Objective:To explore the mediating role of working memory (WM) in the cortisol-awakening response (CAR) and multiple object tracking (MOT) in children with attention deficit hyperactivity disorder (ADHD).Methods:92 children with ADHD (ADHD group) and 94 typically developing children (control group) were selected from January 2022 to October 2022. Salivary cortisol levels were detected and analyzed in all children at four time points after awakening. Children's WM and MOT performance were assessed by the 1-back and MOT paradigms, respectively. SPSS 26.0 software was used for t-test and Pearson correlation analysis of the data, and plug-in PROCESS model 4 of SPSS 26.0 was used for mediated effects analysis. Results:(1) ADHD group showed significantly lower CAR, 1-back accuracy and MOT performance((30.97±5.63), (81.33±10.64) %, (2.36±0.37)) than the control group((32.41±3.48), (91.19±7.12) %, (2.62±0.28))( t=-2.09, -7.22, -5.31, all P<0.05). (2) Pearson analysis showed that CAR was positively correlated with 1-back accuracy ( r=0.293, P<0.01) and MOT performance ( r=0.740, P<0.01). 1-back accuracy was positively correlated with MOT performance ( r=0.368, P<0.01). (3) WM partially mediated the effect of CAR on MOT in children with ADHD, accounting for 6.13% (0.003/0.049) of the total effect. Conclusion:Children with ADHD have deficits in MOT.WM plays a mediating role between CAR and MOT performance in children with ADHD.

Objective:To evaluate the safety and clinical efficacy of hypofractionated radiotherapy (HFRT) at 36.5 Gy in 10 fractions for the chest wall and reginal lymph nodes following modified radical mastectomy for breast cancer.Methods:This was a prospective, single-arm, phase Ⅱ clinical study. A total of 85 patients who received HFRT at 36.5 Gy in 10 fractions to the chest wall ± supraclavicular region following modified radical mastectomy for locally advanced breast cancer from March 2014 to December 2015 were included. The primary endpoint was radiotherapy toxicities. The secondary endpoints were locoregional failure-free survival (LRFFS), disease-free survival (DFS), and overall survival (OS).Results:The median follow-up period was 98 (94.0-109.0) months. Radiotherapy toxicities were mild. The incidence rates of grade 1 acute cutaneous and pulmonary toxicities were 52.9% and 40%, and those of grade 1 late cutaneous, pulmonary, and cardiac toxicities and upper extremity edema were 10.6%, 29.4%, 2.4%, and 21.2%, respectively. Only 1 (1.2%) patient suffered from grade 2 radiation-induced brachial plexus injury. Of the 85 patients, one patient had regional recurrence (supraclavicular lymph nodes), six patients had distant metastasis, and six patients died of breast cancer. The 9-year LRFFS, DFS, and OS were 97.7%, 91.8%, and 92.8%, respectively.Conclusions:HFRT at 36.5 Gy in 10 fractions following modified radical mastectomy for breast cancer is associated with mild toxicities. A phase Ⅲ study is necessary for validating HFRT's clinical efficacy.

The kidneys are one of the main excretory organs for drugs and when drugs are not excreted effectively, they can accumulate in the kidneys or in the interstitial tubules, leading to drug-induced kidney injury. The tubulointerstitium accounts for 80% of the volume of the kidney and is the primary site of response to various types of renal injury. This article focuses on drug-induced acute interstitial nephritis, highlighting its clinical symptoms, listing common induction drugs, analysing pathological features, and explaining its pathogenesis from the perspective of immune response, with the aim of providing a basic and clinical evidence for subsequent studies.

