Role of Bß1 overexpression in the pathogenesis of SCA12.

BACKGROUND: Spinocerebellar ataxia type 12 (SCA12) is a neurodegenerative disease caused by a CAG/CTG repeat expansion at the PPP2R2B locus. OBJECTIVE: We investigated how the CAG repeat expansion within the PPP2R2B 7B7D transcript influences the expression of Bß1 and a potential protein containing a long polyserine tract. METHODS: Transcript and protein expression were measured using quantitative PCR (qPCR) Role of Bß1 overexpression in the pathogenesis of SCA12 and Western blot, respectively, in an SK-N-MC cell model that overexpresses the full-length PPP2R2B 7B7D transcript. The apoptotic effect of a protein containing a long polyserine tract on SK-N-MC cells was evaluated using caspase 3/7 activity. RESULTS: The CAG repeat expansion increases the expression of the PPP2R2B 7B7D transcript, as well as Bß1 protein, in an SK-N-MC cell model in which the full-length PPP2R2B 7B7D transcript is overexpressed. The CAG repeat expansion within the 7B7D transcript is translated into a long polyserine tract that triggers apoptosis in SK-N-MC cells. CONCLUSIONS: The SCA12 mutation leads to overexpression of PPP2R2B Bß1 and to expression of a protein containing a long polyserine tract; both these effects potentially contribute to SCA12 pathogenesis. © 2024 International Parkinson and Movement Disorder Society.

Bidirectional Transcription at the PPP2R2B Gene Locus in Spinocerebellar Ataxia Type 12.

BACKGROUND: Spinocerebellar ataxia type 12 (SCA12) is a neurodegenerative disease caused by expansion of a CAG repeat in the PPP2R2B gene. OBJECTIVE: In this study, we tested the hypothesis that the PPP2R2B antisense (PPP2R2B-AS1) transcript containing a CUG repeat is expressed and contributes to SCA12 pathogenesis. METHODS: Expression of PPP2R2B-AS1 transcript was detected in SCA12 human induced pluripotent stem cells (iPSCs), iPSC-derived NGN2 neurons, and SCA12 knock-in mouse brains using strand-specific reverse transcription polymerase chain reaction. The tendency of expanded PPP2R2B-AS1 (expPPP2R2B-AS1) RNA to form foci, a marker of toxic processes involving mutant RNAs, was examined in SCA12 cell models by fluorescence in situ hybridization. The apoptotic effect of expPPP2R2B-AS1 transcripts on SK-N-MC neuroblastoma cells was evaluated by caspase 3/7 activity. Western blot was used to examine the expression of repeat associated non-ATG-initiated translation of expPPP2R2B-AS1 transcript in SK-N-MC cells. RESULTS: The repeat region in the PPP2R2B gene locus is bidirectionally transcribed in SCA12 iPSCs, iPSC-derived NGN2 neurons, and SCA12 mouse brains. Transfected expPPP2R2B-AS1 transcripts induce apoptosis in SK-N-MC cells, and the apoptotic effect may be mediated, at least in part, by the RNA secondary structure. The expPPP2R2B-AS1 transcripts form CUG RNA foci in SK-N-MC cells. expPPP2R2B-AS1 transcript is translated in the alanine open reading frame (ORF) via repeat-associated non-ATG translation, which is diminished by single-nucleotide interruptions within the CUG repeat and MBNL1 overexpression. CONCLUSIONS: These findings suggest that PPP2R2B-AS1 contributes to SCA12 pathogenesis and may therefore provide a novel therapeutic target for the disease. © 2023 International Parkinson and Movement Disorder Society.

[Intelligent intensive care unit makes medicine more accessible].

In the past half century, critical care medicine has made rapid development, and the survival rate of critically ill patients has significantly improved. However, what does not match the rapid development of the specialty is that the infrastructure of intensive care unit (ICU) has gradually appeared weaknesses and the development of humanistic care in ICU has lagged. Accelerating the digital transformation of the medical industry will help to improve the existing difficulties. The application of 5G and artificial intelligence (AI) technology to build an intelligent ICU,focusing on improving patients' comfort by strengthening humanistic care,while solve the shortcomings of the critical care dimension, such as lack of human and material resources, low alarm accuracy, insufficient response speed and ability, to better meet the needs of society and improve the level of medical services and humanistic care for critical diseases. We will review the development of ICU history, clarify the necessity of intelligent ICU construction and the core issues to be solved after the construction of intelligent ICU. Three components of the construction of intelligent ICU will be needed: intelligent space and environment management, intelligent equipment and goods management, intelligent monitoring and diagnosis and treatment. Finally, the people-oriented diagnosis and treatment concept will be realized through intelligent ICU.

