Cognitive impairment is a kind of senile disease that leads to the decline of personality and behavior ability of the elderly,which seriously affects the quality of daily life of patients.The prevalence rate of the disease increases year by year with the acceleration of the aging process of the society,and its incidence is affected by many risk factors.At this stage,the curative effect for middle and advanced patients is poor.So early identification and intervention to delay the progression of cognitive impairment have become the focus of relevant research.Blood pressure variability can lead to damage of target organs such as heart,brain tissue and kidney,which is closely related to cognitive impairment.In order to expand a new perspective of early intervention in cognitive impairment,this paper reviews the effects of blood pressure variability on different cognitive impairment and its possible pathogenic mechanism.

Objective:To investigate the difference of urinary protein components in pregnant women with pre-eclampsia (PE) with different degrees of proteinuria and the correlation between 24-hour urinary protein quantification and estimated glomerular filtration rate (eGFR).Methods:Clinical data of 101 PE pregnant women who were delivered in Renji Hospital, Shanghai Jiao Tong University School of Medicine from July 2018 to June 2022 were retrospectively analyzed. According to 24-hour urinary protein quantification, they were divided into 3 groups, including 40 cases of mild proteinuria group (24-hour urinary protein quantification ≤2.0 g), 21 cases of moderate proteinuria group (2.0 g<24-hour urinary protein quantification ≤5.0 g), 40 cases of severe proteinuria group (24-hour urinary protein quantification >5.0 g). The general clinical data, urinary protein index and renal function index of PE pregnant women in 3 groups were compared. The eGFR was calculated based on age, serum creatinine (sCr), blood urea nitrogen (BUN) and serum albumin (sAlb). Correlation analysis was conducted between 24-hour urinary protein quantification and each index of eGFR.Results:(1) General clinical data: the median PE onset week (31 weeks) and delivery gestational week [(36.4±3.6) weeks] of PE pregnant women in the mild proteinuria group were later than those in the moderate proteinuria group [median PE onset: 22 weeks, delivery: (32.2±4.2) weeks] and severe proteinuria group [median PE onset: 25 weeks, delivery: (29.6±3.4) weeks]; systolic blood pressure, diastolic blood pressure, alanine aminotransferase, aspartate aminotransferase levels and the incidence of fetal growth restriction were lower than those in the moderate and severe proteinuria groups; median newborn birth weight (3 150 g) was higher than those in the moderate proteinuria group (1 305 g) and the severe proteinuria group (1 042 g), respectively. The differences were statistically significant (all P<0.05). (2) Urinary protein index: the 24-hour urinary protein quantification, urinary microalbumin (mAlb) and urinary transferrin (TRF) levels of PE pregnant women in the mild proteinuria group, moderate proteinuria group and severe proteinuria group were increased successively, and the differences were statistically significant (all P<0.05). The median urinary α1-microglobulin (α1-MG) level of PE pregnant women in the severe proteinuria group (50 mg/L) was significantly higher than those in the mild proteinuria group (17 mg/L) and moderate proteinuria group (22 mg/L; all P<0.05), but there was no significant difference between the mild proteinuria group and the moderate proteinuria group ( P>0.05). There was no significant difference in the median urinary β2-microglobulin (β2-MG) level among the 3 groups ( P=0.632). (3) Renal function index: sAlb and eGFR of PE pregnant women in the mild proteinuria group, moderate proteinuria group and severe proteinuria group were successively decreased, and BUN was successively increased, respectively, and the differences were statistically significant (all P<0.05). The sCr level of PE pregnant women in the severe proteinuria group was significantly higher than those in the mild proteinuria group and the moderate proteinuria group (all P<0.05), but there was no significant difference between the mild proteinuria group and the moderate proteinuria group ( P>0.05). (4) Correlation analysis: the 24-hour urinary protein quantification of PE pregnant women was significantly negatively correlated with eGFR ( r=-0.645, P<0.001), and was correlated with the variables sAlb ( r=-0.549, P<0.001), sCr ( r=0.582, P<0.001) and BUN ( r=-0.657, P<0.001) in the eGFR calculation formula. The 24-hour urinary protein quantification were significantly negatively correlated with the gestational weeks of PE onset, gestational weeks of termination of pregnancy and newborn birth weight (all P<0.05). Conclusions:The protein composition in the urine of PE pregnant women with different degrees of proteinuria is not different, but the protein level is significantly different. There is a significant negative correlation between the increase of 24-hour urinary protein quantification and the decrease of eGFR.

