Objective To investigate the effects and molecular mechanism of Notoginsenoside R1 on hypobaric hypoxia-induced high-altitude pulmonary edema based on nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)/glutathione peroxidase 4(GPX4)signaling pathway.Methods Forty-two 6-week-old male SD rats were acclimatized and fed for one week,and then randomized into the Control group,negative control group(NGR1,100 mg·kg-1),model group(HH),Notoginsenoside R1 low dose group(NGR1-low,50 mg·kg-1),Notoginsenoside R1 high dose group(NGR1-high,100 mg·kg-1),and dexamethasone group(Dex,4 mg·kg-1),with seven rats in each group.After the drug administration group was administered with Notoginsenoside R1 or dexamethasone by intraperitoneal injection,the hypobaric hypoxia simulation chamber was used to simulate the plateau environment for modeling.Detect the total protein concentration in bronchoalveolar lavage fluid(BALF)and measure the lung wet/dry weight ratio(W/D);ELISA to measure inflammation levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-1β in BALF;hematoxylin-eosin(HE)staining to visualize pathomorphologic changes in the lungs of each group;biochemical kit detect the content and activity of reactive oxygen species(ROS),superoxide dismutase(SOD),and reduced glutathione(GSH)in the lung tissues;Western blot to detect the protein expression of Nrf2,HO-1,GPX4,SLC7A11 and NOX1 in lung tissues.Results Compared with the Control group,the total protein concentration in the BALF of rats in the HH group was markedly increased(P<0.01),and the lung W/D was markedly increased(P<0.01);lung histopathology showed obvious thickening of the alveolar wall,interstitial edema,hemorrhage and massive inflammatory exudation in the alveolar lumen,alveolar septa,and interstitium of the lungs;the levels of TNF-α(P<0.001),IL-6(P<0.01),and IL-1β(P<0.0001)in the BALF were significantly elevated;ROS content was significantly increased(P<0.01),and SOD(P<0.01)and GSH(P<0.01)activities were significantly decreased in lung tissues;the expression of Nrf2 in the nucleus of lung was markedly decreased(P<0.001),and that in the cytoplasm of lung was markedly increased(P<0.05),and the expression of HO-1(P<0.01),GPX4(P<0.01),and SLC7A11(P<0.05)was significantly decreased,and that of NOX1 was significantly increased(P<0.01).Compared with the HH group,the total protein concentration in the BALF of rats in each drug intervention group was significantly reduced,and the lung W/D was significantly reduced;the lung histopathology was significantly improved;the levels of TNF-α,IL-6,and IL-1β in the BALF were significantly decreased;the content of ROS in the lung tissues was significantly reduced,and the activities of SOD and GSH were significantly elevated;the expression of Nrf2 in the nucleus of lung was markedly increased,the expression of Nrf2 in the cytoplasm of lung was markedly decreased,the expression of HO-1,GPX4,SLC7A11 was markedly increased,and the expression of NOX1 was markedly decreased.Conclusion Notoginsenoside R1 inhibits hypobaric hypoxia-induced ferroptosis and attenuates pulmonary edema,lung inflammation and oxidative stress by a mechanism that may be related to the regulation of the Nrf2/HO-1/GPX4 pathway.

