Objective:This study aimed to investigate the correlation between serum chitinase-3 like-protein-1(YKL-40), matrix metalloproteinase-9(MMP-9), and imaging markers in middle-aged and elderly patients with cerebral small vessel disease(CSVD).It also sought to elucidate the mechanism underlying the onset and development of CSVD.Methods:A case-control study was conducted with 130 CSVD patients and 20 age-matched controls admitted to the Department of Neurology of the Second Affiliated Hospital of Zhengzhou University between December 2020 and November 2022.Based on their white matter hyperintensity(WMH)and enlarged perivascular spaces(EPVS)scores, CSVD patients were categorized into mild, moderate, and severe groups.Cerebral microbleeds(CMBs)were classified into non-lacunar, lacunar, non-CMBs, and CMBs groups.Patients' general data were collected, and serum levels of YKL-40 and MMP-9 were measured using ELISA.Results:The results showed 34 cases in the severe WMH group, 35 cases in the EPVS severe group, 90 cases in the group with lacunar and 65 cases in the group with CMBs.Statistically significant differences(both P<0.05)in serum YKL-40 and MMP-9 in WMH severe groups compared to age control group.Statistically significant differences(both P<0.05)in serum YKL-40 and MMP-9 in EPVS severe groups compared to age control group.The increase of serum YKL-40 and MMP-9 levels was an independent risk factor for the severity of WMH( OR=1.25, 95% CI: 0.164-0.289, P<0.05)( OR=1.13, 95% CI: 0.090-0.160, P<0.05)and EPVS( OR=1.05, 95% CI: 0.021-0.076, P<0.05)( OR=1.02, 95% CI: 0.006-0.026, P<0.05).There was no significant different in the serum YKL-40 and MMP-9 levels between lacunar group and non-lacunar group( P>0.05).The serum YKL-40 and MMP-9 levels in the group with CMBs were significantly higher than those in the group without CMBs( P<0.05).The ROC curve showed that the optimal cutoff point of YKL-40 was 0.38, the area under the curve was 0.669(95% CI: 0.569-0.768, P<0.01), the optimal cutoff point of MMP-9 was 0.40, and the area under the curve was 0.746(95% CI: 0.644-0.848, P<0.01). Conclusions:Changes in serum YKL-40 and MMP-9 levels in middle-aged and elderly patients with CSVD were found to be associated with various imaging markers, potentially contributing to the onset and development of CSVD.These findings may aid in early CSVD diagnosis and provide insights for potential interventions.

Objective To analyze the frailty of patients with long-term maintenance dialysis(MD)and its influencing factors,and to explore the correlation of different dialysis modalities with the re-infection of novel coronavirus infection(COVID-19)and frailty syndrome.Methods Patients with regular dialysis in Nephrology Department of the Second Affiliated Hospital of Kunming Medical University from February to June 2023 were selected.A cross-sectional survey was conducted to collect clinical data of the patients,including dialysis modality(i.e.maintenance hemodialysis,abbreviated as hemodialysis,and continuous ambulatory peritoneal dialysis,abbreviated as peritoneal dialysis),and whether with re-infection of COVID-19.Patients were divided into 3 groups using Fried's frailty phenotype(FP):non-frailty group,pre-or-intermediate frailty group,and frailty syndrome group.The clinical characteristics of the FP were compared among the three groups.The correlation of frailty with clinical data,dialysis modality,re-infection of COVID-19 in each group was compared.Multifactorial logistic regression was used to analyze the factors influencing the development of frailty syndrome in patients.Results A total of 246 dialysis patients were included in this study,with 77(31.3%)in the non-frailty group,83(33.7%)in the pre-frailty group and 86(35.0%)in the frailty syndrome group.The frailty syndrome group showed characteristics of advanced age,high pre-dialysis creatinine level,low serum albumin level and combined pleural effusion(all P＜0.05).There was no statistically significant difference in the comparison of frailty between the hemodialysis and peritoneal dialysis group(P = 0.960).COVID-19 re-positive patients had higher frailty score than non-re-positive patients.Multifactor logistic regression showed that age,COVID-19 re-infection of COVID-19,serum albumin,pre-dialysis creatinine,and pleural effusion were factors influencing the development of frailty syndrome in dialysis patients(P＜0.05).Conclusion There is high incidence of frailty syndrome in dialysis patients,and there is no correlation of frailty with dialysis modality.High serum albumin level is a protective factor for the development of frailty syndrome in patients,whereas re-infection of COVID-19,advanced age,high pre-dialysis blood creatinine level and pleural effusion are risk factors for the development of frailty syndrome.