[Effect of hyperandrogenism on pregnancy outcomes in women with polycystic ovary syndrome undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer].

Objective: To explore the effects of hyperandrogenism (HA) on pregnancy outcomes in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). Methods: A retrospective study was conducted on infertile women with PCOS undergoing IVF/ICSI-ET from January 2017 to June 2021 in our center. Patients were divided into HA group and NON-HA group according to the levels of testosterone. Propensity score matching (PSM) was used to balance the influence of female age and IVF/ICSI-ET for patients with gonadotropin-releasing hormone (GnRH)antagonist protocol and GnRH agonist protocol, separately. After the PSM procedure, 191 cases in HA group and 382 cases in NON-HA group, were included. Hormone levels and pregnancy outcomes were compared in the two groups. Results: The female age was comparable in two groups [HA: (29.6±3.7) vs NON-HA: (29.5±3.6), P=0.665]. The basal luteinizing hormone [(10.82±6.73) vs (7.76±5.30) IU/L], testosterone [(3.27±0.97) vs (1.60±0.59) nmol/L], free androgen index (7.13 vs 2.77), anti-mullerian hormone [(11.37±5.74) vs (9.67±4.67) ng/ml], fasting glucose [(5.18±0.49) vs (5.06±0.42) mmol/L], 1h glucose [(9.34±2.42) vs (7.99±2.21) nmol/L], 2 h glucose [(7.66±2.17) vs (6.64±1.84) nmol/L], 2 h insulin [(129.81±145.49) vs (97.51±86.92) mU/L], total cholesterol [(5.35±0.89) vs (4.92±0.92) mmol/L], triglycerides [(1.55±1.28) vs (1.33±0.77) mmol/L], and low density lipoprotein cholesterol levels [(3.38±0.66) vs (3.14±0.71) mmol/L] were significantly higher in HA group, compared with NON-HA group (P<0.05). The initiated gonadotropin dose was higher in HA group than that in NON-HA group [(126.96±33.65) vs (137.60±38.12) U, P=0.001], but moderate-severe ovarian hyperstimulation syndrome (OHSS) rate was similar in two groups (P>0.05). The rates of implantation, clinical pregnancy, miscarriage, and live birth were comparable between the two groups (P>0.05). Also, in the subgroups, the rates of implantation, clinical pregnancy, live birth, and miscarriage were similar in HA group and NON-HA group. Conclusions: The risks of hormonal abnormality and glucose-lipid metabolic disorder were higher in PCOS women with HA, whereas satisfactory pregnancy outcomes could be achieved under proper ovarian stimulation undergoing IVF/ICSI-ET.

[Clinical features and related factors of invasive pulmonary aspergillosis in patients with acute exacerbation of chronic obstructive pulmonary disease].

Objective: To study the clinical features and related factors of invasive pulmonary aspergillosis (IPA) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: This retrospective study enrolled patients hospitalized for AECOPD in ten tertiary hospitals of China from September 2017 to July 2021. AECOPD patients with IPA were included as case group, AECOPD patients without IPA were randomly selected as control group from the same hospitals and same hospitalization period as the patients with IPA using the random function in the software of Microsoft Excel 2003, at a ratio of 2∶1. The clinical characteristics, treatment and outcome were compared between the two groups. Binary logistic regression model was used to analyze the factors associated with IPA in AECOPD patients. Results: A total of 14 007 inpatients with AECOPD were included in this study, and 300 patients were confirmed to have IPA, with an incidence rate of 2.14%. According to the above matching method, 600 AECOPD patients without aspergillus infection were enrolled as the control group. The age of the case group and the control group were (72.5±9.7) and (73.5±10.3) years old, with 78.0%(n=234) male and 76.8%(n=461) male, respectively. There were no significant differences in age and gender composition between the two groups (all P>0.05). The prognosis of case group was significantly worse than that of the control group, with longer hospital stay [M(Q1,Q3)], [14 (10-20) d vs 11 (8-15) d, P<0.001], higher ICU admission rate [16.3% (49 case) vs 10.0% (60 case), P=0.006], higher in-hospital mortality [4.0% (12 cases) vs 1.3% (8 cases), P=0.011], and higher hospitalization costs (28 000 ¥ vs 13 700 ¥, P<0.001). The smoking index of the case group and proportions of patients with diabetes mellitus, chronic pulmonary heart disease in the case group were significantly higher than those in control group (all P<0.05). In terms of clinical features, the proportions of patients with cough, expectoration, purulent sputum, hemoptysis and fever in the case group were higher than those in the control group, the serum albumin was significantly lower than that in the control group, and the proportions of patients with bronchiectasis and pulmonary bullae on imaging were significantly higher than those in the control group (all P<0.05). Diabetes (OR=1.559, 95%CI: 1.084-2.243), chronic pulmonary heart disease (OR=1.476, 95%CI: 1.075-2.028), bronchiectasis (OR=1.506, 95%CI: 1.092-2.078), pulmonary bullae (OR=1.988, 95%CI: 1.475-2.678) and serum albumin<35 g/L (OR=1.786, 95%CI: 1.325-2.406) were the related factors of IPA in patients with AECOPD. Conclusions: The incidence of IPA in AECOPD patients is relatively high and the prognosis of these patients is worse. Diabetes, chronic pulmonary heart disease, bronchiectasis, pulmonary bulla, hypoproteinemia are the related factors of IPA in patients with AECOPD.

