BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

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.

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 investigate the effect of lead exposure before pregnancy on bone lead mobilization and bone microstructure in pregnant rats, so as to provide the evidence for illustrating the potential mechanisms of bone lead mobilization during pregnancy. Methods: Twenty-six weaning female specific pathogen-free (SPF) rats of the Wistar strain were randomly divided into the exposure group and the control group. Rats in the exposure group were given 0.05% lead acetate solution for weeks, while animals in the control group were given 0.05% sodium acetate solution. Then, rats in both groups were given distilled water. Following removal of lead exposure for 4 weeks, female rats were co-caged with healthy males at the same age until pregnancy. The blood, femur and tibia specimens were collected from female rats on days 3 (GD3), 10 (GD10) and 17 (GD17) at pregnancy, and the blood and bone lead levels were measured using inductively coupled plasma mass spectrometry (ICP-MS). The unilateral rat femur was scanned using micro-computed tomography (micro CT), and the microstructure changes of cortical and trabecular bones were investigated. The structural and morphological changes of rat femur were observed using hematoxylin-eosin (HE) staining. Results: During the study period, satisfactory mental status and activity and good coat glossiness were observed in female rats in both groups, and there was no significant difference in the increase of rat body weight between groups. The blood lead level at GD17 and bone lead levels at GD3, GD10 and GD17 were significantly higher in rats in the exposure group than in the control group (P<0.05), and the trabecular bone lead level was significantly lower in rats in the exposure group at GD17 than at GD10 (P=0.015). The trabecular bone lead level correlated negatively with blood lead level (r=-0.578, P=0.049), and bone lead contributed 26.8% to blood lead. The bone mass, trabecular number, thickness and density of female rat trabecular bones all reduced in the exposure group at GD17, with an increase in trabecular space, and the proportion of trabecular areas reduced by 27.34% in the exposure group relative to the control group (t=2.851, P=0.046). Conclusions Lead exposure before pregnancy promotes the release of lead from trabecular bones into blood and affects bone microstructure in rats. There is bone lead mobilization during late pregnancy.

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

Lung cancer is one of the most common malignant tumors with poor prognosis in China, and most patients are diagnosed as advanced patients. Studies have shown that the microecological characteristics of lung cancer patients are different from healthy people, and the microorganisms of the respiratory tract can affect the occurrence and development of lung cancer through various mechanisms. In recent years, the study of the correlation between microbiome and disease has become another research hotspot following the Human Genome Project. However, at present, there are relatively few studies on the characteristics of lung cancer and respiratory microbiome. Therefore, it is necessary to further explore the potential relationship between lung cancer and microbial flora. By studying the mechanism of action of respiratory microorganisms in the development of lung cancer, it is expected to provide a clearer scientific basis in the clinical diagnosis, treatment and prognosis assessment of lung cancer. This article reviews the current researches on microbial flora and lung cancer, and provides new ideas for clinical diagnosis and treatment of lung cancer.
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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.

Objective In this study,Protosappanin A,Caesalpinia Sappan L extract and Cisplatin were combined with radiotherapy in gastric cancer cell SGC-7901 to investigate whether the Protosappanin A could in-crease radiosensitivity( SER) in gastric cancer SGC-7901 cells. This will be medication to create new areas of in-novation in the future. Methods The cell proliferation of SGC-7901 cells was detected by MTT assay. The rela-tionship between the effect of the Protosappanin A on cell proliferation and the time of action was determined. Caesalpinia Sappan L extract and Cisplatin were as controls. The fitted cell survival curve and clonal formation as-says were used to determine the SER to analyze the sensitizative effect of Protosappanin A. Results Protosappa-nin A could inhibit the growth of SGC-7901 cells,and its inhibitory effect is relatively weak. Its cytotoxicity has a time-and concentration-dependent manner. Cellular morphological changes were observed accompanying with increased concentrations and time treatments of Protosappanin A. Clonal formation experiment showed that the Protosappanin A significantly increased the radiosensitivity of SGC-7901 cells when compared to the radioactive group. They showed a statistically difference. Conclusion The inhibitory effect of the Protosappanin A on SGC-7901 cells in a concentration and time-dependent manner. Protosappanin A combined radiotherapy can improve the radiosensitization of cells,both of which may have synergistic anti-tumor effect.

ObjectiveTo study the dose distribution of the intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) inverse plans with different energy X-ray, to provide a reference of energy options for radiation therapy. MethodsEight cases with different disease were chosen, the plan for each case were finished with 1Arc (360°) VMAT, 9 fields IMRT and 5 fields IMRT.For each plan project, the energy selections were 4 MV, 6 MV, 8 MV and 15 MV. In the evaluation,homogeneity index ( HI), conformity index ( CI ) and external volume index ( EVI ) of target, the average dose ( Dmean) and 2％ volume in dose volume histogram ( D2 ) of serial organs at risk ( OARs), the average dose ( Dmean ) and a dose level volume ( Vx ) of parallel OARs were chosen and compared . Results Statistical analysis showed that: For the target, the result of HI were F=0. 13,0. 51,0. 09, P=0. 939,0.679,0.965,CI were F=0. 13,0.51,0.09,P=0.939,0.679,0.965, EVI were F=0. 15,0.31,0. 15,P =0. 930,0. 818,0. 931, respectively ; For the OARs of each patient, F ＜ 0. 20, P ＞ 0. 05. All results indicated there was little difference in option of energy for the same field p8roject. ConclusionsThe results indicate that the middle and low energy X-ray (6 MV or 8 MV) can satisfy the needs of IMRT and VMAT radiotherapy. Compared with middle and low energy, the high energy X-ray (15 MV ) showed little advantage in dose distribution.