Objective To investigate the sleep architecture of sleep related bruxism（SB）in adults and the sleep architecture of SB comorbid with obstructive sleep apnea hypopnea syndrome（OSAHS），as well as their correlation with age and other factors. Methods A total of 51 subjects with SB and 67 controls were included in this study to analyze the sleep architecture of SB and compare the sleep architecture of SB comorbid with different severities of OSAHS. Results Compared with the control group，the SB group had a younger age，increases in N1（%TST）and N2（%TST），a reduction in N3（%TST），and an increase in arousal index. The SB group was divided into non-OSAHS group（group 1），mild OSAHS group（group 2），and moderate-to-severe OSAHS group（group 3）. Group 1 had a younger age than group 2 and group 3，and group 3 had increases in body mass index（BMI），N1（%TST），oxygen desaturation index（ODI），and arousal index and a reduction in N3（%TST）. The Spearman's rank correlation analysis showed that BMI，N1（%TST），arousal index，and ODI increased with the increase in apnea-hypopnea index（AHI），while N3（%TST）decreased with the increase in AHI. The binary logistic regression analysis showed that SB was negatively correlated with age and was positively correlated with arousal index. Conclusion SB may affect sleep architecture by increasing light sleep，reducing deep sleep，and increasing the number of awakenings. There are changes in sleep architecture in case of SB comorbid with different severities of OSAHS. SB is negatively correlated with age and is positively correlated with arousal index.
Polysomnography

Background Existing studies have confirmed that fine particulate matter (PM_2.5)is one of the important factors inducing pulmonary fibrosis. Pulmonary fibrosis is the terminal stage of a major category of lung diseases characterized by the destruction of tissue structure, and eventually leading lung ventilation and ventilation dysfunction. No effective pulmonary fibrosis treatment is available yet. Objective To investigate the protective effect of salidroside on pulmonary fibrosis induced by the exposure of PM_2.5 and its molecular mechanism. Methods Seventy 7-week-old male C57BL/6 mice were randomly divided into four groups: control group (intratracheal instillation of normal saline + saline by gavage, n=25), Sal group (intratracheal instillation of normal saline + Sal 60 mg·kg⁻¹ by gavage, n=10), PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ + saline by gavage, n=10), and Sal + PM_2.5 group (intratracheal instillation of PM_2.5 5 mg·kg⁻¹ +Sal 60 mg·kg⁻¹ by gavage, n=10). The mice were administered by gavage once daily, intratracheal instillation once every 3 d, and every 3 d constituted an experimental cycle. At the end of the 26-30th cycles, 3 mice in the control group and 3 mice in the PM_2.5 group were randomly sacrificed, and the lung tissues were collected for Masson staining to verify whether the pulmonary fibrosis model was successfully established. After 30 cycles, the model was successfully constructed. After 1 week of continuous observation, the mice were sacrificed, and the blood and lung tissues of the mice were collected to make lung tissue sections. Assay kits were correspondingly employed to detect oxidative stress indicators such as serum malondialdehyde (MDA) and superoxide dismutase (SOD). Western blotting was used to detect the expression of fibrosis-related proteins (Collagen-III, α-SMA), mitochondrial dynamics-related proteins (MFN1, Drp1), and mitophagy-related proteins (PINK1, Parkin, and LC3). Results Compared with the control group, the weight gain rate of the PM_2.5 group was slowed down (P<0.05), which was alleviated by the Sal intervention (P<0.05). The lung coefficient increased after the PM_2.5 exposure (P<0.05), which was alleviated by Sal intervention. Compared with the control group, the PM_2.5 group showed severe alveolar structure damage, inflammatory cell infiltration, and blue collagen deposition, and significantly increased the lung injury score, collagen volume fraction (CVF), Szapiel score, and Ashcroft score (P<0.05), as well as serum oxidative stress levels (P<0.05). The protein expression levels of Collagen-III, α-SMA, Drp1, PINK1, Parkin, and LC3 II/I were increased (P<0.05), and the expression of MFN1 was decreased (P<0.05). Compared with the PM_2.5 group, the Sal intervention alleviated lung injury, reduced inflammatory cell infiltration and collagen deposition, showing decreased lung injury score, CVF, Szapiel score, and Ashcroft score (P<0.05), and decreased serum oxidative stress levels (P<0.05); the protein expression levels of Collagen-III, α-SMA, PINK1, Parkin, and LC3 II/I were decreased (P<0.05), the expression level of Drp1 was decreased, and the expression level of MFN1 was increased. Conclusion In the process of pulmonary fibrosis induced by PM_2.5 exposure in mice, Sal may affect mitochondrial autophagy through PINK1/Parkin pathway and play a protective role. The specific mechanism needs to be further verified.