[Clinical update in critical care of pulmonary medicine 2022].

In this review, we outlined the clinical studies in critical care field of pulmonary medicine from October 1, 2021 to September 30, 2022. For critically ill patients, frailty before disease onset was a predictor of mortality with increasing ICU length of stay, and the complaints of dyspnea in intubated phase was independently associated with posttraumatic stress disorder. Compared with transbronchial lung biopsy (TBLB) for patients with acute hypoxemic respiratory failure, transbronchial lung cryobiopsy (TBLC) had a positive significance to in leading to an increased chance of establishing a more accurate diagnosis, which could significantly improve the patients' prognosis. M-ROSE (microbiological rapid on-site evaluation) had high diagnostic value for lower respiratory tract pathogens, and the application of M-ROSE in the ICU could contribute to promoting a decrease in patients' inflammation levels and reducing the mortality of patients with invasive mechanical ventilation. EIT (electrical impedance tomography), DPL (transpulmonary driving pressure) and DPaw (airway driving pressure) had excellent positive values on dynamic assessment, guiding individualized respiratory support and prognostic evaluation. In critically ill hospitalized patients with COVID-19 who had received invasive mechanical ventilation or extracorporeal membrane oxygenation, treatment with baricitinib compared with placebo (in combination with standard of care, including corticosteroids) might reduce mortality. Delayed antimicrobial treatment significantly increased the incidence of severe infection and the mortality of shock patients, however, timing of antimicrobial therapy and control of the source of infection was critical. NIV (non-invasive ventilation) alternating with high-flow nasal oxygen immediately after extubation significantly decreased the risk of reintubation and death compared with high-flow nasal oxygen alone in obese or overweight patients at high risk of extubation failure. The effect of Pes-guided positive end-expiratory pressure (PEEP), compared with empirical high PEEP, was associated with lower mortality for more severe acute respiratory distress syndrome (ARDS) ventilated patients (APACHE Ⅱ>27.5). Prone-positioning during veno-venous extracorporeal membrane oxygenation was safe and effective and was associated with a higher probability of surviving and being weaned-off extracorporeal membrane oxygenation at 90 days. Therefore, individualized respiratory support strategies based on dynamic monitoring and assessment were essential for critically ill patients.

[Intelligent intensive care unit design:will it be accessible in the future].

ICU is an essential location for critically ill patients to receive comprehensive diagnosis and treatment. However, the high intensity of ICU clinical work, the difficulty of diagnosis and treatment, and the poor humanistic environment require us to accelerate the pace of ICU reform. Therefore, the use of advanced technology to create an intelligent ICU department is imperative. The modern ICU is rich in electronic data and can collect a large amount of patient data during routine care, making it an ideal place to deploy intelligent digital platforms. The vast amounts of data generated by monitoring systems and electronic medical records provide fertile ground for the development of more accurate predictive models, better Clinical Decision Support System and more personalized diagnosis and treatment. At the same time, a well-designed and well-arranged ICU department will greatly enhance the patient's sense of occupancy, as well as increase the professional pride and sense of belonging. Therefore, the establishment of an intelligent ICU department is the only way for ICU to enter the fast lane of development, which will also have a profound impact on the development of ICU.

RNA Toxicity and Perturbation of rRNA Processing in Spinocerebellar Ataxia Type 2.

