Survey on post competency of general practitioners with completion of residency training / 中华全科医师杂志

Objective:To survey the post competency of general practitioners who completed residency training in Suzhou Municipal Hospital.Methods:A questionnaire survey on post competency of general practitioners was conducted from January to March 2022. General practitioners who completed standardized residential training in Suzhou Municipal Hospital from 2009 to 2021 were randomly selected for the survey. The self-designed questionnaire included the basic information and post competency in terms of clinical, public health, research and teaching abilities as well as medical ethics and humanism. A self-evaluation was also performed and the abilities were graded (A 86-100, B 70-85, C 55-69, D 0-54), and grade A was classified as excellent.Results:A total of 163 questionnaires were distributed and 157 valid ones were collected with a recovery rate of 96.3%. Among 157 respondents 62 (39.5%) were males. The participants mainly worked in urban community health service institutions (78 (49.7%)), and most of them worked as general practice (119 (75.8%)). For the self-assessment of clinical skills, the proportion of respondents with excellent abilities in history taking, basic drug use, diagnosis and treatment of common diseases, and chronic disease management was 58.8% (70/119), 57.1% (68/119), 54.6% (65/119) and 54.6% (65/119), respectively. The proportion of respondents with excellent abilities in evidence-based clinical decision making, physical examination, tests interpretation, referral services, family medical services, rehabilitation services, first aid, and psychological counseling and treatment was 43.7% (70/119), 42.9% (52/119), 38.7% (46/119), 37.8% (45/119), 33.6% (40/119), 22.7% (27/119), 21.0% (25/119), and 16.8% (20/119), respectively. For the self-assessment of basic public health service ability, the proportion of respondents with excellent abilities in health education, disease prevention and control, health management, health care for key and special groups, handling public health emergencies, management of infectious diseases, epidemiology-based community diagnosis and community health leadership was 38.7% (46/119), 33.6% (40/119), 33.6% (40/119), 26.1% (31/119), 25.2% (30/119), 2.7% (27/119), 22.7% (27/119), and 21.0% (25/119), respectively. For humanistic literacy, the proportion of respondents with excellent abilities in privacy protection, sense of responsibility for patients, understanding patients′ needs, effective communication and cooperation with patients was 82.4% (98/119), 73.9% (88/119), 61.3% (73/119), 55.5% (66/119) and 2.1% (62/119), respectively. For research and teaching, the proportion of respondents with excellence abilities in continuous learning and innovation, training and teaching and literature retrieval was 47.9% (57/119), 10.9% (13/119), 10.1% (12/119), respectively. In addition 56.3% (67/119) of respondents were interested in scientific research, 23.5% (28/119) had published articles as the first author or correspondence author, and only 6.7% (8/119) had scientific research projects in the last 5 years.Conclusion:The post competency of general practitioners who received standardized residency training in our hospital varies in different aspects, their abilities in basic public health service, scientific research and teaching are relatively low, which need to be strengthened.

Innovative Teaching of "Doctor-patient" Friendly Model for Diabetes from the Perspective of Deep Blended Learning / 中国医学伦理学

The teaching of diabetes has always been the focus and difficulty of clinical internal science teaching. How to skillfully integrate theoretical knowledge into clinical practice and help students deeply master medical knowledge and clinical skills is a topic that clinical teaching teachers are considering. Under the background of analyzing the concept and connotation of deep blended learning, this paper constructed the diabetes "doctor-patient" friendly model teaching process in the perspective of deep blended learning from the three stages of "learning situation analysis and independent learning" in the early stage, "ability improvement and in-depth research" in the middle stage, and "reflection and ability expansion" in the later stage. This paper expounded the positive role of the "doctor-patient" friendly model of diabetes in clinical teaching from three main aspects: improving the integration effect of theory and practice, fully meeting students’ learning needs, and increasing the connection between doctors, patients, and students.

