Association between the ratio of dietary vitamin A to body weight and hypertension in children / 中国学校卫生

Objective@#To explore the relationship between the ratio of dietary vitamin A (VitA) to body weight and hypertension among children, so as to provide a reference for blood pressure control through dietary nutritional interventions and childhood hypertension prevention.@*Methods@#Utilizing the baseline survey and followup sample data from the Healthy Children Cohort established in urban and rural areas of Chongqing from 2014 to 2019, structured quantitative dietary questionnaire and selfdesigned questionnaire were used to investigate the information of dietary intake and socioeconomic characteristics of 15 279 children, as well as blood pressure, height, weight measurement. The ratio of dietary VitA to body weight was divided into four groups based on quartiles [≤P25(Q1), >P25~P50(Q2), >P50~P75(Q3), >P75(Q4)]. Generalized linear regression models and Logistic regression models were used to analyze the correlation between ratio of dietary VitA to body weight with blood pressure levels and prevalence of hypertension.@*Results@#The results of the 2014 baseline survey indicated that, after adjusting for confounding factors such as demographic indicators and nutritional intake, significant differences were observed in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) among different groups categorized by the ratio of dietary VitA to body weight (F=157.57, 44.71, 95.92, P<0.01). The baseline ratio of dietary VitA to body weight in children exhibited a negative correlation with DBP, SBP and MAP at baseline and in 2019[baseline: β(95%CI)=-0.65(-0.89--0.42), -0.22(-0.42--0.01), -0.36(-0.56--0.16); 2019: β(95%CI)=-0.77(-1.34--0.19), -0.62(-1.21--0.02), -0.77(-1.34--0.19), P＜0.05]. Compared to Q1 group, the risk of hypertension decreased among children in Q4 at baseline and followup in 2019 [OR(95%CI)=0.63(0.49-0.81), 0.18(0.08-0.42), P<0.01].@*Conclusions@#The ratio of dietary VitA to body weight is significantly negatively correlated with blood pressure levels among children, and dietary VitA deficiency is an independent risk factor for hypertension among children. Measures should be taken to actively adjust childrens dietary nutrition and reduce the risk of childhood hypertension.

Genetic and phenotypic analysis of MYO15A rare variants associated with autosomal recessive hearing loss / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze the phenotype and genotype characteristics of autosomal recessive hearing loss caused by MYO15A gene variants, and to provide genetic diagnosis and genetic counseling for patients and their families. Methods:Identification of MYO15A gene variants by next generation sequencing in two sporadic cases of hearing loss at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The sequence variants were verified by Sanger sequencing.The pathogenicity of these variants was determined according to the American College of Medical Genetics and Genomics（ACMG） variant classification guidelines, in conjuction with clinical data. Results:The probands of the two families have bilateral,severe or complete hearing loss.Four variants of MYO15A were identified, including one pathogenic variant that has been reported, two likely pathogenic variants,and one splicing variant of uncertain significance. Patient I carries c. 3524dupA（p. Ser1176Valfs*14）, a reported pathogenic variant, and a splicing variant c. 10082+3G>A of uncertain significance according to the ACMG guidelines. Patient I was treated with bilateral hearing aids with satisfactory effect, demonstrated average hearing thresholds of 37.5 dB in the right ear and 33.75 dB in the left ear. Patient Ⅱ carries c. 7441_7442del（p. Leu2481Glufs*86） and c. 10250_10252del（p. Ser3417del）,a pair of as likely pathogenic variants according to the ACMG guidelines. Patient Ⅱ, who underwent right cochlear implantation eight years ago, achieved scores of 9 on the Categorical Auditory Performance-Ⅱ（CAP-Ⅱ） and 5 on the Speech Intelligibility Rating（SIR）. Conclusion:This study's discovery of the rare c. 7441_7442del variant and the splicing variant c. 10082+3G>A in the MYO15A gene is closely associated with autosomal recessive hearing loss, expanding the MYO15A variant spectrum. Additionally, the pathogenicity assessment of the splicing variant facilitates classification of splicing variations.

Noise Exposure and Stress Hormone Levels:A Review / 中国医学科学院学报

Noise is one of the most common environmental hazards to which people are exposed,and the exposure to noise can cause not only hearing but also non-hearing damage.Although noise under safety limits may not affect the auditory system,it can cause changes in stress hormone levels,which is harmful to health.However,the current studies about the impact of noise on health mainly focus on the auditory system,and little is known about the relationship between noise and stress hormone levels.Therefore,this paper reviews the studies involving noise exposure and stress hormone levels,aiming to provide ideas for strengthening the prevention and control of noise hazards.

