ObjectiveTo explore the morbidity rate and risk factors of proliferative diabetic retinopathy (PDR) in type 2 diabetes.MethodsThe clinical data of patients, with PDR in 2739 consecutive cases of type 2 diabetes diagnosed in this hospital from 1994 to 2001 were analyed retospectively. The diagnosis of diabetic retinopathy (DR) was confirmed by ophthalmoscopy and fundus fluorescein angiography (FFA). Blood pressure, fasting and postprandial blood sugar, glycosylated haemoglobin（HbA1c）, total serum cholesterol, triglyceride, creatinine, and albumin excretion rate were measured.ResultsThe morbidity rate of type 2 DR was 27.8%（761/2739）, and the morbidity rate of PDR was 4.2%（114/2 739） occupying 15% of the patients with DR. The duration, fasting blood sugar, glycosylated haemoglobin, blood pressure and albumin excretion rate were much higher than those in the control（P＜0.01, glycosylated haemoglobin P＜0.05）. The independent risk factors of PDR were duration of the disease （r=0.15, P＜0.01） and albumin excretion rate （r=0.08, P＜0.05）. The risk factors of PDR were albumin excretion rate and fasting blood sugar (r=0.13, P＜0.05) in patients with longer duration(≥5 years). The morbidity rate of PDR was 2.3%, 5.9% and 12.4% in patients with duration less than 5 years, 5 to 10 years and over 10 years groups, respectively. The morbidity of PDR of the patients in normal albuminuria, microalbuminuria and overt albuminuria group was 2.1%、5.3% and 18.8% respectively.ConclusionsType 2 diabetes accompanied with PDR is relative to the duration of the diabetes, albumin excretion rate, fasting blood sugar, blood pressure, and glycosylated haemoglobin, in which the duration of the disease, albuminuria and fasting blood sugar are the risk factors of occurance of PDR. (Chin J Ocul Fundus Dis, 2003,19:338-340)
Objective To detect the expression of copine 1 (CPNE1) in the gastric cancer (GC) and investigate its association with prognosis. MethodsThe clinicopathologic data of 121 patients who underwent radical gastrectomy in the Department of General Surgery, The 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army from March 2017 to December 2018 were retrospectively collected. The protein expression of CPNE1 in the GC tissues was detected by immunohistochemical (IHC) staining, and its association with prognosis was analyzed. GC tissues and adjacent tissues samples from 16 patients in the same time were prospectively collected, and the mRNA and protein expressions of CPNE1 were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Multivariate Cox proportional hazards regression model was used to analyze the prognostic factors of GC patients. ResultsIHC staining results showed that the CPNE1 was mainly expressed in the cell membrane and cytoplasm of gastric epithelial cells, and the color showed different degrees of brown. Among the 121 patients, 70 (57.9%) had high CPNE1 protein expression and 51 (42.1%) had low CPNE1 protein expression. The RT-qPCR and WB results of 16 pairs of fresh tissue specimens showed that the expression levels of CPNE1 mRNA and protein in the GC tissues were higher than those in the corresponding adjacent tissues (CPNE1 mRNA mean value: 1.451 vs. 1.100, P=0.048; CPNE1 protein mean value: 0.995 vs. 0.521, P=0.001). The multivariate Cox proportional hazards regression analysis showed that the high protein expression of CPNE1 [HR (95%CI)=1.931 (1.123, 3.321), P=0.017] was the risk factor affecting the prognosis of the patients with GC. ConclusionCPNE1 highly expresses in GC tissues and is associated with a poor prognosis in patients with GC, and it may be a potential tumor biomarker.
ObjectiveTo improve the knowledge of a rare disease named pyridoxine-dependent epilepsy.MethodsHigh-throughput sequencing and Sanger sequencing were used to validate the genes of epilepsy. Mutation gene validation was performed on two probands and their parents. Analyze clinical manifestations, electroencephalogram (EEG), imaging and prognostic features of the two probands.ResultsProbands 1, seizure onset at 4 months, progress as drug-refractory epilepsy, manifested as seizures types origin of multi-focal lesions. Head MRI and fluorodeoxyglucose-positron-based tomography (FDG-PET) were both normal. Gene detection showed that Aldehydedehydrogenase (ALDH7A1) gene has a complex heterozygous mutation contain c.1442G> and c.1046C> T.Proband 2, seizure onset at 5 months, manifested as a tonic-clonic seizure. Intermittent EEG and head MRI were both normal. Genotyping revealed ALDH7A1 gene contain a complex heterozygous mutation c.1547A> G and c.965C> T. Two cases were both seizure free by vitamin B6 therapy and gradually reduce the antiepileptic drugs.ConclusionsPyridoxine-dependent epilepsy may be late onset, some patient can be atypical and early experimental treatment can help to identify and the diagnosis should be confirmed by gene test.
