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.

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.

Treatment and factors associated with prognosis of hyperkalemia in the emergency department / 中华危重病急救医学

Objective:To survey treatment and prognosis of hyperkalemia patients in the emergency department and to analyze factors associated with all-cause in-hospital mortality.Methods:We implemented electronic hospital information system, extracted demographic characteristics, underlying diseases, laboratory findings, potassium lowering therapy and prognosis of hyperkalemia patients [age ≥ 18 years, serum potassium (K +) concentration ≥ 5.5 mmol/L] in the emergency department of Peking Union hospital in Beijing between June 1st 2019 to May 31st 2020. The enrolled subjects were divided into the non-survival group and the survival group according to their prognosis. Univariate analysis and Cox regression model were adopted to analyze factors affecting all-cause in-hospital mortality of hyperkalemia patients. Results:A total of 579 patients [median age 64 (22) years; 310 men (53.5%) and 269 women (46.5%)] with hyperkalemia were enrolled, among which, 317 (54.7%), 143 (24.7%) and 119 (20.6%) were mild, moderate, and severe hyperkalemia, respectively. 499 (86.20%) patients received potassium-lowering therapy, forty-four treatment regimens were administered. Insulin and glucose (I+G, 61.3%), diuretics (Diu, 57.2%), sodium bicarbonate (SB, 41.9%) and calcium gluconate/chloride (CA, 44.4%) were commonly used for the treatment of hyperkalemiain the emergency department. The combination of insulin and glucose, calcium gluconate/chloride, diuretics and sodium bicarbonate (I+G+CA+Diu+SB) was the most favored combined treatment regimen of hyperkalemia in the emergency department. The higher serum potassium concentration, the higher proportion of administrating combined treatment regimen and/or hemodialysis (HD) (the proportion of administrating combined treatment regimen in mild, moderate, and severe hyperkalemia patients were 58.4%, 82.5% and 94.8%; the proportion of administrating HD in mild, moderate, and severe hyperkalemia patients were 9.7%, 13.3% and 16.0%, respectively). The proportion of achievement of normokalaemia elevated as the kinds of potassium lowering treatment included in the combined treatment regimen increased. The proportion of achievement of normokalaemia was 100% in the combined treatment regimen including 6 kinds of potassium lowering therapy. Among various potassium lowering treatments, HD contributed to the highest rate of achievement of normokalaemia (93.8%). 111 of 579 (19.20%) hyperkalemia patients died in hospital. Cox regression model revealed that complicated with cardiac dysfunction predicted higher mortality [hazard ratio ( HR) = 1.757, 95% confidence interval (95% CI) was 1.155-2.672, P = 0.009]. Achievement of normokalaemia and administration of diuretics attributed to lower mortality ( HR = 0.248, 95% CI was 0.155-0.398, P = 0.000; HR = 0.335, 95% CI was 0.211-0.531, P = 0.000, respectively). Conclusions:Treatment of hyperkalemia in the emergency department were various. Complicated with cardiac dysfunction were associated with higher mortality. Achieving normokalaemia was associated with decreased mortality.

Status survey and countermeasures for trainees in standardized residency training of ultrasound professional base under the novel coronavirus pneumonia epidemic / 中华医学教育探索杂志

Objective:To investigate the behavior and emotion of trainees (residents) in the standardized residency training under the novel coronavirus pneumonia (NCP) epidemic, and adjust the training plan and mode of standardized residency training during the NCP epidemic according to the survey results.Methods:A real-name closed questionnaire survey was conducted among 40 residents (27 ultrasound majors and 13 other majors) in ultrasound department using the "Questionnaire Star" WeChat applet, including basic personal information, questions related to NCP, behavioral change survey, behavioral attitude survey and emotional status survey. All the collected data were further statistically analyzed by Chi-square test and rank sum test using SPSS 19.0Results:There were forty valid questionnaires and the participation rate was 100.0%. The accuracy of 24 NCP-related questions was not significantly different between residents majoring in ultrasound and other specialties [92.0%(596/648) vs. 93.6%(292/312), P>0.05]. All the residents had a good understanding of NCP. The main behaviors of going out were significantly reduced, while various behaviors of being at home were significantly increased. Their interest in learning declined. When the epidemic happened (or possibly) in the community or village they lived in, their negative emotions, such as nervousness, fear pessimism and depression, were obviously expressed. Network teaching and evaluation through WeChat public number were adopted and we guided residents to adjust their home behaviors and emotions according to the survey results. Conclusion:Under the NCP epidemic, the behaviors and emotions of residents had been extensively changed. The training center should adjust the teaching plan and mode of training in time, and provide more counselling service in psychology and learning for residents during the epidemic.