Research Progress in Diagnostic Reference Levels in Interventional Radiology / 中国医学科学院学报

During interventional procedures,subjects are exposed to direct and scattered X-rays.Establishing diagnostic reference levels is an ideal way to optimize the radiation dose and reduce radiation hazard.In recent years,diagnostic reference levels in interventional radiology have been established in different countries.However,because of the too many indicators for characterizing the radiation dose,the indicators used to establish diagnostic reference levels vary in different countries.The research achievements in this field remain to be reviewed.We carried out a retrospective analysis of the definition,establishment method,application,and main factors influencing the dose difference of the diagnostic reference level,aiming to provide a basis for establishing the diagnostic reference level for interventional procedures in China.

Research progress of targeted degradation of Mycobacterium tuberculosis proteins / 药学学报

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb), is still one of the significant threats to human life. In recent years, the continuous exploration of small molecule inhibitors represented by bedaquinoline has brought new vitality into the field of tuberculosis. However, small molecule inhibitors will inevitably occur acquired drug resistance during clinical medication. As a new pharmacological mechanism, targeted protein degradation (TPD) achieves efficacy by destroying rather than inhibiting protein targets. It might be an excellent strategy to develop anti-tuberculosis drugs based on the TPD concept to solve drug resistance. This article reviews the protein degradation pathways of Mtb, such as the Pup proteasome system and the ClpP-ClpC1 complex enzyme system. The future development of these strategies into TPD drugs was prospected and summarized.

A new perspective in the treatment of liver fibrosis: Targeting macrophage metabolism / 临床肝胆病杂志

Liver fibrosis is a pathological process of fibrous scar formation caused by excessive accumulation of extracellular matrix due to various etiologies. At present, etiological treatment, such as effective antiviral therapy, is still the main treatment strategy for liver fibrosis. As the core participant of liver fibrosis, liver macrophages affect the progression and regression of liver fibrosis and are thus considered an important target for the treatment of liver fibrosis. With the recent advances in the field of immune metabolism, metabolic reprogramming has become a key factor for determining the outcome of macrophages and promoting the development of diseases. This article reviews the role and metabolic changes of macrophages during liver fibrosis and discusses the anti-fibrotic potential of targeting macrophage metabolism, so as to provide new ideas for the development, progression, and treatment of liver fibrosis.

Multi-tissue segmentation model of whole slide image of pancreatic cancer based on multi task and attention mechanism / 生物医学工程学杂志

Accurate segmentation of whole slide images is of great significance for the diagnosis of pancreatic cancer. However, developing an automatic model is challenging due to the complex content, limited samples, and high sample heterogeneity of pathological images. This paper presented a multi-tissue segmentation model for whole slide images of pancreatic cancer. We introduced an attention mechanism in building blocks, and designed a multi-task learning framework as well as proper auxiliary tasks to enhance model performance. The model was trained and tested with the pancreatic cancer pathological image dataset from Shanghai Changhai Hospital. And the data of TCGA, as an external independent validation cohort, was used for external validation. The F1 scores of the model exceeded 0.97 and 0.92 in the internal dataset and external dataset, respectively. Moreover, the generalization performance was also better than the baseline method significantly. These results demonstrate that the proposed model can accurately segment eight kinds of tissue regions in whole slide images of pancreatic cancer, which can provide reliable basis for clinical diagnosis.

Effects of Methionine Restriction on Proliferation, Cell Cycle, and Apoptosis of Human Acute Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of methionine restriction on proliferation, cell cycle and apoptosis of human acute leukemia cells.@*METHODS@#Cell Counting Kit-8 (CCK-8) assay was used to detect the effect of methionine restriction on HL-60 and Jurkat cells proliferation. The effect of methionine restriction on cell cycle of HL-60 and Jurkat cells was examined by PI staining. Annexin V-FITC / PI double staining was applied to detect apoptosis of HL-60 and Jurkat cells following methionine restriction. The expression of cell cycle-related proteins cyclin B1, CDC2 and apoptosis-related protein Bcl-2 was evaluated by Western blot assay.@*RESULTS@#Methionine restriction significantly inhibited the proliferation of HL-60 and Jurkat cells in a time-dependent manner (HL-60: r =0.7773, Jurkat: r =0.8725), arrested the cells at G2/M phase (P < 0.001), and significantly induced apoptosis of HL-60 and Jurkat cells (HL-60: P < 0.001; Jurkat: P < 0.05). Furthermore, Western blot analysis demonstrated that methionine restriction significantly reduced the proteins expression of Cyclin B1 (P < 0.05), CDC2 (P < 0.01) and Bcl-2 (P < 0.001) in HL-60 and Jurkat cells.@*CONCLUSION@#Acute leukemia cells HL-60 and Jurkat exhibit methionine dependence. Methionine restriction can significantly inhibit the proliferation, promote cell cycle arrest and induce apoptosis of HL-60 and Jurkat cells, which suggests that methionine restriction may be a potential therapeutic strategy for acute leukemia.