Posterior circulation ischemia is an ischemic cerebrovascular disease frequently seen in clinical practice，which includes transient ischemic attack and cerebral infarction of the posterior circulation. The clinical manifestations of patients with posterior circulation infarction are complex and varied，and diagnosis is mainly based on clinical manifestations and imaging. Transient ischemic attacks in the posterior circulation have neither obvious positive signs nor typical imaging manifestations during the interictal period，making the diagnosis difficult. Brainstem auditory evoked potentials reflect the electrophysiological functioning of the auditory nerves and brainstem auditory conduction pathway. The use of brainstem auditory evoked potentials，especially brainstem auditory evoked potentials at high stimulation rates，in diagnosing posterior circulation ischemia expands and enriches diagnostic methods，which is of great significance for the early diagnosis of the disease. However，there are still many problems worth considering.

Objective To explore the effects of valproate on vestibular migraine （VM） symptom improvement and vestibular function. Methods The patients with VM treated in the Dizziness Diagnosis and Treatment Center of The Second Affiliated Hospital of Naval Medical University from September 1，2019 to May 1，2021 were randomly divided into Valproate group and Flunarizine group. The patients were treated with valproate or flunarizine for three months. Before and after the treatment，the frequency of VM as well as the scores of Visual Analogue Scale （VAS） and Dizziness Handicap Inventory （DHI） items were recorded. Vestibular function was compared in the Valproate group before and after treatment. Results The VM frequency，the total scores of VAS and DHI，and the scores of VAS and DHI items in both groups were significantly reduced after the treatment. The changes in VM frequency，VAS score，DHI-F score，DHI-P score，and total DHI score before and after treatment were significantly greater in the Valproate group than in the Flunarizine group. There was no significant difference in the variation of DHI-E score before and after treatment between the two groups. Abnormal eye movement，gaze，and spontaneous nystagmus decreased significantly in the Valproate group after treatment. There were no significant differences in abnormal caloric test，c-VEMP，o-VEMP，saccade test，smooth pursuit test，and direction-changing positional nystagmus. Conclusion Valproate can significantly improve the symptoms of VM and reduce its frequency. Valproate is more efficient than flunarizine.

Objective To investigate the diagnostic value of lean test in Benign paroxysmal positional vertigo of posterior semicircular canal （PC-BPPV）. Methods We retrospectively included the clinical data of 220 patients with unilateral PC-BPPV who were admitted to the Department of Neurology，Jiaxing Second Hospital.All patients underwent lean test first，and then Dix-Hallpike test was performed to study the clinical characteristics of patients with vertigo induced by lean test. Results 133 （60.5%） patients induced PC-BPPV typical upbeat torsional nystagmus during the lean test. During the Dix-Hallpike test，the maximum slow phase angular velocity （SPV） of the induced upbeat nystagmus was higher than the SPV value induced by the lean test，and the latency and duration of the induced nystagmus were significantly different from the lean test （P 0.001）. Conclusion The lean test has a certain reference value for the diagnosis of PC-BPPV. It is effective for the diagnosis of PC-BPPV. The lean test induces a small nystagmus and mild autonomic symptoms compare to suspension position. In view of its simplicity，the lean test can be performed before the Dix-Hallpike operation.

Objective To explore the research hotspots and development trend on vascular dizziness/vertigo based on visual analysis. Methods The Web of Science Core Collection Database was searched for papers on vascular dizziness/vertigo from January 2008 to March 2023. The CiteSpace 6.2.R2 software was used for visual analysis of the literature. Results There were a total of 1298 papers，with an increasing number of published papers from January 2008 to March 2023. A total of 424 institutions from 83 countries/regions had published relevant papers. The United States ranked first in terms of the number of published papers（331 papers） and betweenness centrality（0.25）. Johns Hopkins University was the number one institution in terms of the number of published papers （56 papers），Newman-toker and David E were the most prolific authors. The most common keyword was ischemic stroke. According to keyword clustering，research in this field focused on early diagnosis of vascular dizziness/vertigo from risk factors and bedside examinations and infarction of the anterior inferior cerebellar artery supply area. In recent years，researchers had more interests in case reports，video electronystagmograms，and pathophysiological mechanisms in this field. Conclusion There are growing international studies on vascular dizziness/vertigo. Early diagnosis of vascular dizziness/vertigo through risk factors and bedside examinations in the emergency room is a research hotspot in this field. Researchers should focus on these topics in future studies.