Objective:To investigate the relationship between intracranial arterial remodeling and imaging markers in patients with cerebral small vessel disease (CSVD).Methods:One hundred and fifty-six patients with CSVD who were admitted to the Department of Neurology of the Second Affiliated Hospital of Zhengzhou University or the Public People′s Hospital of Xinzheng from January 2020 to May 2022 were selected, and their brain artery remodeling (BAR) score was calculated. The patients with BAR score≤-1 standard deviation (SD) were defined as individuals with constrictive remodeling of intracranial arteries, and the patients with BAR score≥1 SD were defined as individuals with dilated remodeling of intracranial arteries. Imaging markers of CSVD [white matter hyperintensities (WMHs), lacune, cerebral microbleeds, enlarged perivascular spaces, and cerebral atrophy] were quantified, total CSVD load was calculated and patients were divided into low load group (0-2 points, n=91) and high load group (3-4 points, n=65) according to the total CSVD load scores. The correlation between intracranial artery remodeling and various imaging markers of CSVD and total load was analyzed by using univariate analysis and binary Logistic regression analysis. A nomogram prediction model was established and a receiver operating characteristic curve (ROC) was drawn to assess the predictive value of intracranial artery remodeling on high total CSVD load. Results:Dilated intracranial arterial remodeling was an independent influence factor on severe WMHs ( OR=3.66, 95% CI 1.38-9.72, P=0.009), lacune ( OR=3.78, 95% CI 1.17-12.19, P=0.026), cerebral atrophy ( OR=3.11, 95% CI=1.10-8.81, P=0.033), and high total CSVD load ( OR=6.66, 95% CI=2.14-20.77, P=0.001). Age was an independent influencing factor for high total CSVD load ( OR=1.12, 95% CI 1.07-1.16, P<0.01). A nomogram prediction model for high total CSVD load with age and BAR score≥1 SD as dependent variables had a good effect (C-index=0.826) and calibration ( P=0.024). The best cut-off point of ROC curve was 0.50, with an area under the curve of 0.83 (95% CI 0.76-0.89, P<0.01), the sensitivity and specificity of 0.72 and 0.82. Conclusions:Patients with dilated intracranial arterial remodeling may have a heavier CSVD load. Dilated intracranial arterial remodeling may serve as a new biomarker for assessing CSVD, but the mechanism of the association needs further study.

Objective:To understand the incidence and clinical characteristics of dopamine agonist(DA) therapy-related impulse control disorders(ICDs) in prolactinoma patients.Methods:Outpatients diagnosed with prolactinoma from the Department of Endocrinology in Huashan Hospital from December 2019 to June 2020 were consecutively included and clinical data were collected. Impulse control disorders were screened with Questionnaire for Impulsive-Compulsive Disorders in Parkinson′s Disease(QUIP). Barratt Impulsiveness Scale 11(BIS-11) was used to evaluate personality construct of impulsiveness from three sub-factors . Health related quality of life was evaluated by the MOS 36-Item Short Form Health Survey(SF-36).Results:Among the 111 cases included, 40 were male and 53 were female, with an average age of(34.74±9.05) years and an average disease duration of(66.69±50.70) months. The initial prolactin level was 147.25(89.97, 470) ng/mL and the percentage of macroadenoma was 46.8%. Ninety cases received DA while 21 cases didn′t. According to the QUIP, any ICD was screened positive in 22 cases(24.7%) in the DA group and 3 cases(14.3%) in the untreated group. The attention impulsiveness scores of BIS-11 in the DA group were higher than the untreated group(23.32±3.67 vs 21.71±2.55, P=0.022). Among the ICDs positive cases in the DA group, the most common disorders were pathological gambling(40.6%) and hypersexuality(40.6%). Compared with the negative group, the non-planning impulsiveness scores of BIS-11 in the positive group were higher, while the scores of social function(69.32±24.62 vs 83.08±17.11, P=0.021), role emotional(50.00±45.72 vs 71.10±40.68, P=0.043) and mental health(55.27±22.75 vs 64.59±17.53, P=0.048) in SF-36 scale were lower in the positive group. Besides, the percentage of male(68.2% vs 38.2%, P=0.014) and initial prolactin level[470.00(130.00, 3 770.00) vs 140.29(79.50, 465.59) ng/mL, P=0.028] in the positive group were higher. Male was an independent risk factor of the presence of ICDs( OR=3.46, 95% CI 1.24-9.61, P=0.017). No significant difference was found in the type of drugs, duration, maximal or cumulative dose of treatment with DA between the two groups. Conclusion:Impulse control disorders may occur in prolactinoma patients receiving DA treatment and affect the quality of life. Endocrinologists should screen impulse control disorders in this patient set.

