Objective To investigate the attributable risk(AR)of Acinetobacter baumannii(AB)infection in criti-cally ill patients.Methods A multicenter retrospective cohort study was conducted among adult patients in inten-sive care unit(ICU).Patients with AB isolated from sterile body fluid and confirmed with AB infection in each cen-ter were selected as the infected group.According to the matching criteria that patients should be from the same pe-riod,in the same ICU,as well as with similar APACHE Ⅱ score(±5 points)and primary diagnosis,patients who did not infect with AB were selected as the non-infected group in a 1:2 ratio.The AR was calculated.Results The in-hospital mortality of patients with AB infection in sterile body fluid was 33.3％,and that of non-infected group was 23.1％,with no statistically significant difference between the two groups(P=0.069).The AR was 10.2％(95％CI:-2.3％-22.8％).There is no statistically significant difference in mortality between non-infected pa-tients and infected patients from whose blood,cerebrospinal fluid and other specimen sources AB were isolated(P＞0.05).After infected with AB,critically ill patients with the major diagnosis of pulmonary infection had the high-est AR.There was no statistically significant difference in mortality between patients in the infected and non-infec-ted groups(P＞0.05),or between other diagnostic classifications.Conclusion The prognosis of AB infection in critically ill patients is highly overestimated,but active healthcare-associated infection control for AB in the ICU should still be carried out.

italic>Anoectochilus roxburghii liquid (spray, a hospital preparation of Wu Mengchao Hepatobiliary Hospital of Fujian Medical University) has shown a good clinical treatment effect during the COVID-19 pandemic, but its material basis and mechanism of action are still unclear. In this study, network pharmacology and molecular docking methods were used to predict the molecular mechanism of A. roxburghii liquid against COVID-19, and pharmacodynamic experiments in vitro were conducted to study the interaction between the current targets with clear preventive and therapeutic effects and the key components of A. roxburghii liquid. UPLC-MS and database were used to compare and analyze the active ingredients in the liquid, and 17 potential active ingredients with good drug-like properties were screened by in vivo pharmacokinetics process in SwissADME database. SwissTargetPrediction and GeneCards were searched to find 93 common targets. Cytoscape 3.8.2 software was used to construct the "component-target" network map, and the Metascape platform was used for gene function annotation and pathway enrichment analysis. It was found that the extract could regulate the positive response to external stimuli, inflammatory response, cytokine production and other biological processes by binding the active ingredients such as isorhamnetin, kaempferol, luteolin, quercetin and apigenin to the common targets (NOS3, MPO, MMP3, etc.), and play an anti-COVID-19 role. In the angiotensin-converting enzyme 2 (ACE2) activity inhibition assay, it was found that the stock solution of A. roxburghii liquid (for spray), and the supernatant after removing polysaccharides (mainly containing flavonoids) could to some extent inhibit the activity of ACE2. Crucially, in the experiment of 2019-nCOV-S pseudovirus infecting HEK-293T-ACE2 cells, we found that A. roxburghii liquid may exert anti-COVID-19 effects by blocking the binding of SARS-CoV-S protein to ACE2.

