Objective To study the factors influencing the blood concentration of caspofungin(CPFG),construct a prediction model,and validate the predictive effect of the model,so as to provide reference for the individualised dosing of patients with fungal infections in haematology.Methods Seventy-five patients admitted to the Department of Haematology,General Hospital of Tianjin Medical University,who were treated with CPFG for antifungal therapy during the period of March 2021 to June 2022 were selected as the study subjects,and CPFG blood concentration monitoring was carried out to explore the influencing factors of CPFG blood concentration and to construct a prediction model accordingly.Hosmer-Lemeshow(H-L)was used to test the goodness-of-fit of the model,and another 30 patients were selected as the verification group,and the predictive effect of the model was verified by the receiver's operating characteristics(ROC)curve.Results The mean blood concentrations of the patients at 0.5,9 and 24 h were(12.54±4.38),(6.80±2.76),(4.13±2.16)μg·mL-1,and the mean AUC0-24h were(152.05±57.60)μg·mL-1·h.AUC0-24h was lower than the reference value(98 μg·mL-1·h)in two patients.The results of correlation analysis showed that gender showed a correlation with 0.5 h blood concentration(P＜0.05),and there was no correlation with the rest of the two time points blood concentration and AUC0-24h(P＞0.05).Body weight and albumin(Alb)concentration showed correlation with 0.5,9,24 h blood drug concentration and AUC0-24 h(P＜0.05),and the rest of the indicators showed no correlation with blood drug concentration and AUC0_24h at each time point(P＞0.05).The results of multifactorial analysis showed that the factors influencing the patients'0.5 h blood concentration were gender,Alb concentration and body weight,and the factors influencing the 9 and 24 h blood concentration and AUC0-24h were Alb concentration and body weight(P＜0.05).Correlation analysis showed that the daily dose was positively correlated with the plasma concentration of CPFG at 0.5,9 and 24 h and AUC0-24h(P＜0.05).The results of multivariate analysis showed that the daily dose was also one of the influencing factors of the plasma concentration of CPFG(P＜0.05).ROC curve shows that the model has good prediction ability.Conclusion Body weight and Alb are significantly associated with CPFG blood concentrations and area under the drug-time curve,which can be used as a basis for preventive risk avoidance.

Objective: To investigate the distribution of blood pressure and analyze the associated factors of blood pressure of the elderly with type 2 diabetes in Jiangsu Province. Methods: The elderly over 60 years old participants with type 2 diabetes in the communities of Huai'an City and Changshu City, Jiangsu Province were selected in this study. They were divided into two groups: taking antihypertensive drugs and not taking antihypertensive drugs. The demographic characteristics, such as age and sex, and relevant factors were collected by questionnaire. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by physical examination. The percentile of SBP and DBP in each age group of men and women were described. The kernel density estimation curve was used to show the blood pressure distribution. The trend of blood pressure with age was fitted by locally weighted regression. The logistic regression model was used to analyze relevant factors of blood pressure. Results: A total of 12 949 participants were included in this study, including 7 775 patients in the antihypertensive drug group and 5 174 patients in the group without antihypertensive drugs. The SBP of participants was concentrated at 140-160 mmHg, and their DBP was concentrated at 75-85 mmHg. There were significant differences in the distribution of blood pressure among the subgroups of body mass index (BMI) and rural areas whether taking antihypertensive drugs and not. For participants aged under 80 years old, the SBP showed an increasing trend with age and the DBP showed a decreasing trend with age. Age, BMI ≥24 kg/m², fasting blood glucose ≥7.0 mmol/L, living in rural areas and no smoking were influencing factors of the elevated SBP; BMI ≥24 kg/m², male, living in rural areas, no smoking, drinking alcohol and not receiving drug hypoglycemic treatment were influencing factors of the elevated DBP. Conclusion: The SBP of older diabetic adults in Jiangsu Province is at a high level, and the distribution of blood pressure is significantly different between men and women in taking antihypertensive drugs group. The SBP presents a rising trend and the DBP is decreasing at the age of 60-80 years. The blood pressure level of this population are mainly affected by age, BMI, urban and rural areas, smoking.
Adult ; Aged ; Humans ; Male ; Female ; Middle Aged ; Aged, 80 and over ; Blood Pressure/physiology* ; Diabetes Mellitus, Type 2/epidemiology* ; Antihypertensive Agents/therapeutic use* ; Smoking ; Body Mass Index ; Hypertension/epidemiology*

