Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

Objective To analyze the epidemiological burden of glaucoma in China based on data from the Global Burden of Disease 2019(GBD 2019)database to provide a theoretical basis for the prevention and control of glaucoma in China.Methods Analysis of the glaucoma epidemic trend and age,period,and gender trends in China from 1990 to 2019 and the correlation between glaucoma and the Socio-Demographic Index(SDI)were conducted according to relevant data on the number of patients,prevalence,disability-adjusted life years(DALYs)and DALY rates downloaded from the GBD 2019 database.Results In 2019,China was ranked globally first for the number of people with glaucoma and second for DALYs due to glaucoma.In 2019,China's glaucoma prevalence was among the highest globally,with the number of pa-tients being 1.92 times that of 1990.Both the prevalence and the DALY rate demonstrated a persistent upward trajectory.The demographic distribution of patients with glaucoma in China revealed a curve which peaked among middle-aged individ-uals,with higher prevalence observed in males than females.An inverse correlation was identified between SDI and the age-standardized prevalence and DALY rates,which exhibited a negative average annual percentage change,indicative of a pro-gressive decline with rising SDI.Conclusion From 1990 to 2019,China experienced a significant increase in the burden of glaucoma,ranking among the highest globally,with a positive correlation observed between the disease burden and the level of social development.

Objective:To investigate the prognostic value and related factors of heart-type fatty acid binding protein (H-FABP) in patients with heart failure.Methods:A total of 877 consecutive patients who were admitted to heart failure care unit of Fuwai hospital and diagnosed as heart failure from July 2015 to July 2017 were enrolled in this study. Baseline serum H-FABP concentration was measured by fluorescence lateral flow immunoassay. According to serum H-FABP levels, patients were divided into three groups: low H-FABP group (H-FABP≤4.04 ng/ml, n=292), middle H-FABP group (H-FABP 4.04-7.02 ng/ml, n=292) and high H-FABP group (H-FABP≥7.02 ng/ml, n=293). The general clinical characteristics were collected and compared among the three groups. According to whether heart failure was caused by coronary artery disease or not, patients with heart failure were divided into ischemic heart failure and non-ischemic heart failure. Multivariate linear regression analysis was performed to explore the independent risk factors of H-FABP. The primary endpoint events were the composite of all-cause death or heart transplantation. Multivariate Cox regression analyses, receiver operating characteristic (ROC) curves, risk prediction tests with multivariate Cox regression model and Kaplan-Meier analyses were conducted to investigate the relationship between H-FABP and the prognosis of heart failure. Results:Multivariate linear regression analysis showed that age, coronary artery disease, alanine aminotransferase, uric acid and N-terminal pro-B type natriuretic peptide (NT-proBNP) were positively associated with H-FABP (β=0.012, 0.238, 0.001, 0.345 and 0.063 respectively,all P<0.05), while female, hemoglobin, albumin, sodium, and estimated glomerular filtration rate (eGFR) were negatively associated with H-FABP (β=-0.184, -0.006, -0.016, -0.034 and -0.006 respectively, all P<0.05). One hundred and nineteen patients (13.6%) lost to follow-up, and 246 patients (32.5%) suffered from all-cause death or heart transplantation during the median follow-up duration of 931 (412-1 185) days. Multivariate Cox regression analysis showed that baseline H-FABP (log 2H-FABP) level was the independent predictor of all-cause death or heart transplantation in patients with heart failure ( HR=1.39, P<0.001). ROC curves showed that baseline H-FABP was a predictor of all-cause death or heart transplantation in patients with heart failure within 3 months, 1 year and 2 years (areas under the curves were 0.69, 0.69 and 0.71 respectively), and the best cut-off values were 5.85 ng/ml, 6.54 ng/ml and 6.54 ng/ml respectively. Risk prediction test with multivariate Cox regression model showed that baseline H-FABP could provide additional prognostic value in predicting all-cause death or heart transplantation for patients with heart failure on top of basic model and baseline NT-proBNP ( P<0.001). Taking 6.54 ng/ml and trisected levels of H-FABP as cut-off values respectively, Kaplan-Meier analyses showed that the survival rates were significantly different among the two or three groups ( P<0.001). Subgroup analyses showed that baseline H-FABP (log 2H-FABP) level was an independent predictor of all-cause death or heart transplantation in patients with ischemic heart failure ( HR=1.74, P<0.001), as well as in patients with non-ischemic heart failure ( HR=1.28, P=0.027). Conclusions:Age, sex, coronary artery disease, hemoglobin, albumin, alanine aminotransferase, sodium, eGFR, uric acid and NT-proBNP are associated with H-FABP level. Baseline H-FABP level is an independent predictor of all-cause death or heart transplantation in patients with heart failure. On top of basic model and baseline NT-proBNP, baseline H-FABP could provide additional prognostic value in predicting adverse events for patients with heart failure.