Renal tubular secretion mediated by organic anion transporters(OATs)and the multidrug resistance-associated protein 4(MRP4)is an important means of drug and toxin excretion.Unfortunately,there are no biomarkers to evaluate their function.The aim of this study was to identify and characterize an endogenous biomarker of the renal tubular OATs-MRP4 channel.Twenty-six uremic toxins were selected as candidate compounds,of which kynurenic acid was identified as a potential biomarker by assessing the protein-binding ratio and the uptake in OAT1-,OAT3-,and MRP4-overexpressing cell lines.OAT1/3 and MRP4 mediated the transcellular vectorial transport of kynurenic acid in vitro.Serum kynurenic acid concentration was dramatically increased in rats treated with a rat OAT1/3(rOAT1/3)inhibitor and in rOAT1/3 double knockout(rOAT1/3-/-)rats,and the renal concentrations were markedly elevated by the rat MRP4(rMRP4)inhibitor.Kynurenic acid was not filtered at the glomerulus(99％of albumin binding),and was specifically secreted in renal tubules through the OAT1/3-MRP4 channel with an appropriate affinity(Km)(496.7 μM and 382.2 μM for OAT1 and OAT3,respectively)and renal clearance half-life(ti/2)in vivo(3.7±0.7 h).There is a strong correlation in area under the plasma drug concentration-time curve(AUC0-t)between cefmetazole and kynurenic acid,but not with creatinine,after inhibition of rOATs.In addition,the phase of increased kynurenic acid level is earlier than that of creatinine in acute kidney injury process.These results suggest that albumin-bound kynurenic acid is an appropriate endogenous biomarker for adjusting the dosage of drugs secreted by this channel or predicting kidney injury.

Objective:To investigate the effects of different doses of dexmedetomidine (Dex) on heart rate variability (HRV) in patients with non-ST-segment elevation myocardial infarction (NSTEMI).Methods:The clinical data of 144 patients with NSTEMI from January 2017 to October 2020 in the 942 Hospital of Chinese PLA were analyzed retrospectively. Among them, 36 cases were treated with Dex 0.05 to 0.15 μg/(kg·h) (Dex1 group), 36 cases with Dex 0.20 to 0.40 μg/(kg·h) (Dex2 group), 36 cases with Dex 0.50 to 0.70 μg/(kg·h) (Dex3 group), and 36 cases without Dex (control group). The changes of HRV time domain indexes, frequency domain indexes and prognosis index before and after treatment were compared among 4 groups, the time domain indexes include normal R-R interval standard deviation (SDNN), mean value of adjacent normal R-R interval standard deviation (SDANNindex), root mean square of adjacent normal R-R interval standard deviation (SDNNindex), square root of adjacent normal R-R interval difference (rMSSD) and percentage of adjacent normal R-R interval difference>50 ms to R-R interval number (PNN50); the frequency domain indexes include total power (TP), low frequency power (LF), high frequency power (HF), ultra-low frequency power (VLF) and LF/HF; the prognostic indexes include ICU stay time, vasoactive drug use time, 28-day mortality and incidence of complication.Results:There was no significant difference in HRV indexes among 4 groups before treatment ( P>0.05); after treatment, except for LF/HF in Dex2 group and Dex3 group was significantly lower than that in control group and Dex1 group, other HRV indexes were significantly higher than those in control group and Dex1 group, and there were statistical differences ( P<0.05). There was no significant difference in 28-day mortality among 4 groups; the ICU stay time and vasoactive drug use time in Dex2 group were significantly shorter than those in control group, Dex1 group and Dex3 group: (7.14 ± 1.25) d vs. (9.08 ± 1.68), (9.53 ± 1.98) and (9.81 ± 1.95) d, (122.67 ± 29.5) h vs. (176.15 ± 23.26), (181.72 ± 23.40) and (180.42 ± 22.90) h, the incidence of complication was significantly lower than that in control group, Dex1 group and Dex3 group: 16.67% (6/36) vs. 72.22% (26/36), 47.22% (17/36) and 61.67% (22/36), and there were statistical differences ( P<0.05); there were no statistical difference in ICU stay time, vasoactive drug use time and incidence of complication among control group, Dex1 group and Dex3 group ( P>0.05). Conclusions:Dex 0.20 to 0.40 μg/(kg·h) is well tolerated, and has less adverse reactions. It can effectively increase HRV, regulate the balance of sympathetic-vagal nerve tension, stabilize cardiovascular response and improve prognosis in patients with NSTEMI.

