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The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (Mpro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851Mpro inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both Mpro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of Mpro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 Mpro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Subject(s)
Humans , Antiviral Agents/chemistry , COVID-19 , COVID-19 Drug Treatment , High-Throughput Screening Assays , Molecular Docking Simulation , Protease Inhibitors/chemistry , SARS-CoV-2/enzymology , Viral Nonstructural ProteinsABSTRACT
Bone defects are bone loss caused by factors such as severe trauma, infection, tumor resection and congenital malformations. Bone transplantation, induced membrane technique or stem cell bone tissue engineering is needed for the defects that are difficult to heal naturally. However, the techniques related to bone transplantation are complex and have limited application scope; the induced membrane technique shows uncontrollable cement degradation rate and requires a second surgery; the stem cell bone tissue engineering still has some unstable factors such as undirected differentiation of stem cells. Exosomes are the key liposomes in the communication between cells. Compared with natural stem cell-derived exosomes, engineered exosomes with the advantages of high production and low immunogenicity are expected to replace stem cells in clinical applications. The authors review the mechanism of action of mesenchymal stem cell (MSC)-derived exosomes in repairing bone defects and application of engineered exosomes based on MSC in bone regeneration, so as to provide new ideas for the basic research and clinical treatment of bone defects.
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Rituximab is currently used as a first-line therapy for phospholipase A 2 receptor-associated membranous nephropathy due to its good efficacy and safety. Although the remission rate after rituximab treatment is more than 60%, nearly 40% patients still do not respond to treatment. We used obinutuzumab to treat 3 cases of rituximab resistant PLA 2R-associated membranous nephropathy. After the first dose of 1 000 mg with or without additional dose, the amount of anti-PLA 2R antibody and urinary protein decreased significantly and the adverse reactions were mild. The results show that obinutuzumab has a certain therapeutic effect on rituximab resistant PLA 2R-associated membranous nephropathy, but the time of follow-up observation is short and can only be used as individual cases, which needs to be confirmed by a large sample and high-quality prospective cohort study.
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Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Subject(s)
Female , Humans , Adolescent , SARS-CoV-2 , Smell , COVID-19/complications , Cross-Sectional Studies , COVID-19 Vaccines , Incidence , Olfaction Disorders/etiology , Taste Disorders/etiology , PrognosisABSTRACT
OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a patient with adolescent-onset hypomyelinated leukodystrophy with atrophy of basal ganglia and cerebellum (H-ABC).@*METHODS@#A patient who was diagnosed with H-ABC in March 2018 at the First Affiliated Hospital of Nanjing Medical University was selected as the study subject. Clinical data was collected. Peripheral venous blood samples of the patient and his parents were collected. The patient was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.@*RESULTS@#The patient, a 31-year-old male, had manifested with developmental retardation, cognitive decline and abnormal gait. WES revealed that he has harbored a heterozygous c.286G>A variant of the TUBB4A gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Analysis with SIFT online software indicated the amino acid encoded by this variant is highly conserved among various species. This variant has been recorded by the Human Gene Mutation Database (HGMD) with a low population frequency. The 3D structure constructed by PyMOL software showed that the variant has a harmful effect on the structure and function of the protein. According to the guidelines formulated by the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic.@*CONCLUSION@#The c.286G>A (p.Gly96Arg) variant of the TUBB4A gene probably underlay the hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum in this patient. Above finding has enriched the spectrum of TUBB4A gene variants and enabled early definitive diagnosis of this disorder.