Objective: To establish reference values for carotid intima-media thickness (CIMT) of adult dwellers in Shenzhen City. Methods: The study was conducted based on the Shenzhen heart failure epidemiological survey from 2021 to 2022. In this survey, residents aged 18 years and above in Shenzhen were selected by using a multi-stage stratified random sampling method. General information, cardiovascular disease (CVD) related behavior and carotid ultrasound examination and etc. were collected from the participants. People with CVD factors, a history of atherosclerotic cardiovascular disease, carotid plaque or having no carotid ultrasound examination results were excluded. The parameter regression model based on fractional polynomial was used to establish the reference values of CIMT by age and sex. Results: A total of 2 163 healthy individuals were enrolled in the final analysis, including 576 males (26.6%) and 1 587 females (73.4%). The fractional polynomial regression of the CIMT mean and standard deviation was obtained. For men, the regression was mean_CIMT=0.324 7+0.006 9×age and SD_CIMT=0.076 9+0.001 2×age. For women, the regression was mean_CIMT=0.354 9+0.005 4×age and SD_CIMT=0.041 6+0.002 0×age. Conclusion: The age and sex reference values for CIMT of adult people in Shenzhen established in this study could provide the latest reference standards for early screening of subclinical CVD.
Male ; Humans ; Adult ; Female ; Carotid Intima-Media Thickness ; Cardiovascular Diseases ; Reference Values ; Carotid Arteries/diagnostic imaging* ; Ultrasonography, Carotid Arteries ; Risk Factors ; Carotid Artery Diseases

OBJECTIVE: To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients. METHODS: Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH). RESULTS: Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression. CONCLUSION There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.
Chromosome Aberrations ; Humans ; In Situ Hybridization, Fluorescence ; Multiple Myeloma/genetics* ; Mutation

Purpose: This study aimed to identify prognostic factors for patients with distant lymph node-involved gastric cancer (GC) using a machine learning algorithm, a method that offers considerable advantages and new prospects for high-dimensional biomedical data exploration. Materials and Methods: This study employed 79 features of clinical pathology, laboratory tests, and therapeutic details from 289 GC patients whose distant lymphadenopathy was presented as the first episode of recurrence or metastasis. Outcomes were measured as anycause death events and survival months after distant lymph node metastasis. A prediction model was built based on possible outcome predictors using a random survival forest algorithm and confirmed by 5×5 nested cross-validation. The effects of single variables were interpreted using partial dependence plots. A contour plot was used to visually represent survival prediction based on 2 predictive features. Results: The median survival time of patients with GC with distant nodal metastasis was 9.2 months. The optimal model incorporated the prealbumin level and the prothrombin time (PT), and yielded a prediction error of 0.353. The inclusion of other variables resulted in poorer model performance. Patients with higher serum prealbumin levels or shorter PTs had a significantly better prognosis. The predicted one-year survival rate was stratified and illustrated as a contour plot based on the combined effect the prealbumin level and the PT. Conclusions Machine learning is useful for identifying the important determinants of cancer survival using high-dimensional datasets. The prealbumin level and the PT on distant lymph node metastasis are the 2 most crucial factors in predicting the subsequent survival time of advanced GC.Trial Registration: ChiCTR Identifier: ChiCTR1800019978

Purpose: While several prognostic models for the stratification of death risk have been developed for patients with advanced gastric cancer receiving first-line chemotherapy, they have seldom been tested in the Chinese population. This study investigated the performance of these models and identified the optimal tools for Chinese patients. Materials and Methods: Patients diagnosed with metastatic or recurrent gastric adenocarcinoma who received first-line chemotherapy were eligible for inclusion in the validation cohort. Their clinical data and survival outcomes were retrieved and documented. Time-dependent receiver operating characteristic (ROC) and calibration curves were used to evaluate the predictive ability of the models. Kaplan-Meier curves were plotted for patients in different risk groups divided by 7 published stratification tools. Log-rank tests with pairwise comparisons were used to compare survival differences. Results: The analysis included a total of 346 patients with metastatic or recurrent disease.The median overall survival time was 11.9 months. The patients were different into different risk groups according to the prognostic stratification models, which showed variability in distinguishing mortality risk in these patients. The model proposed by Kim et al. showed relative higher predicting abilities compared to the other models, with the highest χ 2 (25.8) value in log-rank tests across subgroups, and areas under the curve values at 6, 12, and 24 months of 0.65 (95% confidence interval [CI]: 0.59–0.72), 0.60 (0.54–0.65), and 0.63 (0.56–0.69), respectively. Conclusions Among existing prognostic tools, the models constructed by Kim et al., which incorporated performance status score, neutrophil-to-lymphocyte ratio, alkaline phosphatase, albumin, and tumor differentiation, were more effective in stratifying Chinese patients with gastric cancer receiving first-line chemotherapy.

OBJECTIVETo investigate the antitumor effect of lycorine on renal cell carcinoma ACHN cells and explore the possible mechanism.

METHODSWe used flow cytometry to examine the effect of lycorine on ACHN cell cycle and apoptosis. The cell proliferation, migration and invasion were assessed with MTS assay, wound healing assay, and Transwell assay, respectively. Colony forming assay was performed, and the mRNA and protein levels of Bax, Bcl-2, survivin, caspase-3, cyclin D1 and CDK4 were measured with qRT-PCR and Western blotting.