ObjectiveThe re-hospitalization and death events of patients heart failure caused by coronary heart disease are characterized by non-independence, heterogeneity, and censored data. A joint frailty model is established to jointly model the events, explore the risk factors affecting the prognosis of patients, and reduce the re-hospitalization rate and mortality of patients. MethodsThe sample included 4 682 patients with heart failure caused by coronary heart disease in two tertiary hospitals from January 2014 and June 2019. The electronic medical record information of patients during hospitalization and their follow-up information were collected. The Cox model, conditional frailty model and joint frailty model were used to analyze patient re-hospitalization and death. ResultsThe joint frailty model identified patients with a higher risk of both relapse and death (θ=0.209, P<0.001). Risk factors for re-hospitalization were advanced age, grade 3 hypertension, mental work, no medical insurance, high cystatin C, low ejection fraction, and low free thyroxine-3 and thyroxine-4. Antiplatelet drugs and statins significantly reduced the risk of re-hospitalization. Risk factors for death were advanced age, New York Heart Association classification Ⅲ to Ⅳ, no medical insurance, mental work, high cystatin C level, high troponin-I level, low free thyroxine-3, and low ejection fraction. Percutaneous coronary intervention, and taking antiplatelet drugs and statins significantly reduced the risk of death. ConclusionThe joint frailty model can simultaneously model recurring and terminal events, and accurately predict them. Our results suggest that thyroid hormone levels and cystatin C levels of patients should be considered more carefully. People with mental jobs should change bad working habits to reduce adverse outcomes.
Objective To explore the role and clinical significance of cell-cycle dependent kinase 1 (CDK1) and its upstream and downstream molecules in the development of malignant peripheral nerve sheath tumor (MPNST) through the analysis of clinical tissue samples. Methods A total of 56 tumor samples from MPNST patients (“Tianjin” dataset) who underwent surgical resection, confirmed by histology and pathology between September 2011 and March 2020, along with 17 normal tissue samples, were selected as the research subjects. MPNST-related hub genes were identified through transcriptome sequencing, bioinformatics analysis, immunohistochemistry staining, and survival analysis, and their expression levels and prognostic associations were analyzed. Results Transcriptome sequencing and bioinformatics analysis revealed that upregulated genes in MPNST were predominantly enriched in cell cycle-related pathways, with CDK1 occupying a central position among all differentially expressed genes. Further differential analysis demonstrated that CDK1 mRNA expression in sarcoma tissues was significantly higher than in normal tissues [based on searching the cancer genome atlas (TCGA) dataset, P<0.05]. In MPNST tissues, CDK1 mRNA expression was not only significantly higher than in normal tissues (based on Tianjin, GSE141438 datasets, P<0.05), but also significantly higher than in neurofibromatosis (NF) and plexiform neurofibromas (PNF) (based on GSE66743 and GSE145064 datasets, P<0.05). Immunohistochemical staining results indicated that the expression rate of CDK1 protein in MPNST tissues was 40.31%. Survival analysis results demonstrated that CDK1 expression was associated with poor prognosis. The survival time of MPNST patients with high CDK1 mRNA expression was significantly lower than that of the low expression group (P<0.05), and the overall survival trend of patients with positive CDK1 protein expression was worse than that of patients with negative CDK1 expression. Additionally, differential analysis of CDK family genes (CDK1-8) revealed that only CDK1 was significantly upregulated in MPNST, NF, and PNF. Conclusion Increased expression of CDK1 is associated with poor prognosis in MPNST patients. Compared to other CDK family members, CDK1 exhibits a unique expression pattern, suggesting its potential as a therapeutic target for MPNST.