Subject(s)
Male , Humans , Adolescent , Adult , Magnetic Resonance Imaging , Basal Ganglia/pathology , Cerebellum , Atrophy/pathology , Mutation , Tubulin/geneticsABSTRACT
Objective@#To explore the relationship between different roles of school bullying and self consciousness among adolescents, and to provide a reference for school bullying prevention and control.@*Methods@#In Ezhou and Xiaogan, two cities selected randomly from Hubei Province, 4 336 middle school students randomly selected from Ezhou and Xiaogan City in Hubei Province by stratified cluster sampling method during March to October in 2017, were investigated for an anonymous questionnaire survey. The Chinese version of adolescent school violence questionnaire was used to evaluate the different roles in school bullying, and the Self Consciousness Scale(SCS) was used to assess the level of self awareness.@*Results@#About 18.9% of the respondents (819) were involved in bullying, among 86(2.0%) were pure perpetrators, 369 (8.5%) were pure victims, 364 (8.4%) were perpetrator victims. There were significant differences in public and private self awareness among different roles of campus bullying ( F=4.05, 2.90, P <0.05). The public self awareness score of perpetrator victims was higher than that of the uninvolved. The private self consciousness score of perpetrator victims was lower than that of the uninvolved ( P <0.05). Multivariate Logistic regression showed a negative correlation between private self awareness and perpetrator victims. Private self awareness might reduce the risk of teenagers becoming perpetrator victims ( OR=0.93, 95%CI =0.91-0.96). A positive correlation between public self awareness and perpetrator victims and public self awareness might increase the risk of adolescents becoming perpetrator victims ( OR=1.08, 95%CI = 1.06- 1.11).@*Conclusion@#Self awareness is related to different roles of school bullying, and higher public self awareness and lower private self awareness are important predictors of perpetrator victims of school bullying.
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The beneficial effects of hypoxic preconditioning are abolished in the diabetes. The present study was designed to investigate the protective effects and mechanisms of repeated episodes of whole body hypoxic preconditioning (WBHP) in db/db mice. The protective effects of preconditioning were explored on diabetesinduced vascular dysfunction, cognitive impairment and ischemia-reperfusion (IR)-induced increase in myocardial injury. Sixteen-week old db/db (diabetic) and C57BL/6 (non-diabetic) mice were employed. There was a significant impairment in cognitive function (Morris Water Maze test), endothelial function (acetylcholineinduced relaxation in aortic rings) and a significant increase in IR-induced heart injury (Langendorff apparatus) in db/db mice. WBHP stimulus was given by exposing mice to four alternate cycles of low (8%) and normal air O2 for 10 min each. A single episode of WBHP failed to produce protection; however, two and three episodes of WBHP significantly produced beneficial effects on the heart, brain and blood vessels. There was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) in response to 3 episodes of WBHP. Moreover, pretreatment with the BDNF receptor, TrkB antagonist (ANA-12) and NO synthase inhibitor (LNAME) attenuated the protective effects imparted by three episodes of WBHP. These pharmacological agents abolished WBHP-induced restoration of p-GSK-3β/GSK-3β ratio and Nrf2 levels in IR-subjected hearts. It is concluded that repeated episodes of WHBP attenuate cognitive impairment, vascular dysfunction and enhancement in IRinduced myocardial injury in diabetic mice be due to increase in NO and BDNF levels that may eventually activate GSK-3β and Nrf2 signaling pathway to confer protection.
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BACKGROUND@#Immune checkpoint inhibitor associated pneumonia (CIP) is a serious side effect of immune checkpoint inhibitors. There is a consensus on the treatment of acute phase of CIP, but the treatment of pulmonary interstitial fibrosis after the acute phase is still a clinical problem to be solved.@*METHODS@#The diagnosis and treatment of a non-small cell lung cancer (NSCLC) patient with immune checkpoint inhibitor associated pneumonia in the Stereotactic Radiotherapy Department of Qingdao Central Hospital were retrospectively analyzed, and literatures were reviewed.@*RESULTS@#A 70-year-old male patient was diagnosed with Poorly differentiated squamous cell carcinoma of left lung with mediastinal lymph node metastasis T3N3M0 stage IIIc, EGFR/ALK/ROS1/RAF negative, PD-L1 (22c3) immunohistochemistry negative. After the progression of first-line chemotherapy, the patient was diagnosed as immune checkpoint inhibitor associated pneumonia grade 3 during second-line monotherapy with Nivolumab. After initial high-dose glucocorticoid pulse therapy, the lung computed tomography (CT) imaging and clinical symptoms of the patients were partially relieved, and then pirfenidone (300 mg tid) was given orally for more than 11 months. During the treatment of pirfenidone, the CT imaging and clinical symptoms of the patients were significantly improved, and there were no other adverse reactions except grade 1 nausea. During this period, chemotherapy and Anlotinib was given concurrently with pirfenidone and showed good safety profile.@*CONCLUSIONS@#This case report is the first report of pirfenidone in the treatment of CIP, which provides a new idea for the clinical practice and research of CIP treatment.