Clinical study of TBX21 and ADCY9 polymorphisms in the development of childhood asthma / 中国临床药理学与治疗学

To investigate the clinical role of T-cell transcription factor (TBX21) and adenylate cyclase 9 antibody (ADCY9) gene polymorphisms in the development of childhood asthma. METHODS: Two hundred Han Chinese wheezing children aged 5 years and younger in Henan region from July 2016 to January 2017 were selected as the study group, and another 100 Han Chinese healthy children aged 5 years and younger in the same period were selected as the control group. Oral mucosal exfoliated cells were collected from both groups, and the genotypes of TBX21 gene rs2240017 polymorphic locus and ADCY9 gene rs2230739 polymorphic locus were detected by real-time fluorescence quantitative polymerase chain reaction (PCR) technique, and the risk level of asthma was assessed based on the test results. The children in the low-risk and high-risk groups were compared in terms of serum immunoglobulin E (IgE) levels, API positivity rate and allergic disease incidence, and the correlation between the risk level of asthma-related genetic polymorphisms and serum IgE levels, API and allergic disease incidence was analyzed. All children were followed up until 6 years of age to confirm the diagnosis of asthma, and the incidence of asthma was compared between the low-risk and high-risk groups. Children with asthma were treated with inhaled glucocorticoids and leukotriene receptor antagonists for 3 months, and the control of asthma and the impairment of lung function were compared between the low-risk and high-risk groups. RESULTS: The genotype detection results of rs2240017 polymorphic locus of TBX21 gene and rs2230739 polymorphic locus of ADCY9 gene in the study group compared with those in the control group were statistically significant (P<0.001). The percentages of CC, CT, and TT genotypes of rs2240017 polymorphic locus of TBX21 gene were 19.50%, 56.00%, and 24.50%, respectively, and the percentages of CC, CG, and GG genotypes of rs2230739 polymorphic locus of ADCY9 gene were 86.00%, 10.00%, and 4.00%, respectively, in 200 children with wheezing; serum IgE level, API positivity rate and allergic disease incidence were higher in the high-risk group than in the low-risk group (P< 0.001, <0.001, 0.021, respectively). The degree of risk of asthma-related gene polymorphisms in children with wheezing was positively correlated with serum IgE levels, API positivity, and the incidence of allergic diseases (P<0.001); the incidence of asthma (81.48%) and impaired lung function (74.07%) were higher in the high-risk group than in the low-risk group (4.90%, 3.50%) (P<0.001). There was no statistically significant difference between the asthma control rate of children with asthma in the high-risk group (79.55%) compared with the asthma control rate of children with asthma in the low-risk group (100.00%) (P=0.433). CONCLUSION: Gene polymorphisms at rs2240017 locus of TBX21 gene and rs2230739 locus of ADCY9 gene are closely associated with asthma development and impaired lung function in children with wheezing.

A novel CRISPR/Cas9-hLacI donor adapting system for dsDNA-templated gene editing / 生物工程学报

During the gene editing process mediated by CRISPR/Cas9, precise genome editing and gene knock-in can be achieved by the homologous recombination of double-stranded DNA (dsDNA) donor template. However, the low-efficiency of homologous recombination in eukaryotic cells hampers the development and application of this gene editing strategy. Here, we developed a novel CRISPR/Cas9-hLacI donor adapting system (DAS) to enhance the dsDNA-templated gene editing, taking the advantage of the specific binding of the LacI repressor protein and the LacO operator sequence derived for the Escherichia coli lactose operon. The codon-humanized LacI gene was fused as an adaptor to the Streptococcus pyogenes Cas9 (SpCas9) and Staphylococcus lugdunensis Cas9 (SlugCas9-HF) genes, and the LacO operator sequence was used as the aptamer and linked to the dsDNA donor template by PCR. The Cas9 nuclease activity after the fusion and the homology-directed repair (HDR) efficiency of the LacO-linked dsDNA template were firstly examined using surrogate reporter assays with the corresponding reporter vectors. The CRISPR/Cas9-hLacI DASs mediated genome precise editing were further checked, and we achieved a high efficiency up to 30.5% of precise editing at the VEGFA locus in HEK293T cells by using the CRISPR/SlugCas9-hLacI DAS. In summary, we developed a novel CRISPR/Cas9-hLacI DAS for dsDNA-templated gene editing, which enriches the CRISPR/Cas9-derived gene editing techniques and provides a novel tool for animal molecular design breeding researches.