Effect of lung protective ventilation on lung ventilation function, serum serum Clara cell protein 16 level and prognosis in patients undergoing gynecological laparoscopic surgery / 中国医师进修杂志

Objective:To analyze the effect of lung protective ventilation on lung ventilation function and serum Clara cell protein 16 (CC16) level in patients undergoing gynecological laparoscopic surgery.Methods:The clinical data of 80 gynecological patients who underwent laparoscopic surgery in Yancheng City Jianhu County People′s Hospital from October 2018 to December 2020 were randomly divided into group A and group B by random number table, each group with 40 cases. The patients in group A were treated with intermittent positive-pressure ventilation, and the patients in group B were ventilated with whole course ventilation mode. The pulmonary ventilation function, CC16 level and postoperative pulmonary complications were observed before anesthesia, 10 min of pneumoperitoneum, 30 min of pneumoperitoneum, 5 min of pneumoperitoneum stop and 2 h after operation. The patients were divided into groups according to whether with pulmonary complications, and their pulmonary ventilation function and serum CC16 level were compared. The predictive value of the above indexes for pulmonary complications was analyzed by receiver operating characteristic (ROC) curve.Results:Repeated measurement analysis of variance showed that alveolar arterial oxygen differential pressure (PA-aDO 2) were significant differences in time point factors, time point interaction factors and group factors ( P<0.05); CC16 index were significant differences in time point factor and group factor ( P<0.05). According to the observation from postoperative to discharge, 4 patients (10.0%) in group A had pulmonary complications, 15 cases (37.5%) had pulmonary complications in group B, the levels of PA-aDO 2 and CC16 in patients with complications were significantly higher than those in patients without complications: group A:(332.9 ± 2.0) mmHg (1 mmHg = 0.133 kPa) vs. (290.4 ± 13.2) mmHg, (53.5 ± 1.5) μg/L vs. (39.5 ± 6.5) μg/L; group B: (339.1 ± 8.8) mmHg vs. (305.7 ± 17.9) mmHg, (41.5 ± 4.2) μg/L vs. (39.7 ± 5.8) μg/L, there were statistical differences ( P<0.05). ROC curve analysis showed that the area under the curve(AUC) of PA-aDO 2 and CC16 in predicting pulmonary complications in group A were 0.882 and 0.833, in group B was 0.885 and 0.731. Conclusions:Lung protective ventilation has little effect on lung ventilation function and serum CC16 in patients with gynecological laparoscopic surgery, and the probability of pulmonary complications is lower. The pulmonary ventilation function and CC16 have certain value in predicting postoperative pulmonary complications.

Optimization of quality assessment system of clinical blood transfusion records / 中国输血杂志

【Objective】 To determine the value of quality assessment system in supervising standard clinical blood use and improving the quality of clinical blood transfusion medical records. 【Methods】 The clinical blood transfusion records of Children′s Hospital, Zhejiang University School of Medical every quarter from January 2019 to December 2022 were selected and extracted for evaluation by 5% to 10% for the current season. These blood transfusion medical records were scored and graded A(≥90 points)/B(80-89 points)/C(<80 points)according to the Evaluation Table of Clinical Science Rational Use of Blood in Children′s Hospital of Zhejiang University, and the annual A rate was statistically analyzed. After summarizing the deduction points, a rectification plan was submitted to the medical department and publicized on the hospital network. 【Results】 A total of 1 975 blood transfusion medical records were analyzed from January 2019 to December 2022, including 343 in 2019 (17.37%), 517 in 2020 (26.18%), 556 in 2021 (28.15%) and 559 in 2022 (28.30%), with Grade A rates at 67.06%, 92.07%, 93.17% and 91.06%, respectively. According to Pearson Chi-square test, the Grade A rates of blood transfusion records in 2020, 2021 and 2022 were significantly higher than those in 2019 (P<0.000 1). In the assessment, the main reasons for deduction of points were missed pre-transfusion immunization tests and missed blood transfusion course records. From 2019 to 2022, the missed rates of pre-transfusion immunization tests were 22.68%, 6.47%, 1.26% and 2.49%, and the missed rates of blood transfusion course records were 32.21%, 10.59%, 5.57% and 6.61%, respectively. 【Conclusion】 The regular and reasonable assessment and publicity system of blood transfusion medical records is conducive to improving the quality of blood transfusion medical records, promoting rational blood use and ensuring the safety of blood use for children.