Long non-coding RNA (lncRNA) is a class of transcripts longer than 200 nucleotides, which do not have the function of coding proteins.Widely involved in the progress of various human diseases, lncRNA has become a new research hotspot and the regulatory role of it has been paid more and more attention.Studies in recent years found that lncRNA is abnormally expressed in age-related macular degeneration (AMD) and age-related cataract (ARC) compared with healthy individuals.LncRNA ZNF503-AS1, BANCR and MEG3 can play important roles in regulating function of retinal pigment epithelial cell, which can lead to the development of AMD.LncRNA MIAT, TUG1 and H19 can have important regulatory effects through competitive binding with microRNAs, thus affecting the occurrence and development of ARC.This article reviewed the research progress of lncRNA in the AMD and ARC related field, revealed the role of different lncRNAs in the diseases, provided a new perspective for elucidating the mechanism of the diseases and found a new biomarker for the diagnosis and treatment of the diseases.

Obesity has become one of the most serious issues threatening the health of humankind, and we conducted this study to examine whether and how celastrol protects against obesity.

We fed male Sprague-Dawley rats a high-fat diet and administered celastrol to obese rats for 3 weeks. By recording body weight (BW) and other measures, we identified the effective dose of celastrol for obesity treatment. Feces were collected to perform 16S rRNA sequencing, and hypothalami were extracted for transcriptome sequencing. We then treated leptin knockout rats with celastrol and explored the changes in energy metabolism. Male Institute of Cancer Research (ICR) mice were used to test the acute toxicity of celastrol.

We observed that celastrol reduced BW and promoted energy expenditure at a dose of 500 µg/kg BW but that food intake was not changed after administration. The diversity of the gut microbiota was improved, with an increased ratio of Bacteroidetes to Firmicutes, and the gut microbiota played an important role in the anti-obesity effects of celastrol. Hypothalamic transcriptome analysis showed a significant enrichment of the leptin signaling pathway, and we found that celastrol significantly enhanced energy expenditure, which was mediated by the leptin signaling pathway. Acute lethal toxicity of celastrol was not observed at doses ranging from 0 to 62.5 mg/kg BW.

Our study revealed that celastrol decreased the BW of obese rats by enhancing energy expenditure but not by suppressing food intake and that this effect was mediated by the improvement of the gut microbiota and the activation of the hypothalamic leptin signaling pathway.