Objective To investigate the effects and molecular mechanism of Notoginsenoside R1 on hypobaric hypoxia-induced high-altitude pulmonary edema based on nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)/glutathione peroxidase 4(GPX4)signaling pathway.Methods Forty-two 6-week-old male SD rats were acclimatized and fed for one week,and then randomized into the Control group,negative control group(NGR1,100 mg·kg-1),model group(HH),Notoginsenoside R1 low dose group(NGR1-low,50 mg·kg-1),Notoginsenoside R1 high dose group(NGR1-high,100 mg·kg-1),and dexamethasone group(Dex,4 mg·kg-1),with seven rats in each group.After the drug administration group was administered with Notoginsenoside R1 or dexamethasone by intraperitoneal injection,the hypobaric hypoxia simulation chamber was used to simulate the plateau environment for modeling.Detect the total protein concentration in bronchoalveolar lavage fluid(BALF)and measure the lung wet/dry weight ratio(W/D);ELISA to measure inflammation levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-1β in BALF;hematoxylin-eosin(HE)staining to visualize pathomorphologic changes in the lungs of each group;biochemical kit detect the content and activity of reactive oxygen species(ROS),superoxide dismutase(SOD),and reduced glutathione(GSH)in the lung tissues;Western blot to detect the protein expression of Nrf2,HO-1,GPX4,SLC7A11 and NOX1 in lung tissues.Results Compared with the Control group,the total protein concentration in the BALF of rats in the HH group was markedly increased(P<0.01),and the lung W/D was markedly increased(P<0.01);lung histopathology showed obvious thickening of the alveolar wall,interstitial edema,hemorrhage and massive inflammatory exudation in the alveolar lumen,alveolar septa,and interstitium of the lungs;the levels of TNF-α(P<0.001),IL-6(P<0.01),and IL-1β(P<0.0001)in the BALF were significantly elevated;ROS content was significantly increased(P<0.01),and SOD(P<0.01)and GSH(P<0.01)activities were significantly decreased in lung tissues;the expression of Nrf2 in the nucleus of lung was markedly decreased(P<0.001),and that in the cytoplasm of lung was markedly increased(P<0.05),and the expression of HO-1(P<0.01),GPX4(P<0.01),and SLC7A11(P<0.05)was significantly decreased,and that of NOX1 was significantly increased(P<0.01).Compared with the HH group,the total protein concentration in the BALF of rats in each drug intervention group was significantly reduced,and the lung W/D was significantly reduced;the lung histopathology was significantly improved;the levels of TNF-α,IL-6,and IL-1β in the BALF were significantly decreased;the content of ROS in the lung tissues was significantly reduced,and the activities of SOD and GSH were significantly elevated;the expression of Nrf2 in the nucleus of lung was markedly increased,the expression of Nrf2 in the cytoplasm of lung was markedly decreased,the expression of HO-1,GPX4,SLC7A11 was markedly increased,and the expression of NOX1 was markedly decreased.Conclusion Notoginsenoside R1 inhibits hypobaric hypoxia-induced ferroptosis and attenuates pulmonary edema,lung inflammation and oxidative stress by a mechanism that may be related to the regulation of the Nrf2/HO-1/GPX4 pathway.

【Objective】 To statistically analyze the re-entry test and blood re-donation of HBV, HCV, TP and HIV single-reagent reactive blood donors in Hohhot from 2019 to 2021, so as to demonstrate the rationality, feasibility and necessity of the re-entry strategy of voluntary blood donors in Hohhot, and provide theoretical support for further standardizing of the reentry of blood donors. 【Methods】 A total of 225 samples of blood donors who applied for re-entry in Hohhot from 2019 to 2021 were collected, and HBV, HCV and HIV were tested by two reagent serological tests and nucleic acid tests. TP anti-TP was detected by two reagent serological methods. The test results were all non-reactive and met the requirements of re-entry. The blood donation status of blood donors after re-entry was followed up and analyzed. 【Results】 Among the 225 cases detected for HBV, HCV, TP and HIV from 2019 to 2021 in Hohhot, 178 were qualified for the returning, with a re-entry rate of 79.11%, and 75 donated blood again, with a after re-entry re-donation rate of 42.13%. 【Conclusion】 The strategy of returning for HBV, HCV, TP and HIV single reagent reactive blood donors in Hohhot is effective, and has positive significance for safeguarding the rights and interests of blood donors and alleviating regional blood supply shortages.

OBJECTIVE To screen t he active component s of Euchresta japonica against nasopharyngeal carcinoma. METHODS Main chemical components of E. japonica were selected ，and their target proteins were predicted in Swiss Target Prediction database. The target proteins of nasopharyngeal cancer were obtained with GeneCards database. Protein-protein interaction（PPI）network was established after the target of chemical components of E. japonica was intersected with the target of nasopharyngeal carcinoma ；PPI network was analyzed by using Cytoscape 3.6.1 software，and the potential active components and key targets of E. japonica against nasopharyngeal carcinoma were screened. The molecular docking technology was used to evaluate binding ability of active component-key target ；active components of E. japonica against nasopharyngeal carcinoma were screened. The anti-nasopharyngeal cancer effect of potential active components of E. japonica was verified by cell proliferation experiment. RESULTS Seven potential active components （tonkinensisol，quercetin，sophoranone，matrine，genistein，coumarin，maackiain） and 10 core targets （SRC，PIK3CA，MAPK1，MAPK3，AKT1，MAPK8，MAP2K1，PTK2，EGFR，JAK3）of E. japonica against nasopharyngeal carcinoma were screened. The molecular docking results showed that above potential active components all possessed certain anti-nasopharyngeal cancer effect. Cell proliferation activity test showed that tonkinensisol ，sophoranone and maackiain had a very significant inhibitory activity on nasopharyngeal carcinoma cells CNE- 1. CONCLUSIONS Tonkinensisol， sophoranone and maackiain might be the main active components of E. japonica against nasopharyngeal carcinoma.