Objective To investigate the clinical diagnostic value of routine electroencephalogram(EEG)combined with serum miR-146a and miR-129-5p levels in drug-resistant epilepsy.Methods Sixty patients with refractory epilepsy admitted to our hospital from June 2021 to June 2023 were included in the refractory epilepsy group,and 40 healthy volunteers were included in the control group.Human microvascular endothelial drug-resistant cells(HBMECs)continuously exposed to PHT2 were cultured in vitro and transfected with miR-NC(the miR-NC group),miR-146a mimics(the miR-146a mimics group)and miR-129-5p mimics(the miR-129-5p mimics group),respectively.Western blod assay was used to detect the expression of high-mobility group protein B1(HMGB1)in each group.Serum miR-146a and miR-129-5p levels were detected by fluorescent quantitative PCR(polymerase chain reaction),and serum HMGB1 protein expression was detected by Western blod assay.The sensitivity,specificity and accuracy of routine EEG,serum miR-146a and miR-129-5p levels and combined diagnosis of drug-resistant epilepsy were evaluated using the comprehensive consultation results of several expert physicians as the gold standard,and ROC curves were drawn.Results Compared with the control group,the expression of HMGB1 was significantly decreased in the drug-resistant group.Compared with the miR-NC group,HMGB1 expression was significantly decreased in the miR-129-5p mimics group and the miR-146a mimics group(P＜0.05).Compared with the healthy group,the serum HMGB1 protein expression was down-regulated and miR-146a and miR-129-5p expression levels were significantly up-regulated in the refractory epilepsy group.ROC curve analysis indicated that the area under the curve,sensitivity,specificity and accuracy of conventional EEG combined with serum miR-146a and miR-129-5p levels were higher in the diagnosis of refractory epilepsy than that of single diagnostic method.Conclusion The combination of routine EEG and serum miR-129-5p and miR-146a levels can provide help for the diagnosis of drug-resistant patients.

Objective To investigate the association between sleep structure and respiratory events in patients with epilepsy. Methods A total of 95 patients with epilepsy and 66 control patients who attended our hospital from March 2018 to March 2022 were enrolled,and polysomnography was used to compare sleep structure and respiratory events between the epilepsy group and the control group. Results Compared with the control group,the epilepsy group had significant reductions in REM sleep duration and R%,a significant increase in the longest duration of hypoventilation,and a significant reduction in the lowest oxygen saturation. Conclusion Changes in sleep structure are observed in patients with epilepsy,and patients with epilepsy and obstructive sleep apnea-hypopnea syndrome tend to develop hypoxemia.