Generation of traditional Chinese medicine prescription driven by generative artificial intelligence GPT-4 / 中国药房

OBJECTIVE To evaluate the safety and suitability of traditional Chinese medicine prescriptions generated by generative artificial intelligence （AIGC）， and to provide research ideas for empowering the traditional Chinese medicine industry with AIGC. METHODS Using the 2020 edition of Chinese Pharmacopoeia and the 5th edition of Traditional Chinese Medicine as corpus， GPT-4 and the real-time networking model developed based on GPT-4 （referred to as the “networking model”） were used for deep learning. The clinical cases included in the consensus of traditional Chinese medicine experts in recent years were extracted manually to regenerate prescriptions based on diagnosis using the GPT-4 model and networking model； traditional Chinese medicine experts conducted blind evaluation and scoring of GPT-4 generated prescriptions， networking model generated prescriptions， and expert consensus prescriptions. At the same time， Turing testing was used to evaluate whether the GPT-4 model and networking model had the same ability as human intelligence. RESULTS The average score of traditional Chinese medicine prescriptions generated by the GPT-4 model showed no statistically significant difference compared to manual prescriptions （P＞0.05）， while the average score of prescriptions generated by the networking model showed no statistically significant difference compared to traditional Chinese medicine prescriptions generated by the GPT-4 model （P＞0.05）. The proportion of model-generated prescriptions mistakenly judged as manual prescriptions in the Turing test was 51.11%. CONCLUSIONS The traditional Chinese medicine prescriptions generated by the GPT-4 model have reached a certain level of safety and suitability， and the GPT-4 model has passed the Turing test. The introduction of AIGC in the diagnosis and treatment process may provide technical support for the rational use of clinical traditional Chinese medicine.

Hypercalin B alleviates nonalcoholic steatohepatitis progression via suppressing mTORC1 signaling pathway / 药学学报

The global incidence rate of nonalcoholic steatohepatitis (NASH) continues to rise. The pathogenesis of NASH is complex, and there is no effective clinical treatment. Previous study has shown that DEAD box protein 5 (DDX5) can significantly alleviate the NASH process in mice. This study screened the natural product library of the research group and found that the active compound hypercalin B (HB) in Hypericum beanii N. Robson, a traditional Chinese medicine, can upregulate the expression of DDX5 protein in a dose-dependent manner. In this study, an in vitro model of NASH stimulated by palmitic acid (PA) and an animal model of NASH induced by the methionine- and choline-deficient diet (MCD) were constructed. Different concentrations of HB were used to investigate the effect and mechanism of HB in alleviating NASH progression. All animal experiments in this paper were approved by the Ethics Committee of China Pharmaceutical University (NO: 2021-02-003). In vitro model results showed that HB significantly reduced the intracellular lipid deposition induced by free fatty acid (FFA). Animal experiments showed that HB improved liver injury by significantly reducing lipid accumulation in the liver of NASH mice, and reducing serum aspartate transaminase (AST) and alanine transaminase (ALT) levels. Moreover, HB could inhibit liver inflammation by reducing the mRNA levels of liver pro-inflammatory cytokines including interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor α (TNFα). Further research showed that HB could reduce the phosphorylation level of the mechanical target of rapamycin (mTOR) and reduce the expression of sterol regulatory element binding protein 1 (SREBP1) and fatty acid synthase (FASN), thereby improving lipid metabolism and alleviating NASH progression, and the effects of HB against NASH were dependent on DDX5. In conclusion, HB can improve lipid metabolism and inhibit inflammatory activation by suppressing mTORC1 pathway via upregulating DDX5 protein, and showed promising anti-NASH activity in vitro and in vivo.

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.

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.

Discussion on hot issues in liver transplantation for hepatocellular carcinoma / 中华消化外科杂志

Liver diseases are common in China and the incidence and mortality of primary liver cancer are among the top in the world. As one of the therapeutic methods for hepatocellular carcinoma (HCC), liver transplantation has become an important technique in hepatic surgery. Most of patients with HCC have progressed to stage B or C of Barcelona Clinic Liver Cancer staging when diagnosed. How to reduce the dropout rate of HCC patients due to the progression of tumor when waiting for liver transplantation, develop individualized immunosuppressant plans for HCC patients after liver transplantation, and accurately manage patients with HCC recurrence after liver transplan-tation are the current hotspots of research. The authors review the relevant literature, summarize the treatment experience, and discuss the hot issues in liver transplantation for HCC, in order to provide reference for related treatment.