Rational identification of potent and broad sarbecovirus-neutralizing antibody cocktails from SARS convalescents

SARS-CoV-2 Omicron sublineages have escaped most RBD-targeting therapeutic neutralizing antibodies (NAbs), which proves the previous NAb drug screening strategies deficient against the fast-evolving SARS-CoV-2. Better broad NAb drug candidate selection methods are needed. Here, we describe a rational approach for identifying RBD-targeting broad SARS-CoV-2 NAb cocktails. Based on high-throughput epitope determination, we propose that broad NAb drugs should target non-immunodominant RBD epitopes to avoid herd immunity-directed escape mutations. Also, their interacting antigen residues should focus on sarbecovirus conserved sites and associate with critical viral functions, making the antibody-escaping mutations less likely to appear. Following the criteria, a featured non-competing antibody cocktail, SA55+SA58, is identified from a large collection of broad sarbecovirus NAbs isolated from SARS convalescents. SA55+SA58 potently neutralizes ACE2-utilizing sarbecoviruses, including circulating Omicron variants, and could serve as broad SARS-CoV-2 prophylactics to offer long-term protection. Our screening strategy can also be applied to identify broad-spectrum NAb drugs against other fast-evolving viruses, such as influenza viruses.

BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection

SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility over BA.21. The new variants receptor binding and immune evasion capability require immediate investigation. Here, coupled with Spike structural comparisons, we show that BA.2.12.1 and BA.4/BA.5 exhibit comparable ACE2-binding affinities to BA.2. Importantly, BA.2.12.1 and BA.4/BA.5 display stronger neutralization evasion than BA.2 against the plasma from 3-dose vaccination and, most strikingly, from post-vaccination BA.1 infections. To delineate the underlying antibody evasion mechanism, we determined the escaping mutation profiles2, epitope distribution3 and Omicron neutralization efficacy of 1640 RBD-directed neutralizing antibodies (NAbs), including 614 isolated from BA.1 convalescents. Interestingly, post-vaccination BA.1 infection mainly recalls wildtype-induced humoral memory. The resulting elicited antibodies could neutralize both wildtype and BA.1 and are enriched on non-ACE2-competing epitopes. However, most of these cross-reactive NAbs are heavily escaped by L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1; nevertheless, these NAbs are largely escaped by BA.2/BA.4/BA.5 due to D405N and F486V, and react weakly to pre-Omicron variants, exhibiting poor neutralization breadths. As for therapeutic NAbs, Bebtelovimab4 and Cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, while the S371F, D405N and R408S mutations would undermine most broad sarbecovirus NAbs. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.