Objective:To observe the synaptic plasticity and characteristics of transmembrane calcium flux in the hippocampus of 3xTg-AD mice.Methods:According to different genotypes, 6-month-old mice were divided into two groups: APP/PS1/tau triple transgenic AD (3xTg-AD) model mice and wild type (WT) mice, with 13 mice in each group.Six mice were randomly selected from each group to do in vivo electrophysiological recording.Field excitatory postsynaptic potential (fEPSP) was evoked by test stimulation, paired-pulse facilitation (PPF) was induced by two stimuli, and long-term potentiation (LTP) was induced by high frequency stimulation (HFS) in the hippocampal CA1 region of mice.The remaining seven mice in each group were used to detect the transmembrane calcium influx and efflux in the slices of hippocampal CA1 region by using non-invasive micro-test technology (NMT). In the electrophysiological and NMT experiments, one mouse fell off respectively.Finally, five mice were enrolled in the electrophysiological experiment and six in the NMT experiment.SPSS 18.0 was used for statistical analysis of all data, and two independent sample t-test was used for comparison between the two groups. Results:(1) In the in vivo electrophysiological experiments, the fEPSP slopes of 3xTg-AD mice and WT mice evoked by test stimulation were stable within 30 min, and the average fEPSP slopes were ((97.8±2.3)%) and ((92.6±12.6)%), respectively.There was no statistical difference of the average fEPSP slopes between the two groups ( t=0.91, P>0.05). After paired-pulse stimulation, the PPF values of 3xTg-AD mice and WT mice were (1.58±0.69) and (1.74±0.17) respectively, and there was no statistical difference between the two groups ( t=0.50, P>0.05). At 30 min and 60 min post-HFS, the LTP values in 3xTg-AD mice were ((104.9±10.9)%) and ((98.0±10.8)%) respectively, which were significantly lower than those in WT mice((156.5±21.3)%, t=4.43, P<0.01; (162.5 ±19.7)%, t=5.92, P<0.01). (2) In NMT experiments, the standardized mean and peak velocities of glutamate-induced Ca 2+ influx in hippocampal CA1 region of 3xTg-AD mice were ((-2 166.0±425.0)%) and ((-3 539.6±1 270.9)%) respectively, which were significantly higher than those in WT mice((-735.3±262.9)%, t=6.81, P<0.01; (-917.3±271.7)%, t=4.89, P<0.01). The standardized average and peak velocities of low Ca 2+ solution-induced Ca 2+ efflux in 3xTg-AD mice were ((1 451.6±297.1)%) and ((1 968.7±227.3)%) respectively, which were significantly lower than those in WT mice((2 579.3±810.9)%, t=2.92, P<0.05; (3 420.4±954.8)%, t=3.31, P<0.01). Conclusion:The hippocampal synaptic plasticity impairment observed in 6-month-old 3xTg-AD may be closely related with the intracellular Ca 2+ overload caused by increased calcium influx and decreased calcium efflux.

Objective:Recently, increasing number of lung cancer patients benefit from immune-checkpoint inhibitors (ICIs). However, the data of Chinese small cell lung cancer (SCLC) patients is limited. This study aims to analyze the response and survival data of ICIs treatment in SCLC and to explore the predictive biomarkers.Methods:Forty-seven SCLC patients who received ICIs treatment from Peking University Cancer Hospital from May 2017 to September 2019 was recruited. Clinical characteristics including sex, age, smoking status, ICIs strategy, PD-L1 expression and therapeutic efficacy were collected to explore the clinical predictive biomarkers for SCLC ICIs treatment.Results:Among the 47 patients, 18 (38.3%) cases were partial repose (PR), 11 (23.4%) were stable disease (SD), 18 (38.3%) were progressive disease (PD), and the objective response rate (ORR) was 38.3%, disease control rate (DCR) was 61.7%, the median progression-free survival (PFS) was 5.3 months. ICIs monotherapy accounts for 27.7%, the ORR was 15.4%, DCR was 53.8%, median PFS was 2.7 months. Combined therapy accounts for 72.3%, the ORR was 47.1%, DCR was 64.7%, median PFS was 5.4 months. Fourteen (29.8%) patients received ICIs as the first line treatment, their ORR was 85.7%, DCR was 100%, median PFS was 9.1 month. The ORR was not related to the age, sex, body mass index (BMI), smoking status and programmed death-ligand 1 (PD-L1) expression ( P>0.05). The ORRs were higher in patients underwent PD-L1 monotherapy ( P=0.001), combined therapy ( P=0.002) and received ICIs as the first line treatment ( P<0.001). Log-rank analysis indicated that the PFS of female patients were 12.0 months, significantly longer than 4.4 months of male patients in ICIs treatment ( P=0.038). Patients who received PD-L1 monotherapy, combined treatment, or ICIs as the first line treatment had longer PFS than their counterparts, though no statistical significant was observed ( P>0.05). Cox multivariate analysis showed that, the gender was not an independent predictor for PFS in ICIs treatment ( HR=3.777, 95% CI=0.974~30.891, P=0.054). Conclusions:Immunotherapy is an effective treatment strategy for SCLC. Patients who receive combined ICIs treatment, first line ICIs treatment and PD-L1 treatment may get greater benefits. PD-L1 expression cannot predict the response and PFS in SCLC ICIs treatment.

