Clinical Effect of Feining Paidu Decoction on Refractory Mycoplasma Pneumoniae Pneumonia in Child Patients / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Feining Paidu decoction on refractory Mycoplasma pneumoniae pneumonia in child patients. MethodA randomized controlled trial （RCT） was conducted， with 96 child patients randomly divided into a control group and an observation group， each containing 48 cases. The control group received intravenous azithromycin （10 mg·kg-1·d-1） for 7 days， intravenous methylprednisolone （1 mg·kg-1·d-1） for 3 days， along with supportive treatments such as fluid infusion and antipyretics. The observation group received oral administration of Feining Paidu decoction once a day for 7 days. Changes in traditional Chinese medicine （TCM） syndrome scores， clinical efficacy， serum soluble B7-H3 （sB7-H3）， serum inflammatory factors， coagulation function， and lung imaging ［computer tomography（CT）］ scores were observed in both groups. Adverse reaction events were also recorded. ResultThe total effective rate in the observation group was 95.74% （45/47）， significantly higher than 80.43% （37/46） in the control group （Z=-3.702， P<0.01）. Compared with the results before treatment， TCM syndrome scores， lung imaging scores， sB7-H3， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， D-dimer （D-D）， and fibrinogen （FIB） levels in both groups all significantly decreased after treatment （P<0.05， P<0.01）. After treatment， the observation group showed significantly better results in these indicators than the control group （P<0.05， P<0.01）. There was no statistically significant difference in thrombin time （TT） in the control group before and after treatment， while the observation group showed a significant prolongation after treatment （P<0.05）. There were no statistically significant differences in activated partial thromboplastin time （APTT） and prothrombin time （PT） between the two groups before treatment， and no serious adverse reactions occurred in either group. ConclusionFeining Paidu decoction combined with conventional treatment can alleviate inflammatory responses， improve hypercoagulable states， promote the absorption of pulmonary inflammation， and enhance the clinical efficacy of refractory Mycoplasma pneumoniae pneumonia in children.

HBXIP blocks myosin-IIA assembly by phosphorylating and interacting with NMHC-IIA in breast cancer metastasis

Tumor metastasis depends on the dynamic balance of the actomyosin cytoskeleton. As a key component of actomyosin filaments, non-muscle myosin-IIA disassembly contributes to tumor cell spreading and migration. However, its regulatory mechanism in tumor migration and invasion is poorly understood. Here, we found that oncoprotein hepatitis B X-interacting protein (HBXIP) blocked the myosin-IIA assemble state promoting breast cancer cell migration. Mechanistically, mass spectrometry analysis, co-immunoprecipitation assay and GST-pull down assay proved that HBXIP directly interacted with the assembly-competent domain (ACD) of non-muscle heavy chain myosin-IIA (NMHC-IIA). The interaction was enhanced by NMHC-IIA S1916 phosphorylation via HBXIP-recruited protein kinase PKCβII. Moreover, HBXIP induced the transcription of PRKCB, encoding PKCβII, by coactivating Sp1, and triggered PKCβII kinase activity. Interestingly, RNA sequencing and mouse metastasis model indicated that the anti-hyperlipidemic drug bezafibrate (BZF) suppressed breast cancer metastasis via inhibiting PKCβII-mediated NMHC-IIA phosphorylation in vitro and in vivo. We reveal a novel mechanism by which HBXIP promotes myosin-IIA disassembly via interacting and phosphorylating NMHC-IIA, and BZF can serve as an effective anti-metastatic drug in breast cancer.