Hedgehog pathway orchestrates the interplay of histone modifications and tailors combination epigenetic therapies in breast cancer

Epigenetic therapies that cause genome-wide epigenetic alterations, could trigger local interplay between different histone marks, leading to a switch of transcriptional outcome and therapeutic responses of epigenetic treatment. However, in human cancers with diverse oncogenic activation, how oncogenic pathways cooperate with epigenetic modifiers to regulate the histone mark interplay is poorly understood. We herein discover that the hedgehog (Hh) pathway reprograms the histone methylation landscape in breast cancer, especially in triple-negative breast cancer (TNBC). This facilitates the histone acetylation caused by histone deacetylase (HDAC) inhibitors and gives rise to new therapeutic vulnerability of combination therapies. Specifically, overexpression of zinc finger protein of the cerebellum 1 (ZIC1) in breast cancer promotes Hh activation, facilitating the switch of H3K27 methylation (H3K27me) to acetylation (H3K27ac). The mutually exclusive relationship of H3K27me and H3K27ac allows their functional interplay at oncogenic gene locus and switches therapeutic outcomes. Using multiple in vivo breast cancer models including patient-derived TNBC xenograft, we show that Hh signaling-orchestrated H3K27me and H3K27ac interplay tailors combination epigenetic drugs in treating breast cancer. Together, this study reveals the new role of Hh signaling-regulated histone modifications interplay in responding to HDAC inhibitors and suggests new epigenetically-targeted therapeutic solutions for treating TNBC.

The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro / 中西医结合学报

OBJECTIVE@#JieZe-1 (JZ-1), a Chinese herbal prescription, has an obvious effect on genital herpes, which is mainly caused by herpes simplex virus type 2 (HSV-2). Our study aimed to address whether HSV-2 induces pyroptosis of VK2/E6E7 cells and to investigate the anti-HSV-2 activity of JZ-1 and the effect of JZ-1 on caspase-1-dependent pyroptosis.@*METHODS@#HSV-2-infected VK2/E6E7 cells and culture supernate were harvested at different time points after the infection. Cells were co-treated with HSV-2 and penciclovir (0.078125 mg/mL) or caspase-1 inhibitor VX-765 (24 h pretreatment with 100 μmol/L) or JZ-1 (0.078125-50 mg/mL). Cell counting kit-8 assay and viral load analysis were used to evaluate the antiviral activity of JZ-1. Inflammasome activation and pyroptosis of VK2/E6E7 cells were analyzed using microscopy, Hoechst 33342/propidium iodide staining, lactate dehydrogenase release assay, gene and protein expression, co-immunoprecipitation, immunofluorescence, and enzyme-linked immunosorbent assay.@*RESULTS@#HSV-2 induced pyroptosis of VK2/E6E7 cells, with the most significant increase observed 24 h after the infection. JZ-1 effectively inhibited HSV-2 (the 50% inhibitory concentration = 1.709 mg/mL), with the 6.25 mg/mL dose showing the highest efficacy (95.76%). JZ-1 (6.25 mg/mL) suppressed pyroptosis of VK2/E6E7 cells. It downregulated the inflammasome activation and pyroptosis via inhibiting the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (P < 0.001) and interferon-γ-inducible protein 16 (P < 0.001), and their interactions with apoptosis-associated speck-like protein containing a caspase recruitment domain, and reducing cleaved caspase-1 p20 (P < 0.01), gasdermin D-N (P < 0.01), interleukin (IL)-1β (P < 0.001), and IL-18 levels (P < 0.001).@*CONCLUSION@#JZ-1 exerts an excellent anti-HSV-2 effect in VK2/E6E7 cells, and it inhibits caspase-1-dependent pyroptosis induced by HSV-2 infection. These data enrich our understanding of the pathologic basis of HSV-2 infection and provide experimental evidence for the anti-HSV-2 activity of JZ-1. Please cite this article as: Liu T, Shao QQ, Wang WJ, Liu TL, Jin XM, Xu LJ, Huang GY, Chen Z. The Chinese herbal prescription JieZe-1 inhibits caspase-1-dependent pyroptosis induced by herpes simplex virus-2 infection in vitro. J Integr Med. 2023; 21(3): 277-288.