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After participating in the student selection training and on-site refereeing of the clinical examination skills competition for college students in Sichuan-Chongqing region twice in succession, the author combined the on-site performance and competition results of the participating students with pre-match training experience and normal teaching experience. A comprehensive analysis found that the students' proficiency in basic testing skills, psychological quality and humanistic quality have an important impact on the results of the competition. Teachers should not only pay attention to the quality of basic skills training and theoretical knowledge teaching in practical teaching, but also pay attention to the cultivation of students' teamwork ability and good working habits. Therefore, the clinical laboratory skills competition has a strong leading role in promoting the education and teaching reform of medical laboratory technology and improving the quality of professional practice teaching. It is hoped that more medical colleges and universities will pay attention to and participate in it, and further promote the development of practical teaching of medical laboratory technology.
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In recent years， with the rapid development of traditional Chinese medicine industry in China， the efficacy of Chinese medicinals in treating disease and maintaining health has been increasingly recognized. Tripterygium wilfordii， a Chinese medicinal for expelling wind， dredging collaterals， removing dampness， and relieving pain， is commonly used for treating acute and chronic glomerulonephritis， rheumatoid arthritis， and other diseases. However， the frequent occurrence of adverse reactions has limited its wide application in clinical practice. The existing studies have gradually confirmed that T. wilfordii and its active ingredients exert the bidirectional effects on kidney function. This paper reviewed the related clinical applications and articles published in the past decades and summarized the material basis for its bidirectional effects and the specific action mechanisms in renal protection and renal damage. It was found that the main active ingredients in T. wilfordii were tripterygium glycosides and triptolide， which exerted the protective or toxic and side effects on kidney by regulating immunity， influencing mitogen-activated protein kinases （MAPK） pathway， and changing the expression and function of renal transporters. Besides， the roles of administration time， dosage， and body status in the exertion of protective or toxic and side effects by T. wilfordii were also discussed. The review aimed to provide new ideas for the research on the treatment of kidney diseases with T. wilfordii and its safety application.
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Objective:To evaluate the quality of the current foreign clinical practice guidelines (CPG) on obstetric venous thromboembolism (VTE), providing reference for standardizing the prevention and treatment of domestic VTE clinical practice.Methods:The GPGs for the management of obstetric VTE published abroad from inception to July 2020 were electronically searched. Two researchers independently evaluated the quality of the included guidelines in accordance with the internationally recognized guideline evaluation tool, AGREE Ⅱ.Results:A total of 12 guidelines, 2 recommendations and 1 consensus for obstetric VTE were included, covering 3 continents and 9 countries, and the published time span was 2009-2020. The standardized scores of the six domain (scope & purpose, stakeholder involvement, rigor of development, clarity of presentation, applicability and editorial independence) included in the guidelines were: 99.44%, 62.78%, 70.35%, 95.74%, 68.80% and 76.94% respectively, and the scores in each domain were ≥ 50.00%, indicating that the included CPGs were of good quality. Except for the domain scope & purpose, the ranges of the other five domains were ≥ 50.00%, suggesting that the quality of the CPGs differed significantly. Among the 15 included CPGs, 4 CPGs were level A (recommended), 11 CPGs were level B (recommended after being revised), and there was no CPG in level C (not recommended). The difference in the recommended content of obstetric VTE management mainly focused on the risk assessment, drug type, dosage and period.Conclusions:The overall quality of the CPGs for obstetric VTE management is high, while the quality of the CPGs varies greatly. In addition, there are differences in the recommended content of obstetric VTE management. More high-quality researches are required to provide evidence-based support for the improvement of the CPGs.