Objective:To investigate the clinical effects of intermittent oro-esophageal tube feeding (IOE) combined with Xuanqiaoliyan decotion in stroke patients with dysphagia.Methods:A prospective study was conducted. Stroke patients with dysphagia admitted to Yidu Central Hospital Affiliated Hospital of Weifang Medical University from January 2018 to December 2019 were enrolled. According to the simple random sampling method, the patients were divided into control group and observation group, with 50 cases in each group. The control group was given routine swallowing function training, including low-frequency pulse electrical stimulation, swallowing function training and acupuncture treatment. The observation group was given IOE and Xuanqiaoliyan decoction (prescription composition: Rhizoma acori tatarinowii 15 g, Radix polygalae 10 g, Rhizoma gastrodiae 15 g, Arisaema cum bile 6 g, Rhizoma typhonii 6 g, Scorpio 6 g, Bombyx batryticatus 6 g, Perilla frutescens 10 g, Rhizoma pinelliae 10 g, Pericarpium citri reticulatae 10 g, Rhizoma zingiberis recens 3 tablets, decoction 200 mL, twice in the morning and evening by oral or nasal feeding) on the basis of the control group. Both groups were treated for 14 days. The standard swallowing function assessment (SSA) and water swallow test were used to evaluate the swallowing function before and after treatment. The time required for the improvement of swallowing function, total hospitalization time and the therapeutic effects were observed and the safety assessment was conducted. Results:There were no significant differences in the gender, age, course of disease, and location and frequency of stroke between the two groups. After treatment, both the SSA scores in the two groups were decreased, and the grading of water swallow test was improved. The SSA scores in the observation group were significantly lower than that in the control group (19.8±1.8 vs. 23.2±3.2, P < 0.05), the recovery degree of water swallow test was higher than that in the control group [complete recovery (cases): 18 vs. 13, basic recovery (cases): 23 vs. 18, effective (cases): 9 vs. 19, χ 2 = -2.107, P = 0.008]. The total effective rate of swallowing function in the observation group was higher than that in the control group (94.0% vs. 80.0%, Z = 4.684, P = 0.012), the time for improvement (days: 12.8±2.6 vs. 16.9±4.3, t = 11.628, P = 0.008) and total hospitalization time (days: 20.8±4.2 vs. 33.5±5.6, t = 10.924, P = 0.015) were shorter than those in the control group. In the observation group, there was 1 case of throat discomfort during the operation of IOE, and the symptoms disappeared after the operation; there was 1 case of mild elevation of alanine aminotransferase (ALT) and blood urea nitrogen (BUN) respectively, which returned to normal after the treatment. No adverse symptoms and damage to the liver and kidney were observed in the control group. Conclusion:IOE combined with Xuanqiaoliyan decotion could significantly improve the swallowing function of stroke patients with dysphagia, shorten the hospitalization time, and improve the curative effects and lifequality.

