectively,which were significantly higher than those of female patients(29.59％and 39.37％).The correlations between coronary heart disease and diabetes mellitus,hypertension and coronary heart disease,hypertension and diabetes mellitus were higher(r=0.24,r=0.27,r=0.35,all P＜0.05).Conclusion·The prevalence of chronic diseases and comorbidities is high in the middle-aged and elderly population,and the number of comorbidities increases significantly with the increase of age.

Objective:To investigate the changes of mortality，causes of death，and cause-specific mortality rate（CMR）of hospitalized neonates in NICU of the First Affiliated Hospital of Sun Yat-sen University.Method:A retrospective study was performed to compare the mortality，cause of death，and CMR of hospitalized neonates in period Ⅰ（2005-2009），period Ⅱ（2010-2014）and period Ⅲ（2015-2020）.Result:The overall mortality of hospitalized neonates in NICU of our hospital was 0.51%（104/20 493）through 2005 to 2020. The mortality in period Ⅰ，Ⅱ and Ⅲ were 0.61%（48/7 855），0.43%（27/6 209），and 0.45%（29/6 429），respectively. Compared with period Ⅰ，the mortality of preterm infants decreased significantly in period Ⅱ（3.14% vs 1.24%， χ2=14.076， P<0.01）and in period Ⅲ（3.14% vs 0.90%， χ2=25.157， P<0.01）. Eighty-five（81.7%）neonates were premature，and ninety-one（89.2%）neonates had definite abnormal perinatal factors. The CMR of hospitalized neonates related to pulmonary hemorrhage，congenital anomalies，and NRDS were 1.22‰（25/20 493），0.93‰（19/20 493），and 0.59‰（12/20 493），respectively. The CMR of other causes were sepsis 0.44‰（9/20 493），extremely premature 0.34‰（7/20 493），and perinatal asphyxia 0.24‰（5/20 493），respectively. Compared with period Ⅰ，specific mortality of NRDS in period Ⅱ（1.27‰ vs 0.16‰， χ2=5.487， P=0.016）and period Ⅲ（1.27‰ vs 0.16‰， χ2=5.738， P=0.014）significantly decreased. The leading causes of neonatal death in period Ⅰ，period Ⅱ，and period Ⅲ were NRDS，pulmonary hemorrhage，and congenital anomalies，respectively.And 71.2%（74/104）of neonatal deaths occurred within 7 days after birth. Conclusion:The mortality of preterm infants and specific mortality of NRDS in NICU have significantly decreased over the past 16 years.Congenital anomalies and infections remain important causes of death，and further efforts are needed to improve perinatal care.