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The beneficial effects of hypoxic preconditioning are abolished in the diabetes. The present study was designed to investigate the protective effects and mechanisms of repeated episodes of whole body hypoxic preconditioning (WBHP) in db/db mice. The protective effects of preconditioning were explored on diabetesinduced vascular dysfunction, cognitive impairment and ischemia-reperfusion (IR)-induced increase in myocardial injury. Sixteen-week old db/db (diabetic) and C57BL/6 (non-diabetic) mice were employed. There was a significant impairment in cognitive function (Morris Water Maze test), endothelial function (acetylcholineinduced relaxation in aortic rings) and a significant increase in IR-induced heart injury (Langendorff apparatus) in db/db mice. WBHP stimulus was given by exposing mice to four alternate cycles of low (8%) and normal air O2 for 10 min each. A single episode of WBHP failed to produce protection; however, two and three episodes of WBHP significantly produced beneficial effects on the heart, brain and blood vessels. There was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) in response to 3 episodes of WBHP. Moreover, pretreatment with the BDNF receptor, TrkB antagonist (ANA-12) and NO synthase inhibitor (LNAME) attenuated the protective effects imparted by three episodes of WBHP. These pharmacological agents abolished WBHP-induced restoration of p-GSK-3β/GSK-3β ratio and Nrf2 levels in IR-subjected hearts. It is concluded that repeated episodes of WHBP attenuate cognitive impairment, vascular dysfunction and enhancement in IRinduced myocardial injury in diabetic mice be due to increase in NO and BDNF levels that may eventually activate GSK-3β and Nrf2 signaling pathway to confer protection.
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Objective: To explore the diagnostic significance of the combination of clinical and genetic detection of hereditary hemorrhagic telangiectasia (HHT) by analyzing the clinical and genetic diagnosis of a family with HHT. Methods: Medical history data of the probands and their family members were collected, and the sequence analyses of coding regions of ENG, ACVRL1, SMAD4 and GDF2 genes were performed by PCR-sequencing method, and a comprehensive diagnosis was made based on the clinical features and gene detection results. After the pathogenic gene variation was identified, 11 members of 3 generations of the family were tested for pathogenic gene mutation. Results: There was an ACVRL1 c.715_716delAG mutation in the proband and 9 other family members, which caused p.S239C. Based on the clinical and genetic findings, the 7 suspected were diagnosed and 2 asymptomatic patients were found to carry the mutation site. Conclusion: The combination of clinical features and gene detection can determine the etiology and classification of HHT, which is convenient for the early diagnosis and prevention of the disease.
