Computer-aided discovery of novel aryl hydrocarbon receptor ligands to regulate CYP1A1 expression in inflammatory macrophages.

The environmental factor aryl hydrocarbon receptor (AhR), a key protein connecting the external environmental signals (e.g., environmental endocrine disruptor TCDD) to internal cellular processes, is involved in the activation of peripheral macrophages and inflammatory response in human body. Thus, there is widespread interest in finding compounds to anti-inflammatory response in macrophages by targeting human AhR. Here, ensemble docking based-virtual screening was first used to screen a library (~200,000 compounds) against human AhR ligand binding domain (LBD) and 25 compounds were identified as potential inhibitors. Then, 9 out of the 25 ligands were found to down-regulate the mRNA expression of CYP1A1 (a downstream gene of AhR signaling) in AhR overexpressing macrophages. The most potent compound AE-411/41415610 was selected for further study and found to reduce both mRNA and protein expressions level of CYP1A1 in mouse peritoneal macrophage. Moreover, protein chip signal pathway analysis indicated that AE-411/41415610 play a role in regulating JAK-STAT and AKT-mTOR pathways. In sum, the discovered hits with novel scaffolds provided a starting point for future design of more effective AhR-targeted lead compounds to regulate CYP1A1 expression of inflammatory peritoneal macrophages.

Research on high proportion of clean energy grid-connected oscillation risk prediction technology based on CNN and trend feature analysis.

Oscillations, commonly known as a universal, propagative, and intricate event in the new power system, often give rise to generator tripping and load shedding, not only adversely affecting the power flow limit and the power angle stability but also posing threats to the lines of defense for stability and protection. Traditionally, emphasis has been laid on post-fault oscillation management, an emergency measure to deal with the impact and damage that have already affected the power grid. As such, this paper focuses on an oscillation prediction technique to detect oscillation energy early and intervene proactively to prevent further faults. This technique effectively lessens the damage caused by impacts and disconnects to the power grid. Firstly, this paper proposes the concept of disturbance power density and establishes the correlation between disturbance energy and the time domain, thereby exploring a method for evaluating the pattern of electrical quantities before power system oscillation. Secondly, it speeds up the time it takes to detect faults by catching nuances of voltage-current phase angle and impedance. Lastly, it puts forward a technique to cope with the intricacy and variety of power grid equipment using the convolutional neural network (CNN). This technique incorporates an integrated attention mechanism within a one-dimensional CNN model to capture the implicit mapping between voltage, active power, and reactive power at any time in the power system. This enables the model to self-learn multi-device characteristics and enhances the possibility of using theory in practical ways. Moreover, practical case studies also show that the prediction technique proposed in this paper can effectively issue warnings eight minutes before the occurrence of oscillation.

Functional magnetic resonance imaging study about repetitive transcranial magnetic stimulation for dysfunction after stroke: a scoping review / 中国康复理论与实践

ObjectiveTo explore the brain mechanism of repetitive transcranial magnetic stimulation (rTMS) on dysfunction after stroke using functional magnetic resonance imaging (fMRI). MethodsLiteratures about the functional magnetic resonance imaging study about repetitive transcranial magnetic stimulation for dysfunction after stroke were retrieved in PubMed, Web of Science, CNKI and Wanfang data from establishment to June 1st, 2021. The quality of the literature was evaluated with Physiotherapy Evidence Database (PEDro) scale. Literature screening, and data extraction were performed by two researchers. ResultsA total of 14 randomized controlled trials were finally enrolled. They were of high or very high quality. They mainly involved the therapeutic effect and imaging mechanisms of rTMS on dysfunction after stroke. ConclusionrTMS could change the excitability of the cerebral cortex and the effective connections between brain regions after stroke, promote the reorganization of brain function, and achieve the recovery of post-stroke dysfunction.

ZHUANG Li-xing's experience in treatment of dyskinesia of Parkinson's disease with acupuncture at triple-acupoint prescription / 中国针灸

The paper introduces professor ZHUANG Li-xing's clinical experience in treatment of dyskinesia of Parkinson's disease with acupuncture at triple-acupoint prescription. In pathogenesis, dyskinesia of Parkinson's disease refers to yang deficiency and disturbing wind. In treatment, acupuncture focuses on warming yang, promoting the circulation of the governor vessel, regulating the spirit and stopping trembling; and Baihui (GV 20), Suliao (GV 25) and Dingchanxue (Extra) are selected to be "trembling relief needling". In combination with Jin's three needling, named "three-trembling needling" "three-governor-vessel needling" and "three-spasm needling", the triple-acupoint prescription is composed. To ensure the favorable therapeutic effect, this prescription is modified according to the symptoms and the specific techniques of acupuncture are combined such as conducting qi, harmonizing yin and yang, and manipulating gently for reinforcing and reducing.