Objective To investigate the role and mechanism of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) in the activation of aortic valve interstitial cells (AVICs) in aortic stenosis. Methods Isolating primary AVICs and stimulating their activation with transforming growth factor β1 (TGF-β1, 30 ng/mL), the expression of PGC-1α was detected. The activation of AVICs induced by TGF-β1 was observed after overexpression of PGC-1α by adenovirus or inhibition of PGC-1α function by GW9662. The possible downstream molecular mechanism of PGC-1α in AVICs activation was screened. Finally, the phenotype was further verified in primary human AVICs. Results The expression of PGC-1α decreased after the activation of AVICs induced by TGF-β1 (control group: 1.00±0.18; 24 h: 0.31±0.10; 48 h: 0.32±0.06; 72 h: 0.20±0.07; P<0.05). Specific overexpression of PGC-1α by adenovirus inhibited the activation of AVICs induced by TGF-β1 stimulation (periostin: 3.17±0.64 vs. 1.45±0.54, P<0.05; α-smooth muscle actin: 0.77±0.11 vs. 0.28±0.06, P<0.05). On the contrary, inhibition of PGC-1α function by GW9662 promoted the activation of AVICs (periostin: 2.20±0.68 vs. 7.99±2.50, P<0.05). Subsequently, it was found that PGC-1α might inhibit the activation of AVICs through downregulating the expression of calcium/calmodulin-dependent protein kinase (CAMK1δ) (0.97±0.04 vs. 0.74±0.11, P<0.05), and downregulating the expression of CAMK1δ alleviated the activation of AVICs (periostin: 1.76±0.11 vs. 0.99±0.20, P<0.05). The possible mechanism was that the activation of mammalian target of rapamycin (mTOR) signaling pathway was inhibited by reducing the accumulation of reactive oxygen species (ROS) (778.3±139.4 vs. 159.3±43.2, P<0.05). Finally, the protective effect of PGC-1α overexpression was verified in the activated phenotype of human AVICs (periostin: 2.73±0.53 vs. 1.63±0.14, P<0.05; connective tissue growth factor: 1.27±0.04 vs. 0.48±0.09, P<0.05). Conclusions The expression of PGC-1α significantly decreases during the activation of AVICs induced by TGF-β1. The overexpression of PGC-1α significantly inhibites the activation of AVICs, suggesting that PGC-1α plays a protective role in the activation of AVICs. The possible mechanism is that PGC-1α can inhibit the activation of CAMK1δ-ROS-mTOR pathway. In conclusion, interventions based on PGC-1α expression levels are new potential therapeutic targets for aortic stenosis.
ObjectiveTo explore therapeutic mechanisms and clinical application prospects of novel weight-loss medications in patients with obesity complicated by cardiovascular-kidney-metabolic (CKM) syndrome, aiming to provide theoretical support and therapeutic strategies for personalized precision management of CKM syndrome. MethodsRecent domestic and international studies were retrospectively reviewed, focusing on the mechanisms of action, clinical research outcomes, and application progress of novel weight-loss medications, including glucagon-like peptide 1 (GLP-1) receptor agonists, dual glucose-dependent insulinotropic peptide (GIP)/GLP-1 receptor agonists, triple GIP/GLP-1/glucagon receptor agonists, and amylin analogues. Special emphasis was placed on their comprehensive effects on cardiovascular, renal, and metabolic parameters. ResultsNovel weight-loss medications had demonstrated significant weight reduction and multisystem benefits through precise regulation of central appetite pathways, insulin sensitivity, and lipid metabolism. Among these medications, GLP-1 receptor agonists (e.g., semaglutide) and dual agonists (e.g., tirzepatide) had been confirmed in phase Ⅲ clinical trials (STEP and SURMOUNT studies) to effectively reduce cardiovascular event risks, slow renal function deterioration, and markedly improve glycemic control in obese patients with CKM syndrome. Triple agonists (e.g., retatrutide) and combination therapies (e.g., cagrisema) have further enhanced weight-loss efficacy, providing novel therapeutic avenues for obesity-related diseases. Additionally, these medications usually require combined application with traditional chronic disease medications, such as sodium-glucose linked transporter 2 inhibitors and renin-angiotensin-aldosterone system blockers, to achieve comprehensive therapeutic outcomes in CKM syndrome patients. However, further studies are needed to address long-term safety in real-world settings, optimization of drug formulations, and application in precision medicine. ConclusionsNovel weight-loss medications offer promising strategies for personalized precision treatment of obesity with CKM syndrome due to their significant weight-loss efficacy and multisystem synergistic effects. Although current clinical trials demonstrate substantial therapeutic potential, the complexity of CKM syndrome and individual patient variability necessitate additional in-depth research to facilitate broader clinical adoption and optimization of these medications.