Objective:Recently, increasing number of lung cancer patients benefit from immune-checkpoint inhibitors (ICIs). However, the data of Chinese small cell lung cancer (SCLC) patients is limited. This study aims to analyze the response and survival data of ICIs treatment in SCLC and to explore the predictive biomarkers.Methods:Forty-seven SCLC patients who received ICIs treatment from Peking University Cancer Hospital from May 2017 to September 2019 was recruited. Clinical characteristics including sex, age, smoking status, ICIs strategy, PD-L1 expression and therapeutic efficacy were collected to explore the clinical predictive biomarkers for SCLC ICIs treatment.Results:Among the 47 patients, 18 (38.3%) cases were partial repose (PR), 11 (23.4%) were stable disease (SD), 18 (38.3%) were progressive disease (PD), and the objective response rate (ORR) was 38.3%, disease control rate (DCR) was 61.7%, the median progression-free survival (PFS) was 5.3 months. ICIs monotherapy accounts for 27.7%, the ORR was 15.4%, DCR was 53.8%, median PFS was 2.7 months. Combined therapy accounts for 72.3%, the ORR was 47.1%, DCR was 64.7%, median PFS was 5.4 months. Fourteen (29.8%) patients received ICIs as the first line treatment, their ORR was 85.7%, DCR was 100%, median PFS was 9.1 month. The ORR was not related to the age, sex, body mass index (BMI), smoking status and programmed death-ligand 1 (PD-L1) expression ( P>0.05). The ORRs were higher in patients underwent PD-L1 monotherapy ( P=0.001), combined therapy ( P=0.002) and received ICIs as the first line treatment ( P<0.001). Log-rank analysis indicated that the PFS of female patients were 12.0 months, significantly longer than 4.4 months of male patients in ICIs treatment ( P=0.038). Patients who received PD-L1 monotherapy, combined treatment, or ICIs as the first line treatment had longer PFS than their counterparts, though no statistical significant was observed ( P>0.05). Cox multivariate analysis showed that, the gender was not an independent predictor for PFS in ICIs treatment ( HR=3.777, 95% CI=0.974~30.891, P=0.054). Conclusions:Immunotherapy is an effective treatment strategy for SCLC. Patients who receive combined ICIs treatment, first line ICIs treatment and PD-L1 treatment may get greater benefits. PD-L1 expression cannot predict the response and PFS in SCLC ICIs treatment.

Objective To observe the effects of adiponectin (APN) on anxiety-and depression-like behaviors occurred in APP/PS1/tau triple transgenic Alzheimer's disease (3xTg-AD) model mice and investigate the possible mechanism.Methods The 9-month-old 3xTg-AD mice and wild type (WT) mice were randomly divided into four groups (n=8 for each group):WT+Saline,WT+APN,3xTg-AD+Saline and 3xTg-AD+APN groups.The mouse was chronically intracerebroventricular injection of APN or saline under free moving condition.Elevated plus maze task was used to evaluate the anxiety-like behaviors.Sucrose preference test and tail suspension test were used to evaluate the depression-like behaviors.Western blot was used to detect the protein expression levels of p-AMPK,AMPK,p-GSK-3β (Ser9),GSK-3β and SIRT1 in the hippocampus of each mouse.Results In the elevated plus maze test,the time percentage spent in open arms of 3xTg-AD+Saline mice was ((4.2±2.7) ％),which significantly lower than that in WT+Saline group ((10.1±4.1)％) (q=4.349,P＜0.01) and in 3xTg-AD+APN group ((9.7±3.3)％) (q=4.065,P＜0.01).In the sucrose preference test,the sucrose preference percentage in 3xTg-AD+Saline group((48.8±5.3) ％) was lower than that in WT+Saline group ((60.9±6.7) ％) (q=4.522,P＜0.01) and in 3xTg-AD+APN group ((59.3±6.2)％) (q=3.911,P＜0.05).As for tail suspension test,the immobility time percentage in 3xTg-AD+Saline group((40.7±9.9)％) was higher than that in WT+Saline group ((27.1±4.8)％) (q=5.257,P＜0.001) and in 3xTg-AD+APN group ((31.4±6.0)％) (q=3.624,P＜0.05).The result of Western blot showed that there was no significant difference in expression level of AMPK and GSK-3β among four groups.However,compared with that in WT+Saline group,the expression levels of p-AMPK (q=3.586,P＜0.05),p-GSK-3β (Ser9) (q=3.125,P＜0.05),and SIRT1 (q=3.044,P＜0.05) in 3xTg-AD+Saline group were significantly decreased.In addition,compared with that in 3xTg-AD+Saline group,the expression levels of p-AMPK (q=3.374,P＜0.05) and p-GSK-3β (Ser9) (q=3.063,P＜0.05) in 3xTg-AD+APN group were obviously up-regulated without affecting the SIRT1.Conclusion Adiponectin can effectively alleviate the anxiety-and depression-like behaviors of 9-month-old 3xTg-AD mice by up-regulating the protein expression of p-AMPK and p-GSK-3β (Ser9) in the hippocampus.