Repetitive transcranial magnetic stimulation for lower limb dysfunction post stroke: a scoping review / 中国康复理论与实践

ObjectiveTo summarize and analyze the protocols of repetitive transcranial magnetic stimulation (rTMS) in the treatment of post-stroke lower limb dysfunction. MethodsLiterature about rTMS for lower limb dysfunction of patients post stroke were retrieved from Web of Science, PubMed, CNKI, and Wanfang Data from inception to August 17, 2022. The quality of the literature was evaluated with Physiotherapy Evidence Database (PEDro) scale. Literature quality, data extraction and scoping review were performed by two researchers. ResultsA total of 21 studies were included, in which 20 studies suggested that rTMS treatment could promote the recovery of lower limb motor function after stroke. One study showed negative result. rTMS interventions were reported safe, with no serious adverse reactions. There were great heterogeneity in the demographic and clinical information, study protocols, stimulation parameters, coil types, targets of stimulation, and motor-evoked potential measurement in the included studies. ConclusionThe future protocols of rTMS need to be combined with stroke stage and severity of injury. There is a demand for more real vs. sham rTMS studies, reporting similar designs with sufficient information, to achieve a significant level of evidence regarding the use of rTMS in post-stroke patients.

Research progress on the modulation mechanism of electroacupuncture for learning and memory impairment after ischemic stroke / 中国针灸

Electroacupuncture may play a role in treatment of learning and memory impairment after ischemic stroke by regulating phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA)/cAMP response element binding protein (CREB) signaling pathway, nerve growth factor (NGF)/tyrosine kinase-A (TrkA) signaling pathway, Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, Notch signaling pathway, erythropoietin-producing hepatocyte (Eph)/ephrin signaling pathway. The interactions among these pathways should be further explored in treatment of learning and memory impairment after ischemic stroke.

Anti-Alzheimer's Disease Effect of Polysaccharides from Zanthoxyli Pericarpium and Analysis of Its Structural Characteristics by Sugar Spectrum / 中国实验方剂学杂志

ObjectiveThe therapeutic effect of polysaccharides from Zanthoxyli Pericarpium on Alzheimer's disease（AD） was evaluated through establishing a mouse model of AD， and the structural characteristics of the polysaccharides was analyzed by sugar spectrum. MethodThe AD model of mice with rapid aging was established by intraperitoneal injection of D-galactose combined with gavage of aluminum trichloride， and the learning and memory ability of mice was evaluated by Morris water maze test， the histopathological status of brain and neuronal damage were observed by hematoxylin-eosin（HE） staining and Nissl staining. After hydrolysis of polysaccharides from Zanthoxyli Pericarpium with acid and different glycosidases， the characteristics of hydrolysates were analyzed by high performance thin layer chromatography（HPTLC） and fluorescence assisted carbohydrate gel electrophoresis（PACE）. HPTLC chromatography was performed on a silica gel 60 plate with sampling volume of 5 μL， developing solvent of ethyl acetate-glacial acetic acid-water（2∶2∶1）， developing twice， aniline-diphenylamine-phosphoric acid solution as chromogenic agent， and heating at 105 ℃ for 10 min， and then observed under sunlight. PACE experimental conditions were 34% separation gel and 8% concentration gel， electrophoresis buffer was 0.1 mol·L-1 tris（hydroxymethyl） aminomethane（Tris）-boric acid buffer（pH 8.2）. Electrophoresis was carried out at 0 ℃ and the loading amount was 3-6 μL. The sample ran to the front of the gel with a constant current of 15 mA， and imaged under ultraviolet 365 nm. ResultThe results of Morris water maze test showed that polysaccharides from Zanthoxyli Pericarpium significantly improved the learning and memory ability of AD model mice， shortened the escape latency， and significantly increased the number of crossing and the residence time in the target quadrant. The results of histopathological experiments showed that polysaccharides from Zanthoxyli Pericarpium could improve the pathological conditions and neuronal damage in the CA1 and CA3 regions of hippocampus of AD mice， and the number of Nissl corpuscles was significantly increased. The results of sugar spectrum analysis showed that the results of HPTLC and PACE analysis were basically consistent， polysaccharides from Zanthoxyli Pericarpium could be mainly hydrolyzed into small molecular sugars by cellulase and pectinase， indicating that they mainly contained β-1，4-glucosidic bond and α-1，4-galacturonic acid glycosidic bond， and could be slightly hydrolyzed by glucanase， β-galactosidase and β-mannase， indicating that they contained only a small amount of α-1，6-glucosidic bond， β-galactosidic bond， β-1，4-mannosidic bond. ConclusionPolysaccharides from Zanthoxyli Pericarpium has obvious therapeutic effect on AD mice， and its structure mainly contains β-1，4-glucosidic bond and α-1，4-galacturonic acid glycosidic bond， which can provide a reference for the structural analysis of traditional Chinese medicine polysaccharides.