BACKGROUND: Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease caused by expansion of a CAG repeat in Ataxin-2 (ATXN2) gene. The mutant ATXN2 protein with a polyglutamine tract is known to be toxic and contributes to the SCA2 pathogenesis. OBJECTIVE: Here, we tested the hypothesis that the mutant ATXN2 transcript with an expanded CAG repeat (expATXN2) is also toxic and contributes to SCA2 pathogenesis. METHODS: The toxic effect of expATXN2 transcripts on SK-N-MC neuroblastoma cells and primary mouse cortical neurons was evaluated by caspase 3/7 activity and nuclear condensation assay, respectively. RNA immunoprecipitation assay was performed to identify RNA binding proteins (RBPs) that bind to expATXN2 RNA. Quantitative PCR was used to examine if ribosomal RNA (rRNA) processing is disrupted in SCA2 and Huntington's disease (HD) human brain tissue. RESULTS: expATXN2 RNA induces neuronal cell death, and aberrantly interacts with RBPs involved in RNA metabolism. One of the RBPs, transducin ß-like protein 3 (TBL3), involved in rRNA processing, binds to both expATXN2 and expanded huntingtin (expHTT) RNA in vitro. rRNA processing is disrupted in both SCA2 and HD human brain tissue. CONCLUSION: These findings provide the first evidence of a contributory role of expATXN2 transcripts in SCA2 pathogenesis, and further support the role of expHTT transcripts in HD pathogenesis. The disruption of rRNA processing, mediated by aberrant interaction of RBPs with expATXN2 and expHTT transcripts, suggest a point of convergence in the pathogeneses of repeat expansion diseases with potential therapeutic implications. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

[Establishment and evaluation of a model for predicting ISUP pathological grade≥2 before radical prostatectomy].

Objective: Based on the 2014 version of the International Association of Urological Pathology (ISUP) pathological classification standards, a prediction model that can predict the pathological classification of ISUP ≥2 in patients with prostate cancer (PCa) before radical prostatectomy (RP) was established and evaluated. Methods: The clinical data of 171 patients who had undergone RP from January 2017 to September 2020 in the Second Affiliated Hospital of Soochow University and obtained postoperative pathological results of all specimens were retrospectively collected. The patients were 46-83 (70±7) years old. For patients with RP ISUP pathologic stage as the gold standard, according to the pathological grading is level 2 or higher is divided into two groups(42 patients with ISUP grade=1 and 129 patients with ISUP grade ≥2). the predictors of ISUP pathology grade ≥2 after RP were screened by logistics regression analysis, predictive models were established and ROC curves were used to evaluate the efficacy of each model in diagnosing RP with pathological grade ≥2, and comparisons were conducted by DeLong test. Results: Compared with patients with ISUP grade=1, patients with ISUP grade≥2 had higher prostate specific antigen (PSA) and prostate specific antigen density (PSAD) (14.21(8.57, 24.98)ng/ml vs 7.98(5.41, 12.54)ng/ml, 0.33(0.20, 0.74)µg.L-1.ml-1 vs 0.16(0.12, 0.24)µg.L-1.ml-1), lower prostate volume (PV) (48.62(34.17,73.99)ml vs 38.94(28.15,54.84)ml)(all P<0.05). Multi-parameter magnetic resonance imaging (mp-MRI) prostate imaging and reporting system (PI-RADS) score, the positive ratio of puncture needles and the pathological grade of puncture ISUP were also significantly different between the two groups (all P<0.05). The combined mp-MRI PI-RADS score (OR=3.337, 95%CI: 1.990-5.593, P<0.001) and puncture ISUP pathological grading (OR=4.041, 95%CI: 1.960-8.334, P<0.001) had the highest diagnostic efficacy for pathological grading ≥2 after RP (AUC=0.916, P<0.05). Conclusion: The combined mp-MRI PI-RADS score and puncture ISUP pathological grading had the highest diagnostic efficacy for pathological grading ≥2 after RP.

[Risk factors associated with in-hospital mortality in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease: a multicenter retrospective study].