Analysis of genome copy number variations in fetuses with isolated ventricular septal defect and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of copy number variation sequencing (CNV-seq) for revealing the genetic etiology of fetuses with isolated ventricular septal defect (VSD).@*METHODS@#From December 2017 to December 2020, 69 fetuses with isolated VSD were identified at the First Affiliated Hospital of Zhengzhou University. Meanwhile, 839 similar prenatal cases were selected from public databases including Wanfang data, Wanfang Medicine, and China National Knowledge Infrastructure (CNKI) by using keywords such as "Ventricular septal defect", "Copy number variation", and "Prenatal". A total of 908 fetuses with isolated VSD were analyzed. CNV-seq was carried out for 69 fetuses.@*RESULTS@#Among the 908 fetuses, 33 (3.63%) were found to harbor pathogenic CNVs, which included 11 chromosomal aneuploidies (1.21%) and 22 pathogenic CNVs (2.42%). The pathogenic CNVs have involved 12 genetic syndromes, with those known to involve the heart development including 5 cases of 22q11.21 deletion syndrome, 2 cases of 4q terminal deletion syndrome, and 1 case of 9q subtelomere deletion syndrome. The outcome of pregnancies for 15 fetuses with pathogenic CNVs was known, of which 12 were terminated, and 3 had spontaneous closure of the ventricular septum after birth, but 1 of them had other abnormalities.@*CONCLUSION@#Fetuses with isolated VSD have a relatively high risk for chromosomal abnormalities, for which CNV-seq should be recommended.

Depression and Anxiety During the COVID-19 Pandemic: Epidemiology, Mechanism, and Treatment / 神经科学通报·英文版

The Coronavirus Disease 2019 (COVID-19) pandemic has had an adverse impact on the physical and mental health of the public worldwide. In addition to illness in patients with COVID-19, isolated people and the general population have experienced mental health problems due to social distancing policies, mandatory lockdown, and other psychosocial factors, and the prevalence of depression and anxiety significantly increased during the pandemic. The purpose of this review is to elucidate the epidemiology, contributing factors, and pathogenesis of depression and anxiety. during the pandemic. These findings indicate that physicians and psychiatrists should pay more attention to and identify those with a high risk for mental problems, such as females, younger people, unmarried people, and those with a low educational level. In addition, researchers should focus on identifying the neural and neuroimmune mechanisms involved in depression and anxiety, and assess the intestinal microbiome to identify effective biomarkers. We also provide an overview of various intervention methods, including pharmacological treatment, psychological therapy, and physiotherapy, to provide a reference for different populations to guide the development of optimized intervention methods.

Influence of sports elective courses on college students' physical health / Influência dos cursos eletivos esportivos sobre a saúde física dos estudantes universitários / Influencia de las asignaturas deportivas optativas en la salud física de los estudiantes universitarios

ABSTRACT Introduction The college sports environment is characterized by breadth, diversity, and personality. This is an important period to develop students' physical ability and improve their personality. Objective Compare the effects of different exercise methods on students' health status. Methods 2991 college students participated in different sports activities. These sports were conducted based on the selection course (PE), all during one semester. The students' physical health status was observed through experiments performed before and after the intervention. Results Activities such as basketball and soccer showed high effectiveness in improving students' vital capacity index, volleyball expressively improved students' performance in the long jump, tennis and table tennis were effective in improving students' strength and adherence index, being lower in other indices. Martial arts also stood out in improving the students' vital capacity index. Conclusion Improving physical health should be an overall process of students' fitness development, and universities should actively encourage college students to participate in long-term sports to improve their health. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução O ambiente do esporte universitário é caracterizado pela abrangência, diversidade e personalidade. Este é um período importante para desenvolver a capacidade física dos estudantes e melhorar a sua personalidade. Objetivo Comparar os efeitos de diferentes métodos de exercício sobre o estado de saúde dos estudantes. Métodos 2991 estudantes universitários participaram de diferentes atividades esportivas. Estes esportes foram conduzidos com base no curso de seleção (PE), todos durante um semestre. O estado de saúde física dos estudantes foi observado através de experimentos executados previa e posteriormente à intervenção. Resultados Atividades como basquetebol e futebol demonstraram alta efetividade para melhorar o índice de capacidade vital dos estudantes, voleibol melhorou expressivamente o desempenho dos alunos no salto em distância, o tênis e o tênis de mesa foram efetivos para aprimorar o índice de força e de adesão dos alunos, sendo inferior noutros índices. Também as artes marciais se destacaram ao melhorar o índice de capacidade vital dos alunos. Conclusão O aprimoramento da saúde física deve ser um processo global de desenvolvimento da aptidão física dos estudantes e as universidades devem encorajar ativamente os estudantes universitários a participar de esportes de longo prazo para melhorar sua saúde. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción El entorno del deporte universitario se caracteriza por su alcance, diversidad y personalidad. Es un periodo importante para desarrollar la capacidad física de los alumnos y mejorar su personalidad. Objetivo Comparar los efectos de diferentes métodos de ejercicio sobre el estado de salud de los estudiantes. Métodos 2991 estudiantes universitarios participaron en diferentes actividades deportivas. Estos deportes se llevaron a cabo basándose en el curso de selección (PE), todo ello durante un semestre. El estado de salud física de los alumnos se observó mediante experimentos realizados antes y después de la intervención. Resultados Actividades como el baloncesto y el fútbol mostraron una alta eficacia para mejorar el índice de capacidad vital de los alumnos, el voleibol mejoró expresivamente el rendimiento de los alumnos en salto de longitud, el tenis y el tenis de mesa fueron eficaces para mejorar el índice de fuerza y adherencia de los alumnos, siendo inferiores en otros índices. También las artes marciales se destacaron en la mejora del índice de capacidad vital de los alumnos. Conclusión La mejora de la salud física debería ser un proceso global del desarrollo de la forma física de los estudiantes y las universidades deberían animar activamente a los universitarios a participar en deportes de larga duración para mejorar su salud. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Establishing and evaluating a robust method based on LC-MS/MS for simultaneous determination of Aβ1-42,Aβ1-40 and A β1-38 in cerebrospinal fluid / 中华检验医学杂志