OBJECTIVE：To study t he effects of bro mophenylcurcumin（GL63）on the apoptosis ，migration and invasion of human cholangiocarcinoma RBE cells ，and to investigate its mechanism based on JAK/STAT signaling pathway. METHODS ：MTT assay was used to detect the effects of different concentrations of GL 63 [0（blank control ，similarly hereinafter ），1.25，2.5，5，10， 20，40 μ mol/L] on the proliferation of RBE cells after 48 h treatment ；the IC 50 was calculated. The effects of different concentrations of GL 63（0，5，10，20 μmol/L）on colony formation were detected by crystal violet staining after 48 h treatment. Flow cytometry ，Hoechst 33342 staining，cell scratch test and Transwell chamber invasion test were used to detect the effects of different concentrations of GL 63（0，5，10，20 μmol/L）on cell cycle distribution ，apoptosis，migration and invasion ability after 24 h treatment. Western blotting assay was adopted to detect the effects of different concentration of GL 63（0，5，10，20 μmol/L） on the expression of JAK 2/STAT3 signal pathway associated proteins. RESULTS ：The proliferation inhibition rates of RBE cells in different concentrations of GL 63 groups（1.25-40 μmol/L）were significantly increase d，compared with blank control group （P＜ 0.01），and showed a dose-dependent trend ，with IC 50 of （8.46±1.30）μmol/L. Compared with blank control group， 85917439。E-mail：zhaoji-an-88@163.com inhibition rates of RBE cell colony formation were significantly decreased in different concentrations （5，10，20 μmol/L）of GL 63 groups（P＜0.01）. The percentage of RBE cells at G 0/G1 phase increased significantly ，while that at S phase decreased significantly （P＜0.01）. The apoptotic rate increased significantly（P＜0.01），and the nucleus showed dense pyknosis and apoptotic bodies. The rate of cell migration and healing was significantly decreased （P＜0.01），and the number of invasive cells through basement membrane was significantly decreased （P＜ 0.01）. The protein expression of p-JAK 2， p-STAT3， Bcl-2， MMP-2， MMP-9， Pro-caspase-9 and P ro-caspase-3 were down-regulated significantly while the expression of Bax ，Cyt-c，Cleaved-caspase-9 and Cleaved-caspase- 3 were up-regulated significantly（P＜0.01）. CONCLUSIONS ：GL63 may inhibit the proliferation ，migration and invasion of RBE cells and promote its apoptosis by inhibiting JAK 2/STAT3 signal pathway.

Stroke is considered a leading cause of mortality and neurological disability, which puts a huge burden on individuals and the community. To date, effective therapy for stroke has been limited by its complex pathological mechanisms. Autophagy refers to an intracellular degrading process with the involvement of lysosomes. Autophagy plays a critical role in maintaining the homeostasis and survival of cells by eliminating damaged or non-essential cellular constituents. Increasing evidence support that autophagy protects neuronal cells from ischemic injury. However, under certain circumstances, autophagy activation induces cell death and aggravates ischemic brain injury. Diverse naturally derived compounds have been found to modulate autophagy and exert neuroprotection against stroke. In the present work, we have reviewed recent advances in naturally derived compounds that regulate autophagy and discussed their potential application in stroke treatment.

