Imprinted SARS-CoV-2 humoral immunity induces converging Omicron RBD evolution

Continuous evolution of Omicron has led to a rapid and simultaneous emergence of numerous variants that display growth advantages over BA. 5. Despite their divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots. The driving force and destination of such convergent evolution and its impact on humoral immunity remain unclear. Here, we demonstrate that these convergent mutations can cause striking evasion of neutralizing antibody (NAb) drugs and convalescent plasma, including those from BA.5 breakthrough infection, while maintaining sufficient ACE2 binding capability. BQ.1.1.10, BA.4.6.3, XBB, and CH. 1.1 are the most antibody-evasive strain tested, even exceeding SARS-CoV-1 level. To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies (mAbs) isolated from BA.2 and BA.5 breakthrough-infection convalescents. Importantly, due to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection caused significant reductions in the epitope diversity of NAbs and increased proportion of non-neutralizing mAbs, which in turn concentrated humoral immune pressure and promoted convergent evolution. Moreover, we showed that the convergent RBD mutations could be accurately inferred by integrated deep mutational scanning (DMS) profiles, and the evolution trends of BA.2.75/BA.5 subvariants could be well-simulated through constructed convergent pseudovirus mutants. Together, our results suggest current herd immunity and BA.5 vaccine boosters may not provide good protection against infection. Broad-spectrum SARS-CoV-2 vaccines and NAb drugs development should be highly prioritized, and the constructed mutants could help to examine their effectiveness in advance.

Further humoral immunity evasion of emerging SARS-CoV-2 BA.4 and BA.5 subvariants

Multiple BA.4 and BA.5 subvariants with R346 mutations on the spike glycoprotein have been identified in various countries, such as BA.4.6/BF.7 harboring R346T, BA.4.7 harboring R346S, and BA.5.9 harboring R346I. These subvariants, especially BA.4.6, exhibit substantial growth advantages compared to BA.4/BA.5. In this study, we showed that BA.4.6, BA.4.7, and BA.5.9 displayed higher humoral immunity evasion capability than BA.4/BA.5, causing 1.5 to 1.9-fold decrease in NT50 of the plasma from BA.1 and BA.2 breakthrough-infection convalescents compared to BA.4/BA.5. Importantly, plasma from BA.5 breakthrough-infection convalescents also exhibits significant neutralization activity decrease against BA.4.6, BA.4.7, and BA.5.9 than BA.4/BA.5, showing on average 2.4 to 2.6-fold decrease in NT50. For neutralizing antibody drugs, Bebtelovimab remains potent, while Evusheld is completely escaped by these subvariants. Together, our results rationalize the prevailing advantages of the R346 mutated BA.4/BA.5 subvariants and urge the close monitoring of these mutants, which could lead to the next wave of the pandemic.

Comprehensive genomic, immunological and clinical analysis of COVID-19 vaccine breakthrough infections: a prospective, comparative cohort study

ObjectivesAs the COVID-19 pandemic is still ongoing and SARS-CoV-2 variants are circulating worldwide, an increasing number of breakthrough infections have been detected despite the good efficacy of COVID-19 vaccines. MethodsA prospective, comparative cohort study was conducted in Beijing Ditan Hospital to evaluate the clinical, immunological and genomic characteristics of COVID-19 breakthrough infections. Data on 88 COVID-19 breakthrough cases (vaccinated group) and 41 unvaccinated cases (unvaccinated group) from June 1 to August 20, 2021 were extracted from a cloud database. Among these 129 COVID-19 cases, we successfully sequenced 33 whole genomes, including 16 from the vaccinated group and 17 from the unvaccinated group. ResultsAsymptomatic and mild cases predominated in both groups, but 2 patients developed severe disease in the unvaccinated group. Between the two groups, the median time of viral shedding in the vaccinated group were significantly lower than those in the unvaccinated group (p = 0.003). A comparison of dynamic IgG titres of cases in the two groups indicated that IgG titres in the vaccinated group showed a significantly increasing trend (P =0.028). The CD4+T lymphocyte count was lower in the unvaccinated group, and there was a significant difference between the two groups (p=0.018). In the vaccinated group, the number of moderate cases who received Sinopharm BBIBP (42 cases) was significantly higher than those who received Sinovac Coronavac (p=0.020). Whole-genome sequencing revealed 23 cases of delta variants, including 15 patients from the vaccinated group. However, no significant difference was observed in either the RT-qPCR results or viral shedding time. ConclusionsCOVID-19 vaccine breakthrough infections were mainly asymptomatic and mild, the IgG titres were significantly higher and increased rapidly, and the viral shedding was short. Delta variants may be more likely to cause breakthrough infections, and vaccination may not reduce the viral loads and shedding time.