Subject(s)
Humans , Activin Receptors, Type II/genetics , Endoglin/genetics , Genetic Testing , Mutation , Sequence Analysis , Telangiectasia, Hereditary Hemorrhagic/geneticsABSTRACT
Objective: To explore the effect of perioperative airway management based on the concept of enhanced recovery after surgery (ERAS) on the improvement of preoperative pulmonary function in patients with aspirin intolerance triad (AIT). Methods: Thirty patients with AIT (including 13 males and 17 females, aged from 29 to 75 years old) for sinus surgery from January 2018 to December 2019 were selected, 172 patients (including 105 males and 67 females, aged from 17 to 83 years old) with chronic rhinosinusitis with nasal polyps (CRSwNP) without lower airway disease were selected by random number table at the same period, and their clinical data and preoperative pulmonary function were analyzed and compared retrospectively. FEV1%pred<80% after bronchodilation test was considered as high risk for surgery. Preoperative evaluation and standardized drug intervention were applied in patients with pulmonary function abnormalities at risk for surgery, and improvement of preoperative pulmonary function and tolerability to general anesthesia surgery in the two groups were evaluated. All the statistical analyses were conducted using SPSS 22.0. Results: The main pulmonary function indexes (FEV1%pred, FEV1/FVC%pred, FEF50%pred, FEF75%pred, MMEF%pred) in AIT group decreased significantly than those in CRSwNP group (t values were 10.882, 10.506, 9.141, 10.182, 9.099, respectively, all P<0.001). At admission 86.7% (26/30) patients in the AIT group and 11.6% (20/172) patients in CRSwNP group had high surgical risk for lung function, with significantly difference (χ2 = 81.788, P<0.05); after 3 days with individualized drug intervention, 57.7% (15/26) patients in AIT group reached the standard for surgery, which was significantly less than 90.0% (18/20) patients in CRSwNP group (χ²=4.335,P<0.05); and after 6 days with drug intervention, the patients who reached the standard for surgery in pulmonary function accounted for 92.3% (24/26) in the AIT group and 100% (20/20) in the CRSwNP group. FEV1%pred in the two groups before surgery were significantly improved compared with those at admission respectively ((90.00±6.32)% vs. (64.79±13.60)%,t value was 10.110 in AIT group; (91.65±11.86)% vs. (76.40±9.35)%, t value was 9.346 in CRSwNP group; all P<0.05), and also FEV1/FVC%pred, FEF50%pred, FEF75%pred and MMEF%pred were all significantly improved (all P<0.05). Surgery was completed successfully in the two groups of patients with lung function meeting the surgical standard, and no intraoperative or postoperative airway adverse events occurred. Conclusion: AIT patients have high airway risk for sinus surgery due to poor pulmonary function. Standardized airway management based on the concept of ERAS can improve the pulmonary function of patients, and decrease the incidence of perioperative airway adverse events.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Airway Management , Aspirin , Enhanced Recovery After Surgery , Lung/surgery , Retrospective StudiesABSTRACT
Objective: To explore the application value of enhanced recovery after surgery (ERAS) with the multidisciplinary team (MDT) model in laryngeal cancer surgery. Methods: Eighty patients with laryngeal cancer treated in Department of Otorhinolaryngology Head and Neck Surgery of Yantai Yuhuangding Hospital from May 2016 to June 2017 were selected, including 76 males and 4 females, aged 45 to 75 years old. By random number table method, they were divided into ERAS group (40 cases) and control group (40 cases). Visual analogue scale (VAS), general comfort questionnaire (GCQ) and self-rating Anxiety Scale (SAS) were used to evaluate the symptoms and signs and psychological state of the two groups before and after operation. Mann Whitney U test was used for non-normal distribution data, and chi square test, Fisher exact probability method and covariance analysis were used for classification data. Repeated measures analysis of variance was used for the comparison of each group at different time points. Results: Two cases in the ERAS group and six cases in the control group withdrew from the study for some reason. Finally, 38 cases in the ERAS group and 34 cases in the control group were enrolled in this study. The postoperative pain scores of the two groups were the highest at 6 h after operation, and then gradually decreased. At different time points after operation, the pain scores of ERAS group were lower than those of the control group. At 24 h after operation, the pain relief degree of ERAS group was significantly higher than that of the control group, with a statistically significant difference (P<0.05). Compared to control group, ERAS group had lower preoperative thirst score [(0.15±0.36) vs. (4.29±1.17), Z=-7.695, P<0.001] and hunger score [(0.38±0.49) vs. (3.44±1.13), Z=-7.426, P<0.001]. The total number of postoperative adverse reactions (8 vs.16), oral feeding time [(4.06±4.42) d vs. (9.06±2.42) d] and postoperative hospital stay [(5.91±0.97) d vs. (11.03±2.11)d] in ERAS group were lower than those in control group (statistics 5.461, -4.558, -7.347, P<0.05), but there was no significant difference in postoperative catheter indwelling time and neck drainage tube indwelling time between the two groups (P>0.05). Before discharge, the comfort of ERAS group was significantly higher than that of control group [(60.37±8.78) vs. (50.38±8.08), Z=-4.370, P<0.001]. Before discharge, the anxiety level of ERAS group decreased, while that of the control group increased significantly, which was higher than that of ERAS Group [(59.12±6.43) vs. (52.62±6.25), Z=-4.179, P<0.001]. Conclusion: The application of multidisciplinary ERAS in laryngeal cancer surgery can improve preoperative hunger and thirst, postoperative pain and mental state, shorten the length of hospital stay and reduce postoperative adverse reactions.