Objective:To establish and validate an LC-MS/MS method for simultaneous determination of Aβ 1-42, Aβ 1-40, and Aβ 1-38 in cerebrospinal fluid. Additionally, the consistency between this method and three mainstream detection methods was evaluated.Methods:This study involved method establishment, validation, and consistency evaluation. The N15 labeled β-amyloid protein was used as the internal standard. Extraction was performed using Waters MCX 96-wells solid phase extraction plate, and the eluent was collected to QuanRecovery MaxPeak 700 μl plate. At the positive ion mode, the multi-reaction ion monitoring mode based on electric spray ionization is chosen for the determination of CSF Aβ 1-42, Aβ 1-40, and Aβ 1-38. Referring to the CLSI C62-A and EP-15A3 guidelines, the method is evaluated and verified, including quantitation of limit (LOQ), linearity, recovery, precision, and accuracy. In addition, a total of 57 clinical residual CSF samples were collected and the concentrations of Aβ 1-42 and Aβ 1-40 were determined based on manual INNOTEST ELISA assay and Lumipulse G and Roche Elecsys fully automated biochemical analyzers. The comparison analysis and deviation evaluation were conducted by passing-bablok and Bland Altman methods.Results:The analysis time of this method is 8 min, and the LOQ of Aβ 1-42, Aβ1-40 and Aβ1-38 is 0.1 ng/ml, 0.5 ng/ml, and 0.1 ng/ml, respectively, and the linear range can meet the needs of clinical detection. Respectively, the recovery is 86.2%-93.8%, 100.9%-103.9% and 103.3%-107.1%; the total imprecision is 4.7%-7.4%, 3.5%-4.6% and 5.2%-10.9%. The measured values of Aβ 1-42 certified reference materials are all within the allowable uncertainty requirements. Moreover, the carryover rate of three analytes was all≤0.11%. In addition, the correlations of Aβ 1-42 and Aβ1-40 in CSF between this LC-MS/MS method and the INNOTEST ELISA method, Lumipulse G and Roche Elecsys fully automated biochemical analyzers were all deemed good, with correlation coefficient (r) ranging from 0.920 to 0.970. However, the measured values between the four methods were remarkably different.Conclusion:We established and validated a robust method based on LC-MS/MS technology for simultaneous determination of Aβ 1-42, Aβ 1-40, and Aβ 1-38 in CSF. The method is accurate, simple, and suitable for clinical measurements. However, despite good correlations, there were substantial differences in the measurement results of Aβ 1-42 and Aβ 1-40 among different analytical platforms, indicating the need for further promotion of harmonization and standardization processes for AD classic biomarkers.