COVID-19 cases from the first local outbreak of SARS-CoV-2 B.1.1.7 variant in China presented more serious clinical features: a prospective, comparative cohort study

BackgroundThe SARS-CoV-2 B.1.1.7 variant which was first identified in the United Kingdom (U.K.) has increased sharply in numbers worldwide and was reported to be more contagious. On January 17, 2021, a COVID-19 clustered outbreak caused by B.1.1.7 variant occurred in a community in Daxing District, Beijing, China. Three weeks prior, another non-variant (lineage B.1.470) COVID-19 outbreak occurred in Shunyi District, Beijing. This study aimed to investigate the clinical features of B.1.1.7 variant infection. MethodsA prospective cohort study was conducted on COVID-19 cases admitted to Ditan hospital since January 2020. Data of 74 COVID-19 cases from two independent COVID-19 outbreaks in Beijing were extracted as study subjects from a Cloud Database established in Ditan hospital, which included 41 Shunyi cases (Shunyi B.1.470 group) and 33 Daxing cases (Daxing B.1.1.7 group) that have been hospitalized since December 25, 2020 and January 17, 2021, respectively. We conducted a comparison of the clinical characteristics, RT-qPCR results and genomic features between the two groups. FindingsCases from Daxing B.1.1.7 group (15 [45.5%] male; median age, 39 years [range, 30.5, 62.5]) and cases from Shunyi B.1.470 group (25 [61.0%] male; median age, 31 years [range, 27.5, 41.0]) had a statistically significant difference in median age (P =0.014). Seven clinical indicators of Daxing B.1.1.7 group were significantly higher than Shunyi B.1.470 group including patients having fever over 38{degrees}C (14/33 [46.43%] in Daxing B.1.1.7 group vs. 9/41 (21.95%) in Shunyi B.1.470 group [P = 0 .015]), C-reactive protein ([CRP, mg/L], 4.30 [2.45, 12.1] vs. 1.80, [0.85, 4.95], [P = 0.005]), Serum amyloid A ([SAA, mg/L], 21.50 [12.50, 50.70] vs. 12.00 [5.20, 26.95], [P = 0.003]), Creatine Kinase ([CK, U/L]), 110.50 [53.15,152.40] vs. 70.40 [54.35,103.05], [P = 0.040]), D-dimer ([DD, mg/L], 0.31 [0.20, 0.48] vs. 0.24 [0.17,0.31], [P = 0.038]), CD4+ T lymphocyte ([CD4+ T, mg/L], [P = 0.003]), and Ground-glass opacity (GGO) in lung (15/33 [45.45%] vs. 5/41 [12.20%], [P =0.001]). After adjusting for the age factor, B.1.1.7 variant infection was the risk factor for CRP (P = 0.045, Odds ratio [OR] 2.791, CI [1.025, 0.8610]), SAA (0.011, 5.031, [1.459, 17.354]), CK (0.034, 4.34, [0.05, 0.91]), CD4+ T (0.029, 3.31, [1.13, 9.71]), and GGO (0.005, 5.418, [1.656, 17.729]) of patients. The median Ct value of RT-qPCR tests of the N-gene target in the Daxing B.1.1.7 group was significantly lower than the Shunyi B.1.470 group (P=0.036). The phylogenetic analysis showed that only 2 amino acid mutations in spike protein were detected in B.1.470 strains while B.1.1.7 strains had 3 deletions and 7 mutations. InterpretationClinical features including a more serious inflammatory response, pneumonia and a possible higher viral load were detected in the cases infected with B.1.1.7 SARS-CoV-2 variant. It could therefore be inferred that the B.1.1.7 variant may have increased pathogenicity. FundingThe study was funded by the National Key Research and Development Program (grant nos.2020YFC0846200 and 2020YFC0848300) and National Natural Science Foundation of China (grant no. 82072295).

Proteomics analysis as an approach to understand the formation of pale, soft, and exudative (PSE) pork.

We investigated ten pale, soft, and exudative (PSE), and ten normal meat samples from pig carcasses. The meat quality at 0, 5, 12, and 24 h post-mortem and the key enzyme activities at 0 and 24 h post-mortem were determined. We selected three PSE and three normal samples for proteomics analysis at 0 h and 24 h post-mortem. No remarkable differences in pyruvate kinase (PK) and lactate dehydrogenase (LDH) activity were observed between samples at 0 h post-mortem; however, creatine kinase (CK) activity was significantly higher in PSE meat. Hexokinase (HK) activity in PSE samples was higher than that in normal samples at 24 h post-mortem. Bioinformatics analysis of the proteome showed that PSE was related to glycolysis, TCA cycle, oxidative phosphorylation, muscle tissue structure, signal transduction, and molecular chaperones. This research found that proteins such as troponin T slow skeletal muscle isoform X, GADPH, L-lactate dehydrogenase A chain, and gamma-enolase isoform X1 might be responsible for PSE.