Effect of fraction of inspired oxygen baseline level on the mask ventilation time before intubation in emergency patients by monitoring of expiratory oxygen concentration / 中华危重病急救医学

OBJECTIVE@#To investigate the effect of different fraction of inspired oxygen (FiO2) baseline levels before endotracheal intubation on the time of expiratory oxygen concentration (EtO2) reaching the standard in emergency patients with the EtO2 as the monitoring index.@*METHODS@#A retrospective observational study was conducted. The clinical data of patients receiving endotracheal intubation in the emergency department of Peking Union Medical College Hospital from January 1 to November 1 in 2021 were enrolled. In order to avoid interference with the final result due to inadequate ventilation caused by non-standard operation or air leakage, the process of the continuous mechanical ventilation after FiO2 was adjusted to pure oxygen in patients who had been intubated was selected to simulate the process of mask ventilation under pure oxygen before intubation. Combined with the electronic medical record and the ventilator record, the changes of the time required to reach 0.90 of EtO2 (that was, the time required to reach the standard of EtO2) and the respiratory cycle required to reach the standard after adjusting FiO2 to pure oxygen under different baseline levels of FiO2 were analyzed.@*RESULTS@#113 EtO2 assay records were collected from 42 patients. Among them, 2 patients had only one EtO2 record due to the FiO2 baseline level of 0.80, while the rest had two or more records of EtO2 reaching time and respiratory cycle corresponding to different FiO2 baseline level. Among the 42 patients, most of them were male (59.5%), elderly [median age was 62 (40, 70) years old] patients with respiratory diseases (40.5%). There were significant differences in lung function among different patients, but the majority of patients with normal function [oxygenation index (PaO2/FiO2) > 300 mmHg (1 mmHg ≈ 0.133 kPa), 38.0%]. In the setting of ventilator parameters, combined with the slightly lower arterial partial pressure of carbon dioxide of patients [33 (28, 37) mmHg], mild hyperventilation phenomenon was considered to be widespread. With the increased in FiO2 baseline level, the time of EtO2 reaching standard and the number of respiratory cycles showed a gradually decreasing trend. When the FiO2 baseline level was 0.35, the time of EtO2 reaching the standard was the longest [79 (52, 87) s], and the corresponding median respiratory cycle was 22 (16, 26) cycles. When the FiO2 baseline level was increased from 0.35 to 0.80, the median time of EtO2 reaching the standard was shortened from 79 (52, 78) s to 30 (21, 44) s, and the median respiratory cycle was also reduced from 22 (16, 26) cycles to 10 (8, 13) cycles, with statistically significant differences (both P < 0.05).@*CONCLUSIONS@#The higher the FiO2 baseline level of the mask ventilation in front of the endotracheal intubation in emergency patients, the shorter the time for EtO2 reaching the standard, and the shorter the mask ventilation time.

Progress of therapeutic efficacy and predictive indicators of neoadjuvant chemoradiotherapy for locally advanced rectal cancer / 肿瘤研究与临床

The standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiotherapy(nCRT) followed by surgery. The therapeutic efficacy of patients after nCRT differs greatly. Effective use of nCRT can accurately predict the efficacy and help patients avoid damage caused by excessive treatment. This article describes the main methods of current nCRT and newly proposed concepts, such as totally neoadjuvant therapy, summarzies its impact on the efficacy of locally advanced rectal cancer, introduces the potential predictive biomarkers of efficacy evaluation for nCRT and the latest advances in clinical, histological and molecular predictors, and discusses the potential value of efficacy prediction in nCRT .

Correlations of β-catenin expression with clinical efficacy of tyrosine kinase inhibitors and prognosis of advanced lung adenocarcinoma patients with epidermal growth factor receptor mutations / 肿瘤研究与临床

Objective:To investigate the correlations of β-catenin expression with the efficacy of tyrosine kinase inhibitor (TKI) and prognosis of patients with advanced lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations.Methods:The clinical data of 125 patients with stage Ⅲ B-Ⅳ lung adenocarcinoma who were treated with first-line EGFR-TKI treatment in the 901st Hospital of Joint Logistic Support Force of Chinese PLA from January 2016 to December 2019 were collected. The expression of β-catenin protein was detected by immunohistochemistry, and subtypes of EGFR mutations were detected by amplification refractory mutation system (ARMS). Correlations of β-catenin expression with clinicopathological features, efficacy of EGFR-TKI and prognosis were analyzed. Twenty-eight pairs of specimens were selected before EGFR-TKI treatment and after resistance to EGFR-TKI to observe the changes of β-catenin expression. Results:Among 125 advanced lung adenocarcinoma patients with EGFR mutations, there were 60 cases of EGFR 19 del, 55 cases of L858R mutation and 10 cases of rare sensitive mutation; 79 cases (63.2%) had reduced membranous expression of β-catenin, 66 cases (52.8%) had ectopic expression in cytoplasm and 28 cases (22.4%) had ectopic expression in nucleus. The positive rates of Napsin A protein in the groups with different abnormal expression patterns of β-catenin were lower than those in the corresponding normal expression groups (all P < 0.001). Patients with International Association for the Study of Lung Cancer (IASLC) grade Ⅲ showed more frequent translocation in cytoplasma and nucleus of β-catenin than patients with IASLC gradeⅠ-Ⅱ (ectopic expression in cytoplasm: χ2 = 3.99, P = 0.046,ectopic expression in nucleus: χ2 = 11.07, P = 0.001). The objective remission rate (ORR) in patients with reduced membranous expression of β-catenin and ectopic expression in nucleus was lower than that in patients with normal membranous expression ( χ2 = 4.66, P = 0.031) and negative ectopic expression in nucleus ( χ2 = 10.22, P = 0.001), and the disease control rate (DCR) in patients with ectopic expression in nucleus was lower than that in the corresponding normal expression group ( χ2 = 10.95, P = 0.001). Patients with ectopic expression of β-catenin in nucleus and cytoplasma had worse progression-free survival (PFS) and overall survival (OS) than the corresponding cytoplasmic and nuclear ectopic expression negative groups (both P < 0.05). Multivariate Cox regression analysis showed that nuclear β-catenin ectopic expression was an independent risk factor for both PFS and OS (PFS: HR = 2.088, 95% CI 1.331-3.274, P = 0.001; OS: HR = 3.656, 95% CI 1.795-7.444, P<0.001). β-catenin membranous expression was reduced in 11 of 28 tissue samples that underwent secondary biopsy compared with pre-treatment ( P = 0.049). Conclusions:β-catenin expression in advanced lung adenocarcinoma with EGFR-sensitive mutations can be used as a molecular marker to predict the efficacy of EGFR-TKI and prognosis of patients.

