The improving effect and mechanisms of Anshen Dingzhi Prescription on Alzheimer's disease-like behavior induced by D-galactose combined with AβO in mice / 药学学报

The purpose of this study was to explore the improving effect of Anshen Dingzhi Prescription (ADP) on Alzheimer's disease (AD)-like behavior in mice and its mechanisms. The main chemical components of ADP were identified by ultra performance liquid chromatography-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The AD-like mouse model was induced by D-galactose (D-gal) combined with Aβ1-42 oligomer (AβO). The effect of ADP on AD-like behavior in mice was assessed using various behavioral experiments; pathomorphological changes in mouse hippocampal tissue were observed by Nissl staining and transmission electron microscopy; ELISA was used in the assessment of oxidative stress factors and inflammation-related factor levels; Western blot was performed to detect the expression of Aβ, Tau and glial fibrillary acidic protein (GFAP) proteins. The active components of ADP were screened according to TCMSP and HERB database, and the action targets of active components were predicted by Swiss Target Prediction platform. In addition, the targets of AD were predicted through DisGeNET database. Further, GO and KEGG enrichment analysis of common targets was carried out by Metascape database. Combined with the results of GO and KEGG analysis, in vivo experiments were carried out to explore the potential mechanism of ADP improving AD-like behavior in mice from the PI3K/Akt, calcium signal pathway and synaptic function. Finally, the core components of ADP were molecularly docked to the validated targets using Autodock Vina. Animal experiments were approved by the Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-mouse-2021080). The results showed that the five chemical components, including ginsenoside Rg1, ginsenoside Rb1, tenuifolin, poricoic acid B and α-asarone were found in the ADP. ADP significantly improved the anxiety-like behavior and memory impairment, protected hippocampal neurons, decreased the levels of oxidative stress and inflammation, and inhibited the expression of Aβ and p-Tau induced by D-galactose combined with AβO in mice. The results of network pharmacology suggested that PI3K/Akt, calcium signal pathway and cell components related to postsynaptic membrane might be the key factors for ADP to improve AD. Animal experiments revealed that ADP up-regulated N-methyl-D-aspartate receptor 2A (GluN2A), postsynaptic density protein 95 (PSD95), calpain-1, phosphorylated protein kinase B (p-Akt), phosphorylated cAMP response element binding protein (p-CREB), brain-derived neurotrophic factor (BDNF) expression and inhibited p-GluN2B and calpain-2 expression in the hippocampus of AD-like mice. The molecular docking results demonstrated that the core components of ADP, such as panaxacol, dehydroeburicoic acid, deoxyharringtonine, etc. had a high binding ability with the validated targets GRIN2A, GRIN2B, PSD95, etc. In summary, our results indicate ADP improves AD-like pathological and behavioral changes induced by D-galactose combined with AβO in mice, and the mechanism might be related to the NMDAR/calpain axis and Akt/CREB/BDNF pathway.

Effects of interleukin-17A on liver and kidney injury and prognosis in septic mice / 中华危重病急救医学