Objective: To investigate the risk factors associated with in-hospital mortality in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods: A total of 6 668 patients hospitalized for AECOPD in seven tertiary hospitals from September 2017 to January 2021 were consecutively included, and clinical data related to medical history, laboratory tests, treatment and prognosis were collected, and patients were divided into death group and survival group according to whether they died during hospitalization. After univariate analysis, multivariate logistic regression analysis was then performed to explore the independent risk factors related to in-hospital mortality. Results: Among 6 668 patients hospitalized for AECOPD, 128 patients experienced in-hospital death, with a mortality rate of 1.9%. The mean age of the death group was (81±9) years, which was significantly older than that of the survival group ((72±11) years P<0.001). The proportion of patients in the AECOPD in-hospital death group with a combination of prolonged bed rest, hypertension, myocardial infarction within 3 months, cardiac insufficiency, chronic pulmonary heart disease, pneumonia, type 2 diabetes, venous thromboembolism (VTE), and chronic renal insufficiency was also significantly higher than in the survival group (all P<0.05) The median length of stay in the in-hospital death group was 18 d, which was significantly longer than that in the survival group (9 d, P<0.001), and the proportion of patients admitted to the ICU, receiving invasive mechanical ventilation and non-invasive mechanical ventilation was also significantly higher than that in the survival group (all P<0.05). The white blood cell count, glutamic transaminase, blood creatinine, calcitoninogen, C-reactive protein, D-dimer, N-terminal B-type natriuretic and Pseudomonas aeruginosa infection rates were significantly higher than those in the survival group (all P<0.05). Multifactorial analysis showed that age>80 years (OR=3.82, 95%CI 2.36 to 6.18, P<0.001), prolonged bed rest (OR=2.95, 95%CI: 1.79 to 4.86, P<0.001), chronic pulmonary heart disease (OR=1.85, 95%CI: 1.14 to 3.00, P=0.012), and pneumonia (OR=2.75, 95%CI: 1.65 to 4.60, P<0.001), invasive mechanical ventilation (OR=7.33, 95%CI: 4.40 to 12.21, P<0.001), noninvasive mechanical ventilation (OR=3.73, 95%CI: 2.30 to 6.04, P<0.001), anemia (OR=2.03. 95%CI: 1.21 to 3.42, P=0.008), and calcitoninogen>0.5 ng/ml (OR=2.38, 95%CI: 1.41 to 4.02, P=0.001) were independent risk factors for in-hospital mortality in patients with AECOPD. Conclusion: Advanced age (>80 years), prolonged bed rest, chronic pulmonary heart disease, pneumonia, invasive mechanical ventilation, noninvasive mechanical ventilation, anemia, and calcitoninogen>0.5 ng/ml were independent risk factors for in-hospital mortality in patients hospitalized with AECOPD.

[Clinical characteristics of 21 infertile women with non-classic 21-hydroxylase deficiency].

Objective: To investigate the clinical features of infertile women with non-classic 21-hydroxylase deficiency (21-OHD). Methods: The study enrolled 21 infertile women with non-classic 21-OHD in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2009 to December 2018. The clinical presentation, endocrine hormone, glucolipid metabolism and treatment outcome were retrospectively analyzed. The diagnosis of non-classic 21-OHD was comprehensively based on clinical and hormonal characteristics. Results: Among 21 cases, the age was (29.9±2.9) years, the mean age at menarche was (13.6±2.0) years, body mass index was (22.1±2.9) kg/m2, and 38% (8/21) had oligomenorrhea. Hirsutism was diagnosed in 3 cases (14%, 3/21). Clitoromegaly was seen in 14% (3/21) and polycystic ovarian morphology was found in 33% (7/21) of the patients. The mean serum level of basal progesterone was (11.3±21.0) nmol/L, with 48% (10/21) having high basal progesterone level; after therapy by glucocorticoid, the level of progesterone was (1.9±2.0) nmol/L. Serum 17-hydroxyprogesterone concentration was (66.4±123.6) nmol/L; after therapy by glucocorticoid, it was (2.4±1.8) nmol/L. In the study increased testosterone, androstenedione and dehydroepiandrosterone sulfate were present in 62% (13/21), 52% (11/21) and 43% (9/21), respectively; and 52% (11/21) of patients manifested androgen excess and basal progesterone elevation; androgen levels decreased after therapy by glucocorticoid. The pregnancy rate was 76% (16/21). Out of 19 pregnancies, 6/19 ended in spontaneous miscarriages. Conclusions: Infertile women with non-classic 21-OHD are characterized by hyperandrogenism and basal progesterone elevation, whereas gonad axis disorder is not apparent. After no response to conventional therapy, adult infertile women with non-classic 21-OHD could achieve a desirable pregnancy outcome with proper treatment of glucocorticoid.

Species Identification of Sarcosaprophagous Flies Based on Vein Digital Image Analysis.

ABSTRACT: Objective To identify species of common sarcosaprophagous flies based on digital image analysis of veins, in order to provide new idea for fast and accurate species identification of sarcosaprophagous flies in forensic entomology. Methods Random trapping of 226 male and female sarcosaprophagous flies that comprised of 7 common species, including Sarcophaga peregrina, Parasarcophaga ruficornis, Sarcophaga dux, Seniorwhitea reciproca, Bercaea cruentata, Aldrichina grahami, and Synthesiomysia nudiseta with carrion in the field was conducted. The 17 landmarks on the right wing of each fly were digitally processed and the images were analyzed. The effects of allometry were evaluated using a permutation test. Wing shape variations among 7 sarcosaprophagous fly species and female species was analyzed using canonical variate analysis （CVA）. Additionally, cross-validation test was used to evaluate the reliability of classification. Results Among 7 sarcosaprophagous fly species and female species, the effect of allometry had statistical significance （P<0.05）. The CVA results showed that among 7 sarcosaprophagous fly species and female species, differences in the wing shape were significant, and the first two canonical variates accounted for 82.9% and 84.1% of the total variation of vein shape. Vein digital image analysis can be used to separate the 7 common sarcosaprophagous flies, with an overall species identification accuracy of 81.2%-100.0%, and with a species identification accuracy of 75.0%-100.0% to distinguish the female flies of the 7 sarcosaprophagous flies species. Conclusion Vein digital image analysis is a relatively convenient and reliable method for identification of insect species, which can be used for species identification of common sarcosaprophagous flies.