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Aged , Female , Humans , Male , Middle Aged , Enhanced Recovery After Surgery , Laryngeal Neoplasms/surgery , Length of Stay , Perioperative Care , Postoperative PeriodABSTRACT
Physical fatigue often appears after stroke, which may influence rehabilitation training and recovery. This paper introduced the causes, clinical manifestations and related factors of physical fatigue after stroke. Energy metabolism increases after stroke, which may play a role in physical fatigue after stroke, and can be managed in some ways. It is needed to research the application of energy metabolism measure in physical fatigue after stroke further.
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Objective@#The purpose of this study was to analyze the impact of surgery of primary sites on stage IVB cervical cancer patients from a population-based database, the Surveillance, Epidemiology and End Results (SEER). @*Methods@#Propensity score matching was performed to minimize heterogeneity in patient between with-surgery group and without-surgery group. Clinicopathological characteristics were compared using the χ2 or Fisher's exact test. Survival analysis included the Kaplan-Meier method, log-rank test, and Cox proportional hazards model. @*Results@#Between 2010-2015, a total of 1,139 International Federation of Gynecology and Obstetrics (FIGO) stage IVB cervical cancer patients receiving chemoradiotherapy (CRT) were included in this retrospective study. Within post-matching cohort, the median duration of overall survival (OS) in stage IVB cervical cancer patients receiving CRT was 22 months. The overall 5-year survival rate was 25.7%. The increasing American Joint Committee on Cancer T stage (T1 vs. T2, p=0.033, hazard ratio [HR]=1.79, 95% confidence interval [CI]=1.05–3.05; T1 vs. T3, p=0.003, HR=2.20, 95% CI=1.31–3.67; T1 vs. T4, p=0.037, HR=2.75, 95% CI=1.06–7.12) and visceral metastasis (with vs. without, p=0.038, HR=1.60, 95% CI=1.03–2.49) was reported as independent risk factors of OS. Surgery of primary sites combined with CRT tended to prolong the survival of stage IVB cervical cancer patients (p<0.001, HR=0.36, 95% CI=0.21–0.61) compared with CRT, especially for patients without visceral metastasis (p=0.005, HR=0.31, 95% CI=0.14–0.70). @*Conclusions@#In conclusion, patients with stage IVB cervical cancer may achieve their best outcomes through CRT combined with surgery of primary sites. However, it deserves large scale prospective clinical trials to confirm.
