OBJECTIVE To evaluate the therapeutic effects and safety of everolimus combined with letrozole and conventional chemotherapy for metastatic or recurrent endometrial carcinoma （EC）. METHODS The clinical and follow-up data of 156 patients with metastatic or recurrent EC admitted to Nanyang Central Hospital from January 2020 to January 2024 were analyzed retrospectively. They were divided into a control group （77 cases） and an observation group （79 cases） according to different therapeutic regimens. The control group received paclitaxel+carboplatin/cisplatin regimen， and concurrently took Letrozole tablets at a dose of 2.5 mg orally once daily； the observation group took Everolimus tablets 10 mg orally， once a day， in addition to the treatment regimen given to the control group. Each treatment cycle lasted 21 days， and both groups of patients underwent continuous treatment for 6 to 8 cycles. The short-term efficacy indicators （objective response rate and disease control rate）， the levels of serum tumor markers [carbohydrate antigen 125， human epididymis protein 4， vascular endothelial growth factor and matrix metalloproteinase-9] and medium- to long-term efficacy indicators [progression-free survival （PFS） and overall survival （OS）] were compared between the two groups. Additionally， the occurrence of toxic and side effects in both groups of patients was recorded. RESULTS The objective response rate （53.16%）， disease control rate （89.87%）， median PFS （6.47 months） and median OS （10.79 months） of the observation group were significantly higher or longer than those （22.08%， 68.83%， 4.63 months， 8.84 months） of the control group （P＜0.05）. Compared with before treatment， the levels of serum tumor markers in both groups decreased significantly after 6 cycles of treatment； the above indexes of the observation group were significantly lower than those of the control group （P＜0.05）. The proportion of patients with stomatitis in the observation group was significantly higher than that of the control group （P＜0.05）， and there was no statistically significant difference in the proportions of patients experiencing other toxic and side effects， such as leukopenia， between the two groups （P＞0.05）. CONCLUSIONS The everolimus combined with letrozole and conventional chemotherapy can effectively improve the short-term efficacy and prolong the survival period in patients with metastatic or recurrent EC， but attention should be paid to the occurrence of toxic and side effects， especially stomatitis.

This article reports a case of a male patient with anti-N-methyl-D-aspartate receptor （NMDAR） encephalitis comorbid with early-onset Alzheimer's disease （AD）. The patient presented with depression， hallucinations and delusions syndrome， and cognitive impairment， and was admitted to a psychiatric hospital. Through multidisciplinary consultation， the diagnosis was confirmed based on positive biological and pathological biomarkers. The patient's symptoms improved after receiving a therapeutic regimen comprising high-dose glucocorticoid therapy and psychiatric-related treatments. Based on relevant current research findings domestically and internationally， this article reviews the pathogenesis and clinical manifestations of early-onset AD and anti-NMDAR encephalitis， in order to enhance the discrimination ability of psychiatric specialists for such patients and improve the diagnosis and treatment level. ［Funded by Medical Research Project of Chengdu City （number， 2024403）］

OBJECTIVE: Observational studies have shown inconsistent associations of loneliness or social isolation (SI) with ischemic heart disease (IHD), with unknown mediators. METHODS: Using data from genome-wide association studies of predominantly European ancestry, we performed a bidirectional two-sample Mendelian Randomization (MR) study to estimate causal effects of loneliness ( N = 487,647) and SI traits on IHD ( N = 184,305). SI traits included whether individuals lived alone, participated in various types of social activities, and how often they had contact with friends or family ( N = 459,830 to 461,369). A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators, including metabolic, behavioral and psychological factors. RESULTS: Loneliness increased IHD risk ( OR= 2.129; 95% confidence interval [ CI]: 1.380 to 3.285), mediated by body fat percentage, waist-hip ratio, total cholesterol, and low-density lipoprotein cholesterol. For SI traits, only fewer social activities increased IHD risk ( OR= 1.815; 95% CI: 1.189 to 2.772), mediated by hypertension, high-density lipoprotein cholesterol, triglycerides, fasting insulin, and smoking cessation. No reverse causality of IHD with loneliness and SI was found. CONCLUSION These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD, with several mediators as prioritized targets for intervention.
Loneliness/psychology* ; Humans ; Mendelian Randomization Analysis ; Social Isolation ; Myocardial Ischemia/etiology* ; Male ; Female ; Middle Aged ; Genome-Wide Association Study ; Risk Factors ; Aged