Risk factors for hospitalization of pregnant women with influenza A / 中华传染病杂志

Objective:To investigate the influencing factors of hospitalization for pregnant women with influenza A.Methods:From December 2018 to February 2019, 261 pregnant women with influenza A were admitted to Beijing Ditan Hospital, Capital Medical University. The clinical data of age, gestational period, underlying diseases, time from onset to treatment, white blood cell count and lymphocyte count of these patients were collected. Data of out-patients were compared with those of inpatients. Chi-square test and multivariate logistic regression were used to analyze the influencing factors of hospitalization in pregnant women with influenza A.Results:Among the 261 cases of pregnancy with influenza A, 36 cases (13.79%) were hospitalized, of which 10 (27.78%) were hospitalized due to severe influenza complications, the other 26 cases (72.22%) were hospitalized due to pregnancy related adverse events. The proportions of hospitalized patients with age ≥30 years old, gestational period ≥28 weeks, combined with underlying diseases and lymphocyte count <1×10 9/L were 75.00%(27/36), 83.33%(30/36), 16.67%(6/36) and 50.00%(18/36), respectively, which were significantly higher than those of out-patients (47.11%(106/225), 35.56%(80/225), 0.89%(2/225) and 13.22%(16/121), respectively; χ2=9.66, 29.05, 26.00 and 22.12, respectively, all P<0.05). The proportions of inpatients and out-patients with white blood cell count ≥4×10 9/L were 97.22%(35/36) and 97.52%(118/121), respectively, and there was no significant difference ( χ2=0.01, P=0.921). Multivariate logistic regression analysis showed that age ≥30 years (odds ratio ( OR)=5.181, 95% confidence interval ( CI) 1.628-16.489, P=0.005), gestational period ≥28 weeks ( OR=11.054, 95% CI 3.233-37.796, P<0.01), lymphocyte count <1×10 9/L ( OR=6.864, 95% CI 2.237-20.729, P=0.001), and time from onset to treatment <24 h ( OR=0.076, 95% CI 0.012-0.468, P=0.005) were the influencing factors for hospitalization of pregnant women with influenza A. Conclusion:Age ≥30 years old, gestational period ≥28 weeks, lymphocyte count <1×10 9/L and time from onset to treatment <24 h are the influencing factors for hospitalization of pregnant women with influenza A.

Specific Dynamic Variations in the Peripheral Blood Lymphocyte Subsets in COVID-19 and Severe Influenza A Patients: A Retrospective Observational Study

BackgroundBoth COVID-19 and influenza A contribute to increased mortality among the elderly and those with existing comorbidities. Changes in the underlying immune mechanisms determine patient prognosis. This study aimed to analyze the role of lymphocyte subsets in the immunopathogenesisof COVID-19 and severe influenza A, and examined the clinical significance of their alterations in the prognosis and recovery duration. MethodsBy retrospectively reviewing of patients in four groups (healthy controls, severe influenza A, non-severe COVID-19 and severe COVID-19) who were admitted to Ditan hospital between 2018 to 2020, we performed flow cytometric analysis and compared the absolute counts of leukocytes, lymphocytes, and lymphocyte subsets of the patients at different time points (weeks 1- 4). ResultsWe reviewed the patients data of 110 healthy blood donors, 80 Non-severe-COVID-19, 19 Severe-COVID-19 and 43 severe influenza A. We found total lymphocytes (0.93 x109/L, 0.84 x109/L vs 1.78 x109/L, P < 0.0001) and lymphocyte subsets (T cells, CD4+ and CD8+ T cell subsets) of both severe patients to be significantly lower than those of healthy donors at early infection stages. Further, significant dynamic variations were observed at different time points (weeks 1-4). ConclusionsOur study indicates lymphopenia to be associated with disease severity and suggests the plausible role of lymphocyte subsets in disease progression, which in turn affects prognosis and recovery duration in patients with severe COVID-19 and influenza A.