Comprehensive Epitope Mapping of Broad Sarbecovirus Neutralizing Antibodies

Omicron sub-lineage BA.2 has rapidly surged globally, accounting for over 60% of recent SARS-CoV-2 infections. Newly acquired RBD mutations and high transmission advantage over BA.1 urge the investigation of BA.2s immune evasion capability. Here, we show that BA.2 causes strong neutralization resistance, comparable to BA.1, in vaccinated individuals plasma. However, BA.2 displays more severe antibody evasion in BA.1 convalescents, and most prominently, in vaccinated SARS convalescents plasma, suggesting a substantial antigenicity difference between BA.2 and BA.1. To specify, we determined the escaping mutation profiles1,2 of 714 SARS-CoV-2 RBD neutralizing antibodies, including 241 broad sarbecovirus neutralizing antibodies isolated from SARS convalescents, and measured their neutralization efficacy against BA.1, BA.1.1, BA.2. Importantly, BA.2 specifically induces large-scale escape of BA.1/BA.1.1-effective broad sarbecovirus neutralizing antibodies via novel mutations T376A, D405N, and R408S. These sites were highly conserved across sarbecoviruses, suggesting that Omicron BA.2 arose from immune pressure selection instead of zoonotic spillover. Moreover, BA.2 reduces the efficacy of S309 (Sotrovimab)3,4 and broad sarbecovirus neutralizing antibodies targeting the similar epitope region, including BD55-5840. Structural comparisons of BD55-5840 in complexes with BA.1 and BA.2 spike suggest that BA.2 could hinder antibody binding through S371F-induced N343-glycan displacement. Intriguingly, the absence of G446S mutation in BA.2 enabled a proportion of 440-449 linear epitope targeting antibodies to retain neutralizing efficacy, including COV2-2130 (Cilgavimab)5. Together, we showed that BA.2 exhibits distinct antigenicity compared to BA.1 and provided a comprehensive profile of SARS-CoV-2 antibody escaping mutations. Our study offers critical insights into the humoral immune evading mechanism of current and future variants.

A high-efficiency and versatile CRISPR/Cas9-mediated HDR-based biallelic editing system / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 nuclease (Cas9), the third-generation genome editing tool, has been favored because of its high efficiency and clear system composition. In this technology, the introduced double-strand breaks (DSBs) are mainly repaired by non-homologous end joining (NHEJ) or homology-directed repair (HDR) pathways. The high-fidelity HDR pathway is used for genome modification, which can introduce artificially controllable insertions, deletions, or substitutions carried by the donor templates. Although high-level knock-out can be easily achieved by NHEJ, accurate HDR-mediated knock-in remains a technical challenge. In most circumstances, although both alleles are broken by endonucleases, only one can be repaired by HDR, and the other one is usually recombined by NHEJ. For gene function studies or disease model establishment, biallelic editing to generate homozygous cell lines and homozygotes is needed to ensure consistent phenotypes. Thus, there is an urgent need for an efficient biallelic editing system. Here, we developed three pairs of integrated selection systems, where each of the two selection cassettes contained one drug-screening gene and one fluorescent marker. Flanked by homologous arms containing the mutated sequences, the selection cassettes were integrated into the target site, mediated by CRISPR/Cas9-induced HDR. Positively targeted cell clones were massively enriched by fluorescent microscopy after screening for drug resistance. We tested this novel method on the amyloid precursor protein (APP) and presenilin 1 (PSEN1) loci and demonstrated up to 82.0% biallelic editing efficiency after optimization. Our results indicate that this strategy can provide a new efficient approach for biallelic editing and lay a foundation for establishment of an easier and more efficient disease model.

Effects of ruminative thinking on 1-year outcomes in patients with first-episode depression: the mediating role of family functioning / 中华行为医学与脑科学杂志

Objective:To investigate whether rumination and family functioning can predict the level of depression after 1 year of follow-up in patients with first-episode depression, and whether family functioning plays a mediating role between rumination and depression level.Methods:Sixty-five patients with first-episode depression who met the enrollment requirements were included, and all subjects were assessed the 17-item Hamilton depression scale(HAMD-17), rumination response scale(RRS) and family assessment device(FAD). All subjects were followed up for 1 year, and the predictive effects of rumination and family functioning at baseline on the level of depression after 1 year of follow-up were investigated by hierarchical linear regression analysis and mediation analysis.Results:At the baseline stage, rumination, role, affective involvement (AI) and general functioning (GF) were significantly positively associated with depression level after 1 year of follow-up in patients with first-episode depression ( r=0.49, P<0.01; r=0.30, P=0.02; r=0.43, P<0.01; r=0.50, P<0.01; respectively). Rumination, AI and GF at the baseline stage predicted depression level after 1 year of follow-up ( β=0.315, t=2.954, P=0.005; β=0.261, t=2.550, P=0.013; β=0.323, t=2.952, P=0.005). Mediation analysis showed that AI and GF partially mediated the relationship between rumination at baseline and depression level at 1 year follow-up (point estimate value for AI=0.040, 95% CI=0.012-0.090); point estimate value for GF=0.066, 95% CI=0.017-0.143). Conclusions:Rumination and family functioning at baseline in first-episode depressed patients can predict the depression level at 1 year follow-up.Family functioning partly mediates the relationship between the baseline rumination and the depression level at 1 year follow-up.