Acute ischemic stroke (AIS) is a comprehensive syndrome characterized by neurological dysfunction, resulting from cerebral tissue ischemia and hypoxia due to impaired blood supply, which further leads to tissue softening or even necrosis. Restoring blood flow through recanalization of the occluded vessel is crucial for AIS treatment. Although more and more patients benefit from intravenous thrombolysis or endovascular therapy, some still have poor prognosis after vessel recanalization. Most studies indicate that ineffective recanalization, early neurological deterioration, and hemorrhagic transformation are the three main causes of adverse prognosis after recanalization therapy for AIS. This article systematically reviews the epidemiological characteristics, pathogenesis, and risk factors of the above three aspects based on previous studies, aiming to provide guidance for the diagnosis and treatment of adverse prognosis in AIS patients after recanalization therapy.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

AIM To evaluate the quality of Rubi Fructus.METHODS UPLC-Q-TOF-MS/MS was adopted in the component identification,after which the HPLC fingerprints were established,cluster analysis,principal component analysis and orthogonal partial least squares discriminant analysis were used for chemical pattern recognition.and the contents of chlorogenic acid,ferulic acid,ellagic acid,isoquercitrin,kaempferol-3-O-rutinoside,astragalin,tiliroside quercetin,kaempferol were determined.RESULTS Total 34 constituents were identified.There were 19 common peaks in the fingerprints for 31 batches of medicinal materials with the similarities of more than 0.8.Wild varieties and cultivated varieties,and medicinal materials from different producing areas could be distinguished;4 principal components demonstrated the accumulative variance contribution rate of 84.142％;8 differential components were screened,2 of which were ellagic acid and astragalin.Ellagic acid and astragalin displayed higher contents in the wild varieties than those in the cultivated varieties(P＜0.05,P＜0.01).CONCLUSION UPLC-Q-TOF-MS/MS,HPLC fingerprints combined with content determination can be used for the quality control of Rubi Fructus.

Objective To investigate the expression of NOP2/Sun RNA methyltransferase family member 2(NSUN2)and protein arginine methyltransferase 5(PRMT5)in retinoblastoma(Rb)tissue and their correlation with the survival prognosis of Rb patients.Methods From February 2019 to February 2021,84 patients with Rb(Rb group)were selected from Beijing Anzhen Hospital Affiliated to Capital Medical University Nanchong Hospital,and 50 normal retinal tissues were used as control group.Real-time fluorescence quantitative PCR(qRT-PCR)was used to detect the levels of NSUN2 mRNA and PRMT5 mRNA in retinal tissues.Kaplan-Meier curve was used to analyze the effect of NSUN2 mRNA and PRMT5 mRNA on the prognosis of Rb patients.COX regression analysis was used to analyze the factors affecting the prognosis of Rb.Results The expression of NSUN2 mRNA(3.11±0.42)and PRMT5 mRNA(2.84±0.39)in Rb cancer tissues were higher than that in the control group(0.80±0.23,0.76±0.20),and the differences were statistically significant(t=35.935,35.033,all P<0.001).The expression of NSUN2 mRNA and PRMT5 mRNA in Rb cancer tissues with tumor diameter≥20mm,undifferentiated and ⅡRC stage D～E were higher than that in tumor diameter<20mm,differentiated tissues and ⅡRC stage A～C cancer tissues,and the differences were statistically significant(t=18.297,141.770,16.693;18.663,139.144,39.947,均P<0.001).The 3-year progression-free survival rate in the high expression group of NSUN2 mRNA was lower than that in the low expression group(60.00%vs 88.64%).The 3-year progression-free survival rate in the high expression group of PRMT5 mRNA was lower than that in the low expression group(56.10%vs 93.02%)(Log rank χ2=13.440,19.501,all P<0.001).Undifferentiated type,ⅡRC stage D-E stage,NSUN2 mRNA high,PRMT5 mRNA high were risk factors affecting the prognosis of Rb patients(Waldχ2=5.923～7.161,all P<0.001).Conclusion The expression of NSUN2 mRNA and PRMT5 mRNA in Rb tissues is increased,which is related to the maximum diameter of tumor,pathological classification and ⅡRC stage,and can be used as a tumor marker to evaluate the survival prognosis of Rb.