OBJECTIVES: To explore the mechanism by which Wiskott-Aldrich syndrome protein family verprolin-homologous protein 1 (WAVE1) regulates lipopolysaccharide (LPS)-induced mitochondrial metabolic abnormalities and inflammatory responses in macrophages. METHODS: Macrophage cell lines with overexpressed WAVE1 (mouse BMDM and human THP1 cells) were prepared. The macrophages were treated with LPS (500 ng/mL) to simulate sepsis-induced inflammatory responses. The experiment consisted of two parts. The first part included control, LPS, vector (LPS+oe-NC), WAVE1 overexpression (LPS+oe-WAVE1) groups. The second part included LPS, LPS+oe-NC, LPS+oe-WAVE1 and exogenous high mobility group box-1 (HMGB1) intervention (LPS+oe-WAVE1+HMGB1) groups. RT-PCR was used to measure mitochondrial DNA content, and RT-qPCR was used to detect the mRNA expression levels of WAVE1, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6. Western blot was performed to measure the protein expression of WAVE1, hexokinase 2, and pyruvate kinase M2. ELISA was utilized to detect the levels of TNF-α, IL-1β, IL-6, and HMGB1. JC-1 staining was used to assess mitochondrial membrane potential. Seahorse XP96 was used to evaluate oxygen consumption rate and extracellular acidification rate. MitoSOX probe was employed to measure mitochondrial reactive oxygen species levels, and 2-NBDG method was used to assess glucose uptake. Kits were used to measure pyruvate kinase activity, lactate, adenosine triphosphate (ATP), and HMGB1 levels. RESULTS: Compared with the control group, the LPS group showed lower levels of WAVE1 protein and mRNA expression, mitochondrial membrane potential, oxygen consumption rate, and mitochondrial DNA content (P<0.05), while TNF-α, IL-1β, IL-6 levels and mRNA expression, mitochondrial reactive oxygen species, glucose uptake, lactate, ATP, hexokinase 2, and pyruvate kinase M2 protein expression levels as well as extracellular acidification rate, pyruvate kinase activity, and HMGB1 release were significantly increased (P<0.05). Compared with the LPS+oe-NC group, the LPS+oe-WAVE1 group showed increased WAVE1 protein and mRNA expression, mitochondrial membrane potential, oxygen consumption rate, and mitochondrial DNA content (P<0.05), while TNF-α, IL-1β, IL-6 levels and mRNA expression, mitochondrial reactive oxygen species, glucose uptake, lactate, ATP, hexokinase 2, and pyruvate kinase M2 protein expressions, as well as extracellular acidification rate, pyruvate kinase activity, and HMGB1 release were decreased (P<0.05). Compared with the LPS+oe-WAVE1 group, the LPS+oe-WAVE1+HMGB1 group exhibited increased glucose uptake, lactate, ATP levels, and extracellular acidification rate (P<0.05). CONCLUSIONS WAVE1 participates in the regulation of LPS-induced inflammatory responses in macrophages by modulating the release of inflammatory factors, mitochondrial metabolism, and HMGB1 release.
Lipopolysaccharides ; Humans ; Mitochondria/metabolism* ; Animals ; Macrophages/metabolism* ; Mice ; Hexokinase/genetics* ; Wiskott-Aldrich Syndrome Protein Family/metabolism* ; HMGB1 Protein/physiology* ; Inflammation/metabolism* ; DNA, Mitochondrial ; Pyruvate Kinase/metabolism*

ObjectiveTo investigate the effect and mechanism of total flavones of Spatholobi Caulis （TFSC） against depression in rats. MethodThe fifty KM mice were randomly divided into the normal group and high-， medium-， and low-dose （1， 0.5， 0.25 g·kg^-1） TFSC groups and gavaged with the corresponding drugs for 12 successive days. One hour after the last administration， the immobility time in forced swimming test and tail suspension test was recorded. The SD rats were randomly divided into the normal group， model group， fluoxetine （5 mg·kg^-1） group， and high- and low-dose （1， 0.25 g·kg^-1） TFSC groups. Following the exposure of rats to two different kinds of stimuli daily for inducing chronic unpredictable stress， they were administered with the corresponding drugs for 21 d. After the experiment， the levels of serum neurotransmitters and inflammatory factors in rats were detected by enzyme-linked immunosorbent assay （ELISA）. The changes in hippocampal neurons of rats were observed by hematoxylin-eosin （HE） and Nissl staining. The mRNA expression levels of nuclear factor-κB （NF-κB） and tumor necrosis factor-α （TNF-α） in the hippocampus of rats were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expression levels of cAMP-response element binding protein （CREB）， phosphorylated CREB （p-CREB）， and brain-derived neurotrophic factor （BDNF） in hippocampal tissues by Western blot. ResultCompared with the normal group， TFSC significantly shortened the immobility time of mice in tail suspension and swimming tests （P<0.05）. Compared with the normal group， the model group exhibited reduced sucrose intake and wilderness activity （P<0.01）， decreased 5-HT， DA， NE （P<0.05， P<0.01）， MAO， IL-6， TNF-α （P<0.05， P<0.01）， damaged neurons， increased mRNA levels of TNF-α and NF-κB （P<0.01）， and down-regulated BDNF and CREB protein expression （P<0.05）. Compared with the model group， TFSC significantly enhanced sucrose intake and wilderness activity of rats （P<0.05）， increased the serum 5-HT， DA and NE （P<0.05， P<0.01）， and decreased the serum MAO， IL-6， and TNF-α （P<0.05， P<0.01） as well as NF-κB and TNF-α mRNA expression （P<0.01）， up-regulated the protein expression levels of BDNF and CREB （P<0.01）， and improved the pathological symptoms of hippocampus. ConclusionTFSC improved the hippocampal neurons of rats via CREB/BDNF signaling pathway and reduced depressive pathological damage， thus relieving depression.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Heart Neoplasms/genetics* ; Hemangiosarcoma/genetics* ; Humans ; Mediastinal Neoplasms ; Thymus Neoplasms