BACKGROUND: Family clustering of esophageal cancer (EC) has been found in high-risk areas of China. However, the relationships between cancer family history and esophageal cancer and precancerous lesions (ECPL) have not been comprehensively reported in recent years. This study aimed to provide evidence for identification of high-risk populations. METHODS: This study was conducted in five high-risk areas in China from 2017 to 2019, based on the National Cohort of Esophageal Cancer. The permanent residents aged 40 to 69 years were examined by endoscopy, and pathological examination was performed for suspicious lesions. Information on demographic characteristics, environmental factors, and cancer family history was collected. Unconditional logistic regression was applied to evaluate odds ratios between family history related factors and ECPL. RESULTS: Among 33,008 participants, 6143 (18.61%) reported positive family history of EC. The proportion of positive family history varied significantly among high-risk areas. After adjusting for risk factors, participants with a family history of positive cancer, gastric and esophageal cancer or EC had 1.49-fold (95% confidence interval [CI]: 1.36-1.62), 1.52-fold (95% CI: 1.38-1.67), or 1.66-fold (95% CI: 1.50-1.84) higher risks of ECPL, respectively. Participants with single or multiple first-degree relatives (FDR) of positive EC history had 1.65-fold (95% CI: 1.47-1.84) or 1.93-fold (95% CI: 1.46-2.54) higher risks of ECPL. Participants with FDRs who developed EC before 35, 45, and 50 years of age had 4.05-fold (95% CI: 1.30-12.65), 2.11-fold (95% CI: 1.37-3.25), and 1.91-fold (95% CI: 1.44-2.54) higher risks of ECPL, respectively. CONCLUSIONS: Participants with positive family history of EC had significantly higher risk of ECPL. This risk increased with the number of EC positive FDRs and EC family history of early onset. Distinctive genetic risk factors of the population in high-risk areas of China require further investigation. TRIAL REGISTRATION ChiCTR-EOC-17010553.
Case-Control Studies ; China/epidemiology* ; Esophageal Neoplasms/pathology* ; Humans ; Precancerous Conditions/pathology* ; Risk Factors ; Stomach Neoplasms

Objective:To observe the effects of estradiol on expression of plasma membrane Ca 2+-ATPase isoform 2 in inner ear of rats. Methods:Twenty-five Three-months-old female Sprague-Dawley rats were randomly and equally divided into five groups by random number table mathod,with five rats in each group. Animals in Sham group were sham-operated while others were bilateral ovariactmized. One month after modeling, the OVX groups were supplemented with estradiol (E2 group), progesterone (P group), estradiol and progesterone (E2+P group)and vehicle sesame oil (Veh group), while the Sham operation group (Sham group) was supplemented with vehicle sesame oil.All rats were sacrificed and otocysts were obtained immediately. Enzyme-linked immunosorbent assay was used to detect the changes in serum estradiol and progesterone levels of each group of rats before operation, before treatment and before sacrifice. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression of total PMCA2 protein and mRNA in the inner ear of each group.Results:There was no significant difference in serum estradiol and progesterone levels among the five groups before operated( P>0.05). Before treatment, the serum estradiol and progesterone levels of rats in each group were significantly lower than those in Sham group ( P<0.05). The serum estradiol level in E2 group and E2+P group was not significantly different from that in Sham group ( P>0.05), while the serum estradiol level in P group and Veh group was significantly different from that in Sham group ( P<0.05). The level of progesterone in P group and E2+P group was higher than that in Sham group ( P<0.05), while the level of progesterone in Veh group and E2 group was lower than that in Sham group ( P<0.05). Protein and mRNA expression of PMCA2 in P and Veh groups were significantly decreased compared with that of Sham group ( P<0.05) while the expression levels underwent no significantly change in E2 and E2+P groups ( P<0.05). Conclusion:The decrease of serum estradiol level can reduce the expression of otolith regulatory protein PMCA2 in rats, and then affect otolith metabolism, which may be an important link of estrogen affecting otolith metabolism.