OBJECTIVE: To explore the role of the natural compound hesperidin in glycolysis, the key ratelimiting enzyme, in colorectal cancer (CRC) cell lines. METHODS: In vitro, HCT116 and SW620 were treated with different doses of hesperidin (0-500 µmol/L), cell counting kit-8 and colone formation assays were utilized to detected inhibition effect of hesperidin on CRC cell lines. Transwell and wound healing assays were performed to detect the ability of hesperidin (0, 25, 50 and 75 µmol/L) to migrate CRC cells. To confirm the apoptotic-inducing effect of hesperidin, apoptosis and cycle assays were employed. Western blot, glucose uptake, and lactate production determination measurements were applied to determine inhibitory effects of hesperidin (0, 25 and 50 µmol/L) on glycolysis. In vivo, according to the random number table method, nude mice with successful tumor loading were randomly divided into vehicle, low-dose hesperidin (20 mg/kg) and high-dose hesperidin (60 mg/kg) groups, with 6 mice in each group. The body weights and tumor volumes of mice were recorded during 4-week treatment. The expression of key glycolysis rate-limiting enzymes was determined using Western blot, and glucose uptake and lactate production were assessed. Finally, protein interactions were probed with DirectDIA Quantitative Proteomics, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS: Hesperidin could inhibit CRC cell line growth (P<0.05 or P<0.01). Moreover, hesperidin presented an inhibitory effect on the migrating abilities of CRC cells. Hesperidin also promoted apoptosis and cell cycle alterations (P<0.05). The immunoblotting results manifested that hesperidin decreased the levels of hexokinase 2, glucose transporter protein 1 (GLUT1), GLUT3, L-lactate dehydrogenase A, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), PFKFB3, and pyruvate kinase isozymes M2 (P<0.01). It remarkably suppressed tumor xenograft growth in nude mice. GO and KEGG analyses showed that hesperidin treatment altered metabolic function. CONCLUSION Hesperidin inhibits glycolysis and is a potential therapeutic choice for CRC treatment.
Hesperidin/therapeutic use* ; Colorectal Neoplasms/metabolism* ; Glycolysis/drug effects* ; Animals ; Humans ; Apoptosis/drug effects* ; Mice, Nude ; Cell Movement/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Glucose/metabolism* ; Cell Cycle/drug effects* ; Mice, Inbred BALB C ; Mice ; HCT116 Cells ; Lactic Acid

The prevalence of rheumatoid arthritis (RA) has sharply increased in recent years, posing a serious threat to human health. RA is characterized as a chronic, multisystem disease with morning stiffness and symmetric small joint pain. However, its fundamental processes are poorly understood. With the advancements in molecular biology techniques, a growing body of research indicates that numerous non-coding RNAs (ncRNAs) are essential for the pathogenesis of RA. These ncRNAs not only contribute to the onset of RA but also play a role in the pathological processes of RA development, including synovial immune inflammation and bone destruction. Chinese medicine (single compounds, single herbs, and compound formulae, as well as non-drug therapies such as acupuncture and moxibustion), offer significant benefits for treating RA. This study examined the role of 3 different ncRNA types (circular RNA, long ncRNA, and microRNA) as biomarkers in RA diagnosis, as well as their regulatory roles in rheumatoid arthritis fibroblast-like synoviocytes functions such as inflammatory response, proliferation, cell cycle, apoptosis, and invasion. Additionally, the study explored the mechanisms by which Chinese medicine regulates these ncRNAs, with the goal of offering innovative strategies for RA treatment.
Arthritis, Rheumatoid/pathology* ; Humans ; RNA, Untranslated/metabolism* ; Medicine, Chinese Traditional ; Synoviocytes/metabolism* ; RNA, Circular ; Biomarkers/metabolism* ; Apoptosis/genetics*

OBJECTIVES: To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG). METHODS: A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed. RESULTS: Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group. CONCLUSIONS Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.
Humans ; Glioma/genetics* ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Brain Neoplasms/genetics* ; Molecular Targeted Therapy/adverse effects* ; Adolescent ; Infant ; Proto-Oncogene Proteins B-raf/genetics* ; Pyrimidinones/therapeutic use* ; Mutation