摘要 目的 探讨脑小血管病（CSVD）患者中运动认知风险综合征（MCR）与神经影像学标志物之间的关系，并评估MCR相关的影像学标志物及比较其与轻度认知功能障碍（MCI）的影像学标志物是否不同。方法 研究回顾性选取了河北医科大学第三医院自2023年4月—2024年11月收治的187例脑小血管病患者。根据是否诊断MCR及MCI进行分组。收集患者的临床资料和影像学数据，使用单变量和多因素Logistic回归分析探讨CSVD患者MCR的影像学特征。结果 CSVD患者中MCR阳性组在体重指数（BMI）、男性比例、高血压、存在腔隙、严重的脑白质高信号（WMH）、严重的基底节区扩大的血管周围间隙（EPVS）和严重CSVD总负荷方面患者比例比MCR阴性组更高（P<0.05）。多因素Logistic回归分析显示，WMH总体积是CSVD患者MCR的独立危险因素（OR=1.038，95%CI 1.003~1.075，P=0.033）。以MCI、MCR两个指标分组显示，MCI+/MCR+较其他组比较，高血压病比例更高（其中MCI-/MCR+组较MCI+/MCR-组比高血压病比例更高），WMH总体积、严重的脑深部及脑室旁WMH、严重的EPVS比例更高（P<0.05）。其中单纯MCR阳性组（MCI-/MCR+）与单纯MCI阳性组（MCI+/MCR-）比较，脑室旁及深部WMH有更高的分级（2级、3级高于MCI+/MCR-组）及更大的总体积（P<0.05）。CSVD总负荷方面差异无统计学意义（P>0.05）。结论 WMH是CSVD患者合并MCR的独立危险因素。MCR与更大的WMH体积相关。本研究强调了MCR的脑白质异常，运动评估在早期痴呆风险分层中的潜力。 Abstract Objective To investigate the association between motoric cognitive risk syndrome （MCR） and neuroimaging markers in patients with cerebral small vessel disease （CSVD）， to assess the imaging markers associated with MCR， and to compare the differences in imaging markers between MCR and mild cognitive impairment （MCI）. Methods A retrospective study was conducted among 187 patients with CSVD who were admitted to Department of Neurology， Hebei Medical University Third Hospital， from April 2023 to November 2024， and they were divided into groups based on whether they were diagnosed with MCR or MCI. Clinical and imaging data were collected， and the univariate and multivariate logistic regression analyses were used to investigate the imaging features of CSVD patients with MCR. Results Compared with the MCR-negative group， the MCR-positive group had significantly higher BMI， proportion of male patients，and proportion of patients with hypertension， lacunar infarcts， severe white matter hyperintensity （WMH）， severe enlarged perivascular space （EPVS） in the basal ganglia， and high CSVD total burden （P<0.05）. The multivariate logistic regression analysis showed that the total volume of WMH was an independent risk factor for MCR in CSVD patients（OR=1.038，95%CI 1.003‒1.075，P=0.033）. Stratification by MCI，MCR showed that compared with the other groups， the MCI+/MCR+ group had a significantly higher proportion of patients with hypertension （the MCI-/MCR+ group had a higher proportion of patients with hypertension than the MCI+/MCR- group）， a significantly higher total volume of WMH， a significantly higher proportion of patients with severe deep brain and paraventricular WMH， and a significantly higher proportion of patients with severe EPVS（P<0.05）.Compared with the MCI+/MCR-group， the MCI-/MCR+ group had significantly higher grades （a significantly higher proportion of patients with grade 2 or 3 WMH than the MCI+/MCR- group） and total volume of periventricular and deep WMH（P<0.05）. There was no significant difference in CSVD total burden between groups（P>0.05）. Conclusion WMH is an independent risk factor for MCR in patients with CSVD. MCR is associated with a larger volume of WMH.This study highlights white matter abnormalities in MCR and the potential of motor function assessment in early risk stratification for dementia.