Clinical significance of hepatitis B virus DNA detection in screening patients with hepatitis B / 中华检验医学杂志

Objective:To explore the clinical significance of hepatitis B virus (HBV) DNA detection in screening patients with hepatitis B.Methods:Clinical data of 682 331 hepatitis B patients were retrospectively analyzed. The HBV DNA of these patients was detected in the Fifth Medical Center of the PLA General Hospital from January 2017 to December 2021, there were 481 159 males and 201 172 females in this cohort, the average age was (41.34±16.13) years. Patients were divided into HBV DNA positive group (219 879 cases) and HBV DNA negative group (462 452 cases). Clinical characteristics, data of five serologic markers of hepatitis B and hepatitis B surface antigen quantification (HBsAg-QN), liver function, alpha fetoprotein (AFP) and prothrombin time (PT) results were collected and analyzed and compared between the two groups.Results:The positive rate of HBV DNA was 32.22% (219 879/682 331) in this cohort. Among the different age groups, the positive rate of HBV DNA was the highest (40.34%, 128 038/317 380) in young people aged 18-44 years. The proportion of patients was lower among aged <1, 45-59 and ≥60 years patients in HBV DNA positive group than that in HBV DNA negative group, while the proportion of patients was higher among aged 1-17 and 18-44 years patients in HBV DNA positive group than that in HBV DNA negative group (all P<0.001). Among 2 291 <1-year-old infants tested for HBV DNA, 71 infants were HBV DNA positive. The positive rates of HBV DNA from 2017 to 2021 were 4.86% (27/556), 3.68% (14/380), 3.47% (17/490), 1.55% (6/386) and 1.46% (7/479) respectively, showing a downward trend year by year. The positive rate of HBV DNA in acute hepatitis B (AHB) patients was the highest (49.88%, 208/417) among 680 040 patients with hepatitis B. The proportion of AHB patients (0.09%, 208/219 808) and chronic hepatitis B (80.44%, 176 806/219 808) in HBV DNA positive group was higher than that in HBV DNA negative group [0.05% (209/460 232) and 65.45% (301, 216/460 232)], while the proportion of patients with HBV-related liver cirrhosis (11.28%, 24 793/219 808), HBV-related liver cancer (6.72%, 14 775/219 808), liver cancer surgery (1.39%, 3 055/219 808) and liver transplantation (0.08%, 171/219 808) were lower than that in HBV DNA negative group [22.99% (105 813/460 232), 7.25% (33 385/460 232), 3.50% (16 129/460 232) and 0.76% (3 480/460 232)] (all P<0.001). At the same time, positive rate of hepatitis B surface antigen (HbsAg), HBsAg-QN, hepatitis B e antigen (HbeAg), level of total bilirubin, total bilirubin, AFP and PT were higher in HBV DNA positive group than those in HBV DNA negative group, while the age, male ratio and albumin results in HBV DNA positive group were lower than those in HBV DNA negative group (all P<0.01). The HBV DNA loads were higher in HBsAg positive group, hepatitis B surface antibody positive group and HBeAg positive group than those in respective negative groups, while the HBV DNA loads were lower in hepatitis B e antibody positive group and hepatitis B core antibody positive group than those in respective negative groups (all P<0.001). Conclusions:The mother to child transmission rate of<1-year-old infants decreases year by year. HBV DNA is an important factor for the progression of hepatitis B disease. HBV DNA positive hepatitis B patients with higher HBsAg-QN values are more likely to have abnormal serum markers such as liver dysfunction. HBV DNA detection is therefore of clinical importance in screening patients with hepatitis B.

