To reduce the dependency on high-carbon-load chromatographic columns,a new method has been established for the determination of the content of docusate sodium using ion-pair high-performance liquid chromatography (IP-HPLC). Tetrapropylammonium chloride was used as the ion-pair reagent with a mobile phase, composition of acetonitrile:10 mmol/L tetrapropylammonium chloride solution = 66∶34, adjusting pH to 6.5 with 0.1% phosphoric acid solution,flow rate of 1.5 mL/min, detection wavelength of 214 nm,column temperature of 35 °C, and an injection volume of 25 μL,and quantified by an external standard method. The main peak of docusate sodium exhibited a tailing factor of 1.34. The method showed good linearity within the range of 0.02 mg/mL to 0.40 mg/mL, with a correlation coefficient (r) of 0.999 9. It also demonstrated good repeatability, with recovery ranging from 97.0% to 98.2% (n=6). The quantification limit was 3.31 μg/mL, and the detection limit was 2.76 μg/mL.In summary,the new method shows good durability, a wide linear range, and high sensitivity, it is suitable for the determination of docusate sodium.

Objective To investigate the effect of catalpol(CAT)on necrotic apoptosis in acute myocardial infarction(AMI)rats.Methods Rat AMI model was constructed by ligating the anterior descending branch of the left coronary artery.Sixty SPF grade SD male rats were randomly grouped into sham surgery group(Sham group),AMI model group(Model group),low-dose CAT group(CAT-L group,30 mg·kg-1 CAT),high-dose CAT group(CAT-H group,60 mg·kg-1 CAT),and high-dose CAT+RIP1 activator recombinant RIP1 group(CAT-H+rRIP1 group,60 mg·kg-1 CAT+8 μg·kg-1 rRIP1),12 in each group.CAT was administered by gavage once a day for a total of 4 weeks.Recombinant RIP1 was administered via tail vein injection and the next day for a total of 4 weeks.Sham group and Model group were given equal amounts of physiological saline by gavage and tail vein injection,respectively.The CAT-L group and CAT-H group were injected with physiological saline via the tail vein the next day while receiving gastric lavage.TUNEL staining was applied to observe the apoptosis of rat cardiomyocytes.Western Blot was applied to detect the expression of RIP1/RIP3/MLKL signaling pathway related proteins in rat myocardial tissue.Results The apoptosis rates of myocardial cells in the sham group,model group,CAT-L group,CAT-H group,and CAT-H+rRIP1 group were(4.23±0.63)％,(33.48±3.94)％,(13.50±1.86)％,and(29.62±3.08)％,respectively;the expression levels of RIP1 protein in myocardial tissue were 0.21±0.02,0.86±0.09,0.43±0.04,and 0.72±0.07,respectively;the expression levels of RIP3 protein were 0.30±0.03,0.94±0.09,0.49±0.05,and 0.83±0.08,respectively;the phosphorylation levels of MLKL protein were 0.35±0.04,1.13±0.11,0.64±0.06,and 0.97±0.10,respectively.The above indexes in Model group were compared with those in Sham group,and those in CAT-H group were compared with those in Model group and CAT-H+rRIP1 group,and the differences were statistically significant(all P＜0.05).Conclusion CAT may inhibit necrotic apoptosis of myocardial cells in AMI rats by down-regulating the RIP1/RIP3/MLKL signaling pathway.