Objective:To investigate the clinical and imaging features of bilateral Wallerian degeneration of the middle cerebellar peduncles secondary to isolated pontine infarction.Methods:Patients diagnosed as bilateral Wallerian degeneration of cerebellar middle peduncle after isolated pontine infarction admitted to the Second Affiliated Hospital of Zhengzhou University from June 2017 to December 2021 were retrospectively included. Patients with bilateral Wallerian degeneration of cerebellar middle peduncle after isolated pontine infarction reported between January 2001 and December 2021 were collected by searching Chinese and English databases, and their clinical and imaging characteristics were summarized.Results:A total of 48 patients with bilateral Wallerian degeneration of cerebellar middle peduncle after isolated pontine infarction were included, including 14 patients admitted to the Second Affiliated Hospital of Zhengzhou University, and 34 patients collected by searching the Chinese and English databases. Thirty-three patients were males (68.75%) and 15 were females (31.25%). Their age was 65.8±10.7 years old (range, 37-88 years). Most patients had vascular risk factors, and hypertension was the most common. Dysarthria and limb weakness were the main clinical symptoms at admission. The infarct sites of all 48 patients were located in the blood supply area of paramedian pontine arteries, of which 37 (77.08%) were unilateral (18 on the left and 19 on the right), 6 (12.50%) were bilateral sides, and 5 (10.42%) had incomplete data. When Wallerian degeneration was diagnosed, 8 patients (16.67%) had dizziness or ataxia, 6 (12.50%) had aggravated original symptoms, and the remaining 34 (70.83%) had no new symptoms or aggravated original symptoms. All patients showed symmetrical abnormal signals in bilateral middle cerebellar peduncles, with obvious hyperintensity on T 2 or diffusion-weighted imaging (DWI). One patient showed T 2 hyperintensity in bilateral middle cerebellar peduncle on the next day after the onset of the infarction, which was the earliest case to find secondary Wallerian degeneration after isolated pontine infarction. Conclusions:Wallerian degeneration should be considered when symmetrical lesions of bilateral middle cerebellar peduncles occur after isolated pontine infarction. Wallerian degeneration may occur early after isolated pontine infarction. Most cases have no new symptoms or aggravated original symptoms. Conventional MRI can identify it early.

Objective:To describe the prevalence and clinical characteristics of macroprolactinemia in hyperprolactinemia patients.Methods:Consecutive 111 outpatients diagnosed with hyperprolactinemia were included in this study. Macroprolactin was routinely screened using the polyethylene glycol(PEG) precipitation method. Recovery of monomeric prolactin less than 40% was defined as macroprolactinemia. Clinical characteristics were analyzed in this study.Results:Among the 111 cases included, 99 were female and 12 were male, with an average age of(32.2±7.9) years. There were 32 cases(28.8%) of macroprolactinemia and 28 of them with normal monomeric prolactin levels(simple macroprolactinemia). prolactin levels before precipitation in simple macroprolactinemia were significantly lower than those with true hyperprolactinemia[(49.81±23.58 vs 83.56±65.82) ng/mL, P<0.05]. No amenorrhea and infertility were observed in patients with simple macroprolactinemia. The clinical manifestations of prolonged menstruation, oligomenorrhea and galactorrhea in female patients accounted for 25.9%, 37.0%, and 7.4%, respectively. Imaging data were obtained in 92 cases. The prevalence of pituitary adenomas in simple macroprolactinemia and true hyperprolactinemia was 42.9% and 66.0%, respectively. Fifteen(46.8%) of the macroprolactinemia cases were receiving or had received bromocriptine treatment, and 66.7% of them failed to achieve normal prolactin levels during therapy. Conclusion:Macroprolactinemia might be common in clinical practice. Macroprolactin should be screened in hyperprolactinemia patients lack of amenorrhea and infertility, and with poor response to dopamine agonist therapy.

Objective To explore the potential mechanism of action of estradiol benzoate on proliferation and differentiation of rat hippocampal neural stem cells.Methods Hippocampus tissues from SD rats were dissociated and plated into culture flasks.Neural stem cells were identified by immunofluorescence against Nestin.After treatment with different concentration of estradiol benzoate (10-10,10-9,10-8,10-7,10-6 mol/L),the proliferation and differentiation of neural stem cells were assessed by MTT assay and the proportion of neurons and astrocytes in differentiated cells was assessed by flow cytometry.Western blot assay was performed to detect the expression levels of protein in neural stem cells.Results (1) The neural stem cells formed neurospheres and grew in floating,and were Nestin-positive.Estrogen receptors,including ERα and ERβ,were expressed in neural stem cells;(2)After treatment with 10-8 mol/L estradiol benzoate versus in the control group,the cell viability was significantly increased (t =5.36,P =0.003),and the ratio of neuron-specific nuclear protein(NeuN)-positive neuron cells in total cells was significantly increased (t =4.32,P =0.02),but the ratio of glial fibers acidic protein(GFAP)-positive cell in total cells was decreased(t=4.65,P=0.008).The expression levels of GDNF,GFRal and Ret proteins were enhanced in the estradiol benzoate group compared with the control group.Conclusions Appropriate concentration of estradiol benzoate promotes proliferation and differentiation ofin vitrocultured hippocampal neural stem cells and elevates the ratio between neurons and glial cells differentiated from neural stem cells.

Objective To observe the effect of the three active ingredients of a Chinese traditional medicine compound named Kang Fu Ling( KFL) against PC12 cells oxidative damage induced by microwave radiation.Methods PC12 cells were differentiated into neuros induced by nerve growth factor ( NGF ) .PC12 cells were incubated for 48 hours after astragalosides,total paeony glycoside and tanshinones were added at different concentrations (1, 3, or 9 μg/ml) .The cells in the control group were cultivated with the only medium of the same volume.Then, cells were irradiated with 30 mW/cm2 microwave for 6 minutes.The morphology of PC12 cells was observed under an inverted microscope soon before and after irradiation and the cell viability was measured by methylthiazolyl tetrazolium ( MTT) colorimetry.Reactive oxygen species ( ROS ) was determined using active oxygen probe 2′, 7′-dichlorodihyarofluolescen diacetde ( DCFH-DA ) while malonyldialdehyde(MDA) was measured in the homogenate of PC12 cells through thiobarbituric acid ( TBA) reactive substance assay.Results The cell morphology of each group showed no obvious difference.6 h after irradiation, the viability of irradiation control group measured by MTT declined apparently(P<0.01)compared with the normal control group.The 3 μg/ml astragalosides treatment group increased the viability of PC12 cells after microwave exposure ( P <0.01).The contents of ROS and MDA were increased after irradiation(P<0.01).However, in the three active ingredients of Kang Fu Ling treatment groups, both ROS and MDA were much lower than in irradiation control group.Conclusion Astragalosides, total paeony glycoside and tanshinones, which are the three active ingredients of Kang Fu Ling, all have protective effect against PC12 cell injury caused by microwave radiation,possibly by scavenging free radicals and reducing oxidative stress injury.

Objective To investigate the effect of depression on the incidence of osteoporosis in patients with maintenance peritoneal dialysis (MPD).Methods We enrolled 80 MPD patients,who underwent peritoneal dialysis in our dialysis center.The clinical data and biochemical parameters of all patients were collected,bone mineral density was detected and the Self-rating depression scale was used to evaluate depression state.Results Among the 80 enrolled MPD patients,34 patients had osteoporosis (42.5％),48 patients had the presence of depression (60％).Logistic regression analysis showed that age,dialysis age,gender,diabetes history and depression state were the risk factors for osteoporosis in MPD patients,the depression state was negatively correlated with BMD of lumbar and femoral neck (r=-0.347,r=0.426,P＜0.05).Conclusion Depression state may be a risk factor for osteoporosis in clinic,it is of great significance to focus on the psychological state of MPD patients in the prevention and treatment of osteoporosis.

Objective To study adipose-derived stem cells (ADSCs)differentiation into endothelial cells and smooth muscle cells by induction with supernatant liquid from cerebral infarction tissue in rats.Methods The ADSCs were obtained from retroperitoneal adipose tissue of rats and identified by flow cytometry technology.The normal brain tissues and the infarcted cerebral tissue obtained from rats with middle cerebral artery occlusion were used to induce ADSCs differentiation,and no intervention group was as a control.The mRNA expression level of von willebrand factor (vWF),α-smooth muscle actin (α-SMA) and smooth muscle myosin heavy chain (SM-MHC) in cells after induction were detected using reverse transcriptase-polymerase chain reaction.Immunofluorescence were used to identify the expression of endothelial cells markers and smooth muscle cell markers,and positive expression cell was detected by fluorescence microscope.Results On the ADSCs surfaces,the high expressed-positive antigens included CD90 (96.7％),CD29 (84.4％),CD44 (98.9％),and the low expressed negative antigens included CD45 (6.5％),CD34 (7.4％) and CD31 (3.6％).Compared with no intervention group and normal brain tissue of supernatant liquid group,the cerebral infarction tissue of supernatant liquid-induced group showed the increased mRNA expression level of vWF,α-SMA and SM-MHC(F=5.962,6.756,6.144,P=0.001,0.004,0.003),and showed that the immunofluorescence indicated-cell expression level of vWF,α-SMA and SM-MHC was much more increased (all P ＜ 0.05).Conclusions Under the induction by supernatant liquid of cerebral infarction tissue,ADSCs highly expresses the markers of endothelial cells and smooth muscle cells.This suggests that the cerebral infarction tissue of supernatant liquid-induced ADSCs have a tendency to differentiate into endothelial cells and smooth muscle cells.