Objective To explore the characteristics of trunk muscle activity in persons with Parkinson's disease (PD) in search of better treatments for abnormal posture.Methods Ninety persons with PD of different severity and 8 normal controls were studied using surface electromyography (sEMG).A sixteen-lead sEMG instrument was used to collect sEMG amplitudes from the bilateral thoracic erector spinae,lumbar erector spinae,external oblique and rectus abdominis muscles when the subjects were lying,standing and walking.Results Compared with the control group,a significant increase was observed in the sEMG amplitude of the lumbar erector spinal muscle [(18.56±14.57) μV] and rectus abdominis muscles [(24.00±18.80)μV] of the PD group when lying.Significant relative increases in (P＜0.05),of the external oblique muscles were observed [(27.87± 11.49)μV] when standing (P＜0.05),and in the thoracic erector spinae muscle [(58.74±29.69)μV] and external oblique muscles [(59.01± 25.20) μV] increased when walking (P＜0.05).Compared with the control group,the sEMG activity of the external oblique muscles was significantly elevated in PD patients at Hoehn and Yahr stage 1 to 1.5 when walking.One or more of the trunk muscle groups showed significantly greater activity in the PD patients in Hoehn and Yahr stage 2 or 3 in all three positions.Conclusions The sEMG activities of the extensor and flexor muscles increase simultaneously in PD patients.More trunk muscles are involved in PD patients with higher H-Y grades.These findings provide a neurophysiological basis for the customizaton of rehabilitation therapy for patients with Parkinson's disease and for the precise selection of muscles for botulinum toxin injection.

OBJECTIVETo investigate the prognostic factors of colorectal cancer patients with liver metastasis in order to provide reference for clinical practice.

METHODSClinicopathological and follow-up data of 264 cases of colorectal liver metastasis in our department from January 1997 to January 2012 were analyzed retrospectively. Among these 264 patients, 217 underwent primary colorectal cancer resection, 33 underwent combined resection of primary colorectal lesion plus liver metastasis, and 14 received stoma creation alone. Besides, 197 patients received adjuvant chemotherapy, 14 received adjuvant radiotherapy, and 42 underwent interventional treatment. Clinicopathological features and treatment scheme affecting prognosis were analyzed and prognostic stratification analysis was performed according to emergence time of liver metastasis (synchronous or metachronous).

RESULTSOf 264 patients, 1-, 3-, and 5-year overall survival rates were 77.0%, 31.7%, and 14.0%; median survival time was 25 months; 1-, 3-, and 5-year survival rates of synchronous colorectal liver metastasis were 68.8%, 22.3%, and 7.7%; 1-, 3-, and 5-year survival rates of metochronous colorectal liver metastasis were 95.8%, 49.0%, and 21.3%, whose difference was statistically significant (P<0.05). Multivariate analysis showed that primary tumor differentiation, CEA level, adjuvant chemotherapy, and radical resection were independent prognostic factors of colorectal cancer patients with liver metastasis (all P<0.05), while primary tumor differentiation, CEA level, and radical resection were independent prognostic factors of synchronous liver metastasis (all P<0.05), and primary tumor location and CEA level were independent prognostic factors of metachronous liver metastasis (all P<0.05).

CONCLUSIONSRadical operation and adjuvant chemotherapy should be emphasized for colorectal liver metastasis, especially for synchronous colorectal liver metastasis. Simple resection of primary tumor can not improve the overall survival of patients with colorectal liver metastasis.

Chemotherapy, Adjuvant ; Colorectal Neoplasms ; pathology ; Hepatectomy ; Humans ; Liver Neoplasms ; diagnosis ; secondary ; therapy ; Multivariate Analysis ; Prognosis ; Retrospective Studies ; Survival Rate

Objective To investigate the prognostic factors of colorectal cancer patients with liver metastasis in order to provide reference for clinical practice. Methods Clinicopathological and follow-up data of 264 cases of colorectal liver metastasis in our department from January 1997 to January 2012 were analyzed retrospectively. Among these 264 patients , 217 underwent primary colorectal cancer resection, 33 underwent combined resection of primary colorectal lesion plus liver metastasis, and 14 received stoma creation alone. Besides, 197 patients received adjuvant chemotherapy, 14 received adjuvant radiotherapy, and 42 underwent interventional treatment. Clinicopathological features and treatment scheme affecting prognosis were analyzed and prognostic stratification analysis was performed according to emergence time of liver metastasis (synchronous or metachronous). Results Of 264 patients, 1-, 3-, and 5-year overall survival rates were 77.0%, 31.7%, and 14.0%; median survival time was 25 months; 1-, 3-, and 5-year survival rates of synchronous colorectal liver metastasis were 68.8%, 22.3%, and 7.7%; 1-, 3-, and 5-year survival rates of metochronous colorectal liver metastasis were 95.8%, 49.0%, and 21.3%, whose difference was statistically significant (P<0.05). Multivariate analysis showed that primary tumor differentiation, CEA level, adjuvant chemotherapy, and radical resection were independent prognostic factors of colorectal cancer patients with liver metastasis (all P<0.05), while primary tumor differentiation, CEA level, and radical resection were independent prognostic factors of synchronous liver metastasis (all P<0.05), and primary tumor location and CEA level were independent prognostic factors of metachronous liver metastasis (all P<0.05). Conclusions Radical operation and adjuvant chemotherapy should be emphasized for colorectal liver metastasis, especially for synchronous colorectal liver metastasis. Simple resection of primary tumor can not improve the overall survival of patients with colorectal liver metastasis.