RESULTSLycorine obviously inhibited the proliferation of ACHN cells with an IC(50) of 24.34 µmol/L. Lycorine also induced apoptosis of ACHN cells, caused cell cycle arrest at G(0)/G(1) phase, and suppressed the colony forming ability of the cells in a dose-dependent manner. The migration and invasion of ACHN cells were significantly inhibited by 5 µmol/L lycorine. Lycorine up-regulated the mRNA levels of CDK4, Bax, caspase-3 while down-regulated the levels of survivin, Bcl-2 and Cyclin D1; the protein levels of CDK4 and Bax were increased and cyclin D1, Bcl-2 and surviving expressions were decreased, but caspase-3 expression showed no significant changes following the treatment.

CONCLUSIONLycorine has obvious antitumor effect against ACHN cells, suggesting its value as a new therapeutic agent for renal cell carcinoma.

Amaryllidaceae Alkaloids ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; Carcinoma, Renal Cell ; pathology ; Caspase 3 ; metabolism ; Cell Cycle Checkpoints ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase 4 ; metabolism ; Humans ; Inhibitor of Apoptosis Proteins ; metabolism ; Phenanthridines ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; bcl-2-Associated X Protein ; metabolism

Bovine aortic endothelial cells (BAECs) were cultured with high glucose (33 mmol/L), 4 mg/L green tea polyphenols (GTPs) or 4 mg/L GTPs co-treatment with high glucose for 24 h in the presence or absence of Bafilomycin-A1 (BAF). We observed that high glucose increased the accumulation of LC3-II. Treatment with BAF did not further increase the accumulation of LC3-II. Results also showed an increased level of p62 and decreased Beclin-1. However, GTPs showed inversed trends of those proteins. Furthermore, GTPs co-treatment with high glucose decreased the level of LC3-II and a much higher accumulation of LC3-II was observed in the presence of BAF in comparison with high glucose alone. Results also showed a decreased p62 and increased Beclin-1. The results demonstrated that GTPs alleviated autophagy inhibition induced by high glucose, which may be involved in the endothelial protective effects of green tea against hyperglycemia.
Animals ; Autophagy ; drug effects ; Cattle ; Cells, Cultured ; Endothelial Cells ; drug effects ; metabolism ; Gene Expression Regulation ; drug effects ; Glucose ; toxicity ; Macrolides ; pharmacology ; Polyphenols ; chemistry ; pharmacology ; Tea ; chemistry

BACKGROUND:Dysphagia is one of common early complications after anterior cervical fusion. Medium and severe dysphagia often causes serious influence on the patients. A variety of factors have been shown to have a correlation with the postoperative dysphagia, but specific mechanism is stil unclear. OBJECTIVE:To explore the risk factors for dysphagia after single-level anterior cervical fusion. METHODS:From January 2011 to June 2013, data of 44 patients with dysphagia and 213 patients without dysphagia after single-level anterior cervical fusion were compared. The baseline data (age, gender, ethnicity, body mass index, smoking history, drinking history, hypertension, diabetes, course length, and type of cervical spondylosis) and perioperative data (intraoperative blood loss, internal fixation, the location of the operated level, operation time, and the side of operation approach) between two groups were compared by Logistic regression analysis to determine risk factors for postoperative dysphagia.RESULTS AND CONCLUSION:A total of 257 patients were included with a fol ow-up for 6 to 24 months postoperatively and 44 of them suffered from dysphagia after single-level anterior cervical fusion. The overal prevalence for postoperative dysphagia was 17.1%. Univariate analysis indicated that age, gender, the location of the operated level, and course length were associated with postoperative dysphagia. Logistic regression analysis of multivariate analysis demonstrated that independent predictors for postoperative dysphagia included gender (female), age (>60 years), the location of the operated level (C 4-5 , C 5-6 ), and course length (>12 months). Clinicians should give appropriate recognition and take corresponding measures to avoid it.

OBJECTIVETo investigate the clinical safety and effectiveness of percutaneous embolization in treating the late failed renal allograft in patients with graft intolerance syndrome (GIS).

METHODSTranscatheter embolization of renal graft artery was performed in 18 patients with late graft dysfunction and GIS. The subsequent complications, postoperative symptom remission rate, and prognosis were assessed.

RESULTSGIS was relieved in 15 patients (83.3%), of which 6 patients (33.3%) had severer fever and pain in the area of renal graft after embolization, which lasted for a mean of 3.5 days (range: 2-5 days). GIS persisted for more than 2 weeks in 3 patients (16.7%), who ultimately underwent surgical removal of grafts. No severe embolism-associated complications were noted.

CONCLUSIONPercutaneous embolization can effectively avoid surgical graft removal in patients with late renal allograft failure, and therefore can be used as a safe and effective treatment for the late failed renal allograft combined with GIS.

Adult ; Aged ; Embolization, Therapeutic ; Female ; Graft Rejection ; complications ; therapy ; Humans ; Kidney Transplantation ; Male ; Middle Aged ; Postoperative Complications ; therapy ; Renal Insufficiency ; complications ; therapy ; Transplantation, Homologous ; Treatment Outcome ; Young Adult