Due to the limited treatment options of advanced gastric cancer and prone to chemoresistance,there is an urgent need for novel treatment methods to improve the prognosis of these patients.At present,immunotherapy including immune checkpoint inhibitor,adoptive cell therapy,tumor vaccine,nonspecific immune enhancer and cytokine therapy has shown good curative effect on gastric cancer.Additionally,carrier drugs and 3D printing technology have also achieved curative effects in preclinical experiments.Clinical trials used immunooncology monotherapy or combined immunochemotherapy to improve the overall survival time and objective response rate of patients with gastric cancer.Based on the preliminary evidence,we believe that immunotherapy can positively affect the natural history and improve the prognosis of patients with gastric cancer.

Background::Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism.Methods::This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram.Results::Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276-13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086-0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830-21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001-0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884-0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686-0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations. Conclusion::A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD.Registration::Chictr.org.cn, ChiCTR2100049131.

Objective To develop and validate a prediction model for severe disability or death(SDD)in acute ischemic stroke(AIS)patients who underwent endovascular treatment(EVT).Methods Based on the dataset of ANGEL-ACT study who received EVT for AIS between november 2017 and march 2019,a retrospective analysis was performed on 1 677 patients,including 1 111 males and 566 females,aged ≥ 18 years.Patients were divided into two groups according to whether SDD occurred(mRS 5-6 scores 90 days after surgery):SDD group(n=478)and non-SDD group(n=1 199).Risk factors that might influence SDD after EVT in AIS patients were screened and analyzed by multifactorial analysis,LAS-SO regression,and RF-RFE methods.A nomogram was developed after evaluating the model performance and the execution of internal validation.Results SDD occurred in 380(28.1％)patients in the develop-ment cohort and 98(30.2％)patients in the validation cohort.Combining the three variable screening meth-ods,10 risk factors were selected for inclusion in the final model:age,NIHSS score,whether successful re-canalization,glucose level,hemoglobin,hematocrit,onset to puncture time,systolic blood pressure,AS-PECT score,and whether have treatment-related serious adverse events.A two-stage model means that model 1 contains pre-treatment variables(7 in total)and model 2 contains pre-treatment and post-treatment variables(10 in total).The area under the curve(AUC)of model 1 in the development cohort was 0.705(95％CI 0.674-0.736)and 0.731(95％CI 0.701-0.760)in model 2.Both models had good calibration with aslope of 1.000,and the decision curve analysis showed good clinical applicability.The results of the validation cohort were similar to those of the development cohort.Conclusion Age,admission NIHSS score,whether successful recanalization,admission glucose level,hemoglobin content,erythrocyte pressure volume,onset to puncture time,admission systolic blood pressure,ASPECT score,and whether have treat-ment-related serious adverse events are risk factors for SDD in patients with acute ischemic stroke.The two prediction models based on the above factors were used before and after endovascular treatment to predict SDD occurrence better.

Background: and Purpose Non-high-density lipoprotein cholesterol (non-HDL-C), which represents the total cholesterol content of all pro-atherogenic lipoproteins, has recently been included as a new target for lipid-lowering therapy in high-risk atherosclerotic patients in multiple guidelines. Herein, we aimed to explore the relationship between non-HDL-C level and the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing stroke recurrence. Methods: This study comprised a post hoc analysis of the CHANCE-2 (Ticagrelor or Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II) trial, from which 5,901 patients with complete data on non-HDL-C were included and categorized by median non-HDL-C levels, using a cutoff of 3.5 mmol/L. The primary efficacy and safety outcomes were recurrent stroke and severe or moderate bleeding within 90 days. Results: Ticagrelor-aspirin significantly reduced the risk of recurrent stroke in patients with low non-HDL-C (71 [4.8%] vs. 119 [7.7%]; adjusted hazard ratio [HR] 0.54; 95% confidence interval [CI], 0.40–0.74), but not in those with high non-HDL-C (107 [7.3%] vs. 108 [7.6%]; adjusted HR, 0.88; 95% CI, 0.67–1.16), compared with clopidogrel-aspirin (P for interaction=0.010). When analyzed as a continuous variable, the benefit of ticagrelor-aspirin for recurrent stroke decreased as non-HDL-C levels increased. No significant differences in the treatment assignments across the non-HDL-C groups were observed in terms of the rate of severe or moderate bleeding (5 [0.3%] vs. 8 [0.5%] in the low non-HDL-C group; 4 [0.3%] vs. 2 [0.1%] in the high non-HDL-C group; P for interaction=0.425). Conclusion CHANCE-2 participants with low non-HDL-C levels received more clinical benefit from ticagrelor-aspirin versus clopidogrel-aspirin compared to those with high non-HDL-C, following minor ischemic stroke or transient ischemic attack.