Clinical features and stroke etiology in 10 patients with bilateral middle cerebellar peduncle infarctions: a preliminary study / 中华神经科杂志

Objective:To characterize clinical and neuroimaging features, etiologies, and mechanisms of bilateral middle cerebellar peduncle (MCP) infarctions.Methods:Consecutive patients with bilateral MCP infarctions treated in the Beijing Tiantan Hospital, Capital Medical University between January 1, 2020 and April 30, 2022 were enrolled in this retrospective study. The demographic data, vascular risk factors, clincial manifestations and the National Institutes of Health Stroke Scale (NIHSS) scores were collected. Brain diffusion-weighted imaging was used to assess the regions of cerebral infarction, and the extracranial and intracranial segments of the vertebrobasilar artery were evaluated using magnetic resonance angiography, or computed tomography angiography. The stroke etiology and underlying mechanism were evaluated according to the Chinese Ischemic Stroke Subclassification.Results:Ten patients with bilateral MCP infarctions (8 men and 2 women) were analyzed ultimately. The onset age were 51.0-86.0 (64.8±11.4) years. NIHSS scores were 2.0-12.0 (4.9±2.9) points at admission. All patients had vascular risk factors, most of which were hypertension (10 cases) and dyslipoproteinemia (8 cases). The most common clinical manifestations were vertigo (10 cases), followed by ataxia (9 cases) and dysarthria (8 cases). Four cases were isolated bilateral MCP infarctions, while 6 patients were combined with other vertebrobasilar artery infarctions, 4 of which were combined with cerebellar hemisphere infarctions, consistent with the clinical symptoms. The etiology in all patients was large atherosclerosis (severe stenosis or occlusion of V4 segment of vertebral artery and anterior inferior cerebellar artery; 9 cases). Five patients were classified as hypoperfusion/impaired emboli clearance, while 4 patients were considered as artery-to-artery embolism, and 1 was considered as the parent artery (plaque or thrombosis) occluding penetrating artery.Conclusions:Bilateral MCP infarctions are an extremely rare cerebrovascular disease characterized by vertigo, ataxia, and dysarthria. Cerebral infarction can be isolated or often combined with cerebellar hemisphere infarction. The etiology was mostly stenosis or occlusion of V4 segment of vertebral artery and anterior inferior cerebellar artery.

Factors on malnutrition in patients with Alzheimer′s disease-related cognitive impairment: a preliminary analysis / 中华神经科杂志

Objective:To explore the factors on malnutrition or risk of malnutrition in patients with Alzheimer′s disease (AD)-related cognitive impairment,and to further analyze the association between the severity of behavioral and psychological symptoms in dementia (BPSD) and nutritional status.Methods:The clinical data of 247 patients with AD-related cognitive impairment were collected continuously from the Chinese Imaging, Biomarkers and Lifestyle Study of Alzheimer′s Disease (CIBL) cohort between June 1, 2021 and August 31, 2022. The patients were divided into well-nourished group ( n=128) and malnourished group ( n=119) according to the scores of Mini-Nutritional Assessment scale (MNA). The sociodemographic data (sex, age, body mass index, waist-to-hip ratio, education level), the medical history of olfactory dysfunction, combination with more than two chronic diseases, and gastrointestinal diseases, presenting BPSD, and the scores of the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), Activity of Daily Living (ADL), Caregiver Burden Inventory (CBI) and Dietary Diversity Score (DDS) were compared between the two groups. The factors with statistically significant differences in hypothesis test and univariate Logistic regression analysis were enrolled in multivariate Logistic regression analysis to further identify independent factors associated with malnutrition in patients with AD-related cognitive impairment. Furthermore, the association between NPI scores and MNA scores was analyzed by Spearman′s rank correlation test. Results:Compared with those in the well-nourished group, patients in the malnourished group had higher age [(66.70±7.01) years vs (69.14±8.87) years, t=-2.39, P=0.018], lower body mass index [(24.68±2.84) kg/m 2vs (22.69±3.63) kg/m 2, t=4.78, P<0.001], and higher proportion of presenting BPSD [22.66% (29/128) vs 76.47% (91/119), χ 2=71.49, P<0.001]; lower scores of MMSE, MoCA, and DDS [24.27±4.69 vs 18.95±8.40, t=6.09; 20.29±5.18 vs 14.55±8.12, t=6.56; 8.00 (8.00, 9.00) vs 8.00 (7.00, 8.00), Z=-4.66; all P<0.001], and higher scores of NPI, ADL and CBI [1.00 (0, 6.00) vs 10.00 (2.00, 25.00), Z=-6.50; 20.00 (20.00, 22.00) vs 27.00 (20.00, 40.00), Z=-7.08; 1.00 (0, 14.75) vs 12.00 (2.00, 35.00), Z=-5.13; all P<0.001]. There were no statistically significant differences in the sex, waist-to-hip ratio, education level, and the medical history of olfactory dysfunction, combination with more than two chronic diseases, and gastrointestinal diseases between the two groups. The multiple Logistic regression analysis demonstrated that the decreased body mass index ( OR=0.79, 95% CI 0.70-0.89, P<0.001), presenting BPSD ( OR=7.84, 95% CI 3.67-16.73, P<0.001), elevated ADL scores ( OR=1.15, 95% CI 1.06-1.24, P<0.001) and CBI scores ( OR=0.98, 95% CI 0.97-1.00, P=0.026), and decreased scores of DDS ( OR=0.66, 95% CI 0.51-0.84, P=0.001) were independently associated with malnutrition in patients with AD-related cognitive impairment. The MNA scores were significantly negatively associated with NPI scores ( r=-0.483,95% CI -0.58--0.38, P<0.001). Conclusions:The decreased body mass index, dietary diversity, and ability of daily living, and presenting BPSD and heavy burden of caregivers can independently contribute to the malnutrition in patients with AD-related cognitive impairment. The more serious the BPSD, the worse the nutritional status.