[A pathological report of three COVID-19 cases by minimal invasive autopsies].

Objective: To investigate the pathological characteristics and the clinical significance of novel coronavirus (2019-nCoV)-infected pneumonia (termed by WHO as coronavirus disease 2019, COVID-19). Methods: Minimally invasive autopsies from lung, heart, kidney, spleen, bone marrow, liver, pancreas, stomach, intestine, thyroid and skin were performed on three patients died of novel coronavirus pneumonia in Chongqing, China. Hematoxylin and eosin staining (HE), transmission electron microcopy, and histochemical staining were performed to investigate the pathological changes of indicated organs or tissues. Immunohistochemical staining was conducted to evaluate the infiltration of immune cells as well as the expression of 2019-nCoV proteins. Real time PCR was carried out to detect the RNA of 2019-nCoV. Results: Various damages were observed in the alveolar structure, with minor serous exudation and fibrin exudation. Hyaline membrane formation was observed in some alveoli. The infiltrated immune cells in alveoli were majorly macrophages and monocytes. Moderate multinucleated giant cells, minimal lymphocytes, eosinophils and neutrophils were also observed. Most of infiltrated lymphocytes were CD4-positive T cells. Significant proliferation of type Ⅱ alveolar epithelia and focal desquamation of alveolar epithelia were also indicated. The blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes. Hyaline thrombi were found in a minority of microvessels. Focal hemorrhage in lung tissue, organization of exudates in some alveolar cavities, and pulmonary interstitial fibrosis were observed. Part of the bronchial epithelia were exfoliated. Coronavirus particles in bronchial mucosal epithelia and type Ⅱ alveolar epithelia were observed under electron microscope. Immunohistochemical staining showed that part of the alveolar epithelia and macrophages were positive for 2019-nCoV antigen. Real time PCR analyses identified positive signals for 2019-nCoV nucleic acid. Decreased numbers of lymphocyte, cell degeneration and necrosis were observed in spleen. Furthermore, degeneration and necrosis of parenchymal cells, formation of hyaline thrombus in small vessels, and pathological changes of chronic diseases were observed in other organs and tissues, while no evidence of coronavirus infection was observed in these organs. Conclusions: The lungs from novel coronavirus pneumonia patients manifest significant pathological lesions, including the alveolar exudative inflammation and interstitial inflammation, alveolar epithelium proliferation and hyaline membrane formation. While the 2019-nCoV is mainly distributed in lung, the infection also involves in the damages of heart, vessels, liver, kidney and other organs. Further studies are warranted to investigate the mechanism underlying pathological changes of this disease.

Neutrophil-to-Lymphocyte Ratio Improves the Accuracy and Sensitivity of Pneumonia Severity Index in Predicting 30-Day Mortality of CAP Patients.

BACKGROUND: The pneumonia severity index (PSI) scoring system is one of the tools used to evaluate and predict the prognosis of patients with community-acquired pneumonia (CAP). Although PSI has been widely used in clinical studies of pneumonia, it is still rare to combine it with blood indexes to predict the prognosis of pneumonia. Neutrophil-to-lymphocyte ratio (NLR) is a promising candidate predictor of mortality in CAP patients. The aim of this study was to investigate the efficacy of pneumonia severity index combined with NLR in predicting 30-day mortality in CAP patients. METHODS: We conducted a retrospective study. We analyzed data on 400 non-immune individuals over the age of 18 in this study. All patients received blood routine measurement and PSI score calculation after admission. The primary outcome measures were mortality and survival in CAP patients. The sensitivity and specificity of PSI score, NLR, and the combination of PSI score and NLR in predicting 30-day mortality were assessed using the subject operating characteristic curve (ROC). RESULTS: Data from 400 patients were analyzed, in which the 30-day mortality was 10.5% (42/400). The AUC of NLR and PSI in predicting 30-day mortality of CAP patients were 0.81 (95% CI 0.73 - 0.89) and 0.94 (95% CI 0.90 - 0.98), respectively, with statistically significant differences (p = 0.00). The sensitivity and specificity of NLR were 0.80 and 0.7, respectively. The sensitivity and specificity of PSI were 0.78 and 0.94, respectively. The combined AUC of the two indicators for predicting death in CAP patients was 0.95 (95% CI 0.92 - 0.99), and the sensitivity and specificity were 0.85 and 0.94, respectively. CONCLUSIONS: Neutrophil-to-lymphocyte ratio improves the accuracy and sensitivity of the pneumonia severity index in predicting 30-day mortality of CAP patients.