Immune response of primary and booster immunity of SARS-CoV-2 vaccination among patients with chronic liver disease: a real-world study

AimThe present study discussed the humoral immune response and antibody dynamics after primary and booster immunity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with chronic liver disease (CLD) in the real world. Thus, it provided data to develop SARS-CoV-2 vaccination strategy. MethodsPatients with confirmed CLD and completed primary or booster immunity of SARS-CoV-2 vaccines were enrolled. Serological specimens were collected after primary or booster immunity of SARS-CoV-2 vaccines to detect novel coronavirus neutralizing antibody (nCoV NTAb) and novel coronavirus spike receptor-binding domain antibody (nCoV S-RBD). Thus, we could evaluate the humoral immune response and antibody dynamics after primary and booster immunity of SARS-CoV-2 vaccines among patients with CLD. Simultaneously, baseline demographics, liver disease-related situations, comorbidity-related situations, SARS-CoV-2 vaccination information, and laboratory examination-related indicators of patients were collected. ResultsA total of 315 patients received SARS-CoV-2 vaccines, including 223 patients who completed the primary immunity of SARS-CoV-2 vaccines, 114 patients who completed booster immunity of SARS-CoV-2 vaccines, and 22 patients who underwent the antibody detection of SARS-CoV-2 vaccines after both primary and booster immunities. The positive rate of nCoV NTAb was 59.64% in Primary and 87.72% in Booster (P<0.001). The median level of nCoV NTAb was 11.53 AU/mL in Primary and 31.98 AU/mL in Booster (P<0.001). The positive rate of nCoV S-RBD was 69.06% in Primary and 91.23% in Booster (P<0.001). The median level of nCoV S-RBD was 21.60AU/mL in Primary and 112.65 AU/mL in Booster (P<0.001). After booster immunity of SARS-CoV-2 vaccines in 22 patients, the positive rate of nCoV NTAb increased from 59.09% to 86.36%, and that of nCoV S-RBD increased from 68.18% to 90.91%. The median level of nCoV NTAb increased from 11.24 AU /mL to 59.14 AU /mL after booster immunity. The median level of nCoV S-RBD increased from 27.28 AU/mL to 219.10 AU/mL. Compared to the antibody level of primary immunity, the median level of nCoV NTAb and nCoV S-RBD in 22 patients was increased by 5.26 and 8.03 times, respectively. Among 22 patients, 9 were negative for nCoV NTAb after primary immunity, while 6 were transformed positive after booster immunity, and the positive conversion rate of nCoV NTAb was 66.7%. On the other hand, 7 patients were negative for nCoV S-RBD after primary immunity, while 5 were transformed positive after booster immunity, and the positive conversion rate of nCoV S-RBD was 71.4%. ConclusionPatients with CLD show improved humoral immune response after completing primary and booster immunity of SARS-CoV-2 vaccines, while booster immunity further improves the positive rate and antibody level of patients with CLD. Finally, the positive conversion rate among patients with primary immunity failure also can be improved after booster immunity.

Post-traumatic growth trajectories among frontline healthcare workers during the COVID-19 pandemic: A three-wave follow-up study in mainland China.

