Objective:To study the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with fine needle aspiration biopsy (FNA) for thyroid imaging reporting and data system (TI-RADS) 4 type thyroid micro-nodules (TN).Methods:A total of 121 TI-RADS 4 TN patients admitted to Zhanjiang Central People's Hospital from June 2020 to June 2023 were selected as the research subjects. All patients underwent examinations such as CEUS, FNA, and pathology (as the gold standard). The CEUS manifestations of TI-RADS 4 benign and malignant nodules were observed. The diagnostic accuracy, sensitivity, and specificity of CEUS and FNA alone and in combination for TI-RADS 4 type TN benign and malignant nodules were calculated and compared.Results:Among the 121 patients, there were 109 females and 12 males, with an age of (48.27 ± 7.76) years. Pathological diagnosis showed 74 cases of malignancy and 47 cases of benign. CEUS diagnosed 64 cases of malignancy and 57 cases of benign, with a diagnostic accuracy of 86.49% (64/74); the CEUS manifestations of benign and malignant nodules were compared in terms of enhancement mode, enhancement level, uniformity, peripheral ring shape, and post enhancement boundary, and the differences were statistically significant ( P < 0.001). FNA diagnosed 62 cases of malignancy and 59 cases of benign, with a diagnostic accuracy of 83.78% (62/74). CEUS combined with FNA diagnosed 72 cases of malignancy and 49 cases of benign, with a diagnostic accuracy rate of 97.30% (72/74). The accuracy of CEUS combined with FNA in diagnosing malignant nodules was higher than that of CEUS and FNA alone ( P < 0.05). The sensitivity and specificity of CEUS combined with FNA in diagnosing malignant nodules were higher than those of CEUS and FNA alone ( P < 0.05). Conclusion:The combination of CEUS and FNA has good diagnostic value for TI-RADS 4 type TN, which can improve the accuracy and diagnostic efficiency of malignant nodule diagnosis.

Objective:To study the diagnostic value of contrast-enhanced ultrasound (CEUS) combined with fine needle aspiration biopsy (FNA) for thyroid imaging reporting and data system (TI-RADS) 4 type thyroid micro-nodules (TN).Methods:A total of 121 TI-RADS 4 TN patients admitted to Zhanjiang Central People's Hospital from June 2020 to June 2023 were selected as the research subjects. All patients underwent examinations such as CEUS, FNA, and pathology (as the gold standard). The CEUS manifestations of TI-RADS 4 benign and malignant nodules were observed. The diagnostic accuracy, sensitivity, and specificity of CEUS and FNA alone and in combination for TI-RADS 4 type TN benign and malignant nodules were calculated and compared.Results:Among the 121 patients, there were 109 females and 12 males, with an age of (48.27 ± 7.76) years. Pathological diagnosis showed 74 cases of malignancy and 47 cases of benign. CEUS diagnosed 64 cases of malignancy and 57 cases of benign, with a diagnostic accuracy of 86.49% (64/74); the CEUS manifestations of benign and malignant nodules were compared in terms of enhancement mode, enhancement level, uniformity, peripheral ring shape, and post enhancement boundary, and the differences were statistically significant ( P < 0.001). FNA diagnosed 62 cases of malignancy and 59 cases of benign, with a diagnostic accuracy of 83.78% (62/74). CEUS combined with FNA diagnosed 72 cases of malignancy and 49 cases of benign, with a diagnostic accuracy rate of 97.30% (72/74). The accuracy of CEUS combined with FNA in diagnosing malignant nodules was higher than that of CEUS and FNA alone ( P < 0.05). The sensitivity and specificity of CEUS combined with FNA in diagnosing malignant nodules were higher than those of CEUS and FNA alone ( P < 0.05). Conclusion:The combination of CEUS and FNA has good diagnostic value for TI-RADS 4 type TN, which can improve the accuracy and diagnostic efficiency of malignant nodule diagnosis.