TRIM31 promotes proliferation, invasion and migration of glioma cells through Akt signaling pathway.

This study is intended to investigate the role of Tripartite Motif (TRIM) 31 in glioma. Immunohistochemistry and western blot analysis showed that TRIM31 was overexpressed in high-grade glioma tissues. Univariate survival analysis indicated that high expression of TRIM31 was related to short survival time of glioma patients. Multivariate survival analysis demonstrated that TRIM31 was an independent prognostic factor for glioma patients. In addition, through the experiments on glioma cell lines, we found that after silencing or overexpressing TRIM31 expression, the proliferation, invasion and migration of glioma cells could be downregulated or upregulated through Akt signaling pathway. In short, our study suggests that TRIM31 may be an effective target for glioma intervention.

[Analysis of lens of 1720 medical application radiology workers in Hangzhou].

Objective: To analyze the lens opacity of some hospitals in Hangzhou to provide evidence for further improvement of radiation protection. Methods: Physical examination data of 1720 radiological workers who underwent occupational disease physical examination in our hospital on January1, 2016and December 31, 2017 were collected. Lens turbidity, gender, age, type of work, radiological working age and other influencing factors were statistically analyzed, and logistic regression analysis was used for multipactor analysis. Results: A total of 112 cases of lens turbidity (turbidity rate 6.51%) , after lens turbidity, subcapsular majority (64 cases (57.14%) ) ; lens turbidity increased with age, and showed an increasing trend of radiation working age; the lens turbidity rate was different in different types of work, including nuclear medicine (23.33%) 、radiology (6.76%) 、interventional radiology (6.06%) 、dental radiology (4.26%) and radiotherapy (4.21%) . Type of work、age and length of service are risk factors for lens opacity; Age and type of work were independent risk factors for lens opacity. Conclusion: The turbidity of lens of radiologcial workers is related to age and workering age. Radiological workers engaged in nuclear medicine should strictly strengthen radiation protection.

Identification and functional analysis of a novel chorion protein essential for egg maturation in the brown planthopper.

In insect eggs, the chorion has the essential function of protecting the embryo from external agents during development while allowing gas exchange for respiration. In this study, we found a novel gene, Nilaparvata lugens chorion protein (NlChP), that is involved in chorion formation in the brown planthopper, Nilaparvata lugens. NlChP was highly expressed in the follicular cells of female adult brown planthoppers. Knockdown of NlChP resulted in oocyte malformation and the inability to perform oviposition, and electron microscopy showed that the malformed oocytes had thin and rough endochorion layers compared to the control group. Liquid chromatography with tandem mass spectrometry analysis of the eggshell components revealed four unique peptides that were matched to NlChP. Our results demonstrate that NlChP is a novel chorion protein essential for egg maturation in N. lugens, a hemipteran insect with telotrophic meroistic ovaries. NlChP may be a potential target in RNA interference-based insect pest management.

Role of Autophagy in Ovarian Cryopreservation by Vitrification.

BACKGROUND: Ovarian cryopreservation by vitrification and transplantation are useful methods to recover female fertility after radiotherapy and chemotherapy. As type II programmed cell death, autophagy plays important roles in ovarian follicle development, ovarian follicle atresia and anti-stress injury. OBJECTIVE: The potential role of autophagy in ovarian vitrification was investigated. MATERIALS AND METHODS: Mouse ovaries were cryopreserved by vitrification, and autophagy was treated, after which the ovarian histology was checked, and ovarian follicles were counted. The apoptotic rate was detected by TUNEL, and apoptotic molecular marker cleaved caspase-3 was checked by immunofluorescence and western blot analysis. RESULTS: Our results suggested that autophagy was increased in the process of vitrification compared with the fresh ovaries (p<0.05). The number of primordial follicles was decreased through inhibiting or over-activating the autophagy by autophagy inhibitor or activator (p<0.05). However, the number of primary follicles, antral follicles and atretic follicles was not significantly different compared with vitrified/warmed groups. The apoptotic rate was significantly increased in the vitrified/warmed, autophagy-inhibiting and over-activating groups compared with the fresh group (p<0.05), and this result was further confirmed by western blot analysis. CONCLUSIONS: Taken together, autophagy was activated in the ovarian cryopreservation by vitrification and plays a role in a natural adaptive response to cold stress in ovarian cryopreservation by vitrification.

[The clinical significance of microcirculation and oxygen metabolism evaluation in acute kidney injury assessment in patients with septic shock after resuscitation].