Objectives: The COVID-19 pandemic has taken a significant toll on people worldwide for more than 2 years. Previous studies have highlighted the negative effects of COVID-19 on the mental health of healthcare workers (HCWs) more than the positive changes, such as post-traumatic growth (PTG). Furthermore, most previous studies were cross-sectional surveys without follow-ups. This study draws on PTG follow-up during the COVID-19 outbreak at 12-month intervals for 2 years since 2020. The trajectories and baseline predictors were described. Methods: A convenience sampling method was used to recruit frontline nurses or doctors at the COVID-19-designated hospital who were eligible for this study. A total of 565 HCWs completed the 2 years follow-up and were used for final data analysis. The latent growth mixture models (GMM) was used to identify subgroups of participants with different PTG trajectories. Multinomial logistic regression model was used to find predictors among sociodemographic characteristics and resilience at baseline. Results: Four trajectory PTG types among HCWs were identified: 'Persistent, "Steady increase", "High with drop", and "Fluctuated rise." Comparing the "Persistent low" type, the other three categories were all associated with older age, higher education. Furthermore, "Persistent low" was also negatively associated with resilience at baseline. Conclusion: The PTG of HCWs with different characteristics showed different trends over time. It is necessary to increase the measure frequency to understand the PTG status in different times. Improving HCW's resilience could help improve staff PTG.

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.

DYNC2H1 gene mutation analysis and prenatal diagnosis in two pedigrees affected with short rib-polydactyly syndrome type Ⅲ / 中华围产医学杂志

Objective:To investigate the molecular genetic etiology of two fetuses with short rib-polydactyly syndrome type Ⅲ (SRPS Ⅲ).Methods:Next-generation sequencing (NGS) was used to detect 226 known genes related to inherited skeletal dysplasia in two fetuses with SRPS Ⅲ diagnosed in the First Affiliated Hospital of Zhengzhou University in August 2015 and June 2020. Suspect pathological variants were verified in the pedigree members using Sanger sequencing. The prenatal genetic diagnosis of the high-risk fetus in pedigree one was conducted to identify the confirmed pathogenic variation.Results:The homozygous mutation of DYNC2H1 gene c.5881A>G(p.Lys1961Glu) was identified in the proband in pedigree one, and the parents were the carriers. The proband in pedigree two carried compound heterozygous mutations in the DYNC2H1 gene with c.10606C>T(p.Arg3536*) inherited from the father and c.8954T>G(p.Val2985Gly) from the mother. Autosomal recessive inheritance was confirmed in both pedigrees. Mutations of c.5881A>G(p.Lys1961Glu) and c.8954T>G(p.Val2985Gly) in the DYNC2H1 gene were likely pathogenic variants and had not been reported before. The prenatal diagnosis did not identify the DYNC2H1 gene c.5881A>G(p.Lys1961Glu) mutation in the fetus (Ⅱ-7) in pedigree one, which was confirmed by the umbilical cord blood sample after birth. Conclusion:DYNC2H1 gene mutation underlies the fetal skeletal dysplasia in the two pedigrees.

Symphony of nanomaterials and immunotherapy based on the cancer-immunity cycle

The immune system is involved in the initiation and progression of cancer. Research on cancer and immunity has contributed to the development of several clinically successful immunotherapies. These immunotherapies often act on a single step of the cancer-immunity cycle. In recent years, the discovery of new nanomaterials has dramatically expanded the functions and potential applications of nanomaterials. In addition to acting as drug-delivery platforms, some nanomaterials can induce the immunogenic cell death (ICD) of cancer cells or regulate the profile and strength of the immune response as immunomodulators. Based on their versatility, nanomaterials may serve as an integrated platform for multiple drugs or therapeutic strategies, simultaneously targeting several steps of the cancer-immunity cycle to enhance the outcome of anticancer immune response. To illustrate the critical roles of nanomaterials in cancer immunotherapies based on cancer-immunity cycle, this review will comprehensively describe the crosstalk between the immune system and cancer, and the current applications of nanomaterials, including drug carriers, ICD inducers, and immunomodulators. Moreover, this review will provide a detailed discussion of the knowledge regarding developing combinational cancer immunotherapies based on the cancer-immunity cycle, hoping to maximize the efficacy of these treatments assisted by nanomaterials.

Novel compound heterozygous SCN9A variations causing congenital insensitivity to pain in a patient / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child featuring congenital insensitivity to pain (CIP).@*METHODS@#Targeted capture and next generation sequencing (NGS) was carried out for the proband. Suspected pathogenic variants were confirmed by Sanger sequencing of the proband and his parents.@*RESULTS@#The proband was found to harbor compound heterozygous variants of SCN9A gene, namely c.1598delA (p.N533Ifs*31) and c.295_296delCGinsAT (p.R99I), which were respectively inherited from his father and mother. Both variants were predicted to be pathogenic, and neither was reported previously.@*CONCLUSION@#The compound heterozygous variants of the SCN9A gene probably underlay the CIP in this child. Above finding has enabled genetic counseling for this family.