Objective To investigate the prognostic factors of colorectal cancer patients with liver metastasis in order to provide reference for clinical practice. Methods Clinicopathological and follow-up data of 264 cases of colorectal liver metastasis in our department from January 1997 to January 2012 were analyzed retrospectively. Among these 264 patients , 217 underwent primary colorectal cancer resection, 33 underwent combined resection of primary colorectal lesion plus liver metastasis, and 14 received stoma creation alone. Besides, 197 patients received adjuvant chemotherapy, 14 received adjuvant radiotherapy, and 42 underwent interventional treatment. Clinicopathological features and treatment scheme affecting prognosis were analyzed and prognostic stratification analysis was performed according to emergence time of liver metastasis (synchronous or metachronous). Results Of 264 patients, 1-, 3-, and 5-year overall survival rates were 77.0%, 31.7%, and 14.0%; median survival time was 25 months; 1-, 3-, and 5-year survival rates of synchronous colorectal liver metastasis were 68.8%, 22.3%, and 7.7%; 1-, 3-, and 5-year survival rates of metochronous colorectal liver metastasis were 95.8%, 49.0%, and 21.3%, whose difference was statistically significant (P<0.05). Multivariate analysis showed that primary tumor differentiation, CEA level, adjuvant chemotherapy, and radical resection were independent prognostic factors of colorectal cancer patients with liver metastasis (all P<0.05), while primary tumor differentiation, CEA level, and radical resection were independent prognostic factors of synchronous liver metastasis (all P<0.05), and primary tumor location and CEA level were independent prognostic factors of metachronous liver metastasis (all P<0.05). Conclusions Radical operation and adjuvant chemotherapy should be emphasized for colorectal liver metastasis, especially for synchronous colorectal liver metastasis. Simple resection of primary tumor can not improve the overall survival of patients with colorectal liver metastasis.

This article was aimed to study medication rules of traditional Chinese medicine (TCM) in the treatment of gastric cancer. The history information of 111 hospitalized cases from 2008 to 2011 was collected from the Department of Oncology of Guang'anmen Hospital with the clinical collection system. The medication rules in the treatment of gastric cancer by TCM were explored by the scale-free network analysis from several aspects, such as effects, classifications and compatibility relations of Chinese medicine. The analysis result of 111 gastric cancer cases showed that strengthening the body resistance was the main treatment principle. Liujunzi decoction was the most frequently used prescription. In TCM compatibility, deficiency-nourishing herbs were the main ingredients, especiallyqi-supplementing herbs which take the first place in the prescription. And the heat-reducing herbs, dampness-eliminating herbs, blood-activating and stasis-eliminating herbs, food stagnation resolving herbs and qi regulation herbs were also used in the combination. Core herbs in the prescription for the treatment of gastric cancer were Tuckahoe, Codonopsis pilosula, Astragalus root, Pericarpium Citri Reticulatae, Fructus Aurantii, Nidus Vespae and etc. TCM treatment, syndrome differentiation and medication are varied according to different therapeutic stages and disease stages. The result showed that scale-free network analysis had certain significance in the understanding of medication rules of TCM treatment of gastric cancer.