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Objective To investigate the dietary patterns of rural residents in the high-incidence areas of esophageal cancer (EC), and to explore the clustering and influencing factors of risk factors associated with high-incidence characteristics. Methods A special structured questionnaire was applied to conduct a face-to-face survey on the dietary patterns of rural residents in Yanting county of Sichuan Province from July to August 2021. Univariate and multivariate logistic regression models were used to analyze the influencing factors of risk factor clustering for EC. Results There were 838 valid questionnaires in this study. A total of 90.8% of rural residents used clean water such as tap water. In the past one year, the people who ate fruits and vegetables, soybean products, onions and garlic in high frequency accounted for 69.5%, 32.8% and 74.5%, respectively; the people who ate kimchi, pickled vegetables, sauerkraut, barbecue, hot food and mildew food in low frequency accounted for 59.2%, 79.6%, 68.2%, 90.3%, 80.9% and 90.3%, respectively. The clustering of risk factors for EC was found in 73.3% of residents, and the aggregation of two risk factors was the most common mode (28.2%), among which tumor history and preserved food was the main clustering pattern (4.6%). The logistic regression model revealed that the gender, age, marital status and occupation were independent influencing factors for the risk factors clustering of EC (P<0.05). Conclusion A majority of rural residents in high-incidence areas of EC in Yanting county have good eating habits, but the clustering of some risk factors is still at a high level. Gender, age, marital status, and occupation are influencing factors of the risk factors clustering of EC.

Objective:To investigate the impact of residual cholesterol (RC) on the progression of arteriosclerosis in individuals receiving physical examination.Methods:A cross-sectional study. Participants aged 18 years and above who underwent arteriosclerosis testing at the Health Management Center of Zigong Fourth People′s Hospital from January to December 2023 were selected as the subjects of the study. A total of 9 016 subjects were included in this study, of whom 6 213 were considered to have arteriosclerosis. The physical examination conclusions, basic information (age, gender, body mass index, waist circumference, blood pressure, history of hypertension, history of smoking and drinking), and biochemical indicators (lipids, fasting blood glucose, liver and kidney function) were extracted in those individuals. Based on the examination results, the subjects were categorized into arteriosclerosis and normal groups. The RC levels of the participants were calculated using a formula and then the subjects were categorized into binary and quartile RC groups. Additionally, four regression models were used to analyze the impact of RC levels on the progression of arteriosclerosis while adjusting for various confounding factors.Results:The RC level was (0.63±0.44) mmol/L in the normal group and (0.76±0.61) mmol/L in the arteriosclerosis group. Based on level of RC, the normal group was divided into two subgroups: 652 individuals with elevated RC level and 2 241 with normal RC level. In the arteriosclerosis group, there were 2 069 individuals with elevated RC level and 4 144 with normal RC level. Grouped according to quartiles of RC level, the number of individuals with RC in the Q1-Q4 interval in the normal group was 838 (28.97%), 752 (25.99%), 760 (26.27%), and 543 (18.77%), respectively, showing a gradual decreasing trend. The number of individuals with RC in the Q1-Q4 interval in the arteriosclerosis group was 1 414 (22.76%), 1 438 (23.15%), 1 589 (25.58%), and 1 771 (28.51%), respectively, showing a gradual increasing trend. The difference between the groups was statistically significant ( P<0.05). After adjusting for various factors by four regression models, it was found that elevated RC levels increased the risk of arteriosclerosis progression, with a odds ratio ( OR) of 1.381, 1.242, 1.233, and 1.214, respectively. Additionally, individuals in the Q4 RC level quartile had 1.502, 1.318, 1.311, and 1.284-times higher risk of arteriosclerosis progression when compared to those in the Q1 quartile. Conclusion:The impact of RC on the progression of arteriosclerosis tend to stabilize and remain consistent, indicating that elevated RC is an independent risk factor for the progression of arteriosclerosis.

Objective To observe the RNA expression level of carbohydrate thiotransferase family(CHSTs)in non-functioning adenoma,and to analyze its clinical significance.Methods Ninety tissue samples of clinical non-functioning adenoma were collected.The mRNA expression levels of CHST1/2/7/8,follicle-stimulating hormone subunit(3(FSHb),POU domain transcription factor 1(POU1F1)and steroid-producing factor 1(SF-1)were detected by real time fluorescence quantitative PCR(RT-qPCR).And receiver operating characteristic(ROC)curve was used to screen the CHST molecule possessing the function for diagnosing CHST molecule differentiated by non-functional adenoma lineage.Results The expression amounts of CHST1 gene and CHST7 gene in the tumors with large volume were higher than those with small tumors(P=0.014,P=0.044),and the CHST2 gene level in female patients was higher than that in male patients(P=0.016),and the CHST8 gene level in invasive tumors were lower than in non-invasive tumors(P=0.044).The grouping was conducted according to the intensity of SF-1 staining,there were statistically signif-icant differences in CHST1/2/7/8 gene levels among all groups(P＜0.05);the grouping was performed ac-cording to the intensity of PIT1 staining,there were statistically significant differences in CHST1/7 gene levels among all groups(P＜0.01).The correlation analysis showed that the CHST1 level was positively correlated with the tumor volume and POU1F1 level(r=0.322,P=0.002;r=0.686,P＜0.001)and negatively corre-lated with the NR5A1 level(r=-0.227,P=0.032).The CHST7 level was positively correlated with the POU1F1 level(r=0.774,P＜0.001);the CHST8 level was positively correlated with the FSHb and NR5A1 levels(r=0.485,P＜0.001;r=0.725,P＜0.001).The area under ROC curve(AUC)of CHST1 for diagno-sing the immature POU1F1 lineage was 0.750(P=0.023).AUC of CHST8 for diagnosing SF-1 lineage was 0.776(P=0.008),and the AUC of CHST1 combined with CHST8 was 0.823(P=0.002).Conclusion The CHST family is involved in the proliferation and differentiation of clinical nonfunctional adenomas.CHST1 combined with CHST8 is valuable in the diagnosis of SF-1 lineage differentiation.