B.1.1.529 escapes the majority of SARS-CoV-2 neutralizing antibodies of diverse epitopes

The SARS-CoV-2 B.1.1.529 variant (Omicron) contains 15 mutations on the receptor-binding domain (RBD). How Omicron would evade RBD neutralizing antibodies (NAbs) requires immediate investigation. Here, we used high-throughput yeast display screening1,2 to determine the RBD escaping mutation profiles for 247 human anti-RBD NAbs and showed that the NAbs could be unsupervised clustered into six epitope groups (A-F), which is highly concordant with knowledge-based structural classifications3-5. Strikingly, various single mutations of Omicron could impair NAbs of different epitope groups. Specifically, NAbs in Group A-D, whose epitope overlap with ACE2-binding motif, are largely escaped by K417N, G446S, E484A, and Q493R. Group E (S309 site)6 and F (CR3022 site)7 NAbs, which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but still, a subset of NAbs are escaped by G339D, N440K, and S371L. Furthermore, Omicron pseudovirus neutralization showed that single mutation tolerating NAbs could also be escaped due to multiple synergetic mutations on their epitopes. In total, over 85% of the tested NAbs are escaped by Omicron. Regarding NAb drugs, the neutralization potency of LY-CoV016/LY-CoV555, REGN10933/REGN10987, AZD1061/AZD8895, and BRII-196 were greatly reduced by Omicron, while VIR-7831 and DXP-604 still function at reduced efficacy. Together, data suggest Omicron would cause significant humoral immune evasion, while NAbs targeting the sarbecovirus conserved region remain most effective. Our results offer instructions for developing NAb drugs and vaccines against Omicron and future variants.

Structures of SARS-CoV-2 B.1.351 neutralizing antibodies provide insights into cocktail design against concerning variants

The spread of the SARS-CoV-2 variants could seriously dampen the global effort to tackle the COVID-19 pandemic. Recently, we investigated the humoral antibody responses of SARS-CoV-2 convalescent patients and vaccinees towards circulating variants, and identified a panel of monoclonal antibodies (mAbs) that could efficiently neutralize the B.1.351 (Beta) variant. Here we investigate how these mAbs target the B.1.351 spike protein using cryo-electron microscopy. In particular, we show that two superpotent mAbs, BD-812 and BD-836, have non-overlapping epitopes on the receptor-binding domain (RBD) of spike. Both block the interaction between RBD and the ACE2 receptor; and importantly, both remain fully efficacious towards the B.1.617.1 (Kappa) and B.1.617.2 (Delta) variants. The BD-812/BD-836 pair could thus serve as an ideal antibody cocktail against the SARS-CoV-2 VOCs.

Genome-wide CRISPR activation screen identifies novel receptors for SARS-CoV-2 entry

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been endangering worldwide public health and economy. SARS-CoV-2 infects a variety of tissues where the known receptor ACE2 is low or almost absent, suggesting the existence of alternative pathways for virus entry. Here, we performed a genome-wide barcoded-CRISPRa screen to identify novel host factors that enable SARS-CoV-2 infection. In addition to known host proteins, i.e. ACE2, TMPRSS2 and NRP1, we identified multiple host components, among which LDLRAD3, TMEM30A and CLEC4G were confirmed as functional receptors for SARS-CoV-2. All these membrane proteins bind directly to spikes N-terminal domain (NTD). Their essential and physiological roles have all been confirmed in either neuron or liver cells. In particular, LDLRAD3 and CLEC4G mediate SARS-CoV-2 entry and infection in a fashion independent of ACE2. The identification of the novel receptors and entry mechanisms could advance our understanding of the multiorgan tropism of SARS-CoV-2, and may shed light on the development of the therapeutic countermeasures against COVID-19.