OBJECTIVE@#To explore the effect of interleukin-17A (IL-17A) on liver and kidney injury and prognosis in septic mice.@*METHODS@#A total of 84 SPF male C57BL/6 mice were randomly divided into sham operation group (Sham group), cecal ligation and puncture (CLP) induced sepsis model group (CLP group), and IL-17A intervention group. IL-17A intervention group were then divided into five subgroups according to the dose of IL-17A (0.25, 0.5, 1, 2, 4 μg). Mice in the IL-17A intervention group were intraperitoneally injected with the corresponding dose of IL-17A 100 μL immediately after surgery. The other groups were intraperitoneally injected with 100 μL phosphate buffer solution (PBS). The survival rate of mice was observed at 7 days, and peripheral blood and liver, kidney and spleen tissues were collected. According to the 7-day survival, another 18 mice were randomly divided into Sham group, CLP group, and 1 μg IL-17A intervention group. Peripheral blood samples were collected at 12 hours and 24 hours after CLP, and the mice were sacrificed to obtain liver, kidney, and spleen tissues. The behavior and abdominal cavity of each group were observed. The levels of peripheral blood liver and kidney function indexes and inflammatory factors were detected. The histopathological changes of liver and kidney were observed under light microscope. The peripheral blood and spleen tissues were inoculated in the medium, the number of bacterial colonies was calculated, and the bacterial migration of each group was evaluated in vitro.@*RESULTS@#Except for the Sham group, the 7-day survival rate of mice in the 1 μg IL-17A intervention group was the highest (75.0%), so this condition was selected as the intervention condition for the subsequent study. Compared with Sham group, the liver and kidney functions of CLP group were significantly damaged at each time point after operation. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and serum creatinine (SCr) reached the peak at 24 hours after operation, and the liver and kidney pathological scores reached the peak at 7 days after operation, the levels of inflammatory cytokines interleukin (IL-17A, IL-6, IL-10) reached the peak at 12 hours after operation, and tumor necrosis factor-α (TNF-α) reached the peak at 24 hours after operation. In addition, a large number of bacteria proliferated in the peripheral blood and spleen, which reached the peak on day 7. Compared with the CLP group, exogenous administration of 1 μg IL-17A significantly delayed the rising trend of each index in the early stage of sepsis [24-hour ALT (U/L): 166.95±5.20 vs. 271.30±6.11, 24-hour AST (U/L): 599.42±7.25 vs. 1 013.27±3.37, 24-hour BUN (mg/L): 815.4±26.3 vs. 1 191.2±39.4, 24-hour SCr (μmol/L): 29.34±0.87 vs. 60.75±3.83, 7-day liver pathological score: 2.50 (2.00, 3.00) vs. 9.00 (8.50, 9.00), 7-day kidney pathological score: 1.00 (1.00, 2.00) vs. 5.00 (4.50, 5.00), 12-hour IL-17A (ng/L): 105.21±0.31 vs. 111.28±1.37, 12-hour IL-6 (ng/L): 83.22±1.01 vs. 108.88±0.99, 12-hour IL-10 (ng/L): 731.54±3.04 vs. 790.25±2.54, 24-hour TNF-α (μg/L): 454.67±0.66 vs. 576.18±0.76, 7-day peripheral blood colony count (CFU/mL): 600 (400, 600) vs. 4 200 (4 200, 4 300), 7-day spleen tissue colony count (CFU/g): 4 600 (4 400, 4 600) vs. 23 400 (23 200, 23 500), all P < 0.05].@*CONCLUSIONS@#Appropriate dose (1 μg) of exogenous IL-17A can reduce the lethal inflammatory response induced by CLP and improve the ability of bacterial clearance, thereby alleviating liver and kidney injury and improving the 7-day survival rate of septic mice.

The Risk and Survival Analysis of Multiple Malignancies in Hematologic Malignancy Patients: A Single Chinese Center Retrospective Study, 2009 through 2017 / 中国实验血液学杂志

OBJECTIVE@#To explore the risk and location of multiple malignancies in patients with hematologic malignancies who were followed up for 9 years in Jiangsu Province Hospital and to evaluate the impact of the second primary malignancy on survival of patients.@*METHODS@#The incidence and survival of multiple malignancies in 7 921 patients with hematologic malignancies from 2009 to 2017 were analyzed retrospectively.@*RESULTS@#A total of 180 (2.3%, 180/7 921) patients developed second malignancy, of whom 58 patients were diagnosed with hematologic malignancies as the first primary malignancy, and 98 patients developed hematologic malignancies as second primary malignancy, and the other 24 cases were diagnosed with the second malignancy within 6 months after the first primary malignancy was diagnosed, which was difined as multiple malignancies occurring simultaneously. In 180 patients, 18 cases developed two hematologic malignancies successively, and 11 patients developed more than 3 primary cancers (among them, 2 female patients were diagnosed with 4 primary cancers). Patients with lymphoma and multiple myeloma (MM) as the second primary malignancy had poorer survival than patients with lymphoma and MM as the first primary malignancy. Patients with chronic myeloid leukemia as the second primary malignancy were also associated with inferior overall survival.@*CONCLUSION@#In this study, 2.3% of hematologic malignancy patients had multiple mali-gnancies, lymphoma and MM as the second primary malignancy had poor survival.

Development and validation of a prognostic model for patients with sepsis in intensive care unit / 中华危重病急救医学