Objective:To analyze the prevalence of parturiophobia and its association with preferred mode of delivery in pregnant women in Changning District, Shanghai.Methods:A cross- sectional study was conducted among 1 560 pregnant women in the third trimester who had their antenatal examination in Changning Maternity and Infant Health Hospital from September 2020 to March 2021. Fear of childbirth was measured with a validated Chinese version of Wijma Delivery Expectancy/Experience Questionnaire version A (W-DEQ-A). Based on the W-DEQ-A scores, the participants were divided into two groups: non-clinical parturiophobia group [<85 scores, including mild (≤37 scores), moderate (38-65 scores) and severe (66-84 scores) parturiophobia] and clinical parturiophobia group (≥85 scores). Rank-sum test, Chi-square test and t-test were used for univariate analysis. Multivariate binary logistic regression was used to analyze the factors associated with fear of childbirth and its relationship with preferred mode of delivery. Results:The detection rates of mild, moderate, severe and clinical parturiophobia were 18.8% (294/1 560), 44.9% (700/1 560), 31.1% (485/1 560) and 5.2% (81/1 560), respectively. Multivariate binary logistic regression showed that the participants who were supported by relatives and friends to have cesarean section ( OR=3.45, 95% CI: 1.29-9.22) or had antenatal anxiety ( OR=4.73, 95% CI: 2.49-8.97) were more likely to have clinical parturiophobia, while those with planned pregnancy ( OR=0.49, 95% CI: 0.29-0.82), high intensity physical activity ( OR=0.36, 95% CI: 0.18-0.72) or better/well understanding of the delivery process ( OR=0.42, 95% CI: 0.19-0.97) were less likely to develop clinical parturiophobia (all P<0.05). Compared with the non-clinical parturiophobia women, those with clinical parturiophobia were more likely to choose cesarean section ( OR=2.15, 95% CI: 1.22-3.78, P=0.008). Conclusions:The detection rates of severe and clinical parturiophobia are 31.1% and 5.2% in Changning District, Shanghai. The associated factors mainly include the attitudes of relatives and friends towards the mode of delivery, antenatal anxiety, planned pregnancy or not, physical activity level and the understanding of delivery process. Clinical parturiophobia might be an important factor for cesarean section on maternal request.

ObjectiveTo further assess the safety of clinical application of Shujin Jianyao pills after marketing and find its potential risk factors as early as possible， to obtain the real world medication situation of Shujin Jianyao pills and its incidence of adverse reactions and clinical characteristics， and to explore the factors affecting the occurrence of adverse drug reactions （ADR）. MethodIn this study， prospective， large-sample， multi-center and intensive whole-hospital monitoring with continuous registration was carried out， combined with telephone follow-up visits 2-4 weeks after the end of medication， for whole treatment course monitoring among patients. In addition， the three-level quality control was strictly implemented in the monitoring process. The study used a proprietary electronic data management system for data management， and SAS 9.4 and R software were used for statistical analysis. ResultFrom May 2018 to July 2020， the study completed the safety monitoring of 3 033 patients taking Shujin Jianyao pills in 30 clinical departments of 25 hospitals in China. A total of 36 ADR cases （49 times） were confirmed by expert assessment on data and supervision quality and expert interpretation of ADR. ConclusionAccording to the World Health Organization （WHO）， the symptoms of adverse reactions were mainly classified into occasional adverse reactions （0.1%≤ADR<1%： abdominal distension， oral ulcer， dry mouth， constipation） and rare adverse reactions （0.01%≤ADR<0.1%： loss of appetite， rash， fatigue， increased ALT， increased creatinine， dizziness， stomachache， stomach distension， liver discomfort， pruritus， dysphoria， acid regurgitation， numbness in mouth， abdominal pain， sore throat， earache， tinnitus）. Moreover， through the synthetic minority oversampling technique （SOMTE） combined with logistic regression， the following factors might affect ADR： taking Shujin Jianyao pills for 1-14 days， aged 46-65， 66-80 and 81 and above as well as combined use of atorvastatin， cobamamide， calcitriol capsules， Gushukang capsules， glucosamine， nifedipine， methylcobalamin， metformin， Tenghuang Jiangu pills， Bugu tablets， and diclofenac sodium sustained-release tablets. This study provided a real world basis for the safety and standardized use of Shujin Jianyao pills in clinical practice.