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

Objective:To evaluate the efficacy and safety of comprehensive treatment based on radiotherapy for patients with leptomeningeal metastases (LM) in this prospective study.Methods:A total of 93 patients diagnosed with LM admitted to our hospital undergoing whole brain radiotherapy (WBRT) or craniospinal irradiation (CSI) with or without simultaneous boost from 2014 to 2017 were enrolled. The dynamic changes of clinical signs and symptoms, enhanced magnetic resonance imaging (MRI), cerebrospinal fluid cytology and liquid biopsy detection were recorded. The primary endpoint was overall survival (OS), the secondary endpoints were local control (LC), intracranial progress-free survival (IPFS), brain metastasis specific survival (BMSS) and toxicity.Results:The major primary disease was non-small cell lung cancer. The whole cohort received WBRT with boost (40 Gy in 20 fractions (f) for WBRT and 60 Gy in 20 f for boost), focal radiation to LM, WBRT and CSI (40 Gy in 20 f or 50 Gy in 25 f for WBRT and 36 Gy in 20 f for CSI). For 20 patients, tumor cells were identified and intrathecal chemotherapy was performed. Sixty-three patients received target therapy. The median follow-up time was 33.8 months. The 1-year OS, LC and IPFS was 62.4%, 77.2% and 52.6%, respectively. The median survival time was 15.9 months, and the median BMSS was 42.2 months. Treatment-related grade 3-4 adverse events were rare and only 8 cases was observed to have grade 3 hematological toxicity.Conclusion:Reasonable comprehensive treatment including precise radiotherapy, intrathecal chemotherapy and targeted therapy can be well tolerated and prolong the survival time of LM patients.

Objective:To examine 2019 novel coronavirus (2019-nCoV) RNA in clinical specimens of COVID-19 patients in Anhui province, and provide evidence for laboratory diagnosis of COVID-19 and risk assessment of clinical specimens.Methods:ORF1ab gene and N gene of 2019-nCoV were detected by real-time fluorescence RT-PCR in 466 clinical specimens of 197 COVID-19 cases. Chi-square test was used to analyze the differences in positive rates of specimens with clinical classification and time of onset.Results:The positive rates of 2019-nCoV in throat swab, sputum, serum, blood sample were 88.83%, 94.67%, 6.78% and 5.08%. The positive rate for 2019-nCoV RNA in throat swabs and sputum differed significantly ( χ2=8.994, P=0.003) in common cases during 7 days after illness onset. Conclusions:The positive rate of RNA in sputum was higher than throat swabs. 2019-nCoV RNA was detected in serum and blood specimens of COVID-19 cases. There was a risk of serum and blood specimens for transmission of COVID-19.

Objective To investigate of effect and mechanism of honokiol against acute lung injury (ALI) induced by lipopolysaccharide (LPS).Methods Forty SPF BALB/c mice were randomly divided into 5 groups (N =8),normal control group,LPS group,low-and high-dose magnolol groups,and dexamethasone group.The mouse model of ALI was induced by LPS.After intraperitoneal injection of honokiol,we detected neutrophil count,concentration of albumin,and pulmonary myeloperoxidase (MPO) activity in bronchoalveolar lavage fluid (BALF)as well as alveolar permeability.We also detected the levels of malondialdehyde (MDA),protein carbonyl content(PCC),reactive oxygen species (ROS) and glutathione(CAT),and the activities of superoxide dismutase (SOD),catalase,glutathione peroxidase (GPx),and glutathione-S-transferase(GST) in lung tissue of mice.Results In the LPS group,the neutrophil count,albumin concentration,MPO activity and Evans blue (EB)content were increased (P ＜ 0.05),and anti-oxidase activity was decreased significantly (P ＜ 0.05).After treatment with honokiol,the neutrophil count,albumin concentration,MPO activity,EB content,and lipid peroxidation level were decreased significantly,and the activities of antioxidant enzymes were increased significantly (P ＜ 0.05).Conclusion Honokiol has protective effects against LPS-induced acute lung injury through inhibiting oxidative stress.

Proline-rich transmembrane protein 2 (PRRT2), the causative gene of paroxysmal kinesigenic dyskinesias (PKD), benign familial infantile seizures (BFIS) and infantile convulsions with paroxysmal choreoathetosis (ICCA), also causes a variety of neurological paroxysmal disorders. These diseases share the same characteristics which may be due to the same genetic defect. We therefore propose to name them as PRRT2-related paroxysmal disorders (PRPDs) in order to assist clinical diagnosis, treatment and prognosis. This paper has reviewed the clinical phenotype, common features and pathogenesis of the PRPDs.
Chorea ; genetics ; Epilepsy, Benign Neonatal ; genetics ; Family Health ; Genetic Predisposition to Disease ; genetics ; Humans ; Infant ; Infant, Newborn ; Membrane Proteins ; genetics ; Mutation ; Nerve Tissue Proteins ; genetics