ObjectiveTo explore the mechanism by which Zuoguiwan improves the pancreas development in the gestational diabetes mellitus （GDM） model by observing the effects of Zuoguiwan on the expression of key regulatory factors in different stages of pancreas development. MethodsPregnant Wistar rats were randomly assigned into blank， model， insulin detemir （20 U·kg^-1） and Zuoguiwan （1.89 g·kg^-1） groups （n=18）. GDM was induced by peritoneal injection of streptozotocin on day 6.5 （E6.5d） in the embryonic stage， and the blank group was given an equal volume of sodium citrate buffer. The modeling performance was assessed by measuring the blood glucose of pregnant rats. Except the blank group and model group， pregnant rats in other groups were administrated with corresponding drugs from E9.5d to delivery. The random blood glucose of pregnant rats was monitored， and the embryos and offspring rats were measured for the length and weighed on E12.5d， E18.5d and day 21 after birth （B21d）. The Lee's index of rats on B21d was calculated. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the fasting insulin （FINS） levels of B22d rats and the Homeostasis Model Assessment for Insulin Resistance （HOMA-IR） was calculated. The serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total bilirubin （TBIL）， total cholesterol （CHO）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL）， and low-density lipoprotein cholesterol （LDL） in E18.5d pregnant rats and B22d offspring were determined. The pathological changes in the pancreas of E12.5d， E18.5d and B22d rats were observed by hematoxylin-eosin （HE） staining. Western blot was used to determine the protein levels of pancreatic duodenal homeobox 1 （Pdx1）， pancreas-specific transcription factor 1a （Ptf1a）， and sex-determining region Y-box protein 9 （Sox9） in the pancreas of E12.5d embryos， Pdx1， Nkx2 homeobox 2 （Nkx2.2）， and hairy and enhancer of split-1 （Hes1） in the pancreas of E18.5d embryos， and Pdx1， v-maf musculoaponeurotic fibrosarcoma oncogene homolog A （Mafa）， and NK transcription factor-related homeobox gene family 6 locus 1 （Nkx6.1） in the pancreas of B22d rats. ResultsCompared with the blank group， the model group showed elevated blood glucose levels in pregnant rats on B0d， E9.5d， E12.5d， E15.5d， and E18.5d （P<0.05， P<0.01）， decreased body weight and body length （P<0.01） and increased Lee's index in the offspring. In addition， the B22d offspring showed rising levels of FBG， FINS， HOMA-IR， AST， and TG （P<0.01）， a declined level of HDL （P<0.01）， and pancreatic acinous cells with edema and loose arrangement. The pregnant rats on E18.5d exhibited raised levels of ALT， AST， and TG （P<0.05， P<0.01） in the pancreas and a declined level of HDL （P<0.05）. The E12.5d embryos showed up-regulated protein levels of Pdx1， Sox9， and Ptf1a in the pancreas （P<0.01） and the E18.5d embryos exhibited down-regulated protein levels of Pdx1， Nkx2.2， and Hes1 in the pancreas （P<0.01）. The protein levels of Pdx1， Nkx6.1， and Mafa in the pancreas of B22d offspring were down-regulated （P<0.01）. Compared with the model group， the insulin group exhibited lowered blood glucose in pregnant rats on B0d， E15.5d， and E18.5d （P<0.05， P<0.01）. The offspring in all treatment groups showcased increased body weight and body length （P<0.01） and decreased Lee's index. The B22d offspring exhibited declined levels of FBG， FINS， and HOMA-IR in the insulin group （P<0.01） and lowered levels of FBG and HOMA-IR in the Zuoguiwan group （P<0.01）. The B22d offspring in all the treatment groups showed reduced levels of ALT， AST， TBIL， CHO， TG， and LDL， a raised level of HDL， and alleviated edema of pancreatic acinous cells. The pregnant rats on E18.5d demonstrated declined levels of TG and ALT （P<0.05， P<0.01） and an elevated level of HDL （P<0.05）. The pancreas of E12.5d embryos presented down-regulated protein levels of Pdx1 and Sox9 and an up-regulated protein level of Ptf1a in the insulin group （P<0.05）. The pancreas of E12.5d embryos in the Zuoguiwan group presented down-regulated protein levels of Pdx1， Sox9， and Ptf1a （P<0.01）. All the treatment groups showed up-regulated protein levels of Pdx1， Nkx2.2， and Hes1 in the pancreas of E18.5d embryos （P<0.01） and Pdx1， Nkx6.1， and Mafa in the pancreas of B22d embryos （P<0.05， P<0.01）. ConclusionZuoguiwan can promote the growth and development and ameliorate the pathological changes in the pancreas of the offspring of GDM model by regulating the expression of Pdx1 pathway-related regulatory factors in different stages of pancreas development.