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Objective To compare the pharmacokinetics of moxifloxacin (MXF) administered orally in the plasma and lung tissues of rats with pneumonia infected by Streptococcus pneumoniae (S.p) and normal rats. Methods To establish a model of Streptococcus pneumoniae pneumonia rats and normal rats. Moxifloxacin was administered by intragastric administration at 42 mg/kg. Microdialysis technique was used to sample the blood and lung tissues of pneumonia rats and normal rats to determine the free drug concentration of moxifloxacin in each sample, calculate the pharmacokinetic parameters, and compare the pharmacokinetics of oral moxifloxacin in pneumonia rats and normal rats. Results The t1/2 of moxifloxacin in the blood of normal rats and pneumonia rats were (5.27±4.38) h, (2.15±0.07) h (P>0.05), and Cmax were (4.94±0.98) μg/ml, respectively, (4.83±0.05) μg/ml (P>0.05), Clast_obs/Cmax were 0.02±0.03, 0.27±0.04 (P<0.05), AUC0-t were (22.33±2.02)μg/ml·h, (12.88±1.19)μg /ml·h (P<0.05), CL/F are (1.79±0.11)(mg/kg)/(μg/ml)·h, (2.49±0.26)(mg/kg)/(μg/ml)·h (P<0.05); Cmax of lung tissue of normal rats and pneumonia rats were (1.42±0.05) μg/ml, (4.84±0.02) μg/ml (P<0.05), t1/2 are (1.9±0.63)h, (3.39±0.79)h (P>0.05), AUMC are (11.93±5.14)μg/ml·h2, (107.01±25.39)μg/ml·h2 (P<0.05), AUC0-t are (3.06±1.0) 7μg/ml·h, (13.16±0.53)μg/ml·h (P<0.01). Conclusions ① Under the 400 mg/d dose condition, after intragastric administration of moxifloxacin, the concentration of free drugs in the blood and lung tissues is higher, far exceeding the minimum inhibitory concentration (MIC) and anti-drug resistance concentration (MPC), can effectively remove Streptococcus pneumoniae. ②The free concentration of moxifloxacin in the lung tissue of rats infected with Streptococcus pneumoniae is always higher than that of normal rats, and the Cmax is about 3.4 times that of normal rats. The penetration rate of moxifloxacin in lung tissue of pneumonia rats is significantly higher than that of normal rats.
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OBJECTIVE：To study the ecological suitability zoning of Astragalus membranaceus var. mongholicus in Dingxi city. METHODS ：Taking 1 001 batches of A. membranaceus var. mongholicus in Dingxi city as the investigation samples （each natural village with A. membranaceus var. mongholicus cultivation as the collection unit ），the longitude and latitude information of them were obtained from Dingxi economic crop technology promotion station ，and 55 environmental ecological factors （including climate，terrain，soil，etc.）were obtained from the Grid Database of Spatial Information of TCM Resources . Combined with the information of longitude ，latitude and environmental ecological factors ，the maximum entropy model （MaxEnt model ） was established with 75％ samples as the training set ，and the main ecological factors were screened out ，and 25％ samples were set as the validation set for model validation. Then the suitable growing areas of A. membranaceus var. mongholicus were divided by using ArcGIS. RESULTS ：Established MaxEnt model had good prediction （the area under the working characteristic curve of subjects in training set and verification set was 0.970 and 0.968）. Eight main ecological factors ，such as altitude ，precipitation and temperature ， were selected （the total contribution rate was 98.90％）. The comprehensive analysis found that the altitude was 1 800 to 2 650 m， the average precipitation in April was 25 to 50 mm，the lowest temperature of the coldest month was －16 to －8 ℃，the wettest monthly precipitation was 95 to 110 mm，and the seasonal variation of temperature was 70 to 80，the average temperature in December was －6 to －3 ℃ ，the average precipitation in October was 30 to 50 mm，and the average precipitation in December was 0 to 10 mm，which was the suitable environmental parameter for the growth of A. membranaceus var. mongholicus in Dingxi city. Based the results of ArcGIS analysis ，in Dingxi city ，A. membranaceus var. mongholicus was generally suitable for growth ；in the northwest of Lintao county ，the north of Anding district ，the south of Tongwei county ，a small area in the south of Longxi county and the south of Minxian county ，the border between Weiyuan county ，Zhangxian county and Minxian county ，A membranaceus var. mongholicus was not suitable for growth. CONCLUSIONS： Ther results of established model is in E-mail：961308817@qq.com line with the actual investigation ， can provide reference for the planting regional planning of A. membranaceus var. mongholicus in Dingxi city.
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