Relationship between classroom lighting and poor vision of students in primary and secondary schools in Tianjin / 中国学校卫生

Objective@#To investigate the relationship between classroom lighting and poor vision of students in primary and secondary schools in Tianjin, and to provide reference for targeted prevention measures for comprehensive school eye health programmes.@*Methods@#A total of 623 classrooms and 24 713 students in 89 primary and secondary schools in Tianjin were selected using stratified cluster sampling method in Sep.to Oct. of 2020. The illuminometer was used to monitor the lighting environment of the classroom, and the standard logarithmic vision light box was used to detect the naked eye vision of students. Chisquare test, variance analysis and binary Logistic regression were used in SPSS software.@*Results@#Rate of low vision among primary and secondary school students in Tianjin was 67.86%. The qualification rate of blackboard reflectance, blackboard average illumination, blackboard illumination uniformity, desk average illumination and desk illumination uniformity were 58.11%, 53.13%, 73.19%, 66.61% and 75.12%, respectively. Univariate analyses showed that the blackboard reflectance, blackboard average illumination, desk average illumination, and desk illumination uniformity were associated with low vision among students(χ 2=311.29, 62.54, 61.71, 6.59, P<0.05). Multivariable Logistic regression analysis showed that blackboard reflectance, average illumination of blackboard and desk were associated with higher risk of poor vision[OR(95%CI)=1.19(1.11-1.27),1.27(1.17-1.37),1.11(1.02-1.20), P<0.05].@*Conclusion@#Prevalence of low vision among primary and secondary school students in Tianjin is relatively high. Blackboard reflectance, average illumination of blackboard and desk are the important determinants for poor vision of primary and secondary school students. Creating effective classroom lighting scheme is crucial for vision health among students.

A case of maternal 45,X/46,XX mosaicism detected by non-invasive prenatal testing / 中华医学遗传学杂志

OBJECTIVE@#To report on a case of maternally derived 45,X mosaicism detected by non-invasive prenatal testing (NIPT).@*METHODS@#Fetal sex chromosomal abnormality was detected by NIPT. Maternally derived 45,X mosaicism was confirmed by chromosome karyotype analysis. Fetal sex chromosome aneuploidy was detected by amniotic fluid chromosome microarray analysis.@*RESULTS@#A maternal 45,X mosaicism was diagnosed. The fetus was confirmed to be normal.@*CONCLUSION@#Maternal 45,X masaicism can be diagnosed by NIPT.

A case of maternal 45, X/46, XX mosaicism detected by non-invasive prenatal testing / 中华医学遗传学杂志

Objective@#To report on a case of maternally derived 45, X mosaicism detected by non-invasive prenatal testing (NIPT).@*Methods@#Fetal sex chromosomal abnormality was detected by NIPT. Maternally derived 45, X mosaicism was confirmed by chromosome karyotype analysis. Fetal sex chromosome aneuploidy was detected by amniotic fluid chromosome microarray analysis.@*Results@#A maternal 45, X mosaicism was diagnosed. The fetus was confirmed to be normal.@*Conclusion@#Maternal 45, X masaicism can be diagnosed by NIPT.

