Objective To study the effects of dibutyl phthalate(DBP) on estradiol biosynthesis and the related mechanism in puberty female rats.Methods Thirty-two female SD rats aged 21 days were randomly divided into the control group(corn oil) and low-dose(250 mg/kg),moderate-dose(500 mg/kg),and high-dose(1 000 mg/kg) DBP exposed groups,the rats were treated with DBP through gavage with a dose of 5 ml/kg,once a day for 8 consecutive weeks.After 8 weeks of exposure,the animals were sacrificed at proestrus.Radioimmunoassay was used to detect estradiol in the serum,the expression of aromatase mRNA levels was detected by real-time fluorescent quantitative RT-PCR.Results Compared with the control group,the body weight of rats in the moderate-dose group was significantly higher(P

Objective To compare the distribution of KCNJ11 polymorphisms between elderly Chinese population with and without hypertension. Methods We examined the mutation of KCNJ11 gene by directly sequencing. Data for the present study were obtained from 250 hypertensive subjects (60 to 83 years old) as well as 250 normotensive subjects (60 to 86 years old). Results We found nine different mutations in KCNJ11, including six novel mutations (I131M, L147I, L147V, L147L, Q235H, G245C). None of the novel mutations were found in the normotensive subjects, and all the residues were conserved in other species. These sequence variants in Chinese population indicate the diversity of the human library and the complexity of hypertension. Conclusions The consistent finding of our present study provided a basis for the development of new strategies to diagnosis and treat hypertension in the elderly.

Objective To determine the relationship between serum soluble Klotho (sKL) level and adverse outcome in maintenance hemodialysis (MHD) patients.Methods One hundred and twenty nine cases of MHD patients were collected prospectively.Serum sKL was detected by ELISA.Abdomen lateral plain was used as a criterion to determine the abdominal aortic calcification.The abdominal aortic calcification score (AAC) was calculated.Cox regression analysis was used to determine the risk factor of cardiovascular death (CVD) in MHD patients.Kaplan-Meier showed the relationship between sKL and CVD in MHD patients.Results There were 27 cases (20.9％) of allcause death and 19 cases (14.7％) of cardiovascular death.The median sKL was 612.6(379.2-816.6) nig/L,and log[iPTH] was an independent factor of sKL concentration.Low sKL had high AAC and CVD death rate.Kaplan-Meier method showed that the all-cause death rate was similar between two groups,and CVD death rate increased significantly in low sKL patients (P=0.036).Cox regression indicated that lower sKL level was associated with high CVD death rate [OR=0.352,95％CI(0.127-0.977),P=0.045].After adjustment for the general condition,biochemical indicators,the relationship still existed [OR=0.331,95％ CI (0.117-0.933),P=0.037].In no or mild vascular calcification patients (AAC ≤4),compared with high sKL patients,low sKL patients had no significant difference rate in all-cause mortality.The CVD mortality was significantly higher in high sKL (P=0.035) compared with low sKL.In severe calcification group (AAC ＞ 4),all-cause death and CVD death rates were similar between different sKL groups (P=0.991 and 0.522,respectively).Conclusions Lower sKL has the high CVD death rate and sKL level decreasing is an independent risk factor for CVD death in MHD patients.The lower sKL concentration in MHD patients with no or mild calcification may predict CVD mortality.This study suggests that sKL levels may be helpful in predicting the outcome of patients with MHD.

Objective To investigate the relationship between serum phosphorus variability and mortality in maintenance hemodialysis (MHD) patients. Methods A total of 502 MHD cases from Renji hospital hemodialysis center were registered in Shanghai Registry Network from January 2007 to April 2015. They were recruited with general information, laboratory results and outcomes. According to their median of coefficient of variation (CV) of blood phosphorus, the patients were divided into high variation group (CV≥0.226 mmol/L) and low variation group (CV<0.226 mmol/L). The relationship of serum phosphorus CV with all?cause mortality and cardiovascular disease mortality was assessed respectively. Results The average age was (63.9±14.6) years, the median dialysis age was 82.0 (43.0, 139.0) months, 118 patients (23.5%) died for all cause and 64 patients (12.7%) died for cardiovascular disease. Compared with patients in low phosphorus variation group, patients had a higher all?cause mortality in high phosphorus variation group (27.7% vs 19.3%, P=0.028). Higher cardiovascular disease mortality was observed in high variation group as well, but this difference was no statistical significant (15.4% vs 10.0%, P=0.082). COX regression analysis showed that >60 years of age (HR=2.762, 95%CI 1.707?4.468, P<0.001), low hemoglobin (HR=0.466, 95%CI 0.317?0.686, P<0.001), low albumin (HR=0.555, 95%CI 0.366?0.840, P=0.005), high CV of phosphorus (HR=1.479, 95%CI 1.023 ? 2.139, P=0.037) were independent risk factors for all ? cause mortality. Moreover, >60 years of age (HR=2.666, 95%CI 1.469?4.837, P=0.001), low hemoglobin (HR=0.480, 95%CI 0.238?0.801, P=0.005), and high CV of phosphorus (HR=1.655, 95%CI 1.003?2.729, P=0.049) were independent risk factors for cardiovascular disease mortality. There was no significant statistical difference between patients phosphorus on target and patients phosphorus below target in all?cause disease mortality (P=0.065) and cardiovascular disease mortality (P=0.425). High variation group whose phosphorus on target had higher all?cause mortality and cardiovascular disease mortality than those in low variation group (29.2% vs 16.9%, P=0.047; 15.0% vs 6.0%, P=0.033). Kaplan?Meier method showed that patients with high phosphorus variation had higher all?cause (P=0.023) and cardiovascular disease mortality (P=0.047) than patients with low phosphorus variation. Conclusions The high CV of phosphorus is independently correlated with all?cause and cardiovascular disease mortality. Patients with standard ? reaching phosphorus in the low variation group have a lower mortality. A serum phosphorus level sustainably reaching the standard may improve the survival in MHD patients.