AIM: To study the inhibitory effect of Xihuang Pill on H

Background: and Purpose Previous studies suggested increased visit-to-visit variability of total cholesterol (TC) is associated with stroke. This study aimed to investigate the associations of various lipids measurements variability and the risk of stroke and stroke type (ischemic and hemorrhagic stroke). Methods: Fifty-one thousand six hundred twenty participants in the Kailuan Study without history of myocardial infarction, stroke, and cancer who underwent three health examinations during 2006 to 2010 were followed for incident stroke. Variability in TC, triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) measurements were measured using the coefficient of variation (CV), standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Results: During a median of 6.04 years of follow-up, 1,189 incident stroke (1,036 ischemic and 160 hemorrhagic stroke) occurred. In the multivariable-adjusted model, the hazard ratio (HR) comparing participants in the highest versus lowest quartile of CV of HDL-C were 1.21 (95% confidence interval [CI], 1.02 to 1.45; P for trend=0.013) for ischemic stroke. The highest quartile of CV of LDL-C was associated with 2.17-fold risk of hemorrhagic stroke (HR, 2.17; 95% CI, 1.25 to 3.75; P for trend=0.002) compared with the lowest quartile. We did not observe any significant association between TC and triglycerides variability with any of stroke. Consistent results were obtained when calculating variability index using SD, VIM, or ARV. Conclusions These findings suggest the high visit-to-visit HDL-C and LDL-C variability were associated with an increased incidence of ischemic and hemorrhagic stroke, respectively.

Objective To establish a specialized division of labor system for cerebrovascular disease clinical research and verify the effectiveness of specialized division of labor system in the management of cerebrovascular disease clinical research.Methods Using Delphi method to establish the specialized division of labor system of clinical research,identify personnel responsibilities,access mechanism and access standards.Compare two clinical studies that using and not using this system in terms of clinical research management efficiency,effectiveness of the clinical research progress and quality control.Results Specialized division of labor system can reduce the time spent for research design and preparation,improve the research progress and data integrity,reduce the protocol deviation and the loss of subject follow up.Conclusions Specialized division of labor system can improve the efficiency of clinical research management and improve the research progress and quality.

Objective: To investigate whether the artermisinin has beneficial efficacy to improve the learning and memory in aged mice, as well as the possible mechanisms regarding the inflammatory cytokines and monoamlne neurotransmitters. Methods: 30 aged mice(22 month old) were randomly divided into the aged mouse model control group(n=10), the artemisinin low dose group(artemisinin 0.1% in feed, n=10)and the artemisinin high dose group(artemisinin 0.3% in feed, n=10). Another 10 mice(2 month old) served as young mouse model control group. The artemisinin low dose group and the artemisinin high dose group fed artemisinin feed for 10 weeks. The aged mouse model control group and the young mouse model control group were fed standard feed.Morris water maze test was performed to assess learning and memory capacities for evaluation of the cognitive degree. Serum TNF-α and IL-6 were also detected by ELISA and dopamine, norepinephrine, serotonin in the brain were analyzed by HPLC. Results: (1) Morris water maze test showed, the retention time of the aged mouse model control group was significantly longer than that of the young mouse model control group (P<0.05). The retention time of the artemisinin low dose group and the artemisinin high dose group was significantly shorter than that of the aged mouse model control group (P<0.05). In the ninth days of the reverse recessive platform experiment, the retention time of the artemisinin low dose group ((50.1±19.9) s) and the artemisinin high dose group ((43.2±17.6) s) was significantly shorter than that of the aged mouse model control group ((66.1±29.1)s, P<0.05). (2) Serum inflammatory factors test showed, the level of IL-6 and TNF-αin the artemisinin low dose group (IL-6 : (28.4±4.3) pg/ml, TNF-α: (51.8±8.2) pg/ml) and the artemisinin high dose group(IL-6 : (17.6±2.3) pg/ml, TNF-α: (38.6±12.5) pg/ml) were significantly lower than those in aged mouse model control group(IL-6 : (36.12±7.98)pg/ml), TNF-α : (67.32±10.27) pg/ml, P<0.05). (3) Neurotransmitter content test in the brain showed, the content of DA((19.96±3.89) mmol/ml) and 5-HT((5.73±0.93)mmol/ml) in low dose artemisinin group was higher than that in aged mouth model control group. The content of DA((26.13±5.66) mmol/ml), NE((16.31±2.69) mmol/ml) and 5-HT((8.03±1.93) mmol/ml) in high dose artemisinin group was higher than that in aged mouth model group(DA(13.96±3.89) mmol/ml, NE(8.73±2.16) mmol/ml, 5-HT (3.82±1.09)mmol/ml, all P<0.05). Conclusion Artemisinin can improve the ability of learning and memory in aged mice. The mechanism may be related to inhibiting the inflammation and promoting the level of neurotransmitters in the brain of aged mice.