Formulation and application of drainage tube nursing program in step-up mini-invasive surgery for infected pancreatic necrosis / 中华护理杂志

This paper summarized drainage tube nursing experience instep-up mini-invasive surgery for infected pancreatic necrosis,special management group for drainage nursing was established,and drainage tube management in stages was implemented. Nursing key pointsin the first stage was: catheter puncture assistance,single-site and single-tube fixed drainage,anddynamicdrainage effect observation. Nursing key points in the second stage was:single-site and multi-tube fixed drainage,close surveillance for negative pressure drainage effect,and strengthened protection of drainage tubeduring patient activities. Nursingkey points in the third stage was: multi-site and multi-tube fixed drainage,prevention of hospital-acquired infection,and discharge guidance for patientsin drainage tube care. The cure rate of this group was 91.93% with 62 patients,and there was no occurrence of unplanned extubationduring hospitalization.

Prognosis of patients with coronary heart disease and normal myocardial perfusion imaging / 心血管康复医学杂志

Objective: To observe influence of different risk factors on prognosis of patients with coronary heart disease (CHD) and normal myocardial perfusion imaging outcome.Methods: A total of 99 CHD patients with normal myocardial perfusion imaging outcome were selected.Left ventricular function indexes were measured by gated resting myocardial imaging in resting and stress state.All patients received telephone follow-up until natural death (died of other causes) or fatal or non-fatal heart attacks, or the termination of the experiment after 45 months.Cox proportion risk regression model was used to analyze risk factors of fatal and non-fatal heart attacks.Results: A total of 15 cases died during the 45-month follow-up.Mean all-cause mortality per year was 5.05%.Fatal heart attacks occurred in nine cases (9.09%), and non-fatal heart attacks occurred in 21 cases (21.21%).Cox proportion risk regression analysis indicated that smoking and left ventricular ejection fraction (LVEF) <50% were risk factors for fatal heart attacks (HR=4.887, 3.365, P=0.043, 0.002), while diabetes mellitus, dyslipidemia, smoking and LVEF<50% were risk factors for non-fatal heart attacks (HR=2.215~4.544, P<0.05 all).Conclusion: Incidence rate of cardiovascular events is higher in CHD patients with normal myocardial perfusion imaging.Smoking and impaired heart function suggest poor prognosis in these patients.

Relationship between blood pressure variability and left ventricular diastolic function in patients with ;essential hypertension / 心血管康复医学杂志

Objective:To observe the relationship between dynamic blood pressure variability (BPV) and left ventric‐ular diastolic function in patients with essential hypertension (EH) .Methods :A total of 140 newly diagnosed EH pa‐tients were selected .According to total coefficient of variation (CV) of 24h systolic blood pressure BPV ,they were divided into high CV group (n=70 ,CV>12.16% ) and low CV group (n=70 ,CV≤12.16% ) .Another 70 healthy subjects with corresponding gender and age were enrolled as healthy control group simultaneously .Echocardiography was used to measure mitral early diastolic peak flow velocity (E) ,late diastolic peak flow velocity (A) and decelera‐tion time of E peak (DT);meanwhile ,tissue Doppler mode was used to record early diastolic peak velocity (Em) and late diastolic peak velocity (Am) .All above indexes were compared among all groups .Results:Compared with healthy control group ,BPV significantly rose in EH patients (P<0.05 or < 0.01) .All BPV indexes in high CV group were significantly higher than those of low CV group except daytime mean diastolic blood pressure variability (dDBP‐BPV) and nighttime mean diastolic blood pressure variability (nDBP‐BPV) , P<0.05 all .Compared with healthy control group ,there were significant reductions in E and Em/Am ,and significant rise in DT and E/Em in EH patients ,P<0.05 or <0.01 ;compared with low CV group ,there was significant rise in E/Em [(10.32 ± 3.20) vs .(14.22 ± 2.20) ,P=0.033] in high CV group .Conclusion:Left ventricular diastolic dysfunction is more severe in hypertensive patients with higher dynamic blood pressure variability .