Background and purpose:Amplification of the urokinase plasminogen activator receptor(uPAR)gene is closely associated with poor prognosis in pancreatic cancer patients.uPAR regulates epithelial-mesenchymal transition(EMT)and chemoresistance in pancreatic cancer cells through the mitogen-activated protein kinases(MAPK)signaling pathway,though the specific mechanisms remain unclear.This study aimed to investigate the mechanism by which uPAR promotes proliferation,invasion,and chemoresistance of pancreatic cancer cells by inhibiting autophagy.Methods:Pancreatic cancer tissue samples were collected from patients who underwent surgical resection and biopsy at the Changsha Central Hospital,Affiliated to University of South China(Changsha Central Hospital),between December 2021 and Jun 2022.The study was approved by the Ethics Committee of Changsha Central Hospital(Approval No.:2021-S0182,2022-S0084).Patient-derived organoids(PDOs)from pancreatic cancer samples were cultured in vitro.Six pancreatic cancer cell lines(AsPC-1,PANC-1,CAPAN-1,CAPAN-2,MIA PaCa-2 and PaTu8988T)were used in this study.uPAR-deficient models were constructed using clustered regularly interspaced short palindromic repeats(CRISPR)Cas9 technology.Cell proliferation and invasion abilities were measured using confocal microscopy,Western blot,enzyme-linked immunosorbent assay(ELISA),and MTS assays.Changes in MAPK and autophagy signaling pathways and gemcitabine-induced cell death were analyzed.The synergistic effects of combined treatments were evaluated using gene silencing(siRNA)or autophagy inhibitors.Results:In AsPC-1 cells,uPAR knockout significantly reduced the proliferation and migration abilities of clone cells compared to wild-type cells,as shown by MTS assays and wound healing experiments,and decreased sensitivity to gemcitabine(P＜0.05).Re-expression of uPAR restored the proliferation and invasion abilities of clone cells and partially restored sensitivity to gemcitabine(P＜0.05).Confocal microscopy revealed reduced F-actin and a rounded morphology in clone cells.Western blot analysis showed increased expressions of E-cadherin and Slug,decreased expression of vimentin,and increased expressions of phospho-focal adhesion kinase(p-FAK),p-p38MAPK,and the microtubule-associated protein light chain 3B(LC3B)in clone cells compared to wild-type cells.siRNA results indicated that silencing FAK or p38MAPK or combining autophagy inhibition could resensitize clone cells to gemcitabine(P＜0.05),with p38MAPK silencing reducing LC3B expression.Organoid studies showed varying responses to gemcitabine among 8 organoids,all expressing uPAR.uPAR expression levels were negatively correlated with gemcitabine IC50(r2=0.66,P＜0.05).Three organoids responded well to the combination of gemcitabine and autophagy inhibitors(P＜0.05).Conclusion:uPAR promotes pancreatic cancer cell activity through the p38MAPK signaling pathway,preventing FAK-mediated resistance and cell dormancy.The study suggests that pancreatic cancer patients with high uPAR expression respond better to gemcitabine,while tumors with low uPAR and high p38MAPK expressions may benefit from combined treatment with autophagy inhibitors and cytotoxic chemotherapy.

Objective To explore the relationship between the early stage HbA1c level and two-year prognosis in the patients with first time onset of acute ischemic stroke(AIS).Methods A total of 513 inpa-tients with first time AIS in this hospital during 2018-2019 were selected as the study subjects.The clinical data,biochemical indicators and discharge situation were collected.The multivariate logistic regression was used to analyze the influencing factors of adverse reactions outcome within 2 years.The Kaplan-Meier survival curve was used to analyze the all-cause mortality and stroke recurrence situation within 2 years.Results The sex,age,TOAST type,,diseases history such as diabetes,arrhythmia and coronary heart disease,medication history such as antidiabetic drugs,lipid-lowering drugs and anticoagulants,BMI,Urea,Crea,ALT,SBP,fasting blood glucose(FBG),total cholesterol(TC),triglyceride(TG),HDL-C,NIHSS score at admission,discharge mode,NIHSS score at discharge,hospitalization duration and hospitalization costs had statistical difference a-mong the patients with different HbA1c levels(P＜0.05).The multivariate logistic regression analysis showed that HbA1c＞7.4％was the independent risk factor for adverse outcome within 2 years(OR=4.470,95％CI:1.105-18.087,P=0.036).The Kaplan-Meier survival curve analysis showed that the survival time within 2 years had statistical difference among the patients with different HbA1c levels(P=0.009).The higher the HbA1c level,the shorter the survival time.Conclusion The high HbA1c level has the influence on the stroke recurrence and all-cause mortality within 2 years in the patients with first onset occurrence of AIS.

Objective To investigate the effect of elastic pants on coagulation function and deep vein thrombosis by examining blood coagulation function and deep vein thrombosis in patients with liposuction in the thigh before and after operation.Methods 80 patients with liposuction were randomly divided into Ankle-length elastic pants(Ankle group,A group,n=40)and Knee-length elastic pants(Knee group,K group,n=40)from October 2021 to October 2022.After liposuction surgery,the two groups of patients used elastic bandage to initially compress and bind the thigh.According to the length of the patients'thigh,the patients in A group wore appropriate ankle-length elastic pants and the patients in K group wore appropriate knee-length elastic pants.The index were recorded including the popliteal vein flow rate,the common femoral vein flow rate,the instep temperature,the incidence of deep vein thrombosis(DVT),the incidence of intramuscular vein thrombosis of leg and the coagulation indexes(APTT,PT,Fib,D-dimer).Results Compared with pre-operation,the blood flow rate of popliteal vein and common femoral vein in A group was significantly faster,while the blood flow rate of popliteal vein in K group was significantly slower(P＜0.05).There was no significant change in APTT and PT in the two groups after operation(P＞0.05),but the Fib and D-Dimer increased significantly on the first day after operation,and then decreased gradually(P＜0.05).Compared with K group,the blood flow of popliteal vein and common femoral vein in A group was significantly faster at each time point after operation(P＜0.05).The Fib and D-Dimer of patients in A group were significantly lower than those in K group on the 1st,3rd and 7th day after operation(P＜0.05),and the blood coagulation index between the two groups returned to normal around the 14th day.There was no statistically significant difference in the instep temperature between groups and within groups(P＞0.05).No deep venous thrombosis was found in A group after surgery,while there were 3 cases of deep venous thrombosis without clinical symptoms in K group on the 3rd and 7th day,with no statistical difference(P＞0.05).After surgery,patients in A group and K group had intramuscular venous thrombosis of the leg on the 1st,3rd and 7th day after surgery,and there was statistically significant difference on the 3rd and 7th day between the two groups(P＜0.05).Conclusion Thigh liposuction can lead to deep vein thrombosis without obvious clinical symptoms and intramuscular vein thrombosis of leg.Ankle-length elastic pants are more conducive to blood circulation of patients'legs,improve blood hypercoagulability,and reduce the risk of deep vein thrombosis after operation.

Objectives:To evaluate the early efficacy of Dynesys corrective internal fixation system in the treatment of Lenke1 and Lenke5 adolescent idiopathic scoliosis(AIS).Methods:A retrospective analysis was conducted on 15 AIS patients(4 males and 11 females)who underwent Dynesys corrective and internal fixa-tion treatment in our department from November 2019 to September 2023.The average age of the patients was 15.5±2.2 years(12-21 years).Among the patients,there were 5 cases of Lenke1 type and 10 cases of Lenke5 type,mainly characterized by thoracolumbar deformities.The operative time,bleeding volume,and complications were recorded by reviewing medical records,and imaging data were measured and analyzed.The measurement indicators included Cobb angle,thoracic kyphosis,lumbar lordosis,and lumbar range of mo-tion at preoperation,first follow-up within 1 week after surgery,and final follow-up to evaluate the corrective effect of posterior Dynesys corrective internal fixation on scoliosis.Results:All the patients successfully com-pleted the surgery and were followed up for 3-48 months.The average operative time was 280.8±45.8min,average bleeding volume was 194.0±145.5mL,the number of main curvature segments was 4.7±1.1,and the number of operative segments was 4.7±1.1.The Cobb angle of the coronal plane was 40.8°±5.5° before surgery,5.5°±4.5° after surgery,and 7.6°±5.5° at final follow-up.Coronary scoliosis improved significantly af-ter surgery(P＜0.05),with a total correction rate of 86.9％for the main curvature,89.8％for Lenke1 type,and 85.4％for Lenke5 type.There was no significant statistical difference between the two types.At final follow-up,the range of motion of the thoracolumbar fixed segment was 8.2°±3.1°.All patients did not experience any operation-related complications,and no implant complications such as loose screws or broken ropes were found during follow-up.Conclusions:Dynesys corrective internal fixation surgery can effectively correct Lenke1 and Lenke5 AIS,with minimal surgical trauma,fast postoperative recovery,preservation of partial spinal motor function,which has satisfactory early postoperative outcomes.