Neutrophil-to-Lymphocyte Ratio Predicts Severe Illness Patients with 2019 Novel Coronavirus in the Early Stage

BackgroundSevere ill patients with 2019 novel coronavirus (2019-nCoV) infection progressed rapidly to acute respiratory failure. We aimed to select the most useful prognostic factor for severe illness incidence. MethodsThe study prospectively included 61 patients with 2019-nCoV infection treated at Beijing Ditan Hospital from January 13, 2020 to January 31, 2020. Prognostic factor of severe illness was selected by the LASSO COX regression analyses, to predict the severe illness probability of 2019-CoV pneumonia. The predictive accuracy was evaluated by concordance index, calibration curve, decision curve and clinical impact curve. ResultsThe neutrophil-to-lymphocyte ratio (NLR) was identified as the independent risk factor for severe illness in patients with 2019-nCoV infection. The NLR had a c-index of 0.807 (95% confidence interval, 0.676-0.38), the calibration curves fitted well, and the decision curve and clinical impact curve showed that the NLR had superior standardized net benefit. In addition, the incidence of severe illness was 9.1% in age [≥] 50 and NLR < 3.13 patients, and half of patients with age [≥] 50 and NLR [≥] 3.13 would develop severe illness. Based on the risk stratification of NLR with age, the study developed a 2019-nCoV pneumonia management process. ConclusionsThe NLR was the early identification of risk factors for 2019-nCoV severe illness. Patients with age [≥] 50 and NLR [≥] 3.13 facilitated severe illness, and they should rapidly access to intensive care unit if necessary.

Epidemiological and clinical characteristics of 69 cases with imported corona virus disease 2019 / 中华传染病杂志

Objective:To analyze the epidemiological and clinical characteristics of patients with imported corona virus disease 2019 (COVID-19) in Beijing City.Methods:A case-control study was performed to retrospectively analyze 69 cases of imported COVID-19 from abroad and 147 cases of domestic confirmed COVID-19 from China as a control group from January 20 to March 20, 2020 admitted to Beijing Ditan Hospital, Capital Medical University.The epidemiological and clinical characteristics were compared.Statistical analysis were performed by t test, Mann-Whitney U test, chi-square test and Fisher exact test. Results:The main sources of the cases in the import group were from the United Kingdom, Italy, Spain and other European countries, with 44.9%(31/69) of the overseas students entering the country by air. The age of the imported group (27(21, 40) years) was lower than the domestic group (43 (32, 59)years), the difference between the two groups was statistically significant ( U=2 828.500, P<0.01). Compared with the domestic group, the proportion of cases with contact history of confirmed cases in the imported group was lower (30.4%(21/69) vs 68.0%(100/147)), the interval between onset and admission ≤seven days was higher (81.2%(56/69) vs 66.0%(97/147)), the proportion of cases with underlying diseases was lower (21.7%(15/69) vs 44.2%(65/147)). The differences between the two groups were all statistically significant ( χ2=26.935, 5.233 and 10.175, respectively, all P<0.05). The proportion of mild cases in the imported group was higher than that in the domestic group (42.0%(29/69) vs 10.9%(16/147)). Seventeen cases with olfactory abnormality and 12 cases with taste abnormality were found in the imported group, while no olfactory and taste abnormality was found in the domestic group. The proportions of fever, weakness, muscle soreness and dyspnea were all lower than those of the domestic group, the differences between the two groups were all statistically significant ( χ2=13.851, 8.118, 9.730 and 16.255, respectively, all P<0.01). The proportions of cases with decreased lymphocyte absolute numbers (37.7%(26/69) vs 67.3%(99/147)) and increased C reactive protein level (15.9%(11/69) vs 51.8%(72/139)) were both lower than the domestic group, and the differences between the two groups were both statistically significant ( χ2=18.015 and 24.722, respectively, both P<0.01). The proportions of cases with ground glass shadow and consolidation of chest computed tomography were lower than those of the domestic group and the differences between the two groups were all statistically significant ( χ2=11.961 and 5.099, respectively, all P<0.05). In terms of complications, the proportions of cases with acute respiratory distress syndrome and acute myocardial injury were lower (2.9%(2/69) vs 10.9%(16/147) and 4.3%(3/69) vs 14.0%(16/114), respectively), and there were statistically significant differences between the two groups ( χ2=4.017 and 4.335, respectively, both P<0.05). There were no cases received mechanical ventilation and extracorporeal membrane oxygenation in the imported group, and the proportions of patients received oxygen therapy and antibiotic treatment were significantly lower than those in the domestic group (13.0%(9/69) vs 26.5%(39/147) and 13.0%(9/69) vs 39.5%(58/147), respectively) and the differences between the two groups were statistically significant ( χ2=4.942 and 15.797, respectively, both P<0.05). Conclusions:The majority of imported COVID-19 cases are mainly from European countries, mostly young and middle-aged, and mostly mild and ordinary types.The symptoms of olfactory and taste abnormality are found for the first time.