Objective: To evaluate the value of microcirculation and oxygen metabolism evaluation (MicrOME) in acute kidney injury(AKI) evaluation in patients with septic shock after resuscitation. Methods: Consecutive patients with septic shock after resuscitation and mechanical ventilation were enrolled from October 2016 to February 2017 in ICU at Peking Union Medical College Hospital.Patients were divided into 3 groups based on 10 min transcutaneous oxygen challenge test transcutaneous partial pressure of oxygen(PtcO(2))and venoarterial pressure of carbon dioxide difference (Pv-aCO(2)) /arteriovenous O(2) content difference (Ca-vO(2)) by blood gas analysis, i.e. group A [ΔPtcO(2)>66 mmHg(1 mmHg=0.133 kPa) and Pv-aCO(2)/Ca-vO(2)≤1.23], group B (ΔPtcO(2)≤66 mmHg), group C (ΔPtcO(2)>66 mmHg and Pv-aCO(2)/Ca-vO(2)>1.23). Heart rate,mean arterial pressure,central venous pressure,noradrenaline dose,lactate,Pv-aCO(2),Ca-vO(2), lactate clearance, central venous oxygen saturation(ScvO(2)) and liquid equilibrium were assessed after resuscitation.AKI staging based on Kidney Disease Global Improving Outcomes (KDIGO) clinical practice guideline was analyzed. The predictive value of lactate, ScvO(2), Pv-aCO(2)/Ca-vO(2) to progression of AKI after resuscitation was determined using receiver operating characteristic(ROC)curve analysis. Results: A total of 49 septic shock patients were enrolled including 30 males and 19 females with mean age of (61.10±17.10)years old.There were 19 patients in group A,21 patients in group B, and 9 patients in group C. Acute physiology and chronic health evaluation Ⅱ score was 20.92±7.19 and sequential organ failure assessment score 12.02±3.28. There were 4 patients with AKI and 1 progressed in group A, 11 patients with AKI and 2 progressed in group B, 6 patients with AKI and 4 progressed in group C. The cutoff value of Pv-aCO(2)/Ca-vO(2) was equal or more than 2.20 for predicting progression of AKI, resulting in a sensitivity of 85.7% and a specificity of 73.8%. Conclusion: MicrOME is a significant parameter to predict the progression of AKI in patients with septic shock after resuscitation. Pv-aCO(2)/Ca-vO(2) is also a good predictive factor.

[The relationship between arterial blood lactate clearance, prognosis and myocardial damage in patients with septic shock after early goal-directed therapy].

Objective: To evaluate the prognostic value of arterial blood lactate clearance based on central venous oxygen saturation and perfusion index in patients with septic shock related myocardial injury after early goal-directed therapy. Methods: One hundred and fifty-seven patients with septic shock after early resuscitation were enrolled from August 2013 to July 2016 in ICU at Peking Union Medical College Hospital. Parameters indicating early resuscitation included central venous pressure (CVP) 8-12 mmHg (1 mmHg=0.133 kPa),mean arterial pressure (MAP) >65 mmHg, central venous oxygen saturation(ScvO(2))>70% and urine volume (UO) >0.5ml·kg(-1)·h(-1) and arterial blood lactate (Lac) >2 mmoL/L.Patients were divided into group A [ScvO(2)>80% and perfusion index (PI)>1.4], group B(ScvO(2)>80% and PI<1.4),group C(ScvO(2)<80% and PI>1.4),group D(ScvO(2)<80% and PI<1.4).Hemodynamic parameters and tissue perfusion indexes at 2 hours(T2),4 hours(T4) and 6 hours(T6) after early resuscitation and troponin I which indicated myocardial damage, on day 1 2 3 in ICU were recorded. Results: ⑴Lac clearance in group C was the quickest, which was 34.57% (21.44%, 44.20%) , 58.33% (30.19%, 70.79%) , 71.43% (53.75%, 82.79%) at T2, T4, T6 respectively.⑵The maximal incidence of myocardial damage was in group B(85.0%) and the lowest in group A (45.7%) on day 1 in ICU.Whereas on day 2, group C showed the lowest incidence of myocardial damage (29.3%) and group B the highest(70.0%). On day 3,the proportion of elevated troponin I in group B was 70.0%, which was significantly higher than that of group B (29.3%,P<0.008).⑶Logistic regression analysis suggested that the rate of Lac clearance at T4 in group B was related to the incidence of myocardial damage on day 2 and 3 in ICU. Conclusions: The combination of PI and ScvO(2) as a resuscitation target in patients with septic shock facilitates Lac clearance as the goal of resuscitation.The rate of arterial Lac clearance based on ScvO(2) and PI is correlated with myocardial injury in patients with septic shock after early goal-directed therapy.