OBJECTIVES: Dysthyroid optic neuropathy (DON) is a class of diseases that makes seriously endanger to the vision of patients with thyroid-associated ophthalmopathy. This study aims to observe the visual function changes in patients with DON, and to evaluate the diagnostic value of indicators diagnosing DON. METHODS: A retrospective study was conducted on 98 eyes of 49 patients with dysthyroid optic neuropathy (DON) who were treated in Xiangya Hospital of Central South University from January 2017 to December 2019. All patients were received the examination of best corrected visual acuity (BCVA), Humphrey visual field, visual evoked potential (VEP), and contrast sensitivity. Ninety-eight eyes were divided into a DON group (45 eyes) and a non-DON group (53 eyes). T-test was used to compare the related indicators between the 2 groups. The sensitivity and specificity of each indicator were analyzed by receiver operating characteristic (ROC) curve. RESULTS: The BCVA and visual field index (VFI) of the DON group were significantly lower than those of the non-DON group (all P<0.05). The mean deviation (MD) and pattern standard deviation (PSD) of the DON group were significantly higher than those of the non-DON group (all P<0.05). The low frequency contrast sensitivity (CSL), medium frequency contrast sensitivity (CSM), and high frequency contrast sensitivity (CSH) of the DON group were significantly lower than those of the non-DON group (all P<0.05), with CSH being particularly prominent. Compared with the non-DON group, at spatial frequencies of 15°, 30°, and 60°, the amplitude of N135 wave was significantly reduced, and the latency of N75 wave, P100 wave, and N135 wave was significantly prolonged in the DON group (all P<0.05); at spatial frequencies of 15° and 30°, the amplitude of P100 wave was significantly reduced in the DON group (P<0.05). The ROC curve analysis results showed that the area under the curve (AUC) of VFI, CSL, CSM, CSH and 15° P100 amplitude diagnosing DON were 0.812, 0.841, 0.880, 0.784, and 0.791, respectively, with CSM possessing the highest sensitivity and specificity. CONCLUSIONS The visual function of patients with DON is decreased. VFI, contrast sensitivity of low, medium, and high frequency, and 15° P100 wave amplitude might be effective indicators for early diagnosis of DON.
Humans ; ROC Curve ; Optic Nerve Diseases/complications* ; Retrospective Studies ; Evoked Potentials, Visual ; Graves Ophthalmopathy

OBJECTVE To study the improvement effects of obacunone on renal interstitial fibrosis （RIF） in unilateral ureteral obstruction （UUO） model mice， and to investigate its mechanism based on ferroptosis mediated by nuclear factor erythroid 2- related factor 2（Nrf2）/glutathione peroxidase 4 （GPx4） signaling pathway. METHODS Thirty mice were randomly divided into sham operation group， model group， irbesartan group （positive control， 20 mg/kg）， obacunone low-dose and high-dose groups （10， 40 mg/kg）， with 6 mice in each group. Except for sham operation group， UUO model was established by ligation of unilateral ureter in other groups. After operation， administration groups were given intraperitoneal injection of relevant medicine， and sham operation group and model group were given intraperitoneal injection of constant volume of normal saline， once a day， for 7 consecutive days. The levels of creatinine （Cr） and blood urea nitrogen （BUN）， the content of malondialdehyde （MDA） and the activities of total superoxide dismutase （T-SOD） in serum and the concentration of Fe2+ in renal tissue were all detected. HE staining and Masson staining were performed to observe the morphology and the fibrosis of renal tissues. Immunohisto- chemical staining was used to determine expressions of the fibronectin （Fn）， α-smooth muscle actin （α-SMA）， GPx4 964083717@qq.com and Nrf2 in renal tissue. Western blot and real-time quantitative polymerase chain reaction （RT-qPCR） were used E-mail：834300205@qq.com to detect the protein and mRNA levels of Fn， α-SMA， Nrf2， GPx4 and SLC7A11 in the renal tissues. RESULTS Compared with sham operation group， serum levels of Cr and BUN， the concentration of Fe2+ in renal tissue， the protein and mRNA levels of Fn and α-SMA in model group were increased significantly （P＜0.05）， while the activity of T-SOD in serum， protein and mRNA expressions of Nrf2， GPx4， SLC7A11 in kidney tissue were significantly decreased （P＜0.05）； in the kidney tissue， the renal tubules were dilated， the collagen deposition was obvious， the fibrous bands were thicker and darker， and the renal interstitial inflammatory cells infiltrated significantly. After intervened with obacunone， the levels of above indexes （except for mRNA expression of SLC7A11 in obacunone low-dose group） in serum and renal tissue were reversed significantly （P＜0.05）， and pathological damage and collagen deposition of kidney tissue were alleviated. CONCLUSIONS Obacunone can improve renal interstitial fibrosis of UUO model mice， the mechanism of which may be associated with activating the Nrf2/GPx4 pathway and then inhibiting ferroptosis to relieve RIF in UUO model mice.

Objective To evaluate the effect of targeted monitoring and multi-modular improvement strategy on the prevention and control of catheter-associated urinary tract infection(CAUTI).Methods Patients with indwe-lling urinary catheter in a tertiary first-class hospital from January 2018 to December 2022 were selected as the re-search subjects.Targeted monitoring results and distribution of pathogenic bacteria in 5 consecutive years were ana-lyzed,and a multi-modular improvement strategy based on the targeted monitoring results was implemented.The occurrence of CAUTI before and after implementation,status and effectiveness of training in prevention and control measures were compared respectively.Results Before and after the implementation of the multi-modular improve-ment strategy,health care workers'compliance rate of hand hygiene,awareness rate of prevention and control measures,and implementation rate of prevention and control measures all increased significantly(all P＜0.001).Targeted monitoring results showed that daily test rates of urine culture and routine urine from patients with in-dwelling catheters have been on the rise in 5 consecutive years(P＜0.05).A total of 397 cases of CAUTI occurred in the past 5 years.Incidences of CAUTI in general intensive care unit(ICU)and surgical ICU showed decreasing trends in 5 consecutive years(all P＜0.05).Incidence of CAUTI in general wards showed no statistically significant difference in 5 years(P=0.088).A total of 431 strains of pathogenic bacteria were detected,mainly Gram-negative bacteria.Daily incidence of multidrug-resistant organism infection in patients with indwelling catheters was 0.12‰.After the implementation of the multi-modular improvement strategy,incidence of CAUTI in all departments re-duced significantly(P＜0.05).Conclusion Targeted monitoring can help identify departments with high-risk of CAUTI,multi-modular improvement strategy can raise the quality of prevention and control of CAUTI in all occa-sions,reduce the incidence of CAUTI,and is worthy of clinical promotion and application.

School-age children are in a specific development stage corresponding to juvenility, when the white matter of the brain experiences ongoing maturation. Diffusion-weighted magnetic resonance imaging (DWI), especially diffusion tensor imaging (DTI), is extensively used to characterize the maturation by assessing white matter properties in vivo. In the analysis of DWI data, spatial normalization is crucial for conducting inter-subject analyses or linking the individual space with the reference space. Using tensor-based registration with an appropriate diffusion tensor template presents high accuracy regarding spatial normalization. However, there is a lack of a standardized diffusion tensor template dedicated to school-age children with ongoing brain development. Here, we established the school-age children diffusion tensor (SACT) template by optimizing tensor reorientation on high-quality DTI data from a large sample of cognitively normal participants aged 6-12 years. With an age-balanced design, the SACT template represented the entire age range well by showing high similarity to the age-specific templates. Compared with the tensor template of adults, the SACT template revealed significantly higher spatial normalization accuracy and inter-subject coherence upon evaluation of subjects in two different datasets of school-age children. A practical application regarding the age associations with the normalized DTI-derived data was conducted to further compare the SACT template and the adult template. Although similar spatial patterns were found, the SACT template showed significant effects on the distributions of the statistical results, which may be related to the performance of spatial normalization. Looking forward, the SACT template could contribute to future studies of white matter development in both healthy and clinical populations. The SACT template is publicly available now ( https://figshare.com/articles/dataset/SACT_template/14071283 ).