Study on mechanical ventilation pressure under continuous cuff pressure monitoring in critical patients / 中华危重病急救医学

Objective:To explore the effective pressure range under continuous cuff pressure monitoring in critical patients with mechanical ventilation, so as to achieve the goal of ensuring ventilation quality and reducing mucosal injury without increasing the incidence of endotracheal catheter displacement and aspiration.Methods:Ninety critically ill patients with non-pulmonary diseases admitted to the department of intensive care unit (ICU) of Airport Hospital of Tianjin Medical University from June 2017 to June 2019 were enrolled, and divided into three groups according to the random number table, with 30 patients in each group. For all patients in the three groups , the head of the bed was raised by 30°and the balloon was measured continuously. Cuff pressure in the three groups were maintained at 20, 25 and 30 cmH 2O (1 cmH 2O = 0.098 kPa) respectively. The patient's air leakage, oxygen saturation, tracheal tube displacement of each group were recorded every hour when the patients were calm. Fiberbronchoscope was used to aspirate sputum during extubation to check for mucosal damage. Chest X-ray examination was used to evaluate pulmonary infection and sputum bacteria culture examination was conducted at the same time. Results:There was no significant difference in gender, age and critical condition among the three groups. The number of patients with airway mucosal injury in the 30 cmH 2O group was significantly higher than that in the 20 cmH 2O group (cases: 8 vs. 4, P < 0.05). There was no significant difference in airway mucosal injury between Group 20 cmH 2O and Group 25, Group 25 cmH 2O and Group 30 cmH 2O. When the balloon pressure was 20, 25, and 30 cmH 2O, there was no significant difference in air bag leakage (cases: 14, 10, 12), trachea catheter displacement (cases: 18, 11, 16), ventilator-associated pneumonia (cases: 3, 4, 3), all P > 0.05, and there was no significant difference in mechanical ventilation time and the hospitalization time [mechanical ventilation time (hours): 77.07±65.34, 80.80±70.20, 77.60±65.23; the length of ICU stay (days): 5.70±3.74, 5.30±4.57, 6.23±3.51, all P > 0.05]. Conclusion:The cuff pressure of 20 cmH 2O will not increase the mechanical ventilation time and hospitalization time of patients, while 20 cmH 2O is much safer in airway mucosal injury.

Research on the demand of simulation operations specialists in simulated courses in standardized residency training / 中华医学教育探索杂志

Objective:To investigate the demand and practical utility of simulation operations specialists (SOS) in simulation teaching modules during the standardized residency training.Methods:Based on the feedback for stimulated courses of standardized residency training, subjective evaluation of all residents, teachers and SOS who participated in simulation courses in 2017-2018 academic year were investigated and studied via the mobile phone online investigation. At the same time, the design data of teaching concept map of relevant curriculum were also included. The SPSS 13.0 was used to conduct the t test and chi-square test. Results:At present, only 26.3% of the preset functions were used in the medical simulation courses based on high-tech medical simulator. Tutors commanded less than 30% functions, while SOS participated in the whole process of the course preparation and commanded 63.6% of the course operations, which was higher than the requirement of teaching concept map (45.5%). Among them, ECG monitoring regulation, venous management and special effects makeup were in greatest needs and were items with the biggest gap between ideality and reality. Resident physicians required SOS to replace the tutors to operate teaching facilities, so as to reduce interruption (37.0%), implications (31.3%) during courses, and improvement of experience sense during the course (32.3%). Furthermore, specialists with clinical background needed more assistance from SOS than those without clinical background ( tQ3=3.204, tQ4=2.573, tQ5=2.660; P<0.05). Differences were found between the actual work content of SOS and their job requirement ( χ2=12.632, P<0.01). Conclusion:SOS plays a significant role in the simulation course of standardized residency training, especially in the course of clinical professional physicians. Auxiliary functions of simulated courses, such as teaching aids management, special effects makeup, course designing, qualified SP and others are the main necessities for SOS at present. Participation of tutors and SOS together is essential to ensure a good development and performance of medical simulation courses for standardized residency training.

Progress of diagnosis and treatment of atypical chronic myeloid leukemia / 白血病·淋巴瘤

Atypical chronic myeloid leukemia (aCML) is a rare hematologic malignancy with both bcr-abl-negative and the absence of the Philadelphia chromosome, which is completely different from chronic myeloid leukemia (CML). According to the clinical characteristics and the main hematological characteristics, it is classified as myelodysplastic/myeloproliferative neoplasms. Due to the low incidence and limited understanding of aCML, it can result in the clinical missed diagnosis or misdiagnosis, and the short survival time of patients. In order to further improve the diagnostic rate and survival time, this paper reviews the current diagnostic criteria, differential diagnosis, related gene mutations, prognosis evaluation and clinical treatments of aCML.