Objective:To observe the effects of liver-soothing spirit-regulating acupuncture on the behaviors and expression levels of 5-hydroxytryptamine receptor 1A(5-HT1AR)and 5-hydroxytryptamine receptor 2A(5-HT2AR)in the hippocampus of insomnia rats due to liver Qi stagnation. Methods:Ten of the 70 Wistar rats were randomly selected as the blank group,and the remaining rats were subjected to preparing the insomnia model due to liver Qi stagnation by the chronic tail clamping stimulation combined with intraperitoneal injection of para-chlorophenyl alanine.Fifty successful model rats were randomly divided into a model group,a grasp group,a Western medicine group,an acupuncture group,and a sham acupuncture group,with 10 rats in each group.Rats in the grasp group were grabbed in the same way as those in the acupuncture group.Rats in the Western medicine group were given estazolam solution by intragastric administration.Rats in the acupuncture group received liver-soothing spirit-regulating acupuncture at Baihui(GV20),Neiguan(PC6),Shenmen(HT7),and Taichong(LR3);rats in the sham acupuncture group received acupuncture at 4 non-meridian non-point spots.All groups were treated once a day for 7 d.Pentobarbital sleep test was used to evaluate the sleep latency(SL)and sleep time(ST)of rats in each group after 7 d of intervention;the proportion of the number of entry into the open arms(OE％)and the proportion of the residence time in the open arms(OT％)were monitored by elevated plus maze test(EPMT);the open field test(OFT)was used to monitor the numbers of standing upright,horizontal cross-grid,and fecal grains in rats.The expression levels of 5-HT1AR and 5-HT2AR in rat hippocampus were detected by Western blotting. Results:The body mass gain,ST,OE％,OT％,upright standing times,horizontal cross-grid times,and the 5-HT1AR expression level in the hippocampus were significantly decreased(P<0.01),while the SL and 5-HT2AR expression level in the hippocampus were significantly increased(P<0.01)in the model group compared with the blank group.After intervention,the body mass,ST,OT％,OE％,upright standing times,horizontal cross-grid times,and hippocampal 5-HT1AR expression level were significantly increased(P<0.01 or P<0.05),while the SL and hippocampal 5-HT2AR expression level were significantly decreased(P<0.01 or P<0.05)in the acupuncture group and the Western medicine group compared with the grasp group.Compared with the Western medicine group,OT％,SL,and hippocampal 5-HT1AR expression level were significantly increased in the acupuncture group(P<0.05).The body mass,OT％,OE％,ST,upright standing times,horizontal cross-grid times,and the 5-HT1AR expression level in the hippocampus were significantly increased(P<0.01),while the SL and 5-HT2AR expression level in the hippocampus were significantly decreased(P<0.01)in the acupuncture group compared with the sham acupuncture group. Conclusion:Liver-soothing spirit-regulating acupuncture can not only improve sleep but also improve the abnormal behaviors and mood of insomnia rats due to liver Qi stagnation,and the improvement effect on abnormal mood is better than that of Western medicine.The mechanism may be related to the regulation of 5-HT1AR and 5-HT2AR