ObjectiveTo analyze the expression and clinical significance of cyclin-dependent kinase 1 (CDK1) in lung adenocarcinoma by bioinformatics.MethodsBased on the gene expression data of lung adenocarcinoma patients in The Cancer Genome Atlas (TCGA), the differential expression of CDK1 in lung adenocarcinoma tissues and normal lung tissues was analyzed. The expression of CDK1 gene in lung adenocarcinoma was analyzed by UALCAN at different angles. Survival analysis of different levels of CDK1 gene expression in lung adenocarcinoma was performed using Kaplan-Meier Plotter. Correlation Cox analysis of CDK1 expression and overall survival was based on clinical data of lung adenocarcinoma in TCGA. Gene set enrichment analysis was performed on gene sequences related to CDK1 expression in clinical cases. The protein interaction network of CDK1 from Homo sapiens was obtained by STRING. CDK1-related gene proteins were obtained and analyzed by the web server Gene Expression Profiling Interactive Analysis (GEPIA).ResultsBased on the analysis of TCGA gene expression data, CDK1 expression in lung adenocarcinoma was higher than that in normal lung tissues. UALCAN analysis showed that high CDK1 expression may be associated with smoking. Survival analysis indicated that when CDK1 gene was highly expressed, patients with lung adenocarcinoma had a poor prognosis. Univariate and multivariate Cox regression analysis of CDK1 expression and overall survival showed that high CDK1 expression was an independent risk factor for survival of patients with lung adenocarcinoma. Gene set enrichment analysis revealed that high CDK1 expression was closely related to DNA replication, cell cycle, cancer pathway and p53 signaling pathway.ConclusionCDK1 may be a potential molecular marker for prognosis of lung adenocarcinoma. In addition, CDK1 regulation may play an important role in DNA replication, cell cycle, cancer pathway and p53 signaling pathway in lung adenocarcinoma.
The temperature dependence of relative permittivity and conductivity of ex-vivo pig liver, lung and heart at 2 450 MHz was studied. The relative permittivity and conductivity of three kinds of biological tissues were measured by the open-end coaxial line method. The dielectric model was fitted according to the principle of least square method. The results showed that the relative permittivity and conductivity of pig liver, pig lung and pig heart decreased with the increase of tissue temperature from 20 to 80 ℃. The relative permittivity and conductivity models of pig liver, pig lung and pig heart were established to reflect the law of dielectric properties of biological tissue changing with temperature and provide a reference for the parameters setting of thermal ablation temperature field.
Objective To observe the influence of the transforming growth factor β1(TGF-β1) on the denervated mouse musclederived stem cells（MDSCs） producing the connective tissue growth factor（CTGF）at different time points in vitro. Methods MDSCs from the primarycultureof the denervated mouse skeletal muscle were isolated and purified by the preplate technique, and they were identified before the culture and after the culturein vitro with TGF-β1 (10 ng/ml) for 24 hours. Then, MDSCs were randomlydivided into 6 groups (Groups A, B, C, D, E and F) according to the different time points, and were cultured in vitro with TGF-β1 (10 ng/ml) for 0, 3, 6, 12, 24 and 48 hours, respectively. The levels of CTGF mRNA in MDSCs were measured by the real time RT-PCR and the expression of CTGF protein was detected by the CTGF Western blot. Results The immunohistochemistry revealed that before the adding of TGF-β1, MDSCs highly expressed Sca-1, with a positivityrate of 96%; however, after the adding of TGF-β1, the positive expression of Sca-1 decreased greatly, with a negativity rate gt;99%. The Western blot test showed that the ratios of CTGF to the average absorbance of βactin in Groups A-F were 0.788±0.123, 1.063±0.143, 2.154±0.153, 2.997±0.136, 3.796±0.153 and 3.802±0.175, respectively. In Groups AD，the absorbance increased gradually, with a significant difference between the abovementioned groups (Plt;0.05). However, in Groups D-F, there was no significant difference between the groups as the promotive tendency became less significant (P＞0.05). The RT-PCR test showed that the △Ct values in GroupsA-F were 1.659±0.215, 1.897±0.134, 2.188±0.259, 2.814±0.263,2.903±0.125 and 3.101±0.186, respectively. In Groups A-D, the increase in the △Ct value was gradual, but the differences were significant between the groups (Plt;0.05). But in Groups E and F, the promotive tendency became less significant（Pgt;0.05）. Conclusion TGF-β1 can promote the production of CTGF inthe mouse MDSCs cultured in vitro and the time-dependent relation exists for 3-12 hours.