Objective:To analyze the risk factors related to the prognosis of patients with sepsis in intensive care unit (ICU), construct a nomogram model, and verify its predictive efficacy.Methods:A retrospective cohort study was conducted using data from Medical Information Mart for Intensive Care-Ⅳ 0.4 [MIMIC-Ⅳ (version 2.0)]. The information of 6 500 patients with sepsis who meet the diagnostic criteria of Sepsis-3 were collected, including demography characteristics, complications, laboratory indicators within 24 hours after ICU admission, and final outcome. Using a simple random sampling method, the patients were divided into a training set and a validation set at a ratio of 7∶3. The restricted cubic spline (RCS) was used to explore whether there was a linear relationship between each variable and the prognosis, and the nonlinear variables were truncated into categorical variables. All variables were screened by LASSO regression and included in multivariate Cox regression analysis to analyze the death risk factors in ICU patients with sepsis, and construct a nomograph. The consistency index, calibration curve and receiver operator characteristic curve (ROC curve) were used to evaluate the prediction efficiency of nomogram model. The decision curve analysis (DCA) was used to validate the clinical value of the model and its impact on actual decision-making.Results:Among 6 500 patients with sepsis, 4 551 were in the training set and 1 949 were in the validation set. The 28-day, 90-day and 1-year mortality in the training set were 27.73% (1?262/4?551), 34.76% (1?582/4?551), and 42.98% (1?956/4?551), respectively, those in the validation set were 27.24% (531/1?949), 33.91% (661/1?949), and 42.23% (823/1?949), respectively. Both in training set and the validation set, compared with the final survival patients, the death patients were older, and had higher sequential organ failure assessment (SOFA) score and simplified acute physiology scoreⅡ (SAPSⅡ), more comorbidities, less urine output, and more use of vasoactive drugs, kidney replacement therapy, and mechanical ventilation. By RCS analysis, the variables with potential nonlinear correlation with the prognosis risk of septic patients were transformed into categorical variable. The variables screened by LASSO regression were enrolled in the multivariate Cox regression model. The results showed that age [hazard ratio ( HR) = 1.021, 95% confidence interval (95% CI) was 1.018-1.024], SOFA score ( HR = 1.020, 95% CI was 1.000-1.040), SAPSⅡ score > 44 ( HR = 1.480, 95% CI was 1.340-1.634), mean arterial pressure (MAP) ≤ 75 mmHg (1 mmHg ≈ 0.133 kPa; HR = 1.120, 95% CI was 1.026-1.222), respiratory rate (RR; HR = 1.044, 95% CI was 1.034-1.055), cerebrovascular disease ( HR = 1.620, 95% CI was 1.443-1.818), malignant tumor ( HR = 1.604, 95% CI was 1.447-1.778), severe liver disease ( HR = 1.330, 95% CI was 1.157-1.530), use of vasoactive drugs within 24 hours ( HR = 1.213, 95% CI was 1.101-1.336), arterial partial pressure of oxygen (PaO 2; HR = 0.999, 95% CI was 0.998-1.000), blood lactic acid (Lac; HR = 1.066, 95% CI was 1.053-1.079), blood urea nitrogen (BUN) > 8.9 mmol/L ( HR = 1.257, 95% CI was 1.144-1.381), total bilirubin (TBil; HR = 1.023, 95% CI was 1.015-1.031), and prothrombin time (PT) > 14.5 s ( HR = 1.232, 95% CI was 1.127-1.347) were associated with the death of ICU patients with sepsis (all P < 0.05). Based on the above factors, a nomogram model was constructed, and the model validation results showed that the consistency index was 0.730. The calibration curve showed a good consistency between the predicted results of the nomogram model and observed results in the training and validation sets. ROC curve analysis showed that the area under the ROC curve (AUC) predicted by the nomogram model in the training set and the validation set for 28-day, 90-day and 1-year death risk was 0.771 (95% CI was 0.756-0.786) and 0.761 (95% CI was 0.738-0.784), 0.777 (95% CI was 0.763-0.791) and 0.765 (95% CI was 0.744-0.787), 0.677 (95% CI was 0.648-0.707) and 0.685 (95% CI was 0.641-0.728), respectively. DCA analysis showed that the nomogram model had significant net benefits in predicting 28-day, 90-day, and 1-year death risk, verifying the clinical value of the model and its good impact on actual decision-making. Conclusions:The death risk factors related to ICU patients with sepsis include age, SOFA score, SAPSⅡ score > 44, MAP ≤ 75 mmHg, RR, cerebrovascular disease, malignant tumors, severe liver disease, use of vasoactive drugs within 24 hours, PaO 2, Lac, BUN, TBil, PT > 14.5 s. The nomogram model constructed based on this can predict the death risk of ICU patients with sepsis.

Critical coronavirus disease 2019 caused by Delta variant: a case report with literature review / 中华危重病急救医学

Objective:To investigate the curative efficacy and application value of convalescent plasma (CP)in severe and critical coronavirus disease 2019 (COVID-19) caused by Delta variant.Methods:The treatment process and results of CP therapy for a patient with critical COVID-19 caused by Delta variant were reported. The clinical application value of CP for COVID-19 caused by Delta variant was analyzed along with the literature review.Results:Our case was a 50-year-old male, who was imported from abroad and had not been vaccinated against COVID-19. The novel coronavirus nucleic acid test was negative before entry. On the second day after entry, fever occurred, novel coronavirus nucleic acid test was positive. Chest CT images showed bilateral multiple mottling and ground-glass opacity with symptoms of nausea, headache, loss of appetite, diarrhea, but no running nose, nasal obstruction, dyspnea, abnormal smell and taste. The infection rapidly developed from medium to critical. On the basis of standard treatment, Delta variant CP was intravenous dripped on the 10th day of hospital admission (the 6th day after becoming severe). The patient's condition improved rapidly.Conclusion:The curative efficacy evaluation of this patient proved that CP therapy is of great value in the treatment of severe and critical COVID-19.