Objective To investigate the therapeutic effect of endoscopic plastic stent and metal stent placement in relieving obstructive jaundice in patients with pancreatic cancer,and to analyse the cost effectiveness.Methods A retrospective review was performed on the clinical data of 102 pancreatic cancer patients with obstructive jaundice in General Hospital of Northern Theater Command between January 2013 to January 2014.The patients were divided into plastic stent group (n =26) and metal stent group (n =76)based on the type of biliary stent placed under endoscopy.The complication and short-term therapeutic effect were compared between two groups.The number of endoscopic stent placement,treatment interval,hospitalization cost and median survival time were recorded.Results The levels of alanine aminotransferase (ALT) and total bilirubin (TBiL) in the two groups 5-7 days after endotherapy were significantly lower than those before treatment,but the difference was not statistically significant between the two groups (P ＜0.05).No severe complication was observed.The average number of treatments in the metal stent group was significantly lower than that in the plastic stent group (1.7 times vs 2.9 times),and the treatment interval was significantly longer[(271.7 ± 42.3) d vs (113.4 ± 38.2) d].The difference above between these two groups was statistically significant (P＜0.05).However,there was no significant difference on the average total hospitalization cost (84227.2 yuan vs 86906.8 yuan) or median survival time (15.6 months vs 13.1 months)between these two groups.Conclusions Primary placement of metal biliary stents for obstructive jaundice in adult patients with metastatic pancreatic carcinoma was cost-effective than plastic stents,and their effects were comparable.

Objective To investigate the prevalence of common enterovirus infections among children in Hangzhou ,2016 .Methods A total of 2977 of throat swabs samples or stool samples from suspected children with enterovirus infection at Hangzhou Children′s Hospital in 2016 were collected . Enterovirus universal nucleic acid ,enterovirus type 71 (EV71) ,Coxsackievirus A (CoxA)16 ,CoxA6 , CoxA4 and CoxA10 were detected by real-time fluorescent quantitative polyoneras chain reaction .The detection positive rates among children with different genders and ages were compared by χ2 test .Results The total enterovirus positive rate of 2977 specimens was 49 .7％ (1480/2977) .Among them ,CoxA6 , EV71 ,CoxA16 ,CoxA4 ,CoxA10 and other enteroviruses accounted for 30 .2％ (447) ,19％ (281) , 10 .2％ (151) ,6 .8％ (101) ,3 .4％ (51) and 30 .3％ (449) ,respectively .Among 1480 enterovirus positive children ,882 cases were male and 598 were female ,with no statistical significance (χ2 = 4 .564 , P=0 .471) .The detection rates of enterovirus in children with hand ,foot and mouth disease (HFMD ) , herpangina and other diseases were 64 .4％ (1051/1632) ,52 .4％ (323/616) and 14 .5％ (106/729) , respectively .The difference among groups was significant (χ2 =503 .387 , P<0 .01) .The prevalences of CoxA6 ,EV71 and CoxA16 in enterovirus-positive HFMD children were 36 .7％ (386) ,25 .3％ (266) and 12 .4％ (130 ) , respectively . The prevalences of CoxA4 , CoxA6 and CoxA10 in enterovirus-positive herpangina children were 20 .1％ (65 ) , 14 .9％ (48 ) and 8 .7％ (28) , respectively , and those of entrovirus ,CoxA4 and CoxA6 in other enterovirus-positive specimens were 59 .4％ (63) ,14 .2％ (15) and 12 .3％ (13 ) , respectively . The enterovirus constituent ratios among children with HFMD , herpangina and other diseases was statistically different (χ2 =399 .758 ,P<0 .01) .The positive rates of enterovirus among different age groups were statistically different (χ2 = 142 .899 , P< 0 .01 );the constituent ratios of enterovirus among different age groups were also statistically different (χ2=106 .160 , P<0 .01) .Conclusion The enterovirus detection rate of CoxA6 is highest ,followed by EV71 and CoxA16 among children in Hangzhou ,2016 .