Evaluation of the Xpert MTB/RIF assay for diagnosis of tuberculosis and rifampin resistance in county-level laboratories in Hunan province, China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The Xpert MTB/RIF showed high sensitivity and specificity in previous studies carried out in different epidemiological and geographical settings and patient populations in high-burden tuberculosis (TB) countries. However, there were little data obtained by validation or demonstration study of the assay in China. In this study, the performance of Xpert MTB/RIF was investigated in two county-level laboratories in Hunan Province, China.</p><p><b>METHODS</b>Consecutive patients with suspected pulmonary tuberculosis (PTB) and suspicion for multidrug-resistant tuberculosis (MDR-TB) were enrolled. For each patient suspected to have PTB, three sputum specimens (one spot sputum, one night sputum, and one morning sputum) were collected and each sputum was tested with smear microscopy, Löwenstein-Jensen (LJ) culture, and Xpert MTB/RIF test. For comparison across subgroups and testing methods, 95% confidence intervals were calculated. All analyses were done with SPSS 16.0, and P < 0.05 was regarded as significant.</p><p><b>RESULTS</b>For case detection, the sensitivity of Xpert MTB/RIF was 100% for smear- and culture-positive TB and 88.6% for smear-negative and culture-positive TB; the overall sensitivity was 94.5% for all culture-positive patients. The specificity was 99.8%. The sensitivity of Xpert MTB/RIF assay was 22.0% in clinical TB patients and the specificity reached 100.0% in the group of patients who are infected with nontuberculous mycobacteria. For the detection of rifampin resistance, the sensitivity of MTB/RIF RIF-resistance detection was 92.9%, and the specificity was 98.7%. Of the 26 Xpert MTB/RIF-positive and RIF-resistant patients confirmed by LJ proportion tests, 20 (76.9%) patients were infected by MDR-TB.</p><p><b>CONCLUSIONS</b>The Xpert MTB/RIF assay is a highly sensitive and specific method for diagnosis of TB and RIF resistance, which will enable it to have the potential to be used in county-level laboratories and lead to the reduction of the infectious pool and improvements in TB control in China. Further evaluations in county-level laboratories for implementing the assay are still required.</p>

Role and mechanism of retinoic acid in axonal regeneration / 中国组织工程研究

BACKGROUND:Retinoic acid signaling pathways is very important in the formation pf nervous system, specialization of neurons and outgrowth of axons. The recent studies show that, retinoic acid plays an important role in the process of axonal regeneration, but few research reports its exact molecular mechanism. OBJECTIVE:To analyze and summarize the mechanism underlying retinoic acid signaling pathways in the process of axonal regeneration. METHODS:A computer-based online research was conducted among the VIP, CNKI, PubMed, BioMed Centeral, Springer, The Free Medical Journals, EBSCO and Foreign Journals Integration System between January 2000 and December 2013, with the key words of“retinoic acid, the central nervous system, nerve damage, axon regeneration, and mechanism”in Chinese and English. A total of 43 studies addressing the molecular mechanism of retinoic acid in axonal regeneration were screened. According to the supplementary documents, another five references were added. Repetitive research and atypical reports were excluded. RESULTS AND CONCLUSION:Fol owing acute central nervous system injury, axonal regeneration and functional recovery are extremely limited. For proper functionality fol owing injury, axons must regrow, reinnervate their targets, and remyelinate their axons. When the central nervous system injuries occur, retinoic acid signaling pathways express transcription factor retinoic acid receptorβ2 to induce axonal regeneration fol owing injury;in dorsal root ganglion neurons, cAMP levels are greatly increased by lentiviral retinoic acid receptorβ2 expression and contribute to neurite outgrowth. More recently, retinoic acid-retinoic acid receptorβ2 pathways directly transcriptional y repress a member of the inhibitory Nogo receptor complex, Lingo-1, under an axonal growth inhibitory environment in vitro as wel as fol owing spinal cord injury in vivo. Through these molecular mechanisms, retinoic acid signaling pathways play its important role in the process of axonal regeneration.