Application of information-motivation-behavior skill model in functional exercise after after autologous arteriovenous fistula plasty in hemodialysis patients / 中国实用护理杂志

Objective:Health education program based on information-motivation-behavioral skills model (IMB model) was developed, and its application effect in functional exercise after autogenous arteriovenous fistula (AVF) in hemodialysis patients was explored.Methods:Using the convenient sampling method, 100 patients undergoing AVF surgery in hemodialysis center of Qingdao Municipal Hospital from June 2020 to June 2021 were selected as the study objects. The patients were numbered according to the order of visit. The single number was the observation group, and the double number was the control group. There were 50 patients in each group. The control group was given routine AVF function exercise education, and the observation group was given AVF function exercise education based on the IMB model. Patients′ compliance with functional exercise, cephalic vein diameter, fistula maturation time, and the incidence of complications were compared between the two groups.Results:Finally, 49 cases in the control group and 50 cases in the observation group finished the research. The compliance of function exercise of the observation group was 94.0%(47/50), which was higher than 73.5%(36/49) in the control group, and the difference was statistically significant ( χ2=7.70, P<0.05). The maturation time of plasty in the observation group was (5.18 ± 1.14) weeks, shorter than that in the control group (5.94 ± 1.39) weeks, and the difference was statistically significant ( t=2.98, P<0.05). The cephalic vein diameter and blood flow controlled by hemodialysis pump in the observation group were (5.19 ± 0.28) mm and (218.40 ± 24.19) ml/min, respectively, higher than those in the control group (4.99 ± 0.34) mm and (200.41 ± 23.89) ml/min, the differences were statistically significant ( t=-3.21, -3.72, both P<0.05). The incidence of fistula complications in the observation group was 6.0%(3/50), lower than 22.4%(11/49) in the control group, and the difference was statistically significant ( χ2=5.52, P<0.05). Conclusions:The application of IMB model in hemodialysis patients with functional exercise after AVF plasty can effectively improve patients′ compliance, increase the diameter of cephalic vein and the blood flow controlled by dialysis pump, shorten the maturation time of internal fistula, and reduce the incidence of complications of AVF.

Effect of CXC chemokine receptor 7 on cell cycle of neuronal cells in ischemic stroke / 中华危重病急救医学

Objective:To investigate the function and mechanism of CXC chemokine receptor 7 (CXCR7) in neuronal cells of ischemic stroke.Methods:The expression of CXCR7 in human neuroblastoma SH-SY5Y cells was interfered by small interfering RNA (si-RNA) technique. Oxygen-glucose deprivation/reoxygenation (OGD/R) injury model was constructed in SH-SY5Y cells. CXCR7 protein expression and cell cycle were detected by flow cytometry (FCM). The protein expression of CXCR7 and Akt signaling pathway was detected by Western blotting.Results:After 6 hours of OGD/R, the expression of CXCR7 was significantly decreased compared with OGD/R 0 hour (CXCR7/GAPDH: 0.483±0.098 vs. 1.000±0.000 by Western blotting and 0.686±0.0524 vs. 1.000±0.000 by FCM, both P < 0.01), cell cycle arrest in G0/G1 phase (1.190±0.040 vs. 1.000±0.000, P < 0.01). After CXCR7 si-RNA interference with SH-SY5Y cells, OGD/R was constructed again for 6 hours. Compared with negative control group (si-NC group) under the same environment, the expression of CXCR7 and phosphorylated Akt (p-Akt) was significantly decreased (CXCR7/GAPDH: 0.471±0.051 vs. 1.000±0.000, p-Akt/GAPDH: 0.616±0.027 vs. 1.000±0.000, both P < 0.001) and cell cycle arrest in G0/G1 phase (1.105±0.033 vs. 1.000±0.000, P < 0.05). Conclusion:The CXCR7 could regulate the cycle of neuronal cells in ischemic stroke through Akt signaling pathway, which has a protective effect on neuronal cells.