A multicenter controlled clinical study on the efficacy and safety of recombinant human interferon α2b spray in the treatment of hand, foot and mouth disease in children / 中华传染病杂志

Objective To evaluate the curative effect of recombinant human Interferon α2b (rhIFN α2b) spray in hand,foot and mouth disease (HMFD).Methods In total,313 HMFD children were enrolled from Beijing Ditan Hospital affiliated to Capital Medical University,Tianjing Second People's Hospital,Hebei Children's Hospital,the Second Hospital affiliated to Wenzhou Medical College,Kunming Maternal and Child Health Hospital and Guiyang Public Health Treatment Center from March,2015 to February,2017.They were divided into rhIFN α2b group (148 cases) and ribavirin group (165 cases).The children in rhIFN α2b group were given with the rhIFN α2b spray,and those in ribavirin group were given with the ribavirin spray.Meanwhile,the children were given unified standard interventions for basic treatment.The curative effect and safety between two groups was compared.The t test was used for intergroup comparison and the Wilcoxon rank test was used for non-normal quantitative data.Results At the end of the follow-up period,all kids reached the recovery level,with 144 cases in the rhIFN α2b group and 164 cases in the ribavirin group.Fever,herpes and rashes all disappeared with 7-day follow-up.The total efficiency of the rhIFN α2b group measured at the 72h after treatment was 74.15％,which showed significant differences compared with the ribavirin group with 49.09 ％ efficiency (Z=4.44,P＜0.01).As the secondary outcome measures,the complete disappearance time of fever and the immediate disappearance time of fever in the rhIFN α2b group were significantly shorter than those in the ribavirin group ([27.03±21.99] vs [33.21±26.71],t=-2.13;[23.56±13.96] vs [28.51±18.84],t=-2.07,both P＜0.05).The appetite improvement and the disappearance times of oral herpes and rashes in the rhIFN α2b group were shorter than those in the ribavirin group,with significant differences (x2 =4.94,3.17 and 3.55,respectively,all P=0.000).No adverse event in both groups.Conclusions rhIFN α2b spray treatment in HMFD is proved significantly effective,particularly,it can evidently relieve fever symptoms and promote the disappearance of oral herpes symptoms,and no adverse event is observed throughout the study,which indicates a good safety of the rhIFN α2b spray.Clinical trial registration Chinese Clinical Trial Registry,ChiCTR-OIN-17013182.

Study on reconstruction of rabbit alveolar bone defect with strontium-containing brushite bone ce-ments / 实用医学杂志

Objective To investigate whether 5% strontium-containing brushite bone cements(DCPD) has repair effect on alveolar bone defects in osteoporotic rabbits. Methods Eighteen healthy adult female rabbits were used to establish osteoporosis models and were randomly divided into three groups:the blank control group, DCPD group,doped 5%DCPD group(5%strontium),with 6 rats in each group.In addition to the blank group, rats the other groups were filled with the corresponding bone cements in the bilateral alveolar bone defects. At 4 weeks and 8 weeks after operation,3 rats in each group were killed and given shooting the defect area X-ray.The expression of b-FGF was detected by immunohistochemistry. Results X-ray results showed that the defected of doped 5% DCPD group have been nearly completedat the 8 week,DCPD group partially completed repair,but blank group was not fully repaired. The results of immunohistochemistry showed that the expression of b-FGF was the highest at 4 weeks and decreased at 8 weeks after operation.Expression of b-FGF was significantly different at 4 weeks and 8 weeks among the three groups.Conclusion The 5%strontium-containing brushite bone cements can repair bone defect in osteoporotic rabbits.

Wear matching performance of dental restoration materials oppositing to dentine / 实用口腔医学杂志

Objective:To compare the wear resistance between dentin and dental restoration material in vitro.Methods:The friction and wear behaviors of natural tooth dentin respectively against highly polished polymer ceramic,glass ceramic and zirconia were investigated in an artificial saliva test environment by UMT-2 friction and wear testing machine.Worn surface morphology was observed by scanning electron microscopy(SEM),roughness was measured by roughness instrument,the rigidity value was weighed by electronic balance.Results:The roughness of the 3 materials was similar to that of dentin(P ＞ 0.05),the rigidity of dentin was less than that of the 3 materials (P ＜ 0.05).After friction and wear test,the abrasion quantity of dentin respectively against the 3 materials was less than that of the materials (P ＜ 0.05).There was positive correlation between the wear loss and the hardness of the 3 materials and dentin(r =0.846).The mass loss of the dentin against Poly Ceramic after grinding abrasion was the closest among the 3 materials.Conclusion:Different materials have varying degrees abrasion against dentine.The Polymer Ceramic has closer abrasion performancez with dentin than the other 2 materials.