Effect of transcranial direct current stimulation on neurological injury markers and prognosis in patients with acute and severe carbon monoxide poisoning / 中华劳动卫生职业病杂志

Objective: To observe the effects of transcranial direct current stimulation (tDCS) on nerve injury markers and prognosis in patients with acute severe carbon monoxide poisoning (ASCOP) . Methods: In May 2021, 103 ASCOP patients were treated in the emergency department of Harrison International Peace Hospital of Hebei Medical University from November 2020 to January 2021. The patients were divided into two groups according to whether they received tDCS treatment. The control group (50 cases) were given oxygen therapy (hyperbaric oxygen and oxygen inhalation) , reducing cranial pressure, improving brain circulation and cell metabolism, removing oxygen free radicals and symptomatic support, and the observation group (53 cases) was treated with 2 weeks of tDCS intensive treatment on the basis of conventional treatment. All patients underwent at least 24 h bispectral index (BIS) monitoring, BIS value was recorded at the hour and the 24 h mean value was calculated. Neuron-specific enolase (NSE) and serum S100B calcium-binding protein (S100B) were detected after admission, 3 d, 7 d and discharge. Follow-up for 60 days, the incidence and time of onset of delayed encephalopathy (DEACMP) with acute carbon monoxide poisoning in the two groups were recorded. Results: The NSE and S100B proteins of ASCOP patients were significantly increased at admission, but there was no significant difference between the two groups (P=0.711, 0.326) . The NSE and S100B proteins were further increased at 3 and 7 days after admission. The increase in the observation group was slower than that in the control group, and the difference was statistically significant (P(3 d)=0.045, 0.032, P(7 d)=0.021, 0.000) ; After 14 days, it gradually decreased, but the observation group decreased rapidly compared with the control group, with a statistically significant difference (P=0.009, 0.025) . The 60 day follow-up results showed that the incidence of DEACMP in the observation group was 18.87% (10/53) , compared with 38.00% (19/50) in the control group (P=0.048) ; The time of DEACMP in the observation group[ (16.79±5.28) d] was later than that in the control group[ (22.30±5.42) d], and the difference was statistically significant (P=0.013) . Conclusion: The early administration of tDCS in ASCOP patients can prevent the production of NSE and S100B proteins, which are markers of nerve damage. and can improve the incidence and time of DEACMP.

Chinese translation of benefits and challenges in implementation of artificial intelligence in colonoscopy: World Endoscopy Organization position statement / 中华消化杂志

The number of artificial intelligence (AI) tools for colonoscopy on the market is increasing with supporting clinical evidence. Nevertheless, their implementation is not going smoothly for a variety of reasons, including lack of data on clinical benefits and cost-effectiveness, lack of trustworthy guidelines, uncertain indications, and cost for implementation. To address this issue and better guide practitioners, the World Endoscopy Organization has provided its perspective about the status of AI in colonoscopy as the position statement.

Identification of the mitochondrial protein ADCK2 as a therapeutic oncotarget of NSCLC.

The aarF domain containing kinase 2 (ADCK2) is a mitochondria-locating protein, important for fatty acid metabolism and coenzyme Q biosynthesis. The bioinformatics results show that elevated ADCK2 transcripts in NSCLC correlate with poor overall survival and poor anti-PD-1/PD-L1 therapy response. ADCK2 is overexpressed in local human NSCLC tissues and various primary and established NSCLC cells. In NSCLC cells, ADCK2 shRNA or CRISPR/Cas9 knockout remarkably suppressed cell viability, proliferation, cell cycle progression, cell mobility, and provoked cell apoptosis. Moreover, ADCK2 depletion disrupted mitochondrial functions in NSCLC cells, causing cytochrome C release, mitochondrial depolarization, DNA damage and ATP reduction. Contrarily, ectopic ADCK2 overexpression promoted NSCLC cell growth. Further studies revealed that ADCK2 depletion inactivated Akt-mTOR signaling in primary NSCLC cells. NSCLC xenograft growth in nude mice was significantly hindered after ADCK2 silencing or knockout. ADCK2 depletion, apoptosis induction and oxidative injury as well as ATP reduction and Akt-mTOR inactivation were detected in ADCK2-silenced or ADCK2-knockout NSCLC xenograft tissues. Together overexpressed ADCK2 is important for the growth of NSCLC cells, representing an important therapeutic molecular oncotarget.

Cancer metabolism and tumor microenvironment: fostering each other?

The changes associated with malignancy are not only in cancer cells but also in environment in which cancer cells live. Metabolic reprogramming supports tumor cell high demand of biogenesis for their rapid proliferation, and helps tumor cell to survive under certain genetic or environmental stresses. Emerging evidence suggests that metabolic alteration is ultimately and tightly associated with genetic changes, in particular the dysregulation of key oncogenic and tumor suppressive signaling pathways. Cancer cells activate HIF signaling even in the presence of oxygen and in the absence of growth factor stimulation. This cancer metabolic phenotype, described firstly by German physiologist Otto Warburg, insures enhanced glycolytic metabolism for the biosynthesis of macromolecules. The conception of metabolite signaling, i.e., metabolites are regulators of cell signaling, provides novel insights into how reactive oxygen species (ROS) and other metabolites deregulation may regulate redox homeostasis, epigenetics, and proliferation of cancer cells. Moreover, the unveiling of noncanonical functions of metabolic enzymes, such as the moonlighting functions of phosphoglycerate kinase 1 (PGK1), reassures the importance of metabolism in cancer development. The metabolic, microRNAs, and ncRNAs alterations in cancer cells can be sorted and delivered either to intercellular matrix or to cancer adjacent cells to shape cancer microenvironment via media such as exosome. Among them, cancer microenvironmental cells are immune cells which exert profound effects on cancer cells. Understanding of all these processes is a prerequisite for the development of a more effective strategy to contain cancers.

Effect of Echinococcus granulosus hydatid cyst fluid protein on allergic rhinitis induced by ovalbumin in mice / 中国血吸虫病防治杂志

Objective To investigate the protective effect of Echinococcus granulosus hydatid cyst fluid protein (HCFP) on ovalbumin (OVA)-induced allergic rhinitis (AR) in mice. Methods Twenty-four BALB/c mice at ages of 8 to 10 weeks, each weighing approximately 20 g, were randomly divided into four groups, including groups A (blank control group), B (blank intervention group), C (AR model group) and D (AR+HCFP intervention group), with 6 mice in each group. On days 0, 2, 4, 6, 8, 10 and 12, mice in groups A, B, C and D were injected with 200 μL sterile phosphate buffered saline (PBS), 200 μL sterile PBS containing 20 μg HCFP, 200 μL sterile PBS containing 50 μg OVA and 5 mg Al(OH)3 gel, and 200 μL sterile PBS containing 50 μg OVA, 5 mg Al(OH)3 gel and 20 μg HCFP, respectively. On days 14 to 20, mice in groups A, B, C and D were administered with 40 μL sterile PBS, 40 μL sterile PBS containing 20 μg HCFP, 40 μL sterile PBS containing 2 mg OVA and 40 μL sterile PBS containing 2 mg OVA and 20 μL HCFP by nasal drop, respectively. Mouse behavioral changes were observed and behavioral scores were estimated. The serum levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-5, IL-10, transforming growth factor-β (TGF-β) and OVA-specific IgE antibody (OVA-sIgE) were measured using enzyme-linked immunosorbent assay (ELISA), and the pathological changes of mouse nasal mucosa were observed by hematoxylin and eosin (HE) staining. Results The mean behavioral score was significantly greater in Group C (6.83 ± 0.50) than in groups A (1.17 ± 0.52) and B (1.33 ± 0.52) (P < 0.05), while a lower mean behavioral score was estimated in Group D (3.50 ± 0.50) than in Group C (P < 0.05). There were significant differences among the groups in terms of serum IFN-γ (F = 4.08, P < 0.05), IL-4 (F = 275.90, P < 0.05), IL-5 (F = 96.82, P < 0.05), IL-10 (F = 77.67, P < 0.05), TGF-β (F = 9.98, P < 0.05) and OVA-sIgE levels (F = 44.69, P < 0.05). The serum IFN-γ level was significantly lower in Group C than in groups A, B and C (P < 0.05), and the serum levels of IL-4, IL-5 and OVA-sIgE were significantly higher in Group C than in groups A, B and C (P < 0.05), while the serum IL-10 and TGF-β levels were significantly greater in Group D than in Group C (P < 0.05). Microscopy showed apparent loss of nasal mucosa cilia, increased number and enlargement of goblet cells, interstitial edema and submucous vascular dilation in Group C, while the pathological changes of nasal mucosa were alleviated in Group D relative to Group C. Conclusions E. granulosus HCFP has a protective activity against OVA-induced allergic rhinitis in mice.

The prognostic value of PI combined with Pv-aCO 2 /Ca-vO 2 in patients with septic shock / 中华急诊医学杂志

Objective:To explore the predictive value of peripheral perfusion index (PI) combined with central venous-arterial carbon dioxide tension to arterial-venous oxygen content ratio(Pv-aCO 2/Ca-vO 2)for prognosis after initial resuscitation of septic shock. Methods:A total of 76 cases of patients with septic shock from January 2019 to January 2021 in emergency intensive care unit (EICU) of Harrson international peace hospital affiliated to Hebei Medical University were enrolled. All recovered according to 2016 Severe Sepsis and Septic Shock Treatment International Guidelines 2016 (SSC 2016) , and PI was monitored, central vein and arterial blood gas analysis was performed, and the ratio of Pv-aCO 2/Ca-vO 2 was calculated.The PI and Pv-aCO 2/Ca-vO 2 at 3 h,hemodynamic variables,oxygen metabolism indexes,APACHEⅡ and SOFA score were recorded.Patients were divided into survival group and death group according to 28 d survival condition, the dfferences in demographics and clinical data were compared between two groups.The Kaplan-Meier urviving curve was created and the survival of the patients was analyzed by the Log-rank test. Risk factors associated with the prognosis were analyzed using the Cox regression analysis. The role of PI and Pv-aCO 2/Ca-vO 2 in prediting death was evaluated by receiver operating characteristic curves(ROC). Results:There were 37 cases in survival group and 39 cases in death group.Compared with death group, PI in survival group [(1.77±0.63) vs. (0.89±0.69)]was significantly higher,and Pv-aCO 2/Ca-vO 2[(1.52±0.52) vs. (2.57±0.86)] was significantly lower ( P<0.05). Kaplan-Meier survival curve showed that the median survival time in the high PI group [20.09 d (95% CI:16.95-23.24) vs.11.00d (95% CI:7.14-14.86)] was longer than that in the low PI group(χ 2=12.424, P=0.000),and that in low Pv-aCO 2/Ca-vO 2 group [23.74 d (95% CI:20.35-27.13) vs.12.85d (95% CI:9.75-15.95)] was longer than that in the high Pv-aCO 2/Ca-vO 2 group (χ 2=12.200, P=0.000) .Cox regression analysis showed that both PI ( RR=0.397, 95% CI: 0.230-0.687, P =0.001) and Pv-aCO 2/Ca-vO 2 ( RR=1.878, 95% CI: 1.169-3.019, P =0.009) were predictors of 28 d mortality.The area under the ROC curve of PI and Pv-aCO 2/Ca-vO 2 for predicting 28 d death in patients with septic shock were 0.828 (95% CI: 0.732-0.923) and 0.785 (95% CI: 0.6777-0.893)respectively. The optimal cutoff values were 0.52 (sensitivity 58.3% and specificity 94.4%) and 0.35 (sensitivity 88.9% and specificity 63.9%)respectively, and the AUC of the combined prediction of the two indicators was 0.903 (95% CI: 0.835-0.971). Conclusions:Combination of PI and Pv-aCO 2/Ca-vO 2 is better to predict the risk of adverse outcomes of septie shock patients,and may provide useful information for the resuscitation at early stage.

Levels of DKK-1, MIP-1α and IL-17 in gingival crevicular fluid and serum of patients with chronic periodontitis and their clinical significance / 中国医师杂志

Objective:To investigate the level of gingival crevicular fluid and serum gingival sulcus fluid Dickkopf-1 (DKK-1), macrophage inflammatory protein-1α (MIP-1α) and interleukin (IL)-17 in patients with chronic periodontitis and their clinical significance.Methods:80 patients with chronic periodontitis (observation group) and 40 healthy periodontal subjects (control group) were prospectively selected. The gingival index (GI), bleeding index (BI), probe depth (PD), loss of attachment (AL) levels were compared between the two groups. The IL-6, IL-8, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), DKK1, MIP-1α and IL-17 levels in the gingival sulcus fluid and serum of the two groups were compared, and the correlation of DKK-1, MIP-1α and IL-17 levels with periodontal indexes and inflammatory factors in the observation group were analyzed. The DKK-1, MIP-1α and IL-17 levels in the gingival crevicular fluid and serum before and after treatment were compared among the patients with different disease degrees.Results:The levels of GI, BI, PD and AL in the observation group [(2.11±0.36)points, (3.76±0.65)points, (4.56±0.78)mm, (4.06±0.49)mm, respectively] were higher than those of the control group [(0.53±0.08)points, (1.61±0.33)points, (2.13±0.29)mm, 0 mm, respectively] (all P<0.05). The levels of IL-6, IL-8, TNF-α, DKK-1, MIP-1α and IL-17 in gingival crevicular fluid of the observation group [(65.23±9.30)ng/L, (310.19±42.95)ng/L, (40.46±9.70)ng/L, (13.70±3.62)μg/L, (19.67±8.14)μg/L, (315.84±53.76)pg/μl] were higher than those of the control group [(36.81±5.61)ng/L, (178.21±25.73)ng/L, (26.43±5.76)ng/L, (7.41±2.02)μg/L, (6.23±1.99)μg/L, (266.64±46.27)pg/μl, respectively] (all P<0.05). The serum levels of IL-8, TNF-α, DKK-1, MIP-1α and IL-17 in the observation group were also higher than those in the control group (all P<0.05). In the observation group, the levels of DKK-1, MIP-1α and IL-17 in gingival crevicular fluid and serum were positively correlated with eriodontal indexes (GI, BI, PD, AL) and the IL-8 and TNF-α levels (all P<0.05). In the observation group, the levels of DKK-1, MIP-1α and IL-17 in gingival crevicular fluid and serum of mild patients were lower than those of moderate to severe patients, and the levels of DKK-1, MIP-1α and IL-17 in mild and moderate to severe patients after treatment were also lower than those before treatment, with statistically significant difference (all P<0.05). Conclusions:The levels of DKK-1, MIP-1α and IL-17 in gingival crevicular fluid and serum of patients with chronic periodontitis are increased, which are closely related to the occurrence and development of chronic periodontitis. Detection of these indicators has certain significance for the diagnosis and treatment of the disease.

Effects and significance of continuous hemoperfusion on patients with diquat poisoning / 中华危重病急救医学

Objective:To investigate the effect of continuous hemoperfusion (HP) on the levels of soluble CD14 isoform (sCD14-st) and neutrophil gelatinase-associated lipocalin (NGAL) on patients with diquat (DQ) poisoning and its significance.Methods:A total of 86 patients with acute DQ poisoning admitted to the department of emergency medicine, Harrison International Peace Hospital Affiliated to Hebei Medical University from May 2018 to August 2021 were enrolled and divided into the intermittent HP group (40 cases) and the continuous HP group (46 cases) according to the random number table method. All patients received basic treatment and continuous veno-venous hemofiltration (CVVH) within 24 hours after admission. On this basis, the intermittent HP group received HP treatment within 2 hours, lasting 2 hours each time for every 8 hours, 3 times in all; the continuous HP group received continued HP treatment until there was no DQ component in urine samples. Serum NGAL levels were detected in all patients before treatment and at 3 hours, 12 hours, 24 hours, 2 days, 3 days, 5 days, and 7 days after treatment. At the same time, serum sCD14-st, blood lactate (Lac), arterial partial pressure of oxygen (PaO 2), serum creatinine (SCr), MB isoenzyme of creatine kinase (CK-MB) and interleukin-18 (IL-18) levels were detected before treatment and at 24 hours, 3 days, and 7 days after treatment. Kaplan-Meier survival curve was drawn to analyze the 28-day survival of patients. Results:Before treatment, there was no significant difference in serum NGAL, sCD14-st, Lac, PaO 2, SCr, CK-MB and IL-18 levels between the two groups. With the prolongation of treatment, the serum levels of NGAL, sCD14-st, Lac, SCr, CK-MB and IL-18 in the intermittent HP group increased at first and then decreased. Serum levels of NGAL, sCD14-st, CK-MB and IL-18 reached their peaks at 24 hours after treatment, and the Lac and SCr levels reached their peaks at 3 days after treatment. In addition, the levels of the above indexes at each time point in the continuous HP group were all significantly lower than those in the intermittent HP group [after 24 hours of treatment: NGAL (μg/L) was 345.90±30.75 vs. 404.24±38.79, sCD14-st (ng/L) was 1 941.88±298.02 vs. 2 656.35±347.93, CK-MB (U/L) was 30.67±9.11 vs. 43.28±8.06, IL-18 (ng/L) was 139.49±16.29 vs. 177.98±27.85; 3 days of treatment: Lac (mmol/L) was 2.98±0.26 vs. 3.72±0.49, SCr (μmol/L) was 125.01±24.24 vs. 156.74±28.88; all P < 0.05]. However, there was no significant difference in PaO 2 levels between the two groups at each time point after treatment. The Kaplan-Meier survival curve showed that the 28-day mortality of patients in the continuous HP group was significantly lower than that in the intermittent HP group [26.09% (12/46) vs. 52.50% (21/40); Log-Rank test: χ2 = 7.288, P = 0.007]. Conclusion:Continuous HP could effectively reduce serum sCD14-st, NGAL levels and 28-day mortality in patients with DQ poisoning, with good curative effect.

A quantitative description of the spatial-temporal distribution and evolution pattern of world cultural heritage.

Depicting the temporal and spatial evolution pattern of global world cultural heritage systematically and finely is the basis of heritage recognition and protection. In this study, 869 world cultural heritage inscriptions (through 2019) were selected as the research objects, and the times and types of each World Heritage site were manually annotated from more than 5000 pieces of data. Through time series modelling, the advantages of and changes in heritage declarations in different regions and periods were analysed, and the impact of heritage strategy on the number of heritage sites included in each region was evaluated. The results showed that the implementation of heritage policy greatly impacted each region, especially on the number of heritage sites in Asia and the Pacific region. Using the heritage era to carry out modelling analysis, from the perspective of the integrity of historical heritage cultural types, it is considered that there may be cultural heritage sites in the Caribbean and Latin America that have not been given enough attention. The modelling analysis results of era attributes can support the fairness of heritage determination. By calculating the frequency and peak value of heritage sites at the national scale, the frequency and peak value of each country in the top 10 list are used to characterize the ability of national declarations of cultural heritage and reveal the differences in the ability of each member country to declare heritage sites and the heritage era. By calculating the distribution density of the heritage era, this study finds that the world's cultural heritage is not concentrated in the Middle Ages (600-1450) but the periods of Reformation and Exploration (1450-1700) and Progress and Empire (1850-1914). The above analysis shows that there are imbalances and strategic adjustment effects concerning regions, countries, eras and types in World Heritage list development. The composition types of heritage are complex, and the combination types have obvious changes in different periods. It is suggested that the strategy of world cultural heritage collection should be further optimized to fully guarantee the balance of regions, countries and types, and the heritage value should be fully considered in heritage protection with more diversity and complexity of types.

Predictive value of early cerebral oxygen utilization combined with the bispectral index for delayed encephalopathy after acute carbon monoxide poisoning in elderly patients / 中华老年医学杂志

Objective:To investigate clinical value of early cerebral oxygen utilization(O 2UCc)combined with the bispectral index(BIS)for monitoring delayed encephalopathy after acute carbon monoxide poisoning(DEACMP)in elderly patients. Methods:This was a retrospective analysis.A total of 90 elderly patients with acute severe carbon monoxide poisoning(ASCMP)treated in Harrison International Peace Hospital from Nov.2018 to Jan.2020 were considered as research objects.Patients were divided into the DEACMP group(n=25)and the good prognosis group(n=65)according to their prognosis.Oxygen quantity absorbed into UCC(O 2UCc)and Bispectral index(BIS)at different times in the early stages were compared between the two groups.Correlations of O 2UCc and BIS with the occurrence of DEACMP were analyzed.Clinical significance of O 2UCc or BIS alone and of the two parameters in combination for the prediction of DEACMP was investigated. Results:O 2UCc was higher and BIS was lower in the DEACMP group than in the good prognosis group at 0 h, 6 h, 12 h, and 24 h after admission(all P<0.01). Pearson correlation analysis showed that O 2UCc was negatively correlated with DEACMP( r0 h=-0.482, r6 h=-0.534, r12 h=-0.587, r24 h=-0.514, all P<0.01), BIS was positively correlated with DEACMP( r0 h=0.348, r6 h=0.583, r12 h=0.679, r24 h=0.489, all P<0.01), and the correlation was the strongest at 12h after admission.ROC curve analysis was performed with O2UCc, BIS and the combined predictors at 12 h, and the results showed that the areas under the ROC curve of O 2UCc, BIS and the two in combination for DEACMP prediction were 0.845, 0.850 and 0.909, respectively, the sensitivities were 78.5%, 90.8% and 96.9% and the specificities were 80.0%, 76.0% and 84.0%, respectively. Conclusions:Early detection of O 2UCc or BIS has a good clinical value for predicting the development of ASCMP to DEACMP, and their combined value is even better.