Analysis of potential biomarkers for behavioral and psychological symptoms in patients with Alzheimer′s disease continuum / 中华健康管理学杂志

Objectives:To analyze the potential biomarkers of behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer′s disease (AD) continuum.Methods:A prospective cohort study was consecutively conducted on 179 patients with AD continuum (135 presented with BPSD, 44 patients without BPSD as control) from Capital Medical University, Beijing Tiantan Hospital, the Chinese imaging biomarkers and lifestyle cohort between January 1, 2021 and December 31, 2022. Gender, age, body max index, education level, diagnosis, the apolipoprotein E epsilon4 allele (APOE ε4) carrier status, the scores of the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), cerebrospinal fluid (CSF) AD-related pathological biomarkers (Aβ 42, Aβ 40, Aβ 42/40, tTau, pTau181), and blood biomarkers (white blood cell count, red blood cell count, hemoglobin, platelet, total bilirubin, albumin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting glucose, erythrocyte sedimentation rate, homocysteine, vitamin B 12, folate) were compared between the two groups by using hypothesis testing and univariate logistic regression analysis. Multivariate logistic regression analysis was used to analyze the potential biomarkers associated with BPSD in patients with AD. Results:Among the 179 patients with AD continuum in the final analysis, 77 patients were men, 102 cases were women; 35 patients were identified with mild cognitive impairment (MCI) due to AD and 144 patients with AD dementia stage, the mean age was (66.54±9.75) years. Compared with those in control group, patients with BPSD had lower cerebrospinal fluid (CSF) Aβ 40 and blood hemoglobin levels [7.08 (4.42, 15.42) vs 9.62 (6.45, 12.12) pg/L, (132.70±13.37) vs (138.80±14.38) g/L] ( U=-1.856, t=2.579, P<0.05). The levels of CSF Aβ 40 ( OR=0.030, 95% CI: 0.001-0.760) and blood hemoglobin ( OR=0.051, 95% CI: 0.004-0.670) were independently negatively associated with BPSD in patients with AD continuum (both P<0.05). Conclusion:The decreased levels of CSF Aβ 40 and blood hemoglobin could be considered as potential biomarkers in detecting BPSD in patients with AD continuum.

Correlation of related indexes of blood lipid and insulin resistance with cognition scores in middle-aged and elderly people with mild cognitive impairment / 中华健康管理学杂志