Influence of ulinastatin on inflammatory response and cellular immune function in patients with acute respiratory distress syndrome / 实用医学杂志

Objective To observe the influence of ulinastatin (UTI) on curative effect,inflammatory response and cellular immune function in patients with acute respiratory distress syndrome (ARDS).Methods 96 patients with ARDS were randomly divided into two groups:the control group (48 cases) were treated with conventional treatment,and the UTI group (48 cases) were added with UTI injection based on the control group treatment.The changes of oxygenation index,vital signs,inflammatory factors and T lymphocyte subsets of patients in the two groups were compared before treatment and after treatment in 7 days,recorded the duration of mechanical ventilation time,ICU treatment time and mortality rate in ICU in the two groups.Results After treatment in 7 days,the vital signs (RF,HR,MAP),inflammatory factors (TNF-α,IL-6,IL-8,PCT,CRP,WBC),liver function (AST,ALT),renal function (BUN,Cr) and APACHE Ⅱ score,MODS score of UTI patients in the UTI group were lower than those in the control group (P ＜ 0.05 or P ＜ 0.01).Oxygenation index (PaO2/FiO2) and cellular immunity (CD4+,CD4+/CD8+) in the UTI group were higher than those in the control group (P ＜ 0.01).Mechanical ventilation time,ICU treatment time in the UTI group were shorter than those in the control group (all P ＜ 0.05),the mortality rate of ICU in the UTI group was lower than that in the control group (P ＜ 0.05).There was no significant difference in the incidence of adverse reactions between the two groups (P ＞ 0.05).Conclusions UTI can more effectively improve oxygen metabolism,vital signs for ARDS,liver and kidney function,reduce the APACHE Ⅱ score and MODS score,shorten the mechanical ventilation time and ICU treatment time,reduce the mortality rate of ICU.Its mechanism may relate to clearance of inflammatory factors and regulate cellular immune function of UTI.

Comparison of the clinical effects of general anesthesia and single spinal anesthesia on pregnant women with liver cirrhosis after hepatitis in cesarean section / 临床麻醉学杂志

Objective To explore and compare the clinical effects of pregnant women with liver cirrhosis after hepatitis in cesarean section between general anesthesia and single spinal anesthesia.Methods Clinical data of pregnant women of 35,including compensated cirrhosis 26 cases,decompensated cirrhosis 9 cases,aged 24-45 years,weighing 55-98 kg,falling into ASA Ⅱ or Ⅲ,were divided into group A (general anesthesia group,n=15) and B (single spinal group,n=20).In patients of group A,propofol were infused at 1.5 mg/kg till the time for fetal delivery,after intubation,followed by infusion of remifentanil at a rate of 0.2 μg·kg-1·min-1 TCL combined with propofol until the end of operation.In group B,the puncture was performed at L3-4 interspace,following by intrathecal injection of ropivacaine 10~15 mg and within 10 seconds.With liver cirrhosis after hepatitis were collected and analyzed,retrospectively.Preoperative general status,blood loss and time of operation,Apgar score of neonates compared and analyzed in groups A and B.And the changes of hepatic function and coagulation function of the body under different anesthesia methods were also studied.The influential factors of postoperative elevation of hepatic function were analyzed by non-conditional logistic regression models.Results Blood loss and time of operation,Apgar score of neonates and postoperative hospital stay had no significant differences between the two groups.Postoperative albumin of group A was higher than that of preoperative,with a statistical significance (P<0.05).Alanine aminotransferase,aspartate aminotransferase of postoperative of group B were increased,with a statistical significance (P<0.01).Logistic analysis showed that the type of anesthesia was the possible influencing factor of postoperative elevation of total bilirubin (OR=12.04,95%CI 1.14-127.45).Conclusion The negative effect of single spinal anesthesia on hepatic function more than that of general anesthesia in pregnant women with liver cirrhosis in cesarean section.