Dao-di herbs are an important part of clinical medicine in traditional Chinese medicine. They are also precious wealth left to human beings from history, which contain deep traditional Chinese cultural connotations and play an important role in supporting and serving the Chinese medicine business. The relevant policy documents introduced by various national ministries and commissions have many contents and requirements related to the promotion of Dao-di herbs protection and industrial development. Due to the Dao-di herbs industry has a series of characteristics, such as a long chain, many involved links, long cycles, multiple production entities, multiple locations, and various types, the high-quality development of the industry has put forward higher requirements on the linkage between upstream and downstream, production entities, traceability of the whole process and information sharing. This article takes Dao-di herbs certification work as an application scenario and entry point, and discusses it from the perspective of block chain and information technology. It proposes the following work ideas: establish multi-party consensus from the macro-organizational management, business, and operational technical levels, and unblock channels for data and information, to achieve institutionalization of certification; establish certification-related standards and specifications to achieve certification standardization; build a certification hardware system to achieve certification networking; build a certification software system to develop functions for specific information content such as identity, origin, production, production process, quality, product and brand of authentic medicinal material production interactively, and realize certification programmatic; data security and sharing of related production activities to achieve socialization of certification. Make full use of modern technologies such as blockchain, the internet of things, big data and information technology, and through the joint participation of management, production, use and the public, the whole process information of Daodi herbs is integrated to form an interconnected information sharing application mode, thus, to serve and promote the high-quality development of Dao-di herbs industry.
Blockchain ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Plants, Medicinal ; Technology

Objective: To evaluate the feasibility and potential value of comprehensive geriatric assessment (CGA) in elderly (≥60 years) patients with newly diagnosed acute myeloid leukemia (AML) in China. Methods: The CGA results of 83 newly diagnosed AML (non-APL) patients from 16 hospitals in Beijing and Tianjin between March 2016 and December 2017 were prospectively collected and analyzed. The clinical data, treatment and follow-up information were also collected. Results: Of 83 newly diagnosed elderly AML patients, 81 patients (97.6%) completed all designated CGA assessment. The median number of impaired scales of the CGA assessment in the studied population was 2(0-6). Sixteen patients (19.3%) showed no impairments according to the geriatric assessment scales implem ented by this study. The distributions of impaired scales were as follows: impairment in ADL, 55.4%; IADL impairment, 42.2%; MNA-SF impairment, 48.2%; cognitive impairment, 15.7%; GDS impairment, 31.7%; HCT-CI impairment, 19.5%, respectively. In patients with "good" ECOG (n=46), the proportion of impairment for each CGA scale ranged from 6.5% to 37.0% and 32 patients (68.9%) had at least one impaired CGA scale. Survival analysis showed that the number of impaired scales of the CGA was significantly correlated with median overall survival (P=0.050). Conclusions: CGA was a tool with feasibility for the comprehensive evaluation in elderly AML patients in China. Combined with age and ECOG, CGA may be more comprehensive in assessing patients' physical condition.
Activities of Daily Living ; Aged ; China ; Geriatric Assessment ; Humans ; Leukemia, Myeloid, Acute ; Prospective Studies

Rapid allele-specific PCR primer was designed base on Cytb 155 A/T single nucleotide polymorphism, DNA was extracted by alkaline lysis and the PCR reaction systems including denatured and annealing temperature and cycle numbers were optimized. The results were performed to authenticate Ranae Oviductus and its 4 adulterants. When 100×SYBR Green I was added in the PCR product at 90 ℃ denatured 3 s, 62 ℃ annealing 20 s and 32 cycle. Ranae Oviductus visualized strong green fluorescence under 365 nm UV lamp whereas adulterants appeared negative. The whole process can be completed in 40 minutes．The established method provides the technical support for authentication of the Ranae Oviductus.

Objective To determine the chemical structure of the new compound and investigate the protective effects of Tinosporaic acid A and B towards in-vitro neuro. Methods The structures of two new compounds were established by analyzing its 1D and 2D NMR spectra as well as HRESIMS. Their neuroprotective effects with respect to the antioxidant properties were evaluated by radical scavenging tests and hydrogen peroxide-injured oxidative stress model in PC12 cell lines. Cell morphology of treated PC12 cells was observed by phase contrast microscopy. In-vitro MTT assay, lactate dehydrogenase activity assay and oxidative stress markers (intracellular ROS production, MDA level, and caspase-3 activity) were used to evaluate the protective effects against hydrogen peroxide induced cytotoxicity in PC12 cells. Results The two new compounds, named Tinosporaic acid A and B, were isolated and identified from the stem bark of Tinospora hainanensis. Cell viability studies identified a representative concentration for each extract that was subsequently used to measure oxidative stress markers. Both extracts were able to reverse the oxidative damage caused by hydrogen peroxide, thus promoting PC12 cells survival. The concentration of Tinosporaic acid A and B were 86.34 μg/mL and 22.06 μg/mL respectively, which is neuroprotective for EC50. The results indicated that both of them significantly attenuated hydrogen peroxide-induced neurotoxicity. Conclusion The two new compounds isolated from ethanol extracts of Tinospora hainanensis are the promising natural ones with neuroprotective activity and needed for further research.