Objective:To analyze the correlation between related indexes of serum lipid and insulin resistance and cognitive impairment in middle-aged and elderly people with mild cognitive impairment (MCI).Methods:In this cross-sectional study, 262 middle-aged and elderly patients with a Montreal Cognitive Function Scale (MoCA) cognitive score greater than or equal to 18 points who underwent physical examination in the Health Management Center of Beijing Tiantan Hospital Affiliated to Capital Medical University from January 1 to July 31, 2021 were selected as subjects. According to the cognitive function and MoCA score, the patients were divided into MCI group (143 cases) and normal cognition group (119 cases). Basic data, fasting blood glucose, triglyceride (TG), total cholesterol, apolipoprotein E(ApoE) genotype and other clinical indicators were collected. Hypothesis test was used to compare the differences in basic data, related indicators of blood lipid and insulin resistance between the two groups. Spearman correlation analysis was used to analyze the correlation between related indicators of blood lipid and insulin resistance and MoCA score in the two groups.Results:The age and the proportion of patients with hypertension, coronary heart disease and diabetes in the MCI group were all significantly higher than those in normal cognition group [(54.83±8.29) vs (50.76±6.34) years, 37.76% vs 31.93%, 4.20% vs 0.84%, 16.08% vs 8.40%] (all P<0.05). The elevation of serum TG ( r=-0.50, 95% CI:-0.88--0.12), TG glucose product index (TyG) ( r=-0.75, 95% CI:-1.29--0.20) and TG to high-density lipoprotein cholesterol ratio (TG/HDL-C) ( r=-0.52, 95% CI:-0.91--0.13) were all negatively correlated with MoCA score (all P<0.05). After adjusting for age and gender, the elevation of TG ( r=-0.39, 95% CI:-0.75--0.31) and TG/HDL-C ( r=-0.43, 95% CI:-0.80--0.05) were both still negatively correlated with MoCA score (both P<0.05). There was no significant correlation between all indexes and MoCA scores in the normal cognition group (all P>0.05). The elevated TG was negatively correlated with MoCA score in the MCI group ( r=-0.70, 95% CI:-1.23-0.16, P=0.017). There was no significant correlation between elevated TG and MoCA score in patients carrying ApoE ε2 and ApoE ε3 genotypes in MCI group (all P>0.05). Conclusion:Elevated related indexes of blood lipids and insulin resistance are negatively correlated with cognitive scores in middle-aged and elderly people with MCI, and it′s more obvious in patients with ApoE ε4 genotype.

Influencing factors of post stroke cognitive impairment in patients with acute ischemic stroke and their correlation with cognitive scores / 中华健康管理学杂志

Objective:To analyze the influencing factors of post stroke cognitive impairment (PSCI) and their correlation with cognitive scores in patients with acute ischemic stroke.Methods:In this cross-section study, 36 patients diagnosed with acute ischemic stroke and post stroke cognitive impairment (PSCI) admitted to the Department of Vascular Neurology of Beijing Tiantian Hospital Affiliated to Capital Medical University from June 1, 2022 to September 30, 2022 were selected as the PSCI group. And one to one matching was performed for patients without PSCI (PSNCI group) with an age±1 year and same gender admitted to the hospital during the same period (as control, 36 cases). Basic clinical data of the two groups were collected, the laboratory and imaging examinations were completed. Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA) were used for cognitive evaluation by neuropsychologists. Hypothesis testing was used to compare the differences in basic data, laboratory tests and lesion sites between the two groups. Multi-factor conditional logistic regression was performed to analyze the influencing factors of PSCI, and Spearman correlation analysis was carried out to analyze the correlation between influencing factors of PSCI and the cognitive scores.Results:Compared with those in PSNCI group, the proportion of patients with stroke/transient ischemic attack history, hyperhomocysteinemia (HHcy), apolipoprotein E(ApoE) ε4 carriers and the ratio of temporal lobe and thalamus infarction were higher in PSCI group (41.7% vs 13.9%, 36.1% vs 2.8%, 30.6% vs 5.6%, 22.3% vs 2.8%, 25.0% vs 5.6%), the MMSE and MoCA scores were lower in PSCI group [16.50 (8.25, 19.00) vs 28.00 (27.00, 30.00), 10.00 (4.25, 14.50) vs 27.00 (25.00, 28.00)] (all P<0.05). Logistic regression analysis showed that HHcy was a positive correlation factor for PSCI ( OR=2.342, 95% CI=1.186-4.622, P=0.014). Spearman correlation analysis showed that MMSE ( r=-0.415) and MoCA ( r=-0.417) scores were negatively correlated with homocysteine (Hcy) (both P<0.05). Conclusion:HHcy is an important factor affecting the occurrence and development of PSCI in patients with acute ischemic stroke, and Hcy level is negatively correlated with cognitive scores in those patients.

Recent progress on cGAS-STING pathway in tumor radiotherapy / 中华放射肿瘤学杂志

Radiotherapy is widely used in the treatment of primary and metastatic malignant tumors. It is traditionally believed that the killing effect of radiotherapy on tumor is based on the direct or indirect damage of ionizing radiation to DNA. In recent years, the anti-tumor role and mechanism of anti-tumor immune response induced by ionizing radiation have captivated widespread attention and achieved significant progress. Among them, Cyclic GMP-AMP synthase (cGAS)-stimulator of interference genes (STING) pathway is considered to be one of the key regulatory hubs. cGAS is a cytoplasmic DNA receptor that can bind to tumor-derived double-stranded DNA and activate the downstream STING, thereby activating anti-tumor immune response of the host. In view of the latest progress in this field, the important role and potential mechanism of cGAS-STING pathway in radiotherapy immune effect were mainly summarized, and the application prospect of targeting cGAS-STING pathway in radiotherapy sensitization was explored.