Objective To evaluate the effect of ventilation with different positive end-expiratory pressures (PEEPs) on intracranial pressure in the patients undergoing gynecological laparoscopic surgery.Methods Sixty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients,aged 25-55 yr,with body mass index of 18-27 kg/m2,scheduled for elective gynecological endoscopic surgery,were divided into 3 groups (n=20 each) using a random number table method:routine ventilation group (group A),4 cmH2O PEEP group (group B) and 8 cmH2O PEEP group (group C).The patients were mechanically ventilated with PEEP 4 or 8 cmH2O at 5 min of head-down tilt after start of pneumoperitoneum in group B and group C.The patients were mechanically ventilated in volume-controlled mode,with tidal volume 7 ml/kg,inspired oxygen concentration 50％ and inspiratory/expiratory ratio 1 ∶ 2.Blood samples were collected from the radial artery for measurement of PaCO2 and PaO2 at 5 min after tracheal intubation (T0),5,15 and 30 min of head-down tilt (T1-3),and 5 min of the supine position after the end of pneumoperitoneum (T4).The peak airway pressure (Ppeak) was recorded,dynamic pulmonary compliance (Cdyn)was calculated,and optic nerve sheath diameter was measured using an ultrasonic apparatus at T0-4.Cognitive function was assessed at 1 day before surgery and 7 days after surgery using Mini-Mental State Examination.Results Compared with group A,Ppeak was significantly increased at T1-4,and PaO2 was increased at T2 in group B,and Ppeak and PaO2 were increased at T1-4,and Cdyn was increased at T1,2 in group C (P＜0.05).Compared with group B,Ppeak was significantly increased at T4,and Cdyn was increased at T2 in group C (P＜0.05).There was no significant difference in optic nerve sheath diameter or Mini-Mental State Examination score at each time point among three groups (P＞0.05).No patients developed cognitive dysfunction at 7 days after surgery in three groups.Conclusion Ventilation with different PEEPs causes no increase in intracranial pressure of the patients undergoing gynecological laparoscopic surgery.

OBJECTIVE To investigate the effect of prenatal nicotine exposure on cardiac ejection function and myocardial fibrosis of the offspring of rats.METHODS Pregnant rats were sc given nicotine 6.0 mg· kg-1,once daily for 17 d.The body mass and heart mass of the offspring were detected at the 21th day of gestation,and 15 and 90 d after birth.Heart rate of 90 d offspring was recorded by ECG,and cardiac functions were detected by Doppler ultrasonography,including cardiac output (CO),stroke volume (SV),ejection fraction (EF),left ventricular long axis shortening fraction (FS),interventricular septum diastolic diameter (IVSd) and left ventricular posterior wall diastolic diameter (LVPWd).The myocardial ultrastructure was detected under an electron microscope.Masson staining was used to detect the myocardial collagen fiber deposition.The level of collagen protein type Ⅰ in heart tissue was detected by radioimmunoassay.RESULTS Compared with control group,prenatal nicotine exposure resulted in a decrease of heart mass and body mass in groups of 21 d fetal rats and 15 d offspring(P＜0.05,P＜0.01),but had no effect on the 90 d offspring.Compared with the normal control group,the heart rate of 90 d offspring increased [366+10 vs (418+10) min-1] (P＜0.05),CO,FS and EF decreased (P＜0.01),and IVSd and LVPWd increased (P＜0.05,P＜0.01).Electron microscopy revealed that in the heart of nicotine 90 d offspring,myocardial fiber arrangement was loosened and confused,while extracellular matrix increased.Masson staining showed collagen deposited in the myocardium.The level of collagen type Ⅰ in heart tissue increased [0.59±0.09 vs (0.40±0.05) tμg·g-1 tissue] (P＜0.01).CONCLUSION Prenatal nicotine exposure induces the increased level of cardiac collagen type Ⅰ,myocardial fibrosis and decrease of cardiac ejection function in adult offspring,which may lead to increased susceptibility to cardiovascular diseases.

Objective To explore the clinical effect of multifunction bladder stoma drainage on the patients with permanent cystostomy .Methods Sixty-seven patients with permanent cystostomy were chosen and divided into the control group ( n=35) and the experimental group ( n=32) .The control group used the common balloon catheter , and the experimental group used the multifunction bladder stoma drainage .The cystospasm , pipeline blockage and bacteriuria were compared between two groups .Results The average duration , daily times, continuous days of cystospasm were respectively (3.65 ±1.93)min, (4.24 ±2.68)times,(4.33 ±2.72)d in the experimental group, and were lower than (8.84 ±3.59)min,(12.38 ±5.22),(10.91 ±4.57)d in the control group, and the differences were statistically significant (t=-7.21,-7.87,-7.01, respectively;P<0.01). The number of pipeline blockage was 3 times in the experimental group , and was 11 times in the control group , and the difference was statistically significant (χ2 =4.92,P<0.05).No difference was found in the positive rate of urine culture between two groups (χ2 =0.20,P>0.05).Conclusions Application of the multifunction bladder stoma drainage in the patients with permanent cystostomy can decrease the incidence rate of cystospasm so as to ensure the pipeline unobstructed , and is worthy of clinical promotion and application .