Single-Cell Mapping of Brain Myeloid Cell Subsets Reveals Key Transcriptomic Changes Favoring Neuroplasticity after Ischemic Stroke / 神经科学通报·英文版

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.

Implementation of surveillance,prevention and control of healthcare-asso-ciated infection in maternal and child healthcare institutions:A nation-wide investigation report / 中国感染控制杂志

Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24％of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66％,85.96％,80.77％,and 74.19％,respectively.51.22％MCH institutions adopted information surveillance system on HAI cases.94.31％MCH institutions carried out surveillance on hand hygiene compliance.Over 90％MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54％MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90％MCH insti-tutions established three-level pre-examination triage systems.86.18％set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50％.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.

High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors

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.

Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population / 中华耳鼻咽喉头颈外科杂志

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.

Analysis of TUBB4A gene variant in a patient with adolescent-onset hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum / 中华医学遗传学杂志

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.

Research progress in mechanism of action and application of mesenchymal stem cell-derived exosomes in repair of bone defects / 中华创伤杂志

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.

Three cases of obinutuzumab treatment for rituximab-resistant phospholipase A 2 receptor- associated membranous nephropathy / 中华肾脏病杂志

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.

Analysis of prognostic factors of extranodal NK/T-cell lymphoma treated with pegaspargase/L-asparaginase: a multicenter retrospective study / 中华血液学杂志

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.

Relationship between different roles of school bullying and self consciousness among adolescents / 中国学校卫生

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.

Tripterygium wilfordii in Treatment of Kidney Diseases and Its Toxic and Side Effect： A Review / 中国实验方剂学杂志

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.

Inspiration of clinical laboratory skills competition to the practical teaching of medical laboratory technology / 中华医学教育探索杂志

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.

Quality evaluation of clinical practice guidelines for obstetric venous thromboembolism based on AGREE Ⅱ / 中华妇产科杂志

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.

Whole body hypoxic preconditioning-mediated multiorgan protection in db/db mice via nitric oxide-BDNF-GSK-3β-Nrf2signaling pathway

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.

Application of enhanced recovery after surgery in laryngeal cancer surgery with multi-disciplinary team / 中华耳鼻咽喉头颈外科杂志

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.

Perioperative airway management based on enhanced recovery after surgery for improvement of preoperative pulmonary function in patients with aspirin intolerance triad / 中华耳鼻咽喉头颈外科杂志

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.

Clinical genetic analysis and diagnosis of a family with hereditary hemorrhagic telangiectasia / 中华耳鼻咽喉头颈外科杂志

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.

A Case Report of Checkpoint Inhibitor Pneumonitis Caused by PD-1 Antibody-Safety and Effectiveness of Pirfenidone / 中国肺癌杂志

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.

Whole body hypoxic preconditioning-mediated multiorgan protection in db/db mice via nitric oxide-BDNF-GSK-3β-Nrf2signaling pathway

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.

Advance of Energy Metabolism in Post-stroke Fatigue (review) / 中国康复理论与实践

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.

Comparative of pharmacokinetic of moxifloxacin in the plasma and lung tissues of pneumonia rats and normal rats / 药学实践杂志

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.