3ʹ-Hydroxy-4ʹ-methoxy-2-hydroxy-5-bromochalcone (hereinafter referred to as C13) is a novel chalcone derivative obtained in the process of structural modification of DHMMF, the antitumor active compound of Resina Draconis, in our laboratory. In this study, we investigated the effects of C13 on the proliferation and apoptosis of human gastric cancer HGC-27 and AGS cells and its potential mechanism of action. Firstly, through methyl thiazolyl tetrazolium (MTT), colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) staining, we found that C13 inhibited the proliferation ability of human gastric cancer HGC-27 and AGS cells. Using flow cytometry and Western blot, it was found that C13 induced apoptosis in human gastric cancer HGC-27 and AGS cells, and up-regulated the protein level of cleaved poly ADP-ribose polymerase (cleaved-PARP). The results of RNA sequencing analysis showed that the Erb-b2 receptor tyrosine kinase 4/phosphoinositide 3-kinases/AKT (ErbB4/PI3K/AKT) signaling pathway may be involved in anti-gastric cancer activity of C13. Finally, the results of immunoblotting assay showed that C13 treatment down-regulated the protein levels of ErbB4 and phospho-ErbB4, as well as down-regulated the phosphorylation levels of PI3K and AKT in human gastric cancer HGC-27 and AGS cells, which verified the results from RNA-seq analysis. In conclusion, C13 inhibited the proliferation and induced apoptosis of human gastric cancer cells, which may be related to the down-regulation of ErbB4/PI3K/AKT signaling pathway. This study may provide a candidate drug for the treatment of gastric cancer.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.
Animals ; Mice ; Alzheimer Disease ; Amyloid beta-Peptides ; Monocytes ; Cognition ; Energy Metabolism ; Phagocytosis

Objective:To investigate the impact of sarcopenia on mortality in maintenance hemodialysis (MHD) patients.Methods:It was a retrospective cohort study. MHD patients admitted to the blood purification center of Guangzhou Red Cross Hospital in March 2021 were recruited. Demographic data and laboratory indicators, grip strength, and bioelectrical impedance analysis indexes were collected. The patients were divided into sarcopenia group and non-sarcopenia group based on whether they had sarcopenia or not. By following up for 18 months, the survival status of the patients was documented. Kaplan-Meier method, multivariate Cox regression model, and Fine-Gray competing risk model were used to assess the relationship between sarcopenia and all-cause mortality, cardio-cerebrovascular disease mortality, and infection-related disease mortality.Results:A total of 143 MHD patients were enrolled in this study, with age of 65 (58,74) years old and 89 males (62.24%). The prevalence of sarcopenia was 25.17% (36/143). The sarcopenia group had older age ( Z=3.486, P<0.001), higher single-pool Kt/V ( Z=3.634, P<0.001), interleukin-6 ( Z=3.434, P<0.001) and extracellular water/intracellular water ratio ( Z=2.477, P=0.013), and lower body mass index ( Z=-3.210, P=0.001), serum phosphorus ( t=2.475, P=0.015), serum creatinine ( t=3.319, P=0.001), serum albumin ( t=2.851, P=0.005), serum prealbumin ( t=3.384, P<0.001), extracellular water ( Z=-5.124, P<0.001), intracellular water ( Z=-5.417, P<0.001), grip strength ( Z=-3.796, P<0.001) and appendicular skeletal muscle mass index ( t=3.862, P<0.001) than those in the non-sarcopenia group. Kaplan-Meier survival curves showed that the overall survival rate in the sarcopenia group was lower than that in the non-sarcopenia group (Log-rank test χ2=15.99, P<0.001). Multivariable Cox regression analysis demonstrated that sarcopenia was independently correlated with all-cause mortality in MHD patients after adjusting for confounding factors ( HR=2.75, 95% CI 1.07-7.10, P=0.036). Fine-Gray competing risk model result showed that there was no statistically significant difference in cardio-cerebrovascular disease mortality between sarcopenia group and non-sarcopenia group ( SHR=4.99, 95% CI 0.94-26.85, P=0.069); the risk of infection-related disease mortality in sarcopenia group was 5.76 folds than that in non-sarcopenia group ( SHR=5.76, 95% CI 1.15-28.96, P=0.034). Conclusions:There is prevalent sarcopenia in MHD patients. Moreover, sarcopenia is an independent risk factor of all-cause mortality and infection-related disease mortality in MHD patients.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.
COVID-19 ; Cohort Studies ; Contact Tracing ; Humans ; Incidence ; Prospective Studies

Rocuronium bromide is an acetylcholine N2 receptor antagonist, which can be used as an auxiliary drug for general anesthesia. It has been reported that rocuronium has two possible metabolic pathways: N-dealkylation and O-deacetylation, which are mainly taken up by liver and excreted by bile in the form of primary drugs. In this paper, the metabolites of rocuronium in human bile were detected by UHPLC-QE-orbitrap-MS, thirteen metabolites were detected, including eleven phase I metabolites and two phase II metabolites, eleven of which had not been previously reported. At the same time, HEK293 cells overexpressing transporter were used to explore the transmembrane transport mechanism of rocuronium, the results showed that rocuronium was the substrate of MATE1, OCT1, OATP1B1 and OATP1B3. The above research results enrich the metabolic pathway of rocuronium in vivo, and put forward the possible transport mechanism of liver uptake and bile excretion, which can better guide the accurate and safe clinical drug application. The collection of human bile samples in this study was approved by the ethics committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Approval Number: 2019-775-130-01).

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Objective:To explore the characteristics of local brain neural activity in post stroke aphasia (PSA) patients in different frequency bands and the relationship between Western Aphasia Battery (WAB) scores and specific frequency bands. Methods:From March, 2015 to May, 2018, 15 PSA patients, and 15 healthy adults as controls matched for age, gender and education were recruited. They were assessed with WAB and scaned with resting-state functional magnetic resonance imaging. The amplitude of low-frequency fluctuation (ALFF) and fractional amplitude of low-frequency fluctuation (fALFF) on the frequency bands of 0.01-0.08 Hz, 0.027-0.073 Hz, and 0.01-0.027 Hz were calculated. The ALFF and fALFF in different frequency bands were extracted and the correlation with the WAB scores in the patients were analyzed. Results:On 0.01-0.08 Hz, ALFF increased in the right precentral gyrus in the patients. On 0.027-0.073 Hz, ALFF increased values in the right precentral gyrus, and fALFF decreased in the right cerebellar Crus2 region; fALFF in the right cerebellar Crus2 region negatively correlated with the scores of information content (r = -0.576, P = 0.025), auditory comprehension (r = -0.658, P = 0.008), repetition (r = -0.616, P = 0.014) and aphasia quotient (r = -0.611, P = 0.016) of WAB. On 0.01-0.027 Hz, the fALFF decreased in the left inferior parietal limbic gyrus, and positively correlated with the scores of information content (r = 0.538, P = 0.039) and aphasia quotient (r = 0.526, P = 0.044). Conclusion:Resting-state fALFF abnormalities in PSA patients are frequency-dependent, which associate with some frequency-specific neurofunctional alterations.