Chemical constituents from Nepeta angustifolia / 中成药

AIM To study the chemical constituents from Nepeta angustifolia C.Y.Wu.METHODS The ethyl acetate fraction of N.angustifolia 70％ ethanol extract was isolated and purified by silica,Sephadex LH-20,ODS and semi-preparative HPLC column,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Ten compounds were isolated and identified as oleanolic acid (1),betulinic acid (2),ursolic acid (3),3-sitosterol (4),angelicin (5),bakuchiol (6),blumenol C glucoside (7),psoralen (8),methyl rosmarinate (9),hesperidin (10).CONCLUSION Compounds 5-8are isolated from genus Nepeta for the first time,compounds 1,4-10 are first isolated from this plant.

Distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015: results from a multicenter, retrospective study / 中华血液学杂志

Objective@#To describe the distribution and drug resistance of pathogens at hematology department of Jiangsu Province from 2014 to 2015 to provide reference for empirical anti-infection treatment.@*Methods@#Pathogens were from hematology department of 26 tertiary hospitals in Jiangsu Province from 2014 to 2015. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or agar dilution method. Collection of drug susceptibility results and corresponding patient data were analyzed.@*Results@#The separated pathogens amounted to 4 306. Gram-negative bacteria accounted for 64.26%, while the proportions of gram-positive bacteria and funguses were 26.99% and 8.75% respectively. Common gram-negative bacteria were Escherichia coli (20.48%) , Klebsiella pneumonia (15.40%) , Pseudomonas aeruginosa (8.50%) , Acinetobacter baumannii (5.04%) and Stenotropho-monas maltophilia (3.41%) respectively. CRE amounted to 123 (6.68%) . Common gram-positive bacteria were Staphylococcus aureus (4.92%) , Staphylococcus hominis (4.88%) and Staphylococcus epidermidis (4.71%) respectively. Candida albicans were the main fungus which accounted for 5.43%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were 3.5%-6.1% and 5.0%-6.3% respectively. The rates of Pseudomonas aeruginosa resistant to tobramycin and amikacin were 3.2% and 3.3% respectively. The resistant rates of Acinetobacter baumannii towards tobramycin and cefoperazone/sulbactam were both 19.2%. The rates of Stenotrophomonas maltophilia resistant to minocycline and sulfamethoxazole were 3.5% and 9.3% respectively. The rates of Staphylococcus aureus, Enterococcus faecium and Enterococcus faecalis resistant wards vancomycin were 0, 6.4% and 1.4% respectively; also, the rates of them resistant to linezolid were 1.2%, 0 and 1.6% respectively; in addition, the rates of them resistant to teicoplanin were 2.8%, 14.3% and 8.0% respectively. Furthermore, MRSA accounted for 39.15% (83/212) .@*Conclusions@#Pathogens were mainly gram-negative bacteria. CRE accounted for 6.68%. The rates of Escherichia coli and Klebsiella pneumonia resistant to carbapenems were lower compared with other antibacterial agents. The rates of gram-positive bacteria resistant to vancomycin, linezolid and teicoplanin were still low. MRSA accounted for 39.15%.

Influence of polishing and glazing on the wear of zirconia and enamel / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of different surface treatment of zirconia and to find the best way to reduce the wear of its antagonist.</p><p><b>METHODS</b>Twenty-five plates(5 mm×10 mm×15 mm) made of zirconia were divided into five equal groups. Group A was only ground, group B was ground and polished, group C was ground and polished then polished by prophylaxis paste, group D was ground and glazed, group E was ground, polishsed, and then reglazed. Five central incisors were embedded in autopolymerizing acrylic resin with a size of 5 mm×10 mm×15 mm as the control group F. Thirty upper premolars buccal cusps were prepared as the antagonist. Cusps were embedded in autopolymerizing acrylic resin with a shape of circular column whose diameter were 3.1 mm. The wear test was performed in the universal micro-tribotester in artificial saliva. The roughness of each group was measured with rough meter before the wear test. The volume loss of the antagonist was measured using a 3D scanner. The wear surface was observed with scanning electron microscopy to determine the wear characteristics. Data were analyzed using one-way analysis of variance.</p><p><b>RESULTS</b>Each group of surface roughness and mass loss of antagonist showed significant statistical difference (P<0.05). Antagonist of group D showed the maximum volume loss([0.905±0.018] mm3). Antagonist of control group showed the least volume loss([0.235±0.017] mm3). Antagonist of group C showed less volume loss than antagonist of control group did([0.413±0.017] mm3). Wear type of enamel of control group and the antagonist of the groups in which the samples were polished with prophylaxis paste was fatigue wear, and the other groups showed abrasive and adhesive wear.</p><p><b>CONCLUSIONS</b>In the surface treatment methods of zirconia, polishing is better than glazing. Ground and polishing and then polishing with prophylaxis paste can decrease the wear of the antagonist.</p>