Objective:To investigate the effect of bilateral salpingectomy on ovarian response in controlled ovarian stimulation (COS) cycles of women with hydrosalpinx.Methods:Women with hydrosalpinx who underwent bilateral salpingectomy and COS before and after salpingectomy within 1 year between Jan. 2010 and Nov. 2017 in Peking University Third Hospital were included in study group. Women with male factor infertility who received COS at the same period and matched with age according to the ratio of 1:2 were included in control group. A retrospective analysis of ovarian reserve and COS before and after salpingectomy in study group and between the two groups was performed.Results:A total of 132 patients were recruited in study group and 264 patients in control group. Compared between after and before salpingectomy in study group, there were no significant diffrences in basal serum follicle-stimulating hormorne (FSH) level [(6.76±2.15) IU/L vs. (6.62±2.03) IU/L, P=0.589], estradiol level [(160.77±66.20) pmol/L vs. (161.58±66.42) pmol/L, P=0.922], antral follicle count （AFC） (9.36±4.28 vs. 10.27±5.01, P=0.135), the number of oocytes retrieved (11.18±7.43 vs. 11.68±6.20, P=0.278) and viable embryos (4.82±4.14 vs. 5.14±3.55, P=0.166). Between study group and control group, there were no differences in age, basal FSH, estradiol level, AFC, duration and dosage of gonadotropin （Gn） used, number of oocytes collected and transferable embryos ( P>0.05). Conclusion:Careful bilateral salpingectomy does not decrease ovarian reserve and response in COS cycles of women with normal ovarian reserve.

Objective:To investigate the effect of bilateral salpingectomy on ovarian response in controlled ovarian stimulation (COS) cycles of women with hydrosalpinx.Methods:Women with hydrosalpinx who underwent bilateral salpingectomy and COS before and after salpingectomy within 1 year between Jan. 2010 and Nov. 2017 in Peking University Third Hospital were included in study group. Women with male factor infertility who received COS at the same period and matched with age according to the ratio of 1:2 were included in control group. A retrospective analysis of ovarian reserve and COS before and after salpingectomy in study group and between the two groups was performed.Results:A total of 132 patients were recruited in study group and 264 patients in control group. Compared between after and before salpingectomy in study group, there were no significant diffrences in basal serum follicle-stimulating hormorne (FSH) level [(6.76±2.15) IU/L vs. (6.62±2.03) IU/L, P=0.589], estradiol level [(160.77±66.20) pmol/L vs. (161.58±66.42) pmol/L, P=0.922], antral follicle count （AFC） (9.36±4.28 vs. 10.27±5.01, P=0.135), the number of oocytes retrieved (11.18±7.43 vs. 11.68±6.20, P=0.278) and viable embryos (4.82±4.14 vs. 5.14±3.55, P=0.166). Between study group and control group, there were no differences in age, basal FSH, estradiol level, AFC, duration and dosage of gonadotropin （Gn） used, number of oocytes collected and transferable embryos ( P>0.05). Conclusion:Careful bilateral salpingectomy does not decrease ovarian reserve and response in COS cycles of women with normal ovarian reserve.

Objective To evaluate the therapeutic effects of flute-needle vacuum assistant hole closure technique for large idiopathic macular hole (IMH).Methods The clinical data of 25 eyes with IMH of 408-939 μm in 23 patients who received pars plana vitrectomy with internal limiting membrane (ILM) peeling and flute-needle vacuum assistant hole closure technique from Feburary in 2017 to June in 2018 in Peking University International Hospital were retrospectively analyzed.The changes of best corrected visual acuity (BCVA) before and after operation were evaluated.The shapes of the hole closure were categorized,and the manifestations of outer retina were observed by optical coherence tomography (OCT),including external limiting membrane (ELM) and ellipsoid zone(EZ).Results The hole closure rate after surgery were 100％ (25/25),with the U type closure in 16 eyes and V type closure in 9 eyes.The BCVA was 0.76 ± 0.27 after operation,which was significantly improved in comparison with 1.05 ±0.29 before operation (t =3.61,P =0.01).The ELM of OCT image was (1 050.00±380.39)μm before operation,and that after operation reduced to (623.32 ± 328.66) μm,showing a significant difference between them (t =6.63,P=0.00).A fully reduced EZ band was seen after operation in comparison with before operation ([1 147.28±354.41] μm versus ([818.28±247.33] μm) (t=4.12,P=0.00).Conclusions A combination procedure of vitrectomy with flute-needle vacuum assistant hole closure technique is effective for large IMH,which is beneficial to the anatomical repair and functional recovery of outer retina.