Application of two indexes in the evaluation of carbon monoxide toxic heart disease / 中华急诊医学杂志

Objectives:To investigate the relationship between heart rate adjusted QT dispersion (QTcd) and soluble growth stimulating gene 2 protein (sST2) and the severity and prognosis of patients with acute carbon monoxide toxic heart disease.Methods:Retrospective analysis was performed on 135 patients with acute carbon monoxide toxic heart disease admitted to the Emergency Medical Department of our hospital from January 2017 to 2020. Blood sST2, creatine kinase isoenzyme (CK-MB) and troponin I(cTnI) concentrations were recorded at 3 h, 12 h, 2 d and 3 d immediately after admission.The patient was measured and calculated on the day of admission,2 d,3 d and QTcd at discharge.According to the toxicity of carbon monoxide in heart disease severity was divided into mild heart disease group (58 cases), moderate heart disease group (45 cases), severe heart disease group (32 cases), according to whether severe heart disease were divided into severe group (32 cases) and non severe group (103 cases), according to whether the patients death in patients with severe heart disease.Results:Thirty-two of the 135 patients had severe toxic heart disease, with an incidence of 23.7%.In the severe group, sST2, cTnI and CK-MB increased from 24 h and 2 d after admission, and the detected values were all higher than those of the non-severe group and the normal control group, with statistically significant differences ( P<0.05).Before treatment, there were statistically significant differences in sST2 and QTcd between the toxic group and the non-severe group and the normal control group ( P<0.05).After 2 d and 3 d poisoning, there were statistically significant differences between the two groups ( P<0.05). ROC curve analysis showed that the area under the sST2 curve was 0.726, 95% CI was 0.555-0.898, sensitivity was 56.3%, specificity was 94.1%, and truncation was 88.5 ng/mL.The area under the QTcd curve was 0.745, 95% CI was 0.602-0.889, sensitivity was 56.3%, specificity was 82.4%, and truncation value was 68.5 ms.The area under the combined detection curve was 0.939, 95% CI was 0.874-1.000, sensitivity was 81.3%, specificity was 91.2%. Conclusions:In patients with acute carbon monoxide toxic heart disease, the level of sST2 increased earlier than THAT of cTnI and CK-MB, and the combined observation of sST2 and QTcd can be used as an indicator for early prediction of acute carbon monoxide toxic heart disease and its severity.

A case report of perineal angiomyfibroblastoma / 中华泌尿外科杂志

Angiomyfibroblastoma (AMF)is a kind of rare benign tumour. The clinical and imaging findings of AMF are nonspecific. In October 2019, 1 case of Angiomyfibroblastoma of perineum was admitted to Heze Municipal Hospital for surgical treatment. Final pathological diagnosis was AMF. So far, neither recurrence nor metastasis has been detected for 5 months.

Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network

Additional sex combs-like 1 (ASXL1) interacts with BRCA1-associated protein 1 (BAP1) deubiquitinase to oppose the polycomb repressive complex 1 (PRC1)-mediated histone H2A ubiquitylation. Germline BAP1 mutations are found in a spectrum of human malignancies, while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor prognosis. Nearly all ASXL1 mutations are heterozygous frameshift or nonsense mutations in the middle or to a less extent the C-terminal region, resulting in the production of C-terminally truncated mutant ASXL1 proteins. How ASXL1 regulates specific target genes and how the C-terminal truncation of ASXL1 promotes leukemogenesis are unclear. Here, we report that ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes. We show that the C-terminally truncated mutant ASXL1 proteins are expressed at much higher levels than the wild-type protein in ASXL1 heterozygous leukemia cells, and lose the ability to interact with FOXK1/K2. Specific deletion of the mutant allele eliminates the expression of C-terminally truncated ASXL1 and increases the association of wild-type ASXL1 with BAP1, thereby restoring the expression of BAP1-ASXL1-FOXK1/K2 target genes, particularly those involved in glucose metabolism, oxygen sensing, and JAK-STAT3 signaling pathways. In addition to FOXK1/K2, we also identify other DNA-binding transcription regulators including transcription factors (TFs) which interact with wild-type ASXL1, but not C-terminally truncated mutant. Our results suggest that ASXL1 mutations result in neomorphic alleles that contribute to leukemogenesis at least in part through dominantly inhibiting the wild-type ASXL1 from interacting with BAP1 and thereby impairing the function of ASXL1-BAP1-TF in regulating target genes and leukemia cell growth.