Objective To investigate the inhibitory effect of epigallocatechin gallate(EGCG)on oxidative damage to the retina in a rat model of dry age-related macular degeneration(AMD)induced by sodium iodate.Methods A total of 36 male specific pathogen-free Sprague-Dawley rats were randomly divided into the blank control group,sodium iodate group and sodium iodate+EGCG group,with 12 rats in each group.Rats in the sodium iodate group and the sodium io-date+EGCG group were given 50 mg-kg·1 sodium iodate by tail vein injection by weight to build dry AMD models,while rats in the blank control group were administered with an equal volume of normal saline.Following the modeling proce-dure,rats in the sodium iodate+EGCG group received an intravitreal injection of 4 μL EGCG(0.5 g·L-1)into their right eyes,while the right eyes of rats in both the blank control and sodium iodate groups were treated with the same volume of normal saline.After 21 days,the rats were sacrificed,and ocular samples were collected for detection.Histopathological changes of the retinal tissues in each group were examined using hematoxylin and eosin(HE)staining.Additionally,the levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)in the retinal tis-sues were quantified.Western blot analysis was conducted to assess the protein expression levels of nuclear factor ery-throid-2-related factor 2(Nrf2),NADPH quinone oxidoreductase 1(NQO1),and heme oxygenase-1(HO-1)in the retinas.Furthermore,real-time quantitative polymerase chain reaction was performed to evaluate the relative messenger ribonucleic acid(mRNA)expression levels of Nrf2,NQO1 and HO-1 in the retinas of the rats.Results HE staining revealed that,in comparison to the blank control group,the entire retinal layer in the sodium iodate group exhibited injury,characterized by noticeable injury of the retinal pigment epithelial cells and disordered outer nuclear layer with wavy transformation.The so-dium iodate+EGCG group demonstrated ameliorated retinal injury across all layers compared to the sodium iodate group.Compared to the blank control group,the levels of SOD and GSH-Px were significantly reduced(both P＜0.01),while the level of MDA was significantly elevated(P＜0.01)in the sodium iodate group.Compared with the sodium iodate group,the sodium iodate+EGCG group showed a significant increase in the levels of SOD and GSH-Px(both P＜0.01),along-side a substantial decrease in the content of MDA(P＜0.01).Western blot analyses demonstrated that compared with the blank control group,the protein expression levels of Nrf2,NQO1 and HO-1 were significantly elevated in the sodium iodate group(all P＜0.01);compared with the sodium iodate group,the sodium iodate+EGCG group exhibited relatively higher protein expression levels of Nrf2,NQO1 and HO-1(all P＜0.05).The results from real-time quantitative polymerase chain reaction indicated that the relative mRNA expression levels of Nrf2,NQO1 and HO-1 in the retinas of rats in the sodium io-date group were significantly greater than those in the blank control group(all P＜0.05);compared with the sodium iodate group,the sodium iodate+EGCG group showed a significant increase in the relative mRNA expression levels of Nrf2,NQO1 and HO-1(all P＜0.05).Conclusion EGCG can improve the capacity to scavenge oxygen free radicals by promo-ting the upregulation of Nrf2 expression.This activation subsequently enhances the expression of downstream products such as NQO1 and HO-1,leading to increased levels of SOD and GSH-Px while simultaneously reducing the MDA level.Consequently,this process inhibits oxidative damage to the retina in rats with dry AMD induced by sodium iodate.