Expression of connexin 26 and 30 in cochlea in a rat model of type 2 diabetes / 解剖学报

Objective To stud)' the expression of connexin (Cx) 26 and Cx30 in the cochlea in rat model of type 2 diabetes, and their role in the hearing loss of type 2 diabetes. Methods Sixty wistar rats were randomly divided into a control group(re = 20) and a experimental group(re = 4 0) . Rats in the experimental group received intraperitoneally injection of 10 mg/L streptozotocin to establish model of type 2 diabetes. Auditory brainstem response (ABR) was tested before and after molding at month 1, 2, 3, 4, 5. The morphology of cochlea was observed by HE staining, and the level and pattern of Cx26 and Cx30 expression within the cochlea were detected by immunofluorescence and Western blotting. Results In rats in the diabetes group, wave IH and V latency, I -IH and I - V interval of Click-ABRs (60 dBSPL) prolonged at month 1, 2, 3, 4, 5 after molding compared to the control (P < 0 . 0 5) . The number of cells was obvious reduced in the spiral ligament and ganglion of the experimental group (P < 0. 0 5) . Immunofluorescence and Western blotting results showed decreased expression of Cx26 and Cx30 in the experimental group at 2, 3, 4, 5 month(P<0. 05), and the expression of the two proteins decreased gradually with the time extension. Conclusion Expression of Cx26 and Cx30 is reduced at the same time as the occurrence of hearing impairment in rat cochlea with type 2 diabetes.

Antagonism of Protease-Activated Receptor 4 Protects Against Traumatic Brain Injury by Suppressing Neuroinflammation via Inhibition of Tab2/NF-κB Signaling / 神经科学通报·英文版

Traumatic brain injury (TBI) triggers the activation of the endogenous coagulation mechanism, and a large amount of thrombin is released to curb uncontrollable bleeding through thrombin receptors, also known as protease-activated receptors (PARs). However, thrombin is one of the most critical factors in secondary brain injury. Thus, the PARs may be effective targets against hemorrhagic brain injury. Since the PAR1 antagonist has an increased bleeding risk in clinical practice, PAR4 blockade has been suggested as a more promising treatment. Here, we explored the expression pattern of PAR4 in the brain of mice after TBI, and explored the effect and possible mechanism of BMS-986120 (BMS), a novel selective and reversible PAR4 antagonist on secondary brain injury. Treatment with BMS protected against TBI in mice. mRNA-seq analysis, Western blot, and qRT-PCR verification in vitro showed that BMS significantly inhibited thrombin-induced inflammation in astrocytes, and suggested that the Tab2/ERK/NF-κB signaling pathway plays a key role in this process. Our findings provide reliable evidence that blocking PAR4 is a safe and effective intervention for TBI, and suggest that BMS has a potential clinical application in the management of TBI.

Acrolein Induces Systemic Coagulopathy via Autophagy-dependent Secretion of von Willebrand Factor in Mice after Traumatic Brain Injury / 神经科学通报·英文版

Traumatic brain injury (TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes, but the pathogenesis remains poorly understood. In this study, we aimed to investigate the causal role of acrolein, a typical lipid peroxidation product, in TBI-induced coagulopathy, and further explore the underlying molecular mechanisms. We found that the level of plasma acrolein in TBI patients suffering from coagulopathy was higher than that in those without coagulopathy. Using a controlled cortical impact mouse model, we demonstrated that the acrolein scavenger phenelzine prevented TBI-induced coagulopathy and recombinant ADAMTS-13 prevented acrolein-induced coagulopathy by cleaving von Willebrand factor (VWF). Our results showed that acrolein may contribute to an early hypercoagulable state after TBI by regulating VWF secretion. mRNA sequencing (mRNA-seq) and transcriptome analysis indicated that acrolein over-activated autophagy, and subsequent experiments revealed that acrolein activated autophagy partly by regulating the Akt/mTOR pathway. In addition, we demonstrated that acrolein was produced in the perilesional cortex, affected endothelial cell integrity, and disrupted the blood-brain barrier. In conclusion, in this study we uncovered a novel pro-coagulant effect of acrolein that may contribute to TBI-induced coagulopathy and vascular leakage, providing an alternative therapeutic target.

Comparison of Liver Transplantation and Liver Resection for Hepatocellular Carcinoma Patients with Portal Vein Tumor Thrombus Type I and Type II

Purpose@#The aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis. @*Materials and Methods@#A total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involved and divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were compared before and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored. @*Results@#Two treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR (p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longer median RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335, respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase (AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS. @*Conclusion@#LT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels >200 ng/mL.