Evaluation on the post competency of "Academic-Practical" of clinical nursing teachers and analysis of related influencing factors / 中华医学教育探索杂志

Objective:To investigate the post competency of "Academic-Practical" of clinical nursing teachers, and analyze related influencing factors.Methods:A total of 312 "Academic-Practical" and "Non-Academic-Practial" clinical nursing teachers from The Affiliated Hospital of Southwest Medical University were surveyed by the Clinical Nursing Teacher Post Competency Evaluation Questionnaire. SPSS 20.0 software was used for t test, chi-square test and rank sum test. Results:The average self-evaluation scores of post competency of "Academic-Practical" clinical nursing teachers were (4.26±0.41) points, which were higher than those of the "Non-Academic-Practical" teachers [(3.19 ±0.50) points], showing good post competency. There were significant differences in the scores of professional quality (17.39±1.54), professional attitude (21.75±2.21), professional ability (21.14±2.31), teaching ability (50.39±5.93), interpersonal coordination ability (25.57±3.04), and personality characteristics (17.27±2.04) between the "Academic-Practical" and "Non-Academic-Practical" teachers (all P<0.01). And there were significant differences in self-evaluation post competency scores of "Academic-Practical" teachers in "with or without teacher qualification certificate" ( P=0.001), "whether she/he is the backbone of the department" ( P=0.002), degree ( P=0.001), age ( P<0.001), positional title ( P<0.001) and working year ( P<0.001) (all P<0.01). But there was no significant difference in gender ( P=0.735) and "whether she/he is a specialized nurse" ( P=0.335). Conclusion:"Academic-Practical" and "Non-Academic-Practical" medical teachers should take the post competency as the core orientation, adopt the "Ladder" mode of training and management, and constantly improve the training plan of post competencey.

Mechanism of white matter hyperintensity involved in hemorrhagic transformation after intravenous thrombolysis / 国际脑血管病杂志

Cerebrovascular disease is a common disease that seriously endangers the health of Chinese people. White matter hyperintensities (WMHs) are the most common in elderly patients. Intravenous thrombolysis is currently the most effective drug treatment for acute ischemic stroke. Hemorrhagic transformation (HT) is the most common serious complication after intravenous thrombolysis in patients with acute ischemic stroke. The destruction of blood-brain barrier in patients of WMHs can increase the risk of HT after intravenous thrombolysis. Matrix metalloproteinases and S100B jointly participate in the destruction process of blood-brain barrier in WMHs and HT after intravenous thrombolysis. At present, the pathogenesis of WHM and HT is not completely clear, and whether mild and moderate WMHs will aggravate HT is still controversial. Nevertheless, WMHs are still the independent risk factor for HT.

Variation of SARS-CoV-2 spike protein and its effects on neutralization sensitivity / 中华微生物学和免疫学杂志

The COVID-19 epidemic that occurred at the end of 2019 spreads rapidly to all parts of the world, putting the global public health system to a severe test. With the continuation of the epidemic, SARS-CoV-2 variants are constantly emerging. In particular, the mutation of the spike protein can cause changes in the infectivity and antigenicity of the virus, resulting in an increase in the infectivity and a decline in the protective efficacy of existing vaccines, and even the replacement of epidemic strains. This is also one of the reasons why the epidemic has not been effectively controlled so far. Nowadays, the main circulating variants have changed their characteristics to a certain extent, and the neutralization sensitivity of some variants to neutralizing monoclonal antibodies, immune sera and convalescent sera has decreased to a certain extent compared with the original strains. The emergence of variants is not only related to the characteristics of the virus itself, but also to the changes of transmission host and the chronic infection in people with deficient immunity. The emerging variants should be closely monitored, and their functional characