Working memory is an executive memory process that includes encoding, maintenance, and retrieval. These processes can be modulated by transcranial alternating current stimulation (tACS) with sinusoidal waves. However, little is known about the impact of the rate of current change on working memory. In this study, we aimed to investigate the effects of two types of tACS with different rates of current change on working memory performance and brain activity. We applied a randomized, single-blind design and divided 81 young participants who received triangular wave tACS, sinusoidal wave tACS, or sham stimulation into three groups. Participants performed n-back tasks, and electroencephalograms were recorded before, during, and after active or sham stimulation. Compared to the baseline, working memory performance (accuracy and response time) improved after stimulation under all stimulation conditions. According to drift-diffusion model analysis, triangular wave tACS significantly increased the efficiency of non-target information processing. In addition, compared with sham conditions, triangular wave tACS reduced alpha power oscillations in the occipital lobe throughout the encoding period, while sinusoidal wave tACS increased theta power in the central frontal region only during the later encoding period. The brain network connectivity results showed that triangular wave tACS improved the clustering coefficient, local efficiency, and node degree intensity in the early encoding stage, and these parameters were positively correlated with the non-target drift rate and decision starting point. Our findings on how tACS modulates working memory indicate that triangular wave tACS significantly enhances brain network connectivity during the early encoding stage, demonstrating an improvement in the efficiency of working memory processing. In contrast, sinusoidal wave tACS increased the theta power during the later encoding stage, suggesting its potential critical role in late-stage information processing. These findings provide valuable insights into the potential mechanisms by which tACS modulates working memory.
Humans ; Memory, Short-Term/physiology* ; Male ; Female ; Young Adult ; Transcranial Direct Current Stimulation/methods* ; Brain/physiology* ; Adult ; Electroencephalography ; Single-Blind Method

This study aims to prepare altrenogest extended-release tablets,evaluate their quality and establish a content determination method.The hydrophilic gel skeleton type,dosage and core thick-ness of altrenogest extended-release tablets were used as the investigating factors,and the release degree of the tablets was used as the investigating index,the prescription process of altrenogest ex-tended-release tablets was optimized by one-factor screening and central combinatorial design re-sponse surface method,and quality evaluation was carried out,the in vitro release model was es-tablished,and a high-performance liquid chromatography(HPLC)assay method was set up for the determination of altrenogest extended-release tablets.The results showed that the optimal pre-scription of altrenogest extended-release tablets was 2％as the main drug,70％as the solubilizer,0.5％as the lubricant,19.1％as the filler,8.4％as the hydrophilic gel skeleton material,and the thickness of the tablets was 3.8 mm.The in vitro drug release conformed to the Higuchi model,and the altrenogest showed a good linear relationship with the R2=0.999 98 in the range of 10-80 mg/L.The optimized process for the extended-release tablets was stable and had a good quality.The extended-release tablets were stable and had significant slow-release effect.The HPLC method is accurate and reliable and can be used for the determination of altrenogest in extended-release tablets.

Albendazole sulfoxide and ivermectin compound pouring agent were prepared with dime-thyl sulfoxide and 1,2-propanediol as solvents.The central composite design response surface method was used to optimize the formula of pouring agent.Franz diffusion cell method was used to investigate the transdermal performance of pouring agent in vitro.The permeation amounts of the two drugs were determined by HPLC.The best formula of pouring agent was ivermectin 0.5％,al-bendazole sulfoxide 5％,dimethyl sulfoxide 52％,propylene glycol 39％,and the rest was 100％anhydrous ethanol.The cumulative permeation amounts of ivermectin and albendazole sulfoxide were up to 20.78 μg/cm2 and 249.02 μg/cm2,respectively.The in vitro release model of the two drugs accords with the first-order kinetic equation.There is a good linear relationship between al-bendazole sulfoxide and ivermectin in the range of 1-100 mg/L and the peak area.The precision and stability RSD of the two methods are less than 2％.The preparation process of albendazole sul-foxide compound pouring agent is simple,stable and easy to pour.The established HPLC method is simple and accurate,and can be used for the determination of albendazole sulfoxide and ivermectin in pouring agent.

Objective:To identify the risk factors for intraoperative hemorrhage and transfusion in patients undergoing off-pump coronary artery bypass grafting (OPCABG).Methods:A total of 1, 442 patients, regardless of gender, of American Society of Anesthesiologists Physical Status classification≥Ⅱ, scheduled for elective OPCABG from June 7, 2021 to March 8, 2023, were enrolled in a prospective, observational study. Patients′ general characteristics, preoperative hemodynamics, preoperative blood routine, duration of operation, the number of transplanted vessels, intraoperative application of vasoactive agents, intraoperative consumption of crystalloid and colloid, urine volume, blood products, use of tranatemic acid and ulinastatin were collected. Univariable and multiple linear regression models were used to screen the risk factors for intraoperative blood loss and infusion volume of concentrated red blood cell (CRBC), and univariable and multivariable logistic regression models were used to screen the risk factors for intraoperative CRBC infusion requirement.Results:One thousand four hundred and twenty patients were finally included. Prolonged operation duration, increased number of transplanted vessels and older age were risk factors for intraoperative blood loss, while male, increased intraoperative usage of fresh frozen plasma (FFP), increased urine volume, and application of ulinastatin and tranexamic acid were protective factors for intraoperative blood loss in OPCABG patients ( P<0.05). Prolonged operation duration and increased intraoperative usage of FFP were risk factors for intraoperative CRBC transfusion volume, while elevation of preoperative hemoglobin levels was a protective factor for intraoperative CRBC transfusion volume in OPCABG patients ( P<0.05). Prolonged operation duration and increased intraoperative usage of FFP were risk factors for intraoperative CRBC infusion requirement, while increased body mass index, elevation of preoperative hemoglobin levels and application of ulinastatin were protective factors for CRBC infusion requirement ( P<0.05). Conclusions:Prolonged operation duration, increased number of transplanted vessels and older age are risk factors for intraoperative blood loss, and increased intraoperative usage of FFP, increased urine volume, and application of ulinastatin and tranexamic acid are protective factors for intraoperative blood loss in OPCABG patients. Prolonged operation duration and increased intraoperative usage of FFP are risk factors for intraoperative CRBC infusion requirement and transfusion volume, elevation of preoperative hemoglobin levels is a protective factor for intraoperative CRBC infusion volume, and increased body mass index, elevation of preoperative hemoglobin levels and intraoperative application of ulinastatin are protective factors for intraoperative CRBC infusion requirement in patients undergoing OPCABG.

Objective:To evaluate the effects of sevoflurane on right ventricular myocardial fibrosis caused by pulmonary arterial hypertension (PAH) in rats.Methods:Eighteen SPF healthy adult male Wistar rats, weighing 260-300 g, were divided into 3 groups ( n=6 each) by a random number table method: control group (group C), group PAH and PAH plus sevoflurane group (group PS). The PAH model was established by single intraperitoneal injection of monocrotaline 60 mg/kg in group PAH and group PS, while the equal volume of normal saline was intraperitoneally injected in group C. Sevoflurane 1.5 MAC was inhaled for 1 h starting from the end of injection, twice a week for 6 weeks in total, in group PS.Echocardiography was performed at the end of 6th week to measure right ventricular end-diastolic diameter (RVEDD), right ventricular anterior wall end-diastolic thickness (RVWTd), interventricular septal end-diastolic thickness (IVSTd), pulmonary artery inner diameter (PAID) and pulmonary valve orifice maximum peak velocity (PV). At the end of 6th week, the hearts were taken to measure the weight of right ventricle, interventricular septum and left ventricle, and Fulton′s index was calculated, and the tissue of the lower lobe of the right lung was taken, the outer diameter and inner diameter of the vascular wall were measured to calculate the vascular wall thickness index (WT), and total vascular area and lumen area were measured to calculate the vascular wall area index (WA) after HE staining.The myocardial tissue of the right ventricle was obtained to observe the degree of myocardial fibrosis (with a light microscope after Masson staining) and to detect the expression of TGF-β1 (after immunofluorescence staining) and expression of TGF-β1, phosphorylated Smad3 (p-SMad3) and Smad7 (by Western blot). Results:Compared with group C, Fulton′s index, RVEDD, RVWTd, IVSTd, PAID, WT and WA were significantly increased, PV was decreased, the expression of TGF-β1 and pSmad3 in right ventricular myocardial tissues was up-regulated, the expression of Smad7 was down-regulated( P<0.01), and myocardial fibrosis occurred in group PAH.Compared with group PAH, Fulton′s index, RVEDD, RVWTd, IVSTd, PAID, WT and WA were significantly decreased, PV was increased, the expression of TGF-β1 and pSmad3 in right ventricular myocardial tissues was down-regulated, the expression of Smad7 was up-regulated ( P<0.05 or 0.01), and myocardial fibrosis was significantly improved in group PS. Conclusion:Sevoflurane can improve the myocardial fibrosis in right ventricle induced by PAH in rats, and the mechanism may be related to inhibiting activation of TGF-β1/Smad3 signaling pathway.

Objective:To study the clinical features of children with Prader-Willi syndrome(PWS).Methods:Eighteen cases of PWS were collected from July 2016 to November 2018 in Shenzhen Maternal and Child Healthcare Hospital, Southern Medical University.The clinical data of children with PWS were analyzed retrospectively.Results:There were 12 males and 6 females in 18 cases with PWS.The diagnosis age ranged from 25 days to 9.5 years old [(3.09±3.02) years old]. Among them, 11 cases were in infancy (≤3 years old) and 7 cases after infancy (>3 years old). The main clinical features of infants with PWS were 11 cases of gonadal dysplasia (100.0%), 11 cases of psychomotor retardation (100.0%), 10 cases of hypotonia (90.1%), 6 cases of feeding difficulty and weak cry (54.5%). After infancy the main clinical features included 7 cases of psychomotor retardation (100.0%), 5 cases of hyperphagia(71.4%), 5 cases of obesity (71.4%), 5 cases of abnormal behavior problems (71.4%) and 4 cases of visual problems (57.1%). The clinical features of all patients throughout the developmental stage were as follows: decreased fetal movement, hypoplasia, neonatal hypotonia, weak cry, feeding difficulty, psychomotor delay, hyperphagia, obesity, abnormal behavior problems, and so on.Conclusions:The clinical features of PWS vary with age.The main clinical features in the infancy are hypotonia, weak cry, difficulty feeding and gonadal dysplasia.After infancy, there are hyperphagia, obesity, behavior and visual problems.And psychomotor retardation is present in the whole developmental stage of children with PWS.Early diagnosis and treatment are important for improving the prognosis of PWS.

[摘 要] 目的：探讨过表达miR-497靶向细胞周期蛋白E1（cyclin E1，CCNE1）对肺癌A549细胞上皮间质转化（epithelial-mesenchymal transition，EMT）的影响。方法：常规培养人肺癌A549细胞，细胞实验分为正常组（不加干预）、对照组（转染miR-497 mimics-NC）、实验组（转染miR-497 mimics）。采用Transwell小室实验、免疫荧光染色、qPCR、Western blotting法分别检测各组细胞迁移和侵袭能力、蛋白间质标志物α-SMA和上皮标志物E-cadherin的表达、miR-497和CCNE1的表达水平，荧光素酶基因基因报告实验验证miR-497和CCNE1的靶向关系。结果：与对照组和正常组相比，实验组A549细胞迁移和侵袭的数量明显减少（均P<0.05），细胞的间质标志物α-SMA的绿色荧光强度明显减弱[（36.95±5.81） vs （98.69±2.36）、（97.94±2.63），均P<0.05]，上皮标志物E-cadherin的绿色荧光强度明显增强[（388.41±10.93） vs （100.95±6.37）、（102.55±3.18），均P<0.05]，miR-497的表达明显升高（均P<0.05），CCNE1的表达均明显下降（均P<0.05）。miR-497能够靶向调控CCNE1的表达。结论：在肺癌A549细胞中miR-497能够靶向调控CCNE1的表达，上调miR-497的表达后能明显抑制A549细胞迁移和侵袭能力，影响EMT相关蛋白的表达。

Objective To prepare naloxone hydrochloride nasal spray and evaluate the ciliotoxicity and pharmacokinetics of the formulation. Methods The stability of naloxone hydrochloride was studied in pH3.5-5.5. Penetration promoting effects of absorp-tion enhancers on the naloxone hydrochloride were evaluated. Nasal ciliotoxicity studies were carried out using isolated toad palate. Rats were treated with naloxone hydrochloride solution by intramuscular injection of nasal drops to evaluate the pharmacokinetics. Results Naloxone hydrochloride solution was stable in pH3.5-5.5. Disodium ethylenediaminetetraacetic acid(0.2%,W/V)had the best penetration promoting effect on naloxone hydrochloride. Naloxone hydrochloride nasal spray did not exhibit obvious nasal ciliotox-icity compared to the negative control. The nasal spray had a faster therapeutic effect and its bioavailability was similar to that of the in-tramuscular injection. Conclusion Naloxone hydrochloride nasal spray prepared in this research is stable with no obvious nasal cilio-toxicity,has faster therapeutic effect,and good bioavailability,so may have a broad application prospect.

Objective To compare the release rate and bioavailability of progesterone injection with different particle sizes. Methods The preparation of progesterone nano sized injection and micron sized injection were performed by power X-ray diffraction (PXRD)and Fourier trensform infrared spectooscory(FTIR). The dissolution rate of two preparations and progesterone was compared by dialysis Method. HPLC-MS method was used to determine the progesterone concentration of plasma in rats after intramuscular injec-tion of different preparations,and the main pharmacokinetic parameters were calculated and analyzed statistically. Results Based on the analysis of PXRD and FTIR,there were no crystal structure changes between the two preparations and progesterone. The complete release of progesterone nano sized injection and micron sized injection required 2 and 4 h in the PBS solution,respectively,while the release of progesterone required nearly 40 h. In the pharmacokinetic experiment,compared with progesterone injection,the Cmax of pro-gesterone nano sized injection and micron sized injection were increased by 1.8 and 1.7 times,respectively;the AUC0-t were increased by 2.95 and 1.63 times,respectively. The bioavailability of both was higher than that of progesterone injection. Conclusion The re-lease rate bioavailability of progesterone nano sized injection and micron sized injection is higher than that of progesterone and proges-terone injection. Bioavailability of progesterone nano sized injection is higher than that of progesterone micron sized injection.

ObjectiveTo explore the construction of mouse model of liver implanted tumor after hepatectomy by implantation of liver tumor tissue.MethodsH22 hepatocellular carcinoma (HCC) cells of mice were implanted to the scapula of 2 BALB/c (nu/nu) nude mice and tumors developed in 2 weeks. Eighteen nude mice were divided into three groups according to random number table method: non-hepatectomy group (group A), 30% hepatectomy group (group B) and 70% hepatectomy group (group C) with 6 mice in each group. The hepatectomy model of nude mice was established. The left lateral lobe and middle lobe were dissected for the nude mice in group A. The tissues of left lateral lobe were ligated and resected in group B. And the tissues of left lateralobe and middle lobe were ligated and resected in group C. The tumor tissues incised from the scapula were implanted to the livers of nude mice in three groups. The tumor formation rate and the volume of implanted tumors of three groups were compared. The tumor formation rate was compared using Fisher's exact probability test, and the volume of implanted tumors was compared using Kruskal-Wallis test and Bonferroni method.ResultsThe tumor formation rate of group A, B and C after 2 weeks was respectively 6/6, 6/6 and 5/6, and no signiifcant difference was observed (P=1.000). The median volume of implanted tumors in group A, B and C was respectively 19(6-33), 22(8-44) and 150(58-186) mm3. The median volume of implanted tumors in group C was signiifcantly larger than those in group A and B (Z=9.03, 7.12;P<0.0167). The implanted tumors in three groups were all conifrmed as HCC and with different degrees of necrosis and inlfammatory cell inifltration by histopathological examination.ConclusionsImplantation of liver tumor tissue can be used to construct an ideal mouse model of liver implanted tumor after major hepatectomy with the advantages of short experimental period, high tumor formation rate and good stability.