Research ideas and method on screening active components of traditional Chinese medicine against hepatotoxicity with mitochondria as target / 中国中药杂志

Liver is the main place of drug metabolism. Mitochondria of hepatocytes are important targets of drug-induced liver injury. Mitochondrial autophagy could maintain the healthy operation of mitochondria in cells and the stable proliferation of cells. Therefore, the use of mitochondrial autophagy to remove damaged mitochondria is an important strategy of anti-drug-induced liver injury. Active ingredients that could enhance mitochondrial autophagy are contained in many traditional Chinese medicines, which could regulate the mitochondrial autophagy to alleviate relevant diseases. However, there are only a few reports on how to accurately and efficiently identify and evaluate such components targeting mitochondria from traditional Chinese medicine. Liquid chromatography-mass spectro-metry(LC-MS) combined with serum pharmacology in vivo can be used to accurately and efficiently find active ingredients of traditional Chinese medicine acting on mitochondrial targets. This paper reviewed the research ideas and methods of traditional Chinese medicine ingredients for increasing the hepatotoxicity of mitochondrial autophagy, in order to provide new ideas and methods for the study of active ingredients of traditional Chinese medicine targeting mitochondria.

Progress in application of Bletilla striata polysaccharide in novel drug delivery systems and biomaterials / 中国中药杂志

As the main active ingredient of the orchidaceous herb Bletilla striata, B. striata polysaccharide(BSP) has pharmacological activities such as promoting coagulation, anti-inflammation, anti-oxidation, promoting wound healing, anti-tumor, and immunomodulation, and is biodegradable and non-toxic. Additionally, it has the material properties of suspension thickening, film-forming adhesion, coating and solubilizing, targeting and slow releasing, effect-enhancing and toxicity-reducing, etc., playing the role of unification of medicines and excipients. Therefore, BSP has a wide application prospect in the fields of drug delivery system and trauma repair. This paper reviews the research progress of BSP application in new drug delivery systems and biomaterials based on the related li-terature in recent years, with the aim of providing reference for the further research and application of BSP.

Study on material basis of Açaí cold drug based on neuro-endocrine-immune network / 中国中药杂志

To investigate the characteristics of the cold and heat properties of each resolution component of Açaí and the material basis of cooling by observing the effect of resolution components, such as Açaí oil, alcohol extract and water extract, on the neurotransmitter, endocrine hormone and immune factor level in mice with deficiency-heat and deficiency-cold syndrome. KM male mice were randomly divided into 12 groups, namely blank group, deficiency-heat model group, deficiency-heat+Açaí group, deficiency-heat+Açaí oil group, deficiency-heat+Açaí alcohol extract group, deficiency-heat+Açaí water extract group, deficiency-cold model group, deficiency-cold+Cinnamomi Cortex group, deficiency-cold+Açaí group, deficiency-cold+Açaí oil group, deficiency-cold+Açaí alcohol extract group, and deficiency-cold+Açaí water extract group. The mice in deficiency-heat group were given with thyroid tablet solution(160 mg·kg~(-1)), and the mice in deficiency-cold group were given with hydrocortisone solution(25 mg·kg~(-1)) by intragastric administration every afternoon for 14 days. The mice in each administration group received corresponding drug. The neurotransmitter, endocrine hormone and immune factor levels in the mice were measured after the experiment. The Açaí alcohol extract, consistent with the Açaí powder, showed a regulatory effect on the deficiency-heat model mice; Açaí oil and its water extract were consistent with Cinna-momi Cortex, showing a regulatory effect on the deficiency-cold model mice. In this study, on the basis of proving that Açaí was was cool in property, it also revealed that alcohol extract of Açaí was cool while oil and water extract were warm in property based on the effect of Açaí on neuro-endocrine-immune network. The results suggested that the medicine property of Açaí was the result of the comprehensive action of the resolution components with different properties, and the alcohol extract of Açaí was proved as the material basis of Açaí cold medicine by using the methods of homogeneous comparison and heterogeneous disproval.

Detection and analysis of carbapenem-resistant Klebsiella pneumoniae resistance genes in five hospitals in Qingdao City / 中华危重病急救医学

Objective:To clarify the distribution and composition of drug-resistant genes of carbapenem-resistant Klebsiella pneumoniae (CRKP) in Qingdao City and to provide rationale for clinical application of antibacterial treatment by screening for carbapenemase phenotype and detecting resistance genes of CRKP. Methods:Fifty-four clinically isolated non-repeating CRKP from five Third Grade & Class A Hospitals in Qingdao City from October 2016 to September 2019 were collected. Kirby-Bauer method was used for drug sensitivity tests of commonly used antibacterial drugs; modified Hodge test was used for carbapenemase phenotypic screening; and polymerase chain reaction (PCR) was used to amplify blaKPC-2, blaNDM-1, blaOXA-48, blaIMP, blaVIM target genes. The amplified products were subjected to agarose gel electrophoresis. Results:Drug susceptibility tests showed that CRKP had the lowest resistance rate to amikacin (35.2%), followed by compound sinomine (53.7%), gentamicin (55.6%), levofloxacin (75.9%), and imipenem-cilastatin (88.9%); piperacillin-tazobactam, meropenem, cefotaxime, and cefoperazone-sulbactam were all higher than 90%. There were 43 positive strains in the modified Hodge test (the positive rate was 79.63%) and 11 negative strains. A total of 40 strains with carbapenemase resistance were detected by PCR resistance gene detection. The detection rate of target drug-resistant genes was 74.07%. Among them, 35 strains carry the KPC-2 gene, 7 strains carry the OXA-48 gene, 4 strains carry the NDM-1 gene, and 1 strain carries the IMP gene. All strains carrying the OXA-48 gene also carried the KPC-2 gene, which was not detected. Strains carrying the VIM gene were identified, and the remaining 14 strains did not detect the target carbapenem gene.Conclusion:The carbapenem-producing genes carried by CRKP in five hospitals in Qingdao City are mainly KPC-2, followed by OXA-48 and NDM-1.