Objective:To evaluate the effect of preoperative plasma D-dimer level on the risk of cardiac surgery-associated acute kidney injury (CSA-AKI). Methods:The clinical data of patients who underwent cardiac surgery with cardiopulmonary bypass in the First Affiliated Hospital of Nanjing Medical University from January 2017 to December 2018 were collected retrospectively. All patients were distributed into two groups (normal D-dimer group with D-dimer level≤0.55 mg/L and elevated D-dimer group with D-dimer level>0.55 mg/L) according to the D-dimer threshold of 0.55 mg/L and the differences of clinical data between the two groups were compared. Kaplan-Meier survival analysis method was used to analyze the difference of the cumulative incidence of CSA-AKI between the two groups. Logistic regression analysis and restricted cubic splines analysis were used to analyze the association between serum D-dimer and the incidence of CSA-AKI. Results:There were 871 patients enrolled in the study with 427 females (49.0%) and age of (56.6±12.3) years, including 215 patients (24.7%) with high D-dimer and 259 patients (29.7%) with CSA-AKI. Compared with the normal D-dimer group, patients with elevated D-dimer had higher baseline serum creatinine, proportion of chronic kidney disease stage 3, international normalized ratio, fibrinogen, proportion of receiving renal replacement therapy and incidence of CSA-AKI (all P<0.05). The prothrombin time, operation time, extracorporeal circulation time, aortic occlusion time and hospital stay in the elevated D-dimer group were longer (all P<0.05), and the preoperative estimated glomerular filtration rate (eGFR) and hemoglobin levels were lower than those in the normal D-dimer group (both P<0.05). There was no statistical difference between the two groups in terms of age, gender, comorbid diseases, cardiac function classification, and hospital mortality (all P>0.05). Kaplan-Meier survival curve results showed that compared with the normal D-dimer group, the risk of CSA-AKI in the elevated D-dimer group was significantly increased (Log-rank χ2=14.227, P<0.001). The multivariate logistic regression showed that after adjusting variables including gender, age, diabetes mellitus, preoperative eGFR, cardiopulmonary bypass time and so on, the higher level of preoperative D-dimer (>0.55 mg/L) was still related to CSA-AKI ( OR=1.476, 95% CI 1.038-2.098, P=0.030). Restricted cubic splines analysis showed that the incidence of CSA-AKI raised when preoperative serum D-dimer concentration increased (non-linear P=0.262). Conclusion:Patients with high preoperative serum D-dimer have an increased risk of CSA-AKI.

Objective:To prepare the self-microemulsifying drug delivery system (SMEDDS) and relevant tablets of atorvastatin calcium and ezetimibe(Ato-Eze),and investigate the in vitro release of Ato-Eze SMEDDS tablets. Methods:The solubility and excip-ient compatibility of Ato and Eze in different excipients were investigated. The pseudo-ternary phase diagram composed of different oil phase,emulsifier and co-emulsifier was used to obtain the self-emulsifying area. The morphology,particle size distribution and zeta po-tential of microemulsion were determined by a dilution method. The optimal formula of Ato-Eze SMEDDS was prepared into tablets. The drug release profiles of the commercial formula,Ato-Eze SMEDDS and Ato-Eze SMEDDS tablets were compared. Results:The op-timal formula was as follows:propylene glycol monocaprylate as the oil phase,Solutol HS 15 as the surfactant and polyethylene glycol 600 as the co-surfactant with the best ratio of 5 :3.75:1.25. Ato-Eze SMEDDS was a clear and transparent microemulsion solution with homogeneous small spheres as seen under a transmission electron microscope. The particle size and zeta potential of Ato-Eze SMEDDS was(44.2 ± 19.5) nm and( -24.1 ± 1.3) mV,respectively. The in vitro release profile indicated that the accumulated re-lease of Ato-Eze SNEDDS and the tablets reached up to nearly 100% in 45 min. Conclusion: Ato-Eze SMEDDS tablets can signifi-cantly improve the in vitro dissolution rates of the two drugs,and the preparation process is simple and feasible.

Objective:To study the in vitro and in vivo anti-tumor effect of lentinan combined with 5-FU. Methods:MTT method was used to determine the proliferation of H22 in vitro, and the cell cycle changes were analyzed by a flow cytometry. The in vivo anti-tumor effect was evaluated in Kunming mice. The tumor inhibitory rate, thymus/spleen index, IL-2, IL-6 and TNF-α were deter-mined. Results:The in vitro results revealed that lentinan had no obvious effect on the inhibitory rate and cell cycle of the cells treated with 5-FU. In vivo results showed that lentinan at the dosage of 25 and 50 mg·kg-1 could obviously enhance the anti-tumor effect of 5-FU(P<0. 05). Furthermore, lentinan could increase the thymus/spleen index of the tumor-bearing mice. Conclusion:Lentinan com-bined with 5-FU has synergistic effects on anti-tumor activity through nonspecific immune stimulation rather than the direct killing of tumor cells.

Objective:To prepare sustained-release pellets of memantine hydrochloride and investigate the in vitro drug release be-havior. Methods:The drug-loaded pellets were prepared by a fluid bed coating technology, the sustained-release pellets were prepared with Eudragit RL 30D and Eudragit RS 30D as the coating materials, and in vitro drug release behavior of the sustained-release pellets was studied. Results:The in vitro drug release was steady and complete in 24h, which fit a zero-order kinetics model. Conclusion:The memantine hydrochloride sustained-release pellets has the sustained-release property.

To prepare simvastatin nanostructured lipid carriers ( simvastatin-NLCs) . Methods:The simvastatin-NLCs were prepared by melt-emulsion ultrasonication and low temperature-solidification methods. Using the particle size, polydispersion in-dex, encapsulation efficiency and drug loading as the idices, the ratio of solid to liquid, lipid concentration, ratio of surfactant to cosur-factant, emulsifier concentration and drug concentration were optimized. The optimized simvastatin-NLCs were characterized for the en-capsulation efficiency, particle size, zeta potential and morphology. In vitro drug release behavior and stability of NLCs were also stud-ied. Results:The optimized simvastatin-NLCs formula was as follows:the concentration of simvastatin, cetyl palmitate, Miglyol? 812, soy lecithin and solutol HS15? was 0. 5%, 1. 5%, 4. 5%, 2. 5% and 1. 5%, respectively. The particle size and zeta potential of NLCs was (102. 2 ± 42. 1) nm and ( -33. 1 ± 4. 1) mV, respectively. The simvastatin-NLCs were found to be small and spherical with smooth surface under a transmission electron microscope. The in vitro release profile indicated that the accumulated release of sim-vastatin reached up to (59. 1 ± 4. 8) % in 24 h. The stability studies showed that simvastatin-NLCs were stable in 3 months after stored at 5℃. Conclusion:The formula of simvastatin-NLCs prepared by melt-emulsion ultrasonication and low temperature-solidifica-tion method is feasible.

Objective:To develop a dissolution method for olanzapine pamoate long-acting injections. Methods:The in vitro dis-solution profile of olanzapine pamoate was detected by an oar method and an HPLC method. The stirring speed respectively was 25, 50 and 75 r·min-1, and 500 ml of sodium lauryl sulfate simulated muscle fluid [0.5% , with pH of (7.0 ±0.05)] at (37 ±0.5)℃was used as the bio-relevant dissolution media. Results: The linearity between the peak areas and the concentrations was observed within the range of 2. 15-107. 40 mg·L-1(r=0. 999 9) for pamoate and 1. 75-87. 40 mg·L-1(r=0. 999 9) for olanzapine, respec-tively, and the average recovery of olanzapine pamoate was 99. 80%(RSD=0. 55%, n=9). The f2 for the dissolution in the dissolu-tion medium of shelf-prepared products and the innovation preparations was 70. 80. Conclusion:The dissolution method can be utilized to control the quality of olanzapine pamoate long-acting injections.

AIM:To study the effects and mechanisms of ethanol on chloride channels in poorly differentiated nasopharyngeal carcinoma CNE-2Z cells.METHODS:The effect of ethanol on the cell growth was analyzed by MTT as-say.The technique of whole-cell patch-clamp was used to detect the chloride current .The characteristics of the chloride current were analyzed by using the chloride channel blockers .The siRNA technique was used to analyze the molecular basis of the ethanol-sensitive chloride channels .RESULTS: Under isotonic conditions , the background current was weak and stable.Ethanol at concentrations of 0.17~170 mmol/L activated a chloride current in a concentration-dependent manner (an inverted U-shape), with a maximum effect at the concentration of 17 mmol/L.The currents showed obviously outward rectification and were susceptible to extracellular hypertonicity and the chloride channel blocker , 5-nitro-2-(3-phenylpropyl-amino) benzoic acid ( NPPB) .ClC-3 siRNA obviously decreased the currents activated by ethanol .CONCLUSION:Ex-tracellular ethanol induces chloride currents through activating the ClC-3 chloride channels .