Objective:To study the cut-off values of urinary microalbumin (mAlb), transferrin (TRF) and α1-microglobulin (α1-MG) during pregnancy in pre-eclampsia (PE) with proteinuria.Methods:A total of 210 pregnant women were enrolled in Renji Hospital from January 2016 to December 2019, including 92 (43.8%) cases of PE pregnant women and 118 (56.2%) cases of normal pregnant women. According to the diagnostic test evaluation method, the positive predictive values, negative predictive values and accuracy of non-pregnant cut-off values of urinary mAlb, TRF and α1-MG for the quantitative determination of 24-hour proteinuria were analyzed. The receiver operating characteristic (ROC) curve was applied to determine the optimal cut-point values of urinary mAlb, TRF and α1-MG during pregnancy.Results:(1) The diagnostic study of non-pregnant adults urinary mAlb, TRF and α1-MG cut-off values for the determination of 24-hour proteinuria value: when urinary mAlb was 30.0 mg/L, TRF was 2.5 mg/L, α1-MG was 12.5 mg/L as the cut-off value, the positive predictive values of the corresponding 24-hour proteinuria value≥ 300 mg were 88.1% (89/101), 88.2% (90/102) and 78.9% (75/95), its negative predictive values were 97.2% (106/109), 98.1% (106/108) and 85.2% (98/115), its diagnostic accuracy were 92.9% (195/210), 93.3% (196/210) and 82.4% (173/210), respectively. As the 24-hour proteinuria value≥ 300 mg was the golden standard, there were significant differences between the diagnostic method of the non-pregnant cut-off value of urinary mAlb, TRF and the golden standard ( P<0.05). There was no significant difference between the diagnostic method of the non-pregnant cut-off value of urinary α1-MG and the golden standard ( P>0.05). (2) Research on the ROC curve and the optimal cut-point value of urinary mAlb, TRF and α1-MG value: as the 24-hour proteinuria value≥ 300 mg as the criterion, the ROC curve of urinary mAlb, TRF and α1-MG were 0.992, 0.984 and 0.907, respectively. The optimal cut-point values of urinary mAlb, TRF and α1-MG were 86.5 mg/L (Youden index=0.927), 5.5 mg/L (Youden index=0.923), and 15.4 mg/L (Youden index=0.687). (3) The diagnostic study of the optimal cut-point value of urinary mAlb, TRF and α1-MG for the determination of 24-hour proteinuria value: according to the ROC results, when urinary mAlb was 86.5 mg/L, urinary TRF was 5.5 mg/L, and urinary α1-MG was 15.4 mg/L as the cut-off value, the positive predictive values of the corresponding 24-hour proteinuria value≥300 mg were 98.9% (86/87), 95.7% (88/92), 87.7% (71/81), and its negative predictive values were 95.1% (117/123), 96.6% (114/118), 83.7% (108/129), and its accuracy were 96.7% (203/210), 96.2% (202/210), 85.2% (179/210). As the 24-hour proteinuria value≥ 300 mg was the golden standard, there was no significant difference between the diagnostic method of the best cut-off values of urinary mAlb, TRF, α1-MG and the golden standard ( P>0.05). Conclusion:It is recommended to define the cut-off values of mAlb, TRF and α1-MG as 86.5 mg/L, 5.5 mg/L and 15.4 mg/L, respectively, during pregnancy.

The occurrence and development of chronic insomnia involves subjective and objective factors, which can be classified as predisposing factors, precipitating factors and perpetuating factors. Cognitive behavioral therapy for insomnia (CBT-I) evolves from the pathopsychological analysis of chronic insomnia patients, and selectively combines the sleep hygiene, cognitive therapy and behavioral therapy to improve the symptoms of patients. With the popularity of internet, the digital cognitive behavioral therapy for insomnia has an convenient advantage over the traditional therapy, and has become the focus of research. Researchers have proposed multiple therapies for chronic insomnia, including drug therapy and non-drug therapy, which improve the treatment effect of chronic insomnia from different perspectives.