Objective To construct a comprehensive cost management index system for public hospitals.Methods Literature review,policy analysis,and the Delphi expert consultation method were used to establish the index system.Data from a tertiary grade A public hospital in Beijing from 2019 to 2024 were analyzed.Results The response rate for both rounds of expert consultation was 100％,indicating high expert engagement.The average authority level of the experts was 0.905.x2 tests of Kendall's W coefficient for the importance,operability,and sensitivity of the indicators yielded P＜0.001.A comprehensive cost management system comprising 5 dimensions and 13 indicators was established.Conclusion The constructed comprehensive cost management index system for public hospitals is scientifically sound and highly reliable.It enables effective cost control,risk warning,and continuous improvement,laying a solid foundation for the comprehensive advancement of cost management efforts.

Objective:To investigate the correlation between the density and volume of left atrial-epicardial adipose tissue(LA-EAT)and the occurrence and severity of atrial fibrillation(AF)in elderly patients.Methods:This was a retrospective case-control study.A total of 197 elderly patients with AF and 82 patients with sinus rhythm who were hospitalized in the Department of Cardiology and Geriatric Cardiology of the First Affiliated Hospital of Nanjing Medical University from June 2023 to July 2024.were selected.The AF group was further divided into paroxysmal AF(PAF)subgroup(111 cases)and persistent AF(PeAF)subgroup(86 cases). The density and volume of LA-EAT in all patients were meansured by coronary artery enhanced CT or left atrial enhanced CT.The differences in LA-EAT density, volume and related data among the 3 groups were compared, and their relationship with different severity of senile AF was analyzed.Logistic regression was used to analyze whether LA-EAT density and volume were risk factors for senile AF.The predictive value of LA-EAT density and volume for AF in the elderly was compared throuh restricted cubic spline analysis.Results:The average LA-EAT density in the sinus rhythm group, PAF group and PeAF group was -82.75(-87.15, -79.63), -81.70(-85.55, -75.85)and -80.45(-83.40, -76.10)HU, respectively; the standard deviation of density was 34.70(31.93, 36.28), 36.20(34.30, 37.65)and 35.45(33.63, 37.28)HU, respectively; the LA-EAT volume was 23 483.40(13 964.10, 31 645.53), 25 112.20(18 479.10, 36 917.50)and 37 836.50(25 933.80, 45 537.90)mm 3, respectively.The LA-EAT density and volume in the PAF group and PeAF group were higher than those in the sinus rhythm group(all P<0.05). The LA-EAT volume in the PeAF group was greater than that in the PAF group( P<0.001), but there was no significant difference in LA-EAT density between the two groups( P>0.05). Multivariate logistic regression analysis showed that LA-EAT density and volume, left atrial diameter(LAD)and body mass index(BMI)were the independent risk factors for AF in the elderly( P<0.05). Conclusions:LA-EAT density and volume are significantly correlated with occurrence of senile AF, and show a positive dose-response relationship.LA-EAT volume is significantly related to the severity of AF( P<0.05), while the density is not significantly related to it( P>0.05).

Objective:To design and synthesize a 18F-labeled small molecule PET imaging probe targeting carbonic anhydrase Ⅸ (CAⅨ), named as 18F-single-acetazolamide (SAZ), and to evaluate its biological properties preliminarily. Methods:Acetazolamide was used as raw material to synthesize the precursor SAZ, and the target probe 18F-SAZ was obtained through nucleophilic substitution and other reactions. The radiochemical yield, radiochemical purity, specific activity, lipid water partition coefficient log P, and stability of 18F-SAZ were determined. Cancer cell lines OS-RC-2 (CAⅨ-positive) and HCT116 (CAⅨ-negative) were used for cell uptake experiments, and corresponding tumor-bearing mice were constructed for microPET imaging. Biodistribution of the probe in OS-RC-2 tumor-bearing mice was analyzed. The difference among groups was analyzed by repeated measures analysis of variance and Bonferroni method. Results:The probe 18F-SAZ was successfully prepared with the labelling yield of (5.60±0.51)%, specific activity of (7.90±0.62)MBq/nmol, radiochemical purity more than 99%, and the lipid water partition coefficient log P of -0.38±0.01. After incubation with PBS or mouse serum for 4 h, the radiochemical purity was still more than 99%. The uptake of 18F-SAZ in OS-RC-2 cells reached (1.47±0.24) percentage of the added radioactivity dose (%AD) at 30min, which was significantly higher than the uptake in the blocked group and that in HCT116 cells ((0.60±0.07)%AD, (0.50±0.05)%AD; F=24.31, P values: 0.012, 0.013 (Bonferroni correction method)). The results of microPET imaging showed that the uptake of 18F-SAZ in OS-RC-2 tumors reached the maximum at 30min ((2.92±0.07) percentage activity of injection dose per gram of tissue (%ID/g)), while the maximum uptakes in the blocked group and HCT116 tumors were only (1.36±0.02) and (1.12±0.07)%ID/g, respectively. 18F-SAZ was mainly distributed in tumors and organs including kidney, intestine, liver, stomach in OS-RC-2 tumor-bearing mice. Conclusions:The probe 18F-SAZ is successfully synthesized. It has high radiochemical purity and good stability in vitro, and can specifically target tumor cells with high expression of CAⅨ. It is expected to be a new CAⅨ-targeting PET imaging probe.

The paper reports a case of Fabry disease in a child with non-singular nocturnal enuresis as the first symptom. The boy developed unexplained nocturnal enuresis with frequent daytime urination since the age of 6. Fabry disease was detected and diagnosed by chance through high-risk screening. The activity of α-galactosidase A by dry blood spot was 1.97 μmol·L -1·h -1 , and there was c.640-801G>A mutation in GLA gene. Urine routine, urinary microprotein and renal function were normal. However, there were mulberry bodies found in urine deposition microscopy, suggesting the presence of kidney injury. This case suggests that enuresis can be the first symptom of Fabry disease, and mulberry bodies can be seen in the urine at the early stage of the disease.

Bisphenol A(BPA)is an environmental endocrine disruptor commonly found in industri-al products such as plastics,resin coatings,and paper coatings,and it poses potential reproductive hazards.Despite extensive research,studies examining its effects on the F1 generation of rabbits are limited.This study established a BPA exposure model in pregnant female rabbits to investigate its impact on reproductive hormones,apoptosis,oxidative stress,inflammatory responses,and tissue integrity in weaned female offspring.The results indicate that BPA exposure induces oxidative stress and inflammation in F1 rabbits,disrupts hormonal balance,and affects antioxidant enzymes and inflammatory mediators through the modulation of the Nrf2 and NF-κB signaling pathways,ultimately leading to apoptosis and tissue damage.

Objective:To investigate the changes of home blood pressure from weekdays to weekends and its influencing factors.Methods:This study was a national multicenter prospective registry study. Data came from the registry study on the “Action of controlling home blood pressure to target in ten thousand patients”. Hypertension patients receiving antihypertensive drugs in the above study were included, and the general clinical data of the enrolled patients were collected. Patients′ office and home blood pressure were measured at baseline, followed by home blood pressure measurements for 7 consecutive days, and blood pressure trends over a one-week period were analyzed. Multivariate linear stepwise regression was used to investigate the influencing factors of blood pressure change from weekdays to weekends, and subgroup analysis was conducted according to body mass index, alcohol consumption, fasting blood glucose ≥6.1 mmol/L or diabetes mellitus. Kappa consistency test was used to analyze the influence of removing weekend blood pressure data on home blood pressure monitoring results. Results:A total of 3 228 hypertensive patients aged (66.2±7.6) years were included, including 1 612 (49.9%) males. The weekly blood pressure changes of the study subjects showed a trend of gradually increasing during working days (Monday to Friday) and decreasing during weekends (Saturday to Sunday). The blood pressure on weekends was lower than that on weekdays, but the difference was not statistically significant ((128.2±13.7)/(79.7±8.7) mmHg vs. (128.3±12.9)/(79.8±8.3) mmHg, all P>0.05; 1 mmHg=0.133 kPa). The blood pressure on Sunday was significantly lower than that on Friday ((127.9±13.3)/(79.6±9.1) mmHg vs. (128.5±13.3)/(80.0±9.0) mmHg, all P<0.05). Subgroup analysis showed that hypertensive patients who were overweight and obese, drank alcohol, and had fasting blood glucose≥6.1 mmol/L or combined diabetes mellitus had a smaller decrease or increasing trend in home blood pressure from weekdays to weekends. Consistency test results showed that the mean blood pressure after removing the 2-day home blood pressure data on weekends was consistent with the mean blood pressure of one week ( Kappa=0.90). The mean blood pressure after removing only the blood pressure data of Sunday was slightly less consistent with the mean blood pressure of one week ( Kappa=0.88). Conclusions:The home blood pressure level of hypertensive patients receiving antihypertensive drugs showed a trend of gradually increasing during working days and decreasing at weekends. People with hypertension who were overweight and obese, drank alcohol, had high fasting blood sugar, or had combined diabetes mellitus, and their home blood pressure decreased less or increased from weekdays to weekends. The removal of 1-day Sunday blood pressure data but not 2-day weekend blood pressure data had impact on the one-week home blood pressure monitoring results.

Objective To systematically explore influencing factors of internet addiction behaviors among junior school students across different grades from multiple dimensions.Methods This study enrolled all students from a junior high school in Wuhan.Annual questionnaire surveys were conducted from October 2021 to September 2024 to collect data on demographic characteristics,study and living situation,mental health,and internet addiction behaviors.Students were combined according to grade level during the survey period.An exposure-wide association analysis(ExWAS)strategy was employed to identify grade-specific influencing factors in each dimension of internet addiction.Results Common influencing factors across all three grades included academic interest(OR=0.45～0.50,95％CI:0.29～0.76)in the study dimension and living situation dimension and stress(OR=1.06,95％CI:1.03～1.10)in mental health dimension.Grade-specific influences of internet addiction existed in these two dimensions:In grade 7,the affinity with father(OR=0.97,95％CI:0.94～1.00),alcohol experimentation(OR=2.33,95％CI:1.54～3.53),and perpetrating bullying(OR=2.16,95％CI:1.04～4.49)were the main factors;In grade 8,mod-erate-to-high intensity physical activity(OR=0.50,95％CI:0.31～0.81),the affinity with father(OR=0.97,95％CI:0.94～1.00),bullying victimization(OR=2.32,95％CI:1.50～3.60),and anxiety symptoms(OR=2.01,95％CI:1.26～3.20)were the main factors;In grade 9,perpetrating bullying(OR=3.19,95％CI:1.31～7.78)and anxiety symptoms(OR=1.91,95％CI:1.18～3.10)were the main factors.Conclusion Influencing factors of internet addiction behaviors vary across grades in junior high school.Prevention and control strategies should incorporate grade-specific characteristics to implement targeted measures,thereby enhancing early identification capabilities and intervention effectiveness.

BACKGROUND:A novel aggregation induced luminescence fluorescence probe based on the mechanism of intramolecular motility restriction can be used for the detection of disease markers,tumor diagnosis,and bacterial imaging recognition.OBJECTIVE:To prepare a near-infrared Ⅱ nanoprobe called FA-DSPE-PEG-AIE@NPs based on aggregation-induced luminescence,and to explore its potential of targeted fluorescence imaging and photothermal therapy for prostate cancer.METHODS:Lecithin,polyethylene glycol phospholipids,folate polyethylene glycol phospholipids,and aggregation induced luminescent molecule 2TT-oC26B were used as raw materials.The folate-targeted nanoprobe FA-DSPE-PEG-AIE@NPs were prepared by nanoprecipitation method,and basic characterization of the nanoprobe was detected.PC3 human prostate cancer cells and human umbilical vein endothelial cells were selected as experimental objects.The cytotoxicity and phototoxicity of FA-DSPE-PEG-AIE@NPs were detected.PC3 human prostate cancer cells were selected as the experimental objects.Flow cytometry and calcein/propidium iodide staining were used to assess the efficacy of photothermal therapy.PC3 human prostate cancer cells were injected subcutaneously into the abdomen of BALB/C nude mice to establish a tumor model,and nanoprobes FA-DSPE-PEG-AIE@NPs were injected into the tail vein.The mice were immediately subjected to near-infraced Ⅱ fluorescence imaging.12 hours later,the tumor was irradiated by laser for 5 minutes,and the photothermal treatment effect was observed within 14 days.RESULTS AND CONCLUSION:(1)The nanoprobes FA-DSPE-PEG-AIE@NPs with a mean diameter of(171.0±0.3)nm showed a well-defined spherical morphology.The nanoprobe had a wide absorption spectrum and tail emission extending to the near-infrared Ⅱ which emitted a bright near-infrared Ⅱ fluorescence signal under laser irradiation.(2)The nanoprobes FA-DSPE-PEG-AIE@NPs had low cytotoxicity and high phototoxicity.The results of flow cytometry and calcein/propidium iodide staining showed that nanoprobes FA-DSPE-PEG-AIE@NPs had an obvious photothermal killing effect on human prostate cancer cells.(3)The nanoprobes FA-DSPE-PEG-AIE@NPs successfully achieved near-infrared Ⅱ fluorescence imaging of mouse blood vessels and the maximum enrichment time of the tumor was 12 hours.The vessel widths of the hind leg and single blood vessels of abdomen were estimated to be 0.63 mm and 0.42 mm.The tumor volume of mice was significantly smaller after 14 days of treatment.(4)The results show that nanoprobes FA-DSPE-PEG-AIE@NPs can achieve near-infrared Ⅱ fluorescence imaging and photothermal therapy of prostate cancer effectively,which may provide a new method for early diagnosis and combined treatment of prostate cancer.