Objective:To explore the pain points of outpatient service in hospital from the patient′s perspective, and to provide new ideas for optimizing management of service quality.Methods:Ten top hospitals in China were selected to collect the poor evaluation texts of outpatient services published by patients on the Dianping.com from January 1, 2017 to December 31, 2019. The user′ pain-point analysis model was introduced, the pain-point index word collection was constructed according to the word frequency, the pain-point index was quantitatively analyzed combined with the sentimental value, and the content of the index words was analyzed through conceptual annotation.Results:The analysis of 1 259 poor evaluation texts showed that patients′ poor evaluation of outpatient service quality mainly focused on four aspects: interpersonal interaction, process factors, human-computer interaction and environmental factors. The poor attitude of medical staff in interpersonal interaction and the long queuing time and short treatment time in process factors were the most prominent.Conclusions:Online patient comment analysis is suitable for the identification and perception of pain points in outpatient service, and is helpful for the hospital to choose the direction and items of service improvement.

Objective To explore the association of fibroblast growth factor-23 (FGF23) with abdominal aortic calcification(AAC) and adverse outcomes in maintenance hemodialysis patients.Methods One hundred and fourteen cases of MHD patients were collected prospectively.Serum intact FGF23 was detected by ELISA.Abdomen lateral plain was used as a criteria to determine the abdominal aortic calcification and the abdominal aortic calcification score was counted.Logistic regression analysis was used to determine the risk factors of AAC.Kaplan-Meier analysis was applied to compare the survival rate among different groups and COX regression analysis was used to determine the association of FGF23 and mortality in MHD patients.Results Seventy-six patients present abdominal aortic calcification.The median of AACS was 4.0(0.0,11.0).The median level of FGF23 was 7277.4(2535.0,9990.8) pg/ml.The median follow-up duration was 72.0(67.8,72.8) months.During the follow-up,22 patients (19.3％) died of all-cause death and 17 cases (14.9％) died of cardiovascular diseases.Serum FGF23 level was positively correlated with AAC (r=0.285,P=0.002).Logistic regression analysis showed that longer age (OR=1.059,95％CI:1.020-1.100,P=0.003) and dialysis vintage (OR=I.009,95％CI 1.000-1.017,P=0.039),smoking history (OR=3.010,95％CI 1.177-7.696,P=0.021) and higher FGF23 level(OR=2.831,95％CI 1.010-7.937,P=0.048) were independent risk factors of moderate to severe AAC in MHD patients.Kaplan-Meier survival curves showed that the patients with AACS≥ 5 had significantly higher all-cause mortality(P=0.028) and CVD mortality (P=0.035) than those with AACS ＜ 5.However,the Kaplan-Meier analysis showed no significant difference regarding the level of serum FGF23 with the all-cause and CVD mortality.Cox regression demonstrated that FGF23 was not associated with increased mortality risk,neither in crude nor in multivariate adjusted models.Conclusions Abdominal aortic calcification had a high prevalence in MHD patients.The all-cause and CVD mortality was higher in patients with moderate to severe AAC.FGF23 was an independent risk factor of moderate to severe AAC,but it can't yet be a predictor for the allcause and CVD mortality of MHD patients.

Antimicrobial de-escalation is defined as the discontinuation of one or more components of combination empirical therapy, and/or the change from a broad-spectrum to a narrower spectrum antimicrobial.Antimicrobial de-escalation is one of the mostly used antibiotic management strategies in intensive care units.This review discussed current situations and possible obstacles for its implementations.

The rapidly growing emergence of drug resistant bacteria has become one of the most important public health concerns.However, the development of new drugs is of more difficulties.Extended infusion or prolonged infusion of antibiotics is a significant way of antimicrobial stewardship programs, which has been proven beneficial to better pharmacokinetic/pharmacodynamic targets attainment and improved clinical outcomes.This review discussed the rationality of prolonging the infusion time of commonly used antibiotics in PICU.

Objective:To explore the interplay between tumor microenvironment (TME)-associated genes, cuproptosis, and the prognosis of liver cancer through transcriptome sequencing and functional genomics analysis.Methods:Employing a hybrid approach that integrates bioinformatics with fundamental experimental research, we utilized the TCGA database to acquireexpression profiles and clinical-pathological information from 424 liver hepatocellular carcinoma patients. We evaluated ImmuneScore and StromalScore to categorize patients into high and low groups, subsequently identifying differentially expressed genes (DEG) at the intersection of these groups. Core DEG were identified through univariate Cox regression analysis and protein-protein interaction (PPI) network analysis. The association between the expression levels of core genes and the survival time of liver cancer patients was analyzed using the R language and Kaplan-Meier analysis, and verified using the Kaplan-Meier Plotter online database. We established a cuproptosis cell model and performed RNA-seq to examine gene expression alterations during copper-induced cell death, followed by in vitro cell experiments for verification.Results:A total of 1 701 and 2 041 DEG were llinked t ImmuneScore and StromalScore, respectively, encompassing 1 134 commonly upregulated genes and 60 commonly downregulated genes. The top 30 core genes from the PPI network's dominant nodes were cross-referenced with univariate Cox regression results, leading to the identification of the pivotal immune gene CCR7. CCR7 mRNA expression levels were higher in hepatocellular carcinoma tissues than in normal tissues ( P<0.05). Patients with high expression of CCR7 in liver cancer had a longer overall survival compared to those with low expression ( P=0.003). Treatment with elesclomol-CuCl2significantly curtailed the survival of hepatocellular carcinoma cel ( P<0.001). RNA-seq data from the cuproptosis model indicated a downregulation of CCR7 expression during the onset of cuproptosis [|log 2(FC)|=2.27, P<0.001], and downregulation of CCR7 expression enhanced the sensitivity of hepatocellular carcinoma cells to cuproptosis inducers. Conclusion:The TME-related gene CCR7 is implicated in cuproptosis, and its downregulation might facilitate the process in liver cancer.CCR7 holds potential as a biomarker for liver cancer prognosis.

Claudin18.2(CLDN18.2)is a tight junction protein that is overexpressed in a variety of solid tumors such as gastrointestinal cancer and oesophageal cancer.It has been identified as a promising target and a potential biomarker to diagnose tumor,evaluate efficacy,and determine patient prognosis.TST001 is a recombinant humanized CLDN18.2 antibody that selectively binds to the extracellular loop of human Claudin18.2.In this study,we constructed a solid target radionuclide zirconium-89(89Zr)labled-TST001 to detect the expression of in the human stomach cancer BGC823CLDN18.2 cell lines.The[89Zr]Zr-des-ferrioxamine(DFO)-TST001 showed high radiochemical purity(RCP,＞99％)and specific activity(24.15±1.34 GBq/μmol),and was stable in 5％human serum albumin,and phosphate buffer saline(＞85％RCP at 96 h).The EC50 values of TST001 and DFO-TST001 were as high as 0.413±0.055 and 0.361±0.058 nM(P＞0.05),respectively.The radiotracer had a significantly higher average standard uptake values in CLDN18.2-positive tumors than in CLDN18.2-negative tumors(1.11±0.02 vs.0.49±0.03,P=0.0016)2 days post injection(p.i.).BGC823CLDN18.2 mice models showed high tumor/muscle ratios 96 h p.i.with[89Zr]Zr-DFO-TST001 was much higher than those of the other imaging groups.Immunohistochemistry results showed that BGC823CLDN18.2 tumors were highly positive(+++)for CLDN18.2,while those in the BGC823 group did not express CLDN18.2(-).The results of ex vivo biodistribution studies showed that there was a higher distribution in the BGC823CLDN18.2 tumor bearing mice(2.05±0.16％ID/g)than BGC823 mice(0.69±0.02％ID/g)and blocking group(0.72±0.02％ID/g).A dosimetry estimation study showed that the effective dose of[89Zr]Zr-DFO-TST001 was 0.0705 mSv/MBq,which is within the range of acceptable doses for nuclear medicine research.Taken together,these re-sults suggest that Good Manufacturing Practices produced by this immuno-positron emission tomog-raphy probe can detect CLDN18.2-overexpressing tumors.