Comparative study on nutritional status of patients in intensive care unit with different assessment tools / 中华危重病急救医学

Objective:To evaluate the nutritional status of patients in intensive care unit (ICU) by using nutritional risk screening 2002 scale (NRS2002), subjective general assessment (SGA) and critical illness nutritional risk score (NUTRIC), and to compare the characteristics and applicability of three scoring tools.Methods:A cross-sectional survey was conducted. 315 patients admitted to the comprehensive ICU of Affiliated Qingdao Municipal Hospital of Qingdao University from April 2018 to July 2019 were enrolled. Basic information of patients was collected, and patients were divided into two groups with 65 years old as the standard to compare the nutritional status of patients among different genders and ages. The nutritional status of patients were assessed by NRS2002, SGA, and NUTRIC. Height, weight, body mass index (BMI), triceps skinfold thickness (TSF), upper arm circumference (AC), leg circumference (LC), and other related parameters of human nutrition were measured. Total protein (TP), albumin (Alb), prealbumin (PA), serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), total number of lymphocytes (LYM), hemoglobin (Hb), C-reactive protein (CRP) and other blood biochemical indicators were performed. Spearman rank correlation analysis was used to analyze the correlation between the three nutrition evaluation scales and other objective nutrition parameters. Binary multivariate Logistic regression analysis was used to evaluate the influencing factors of nutritional status with three scales of patients in ICU.Results:Among 315 patients in ICU, 183 were male and 132 were female. There were 143 patients < 65 years old and 172 ≥ 65 years old. In male patients, the acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, age and BUN of patients aged ≥ 65 years old were significantly increased, and the height, weight, BMI, TSF, AC, LC, Alb and PA were significantly lowered as compared with those aged < 65 years old, while the difference in other indicators was not statistically significant. In the female patients, the APACHEⅡ score, age, SCr and BUN of the patients aged ≥ 65 years old were significantly increased, the height, Alb, PA and Hb were significantly decreased as compared with those aged < 65 years old, and the difference in other indicators was not statistically significant. The proportion of patients with nutritional risk evaluated by NRS2002 (NRS2002 score ≥ 3) was 87.62% (276/315). SGA showed that the proportion of malnourished patients (SGA was grade B or C) was 62.86% (198/315). NUTRIC showed 66.03% of patients (208/315) in high nutritional risk (NUTRIC score ≥ 5). Spearman rank correlation analysis showed that there were significant correlations among NRS2002, SGA and NUTRIC of patients in ICU ( rNRS2002 with SGA = 0.522, rNRS2002 with NUTRIC = 0.392, rSGA with NUTRIC = 0.442, all P < 0.01). Among the three assessment tools, SGA had the best correlation with blood biochemical indicators and body measurements to assess nutritional status, followed by NRS2002, and NUTRIC had the worst correlation. Binary multivariate Logistic regression showed that APACHEⅡ score, BMI, AC, BUN and TG were factors influencing NRS2002 assessment of nutritional status in ICU patients [odds ratio ( OR) were 2.535, 0.404, 1.438, 0.858, and 2.391, respectively, all P < 0.05]; APACHEⅡ score, age, weight, TP, BUN, LYM and CRP were influence factors of SGA for evaluating the malnutrition of patients in ICU ( OR values were 1.074, 1.038, 0.921, 0.947, 1.077, 1.625 and 0.991, respectively, all P < 0.05); APACHEⅡ score, age, LYM and CRP were the influence factors of NUTRIC assessment for malnutrition of patients in ICU ( OR values were 1.159, 1.049, 0.715 and 0.995, respectively, all P < 0.05). Conclusions:The nutrition status of ICU patients evaluated by NRS2002, SGA and NUTRIC was simple and easy to operate, and the positive screening rate of NRS2002 was the highest, which was suitable for patients with mild conditions in ICU. SGA is the most valuable tool to evaluate the nutritional status of ICU patients. NUTRIC has a poor correlation with objective indicators reflecting nutritional status, while its indicators are objective and easy to obtain, which is suitable for ICU patients with critical condition and unclear consciousness. Nutritional assessment tools should be integrated with the patient's gender, age, anthropometric and biochemical indicators.

Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative Damage in Mice / 神经科学通报·英文版

Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury.

Acrolein Aggravates Secondary Brain Injury After Intracerebral Hemorrhage Through Drp1-Mediated Mitochondrial Oxidative Damage in Mice / 神经科学通报·英文版

Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury.

Detection and clinical significance of APRI and FIB-4 in patients with chronic HBV infection / 中国综合临床

Objective To detect the changes of aspartate aminotransferase-to-platelet ratio index ( APRI) and fibrosis index based on the four factors (FIB-4) in patients with chronic HBV infection,and to analyze and evaluate the status of liver function,and explore the clinical significance in order to find a simple non-invasive diagnostic method for liver fibrosis. Methods From January 2016 to June 2017, a clinical controlled study was conducted to select one hundred and twenty patients with chronic HBV infection in outpatient and inpatient clinics of the Second Affiliated Hospital of Medical College of Qingdao University. They were divided into three groups: HBV carriers,chronic hepatitis B patients and hepatitis B cirrhosis patients. Serum total bilirubin,albumin,alanine aminotransferase (ALT),aspartate aminotransferase (AST) and platelet levels were measured. According to the formula, the values of APRI and FIB-4 were calculated,and the numerical changes of APRI and FIB-4 in patients with different types of chronic HBV infection were studied. The correlation between total bilirubin and albumin was analyzed. At the same time,30 healthy persons were selected as healthy control group for clinical analysis. Results The APRI values of patients with chronic HBV infection and healthy control group were ( 1. 17 ± 0. 71) and ( 0. 50 ± 0. 23), respectively. The FIB-4 values of patients with chronic HBV infection and healthy control group were (1. 90± 0. 84) and (1. 08±0. 58),respectively. The differences were statistically significant (P＜0. 01). The APRI values of HBV carriers group,chronic hepatitis B group and hepatitis B cirrhosis group were(0. 53±0. 22), (1. 14± 0. 61) and ( 1. 84 ± 0. 49) . The values of FIB-4 were ( 1. 22 ± 0. 54),( 1. 85 ± 0. 48) and ( 2. 64 ±0. 77) respectively. The values of APRI and FIB-4 of chronic HBV infection patients in each group increased with the increase of liver fibrosis, and there was significant difference between the groups ( P＜0. 01). The results showed that hepatitis B cirrhosis grouP＞chronic hepatitis B grouP＞HBV carrier grouP＞healthy control group. There were significant differences between hepatitis B group and healthy control group,hepatitis B cirrhosis group and HBV carrier group,chronic hepatitis B group and HBV carrier group (P＜0. 01). There was no significant difference between HBV carriers and healthy controls (P＞0. 05). The results of correlation analysis showed that there was a positive correlation among APRI, FIB-4 and total bilirubin (P＜0. 01) and a negative correlation with albumin ( P＜0. 01) in patients with chronic HBV infection. Conclusion The changes of APRI and FIB-4 values in patients with chronic HBV infection have diagnostic value for liver fibrosis in different clinical infection states can reflect the liver function status of patients,and help judge the severity and prognosis of patients with chronic HBV infection.

Correlation of Peripheral Blood T Lymphocyte Subsets with Prognosis of Elderly Patients with Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression level of T lymphocyte subsets in elderly patients with newly diagnosed multiple myeloma (NDMM), and to evaluated the prognostic value of T lymphocytic abnormalities in elderly NDMM patients.@*METHODS@#Pretreated peripheral blood of 39 newly diagnosed elder patients with MM was tested by multi-parameter flow cytometry (MFC) to quantitatively detect T lymphocyte subsets, including CD4T cell, CD8T cell, and CD4/CD8 ratio. The prognostic values T-lymphocyte subset were evaluated in newly diagnosed elderly patients with MM.@*RESULTS@#The median follow-up time was 21.5 (range, 3.0-66.0) months. Absolute counts of CD4T cell and CD4/CD8 ratio positively correlated with prognosis. In the multivariate COX analysis, lower CD4/CD8 ratio and CD4T cell counts were identified to be independent adverse prognostic factors for OS.@*CONCLUSION@#Lower CD4/CD8 ratio and CD4T cell counts at initial diagnosis are independent unfavorable prognostic factors for elderly patients with MM, and T lymphocyte subsets are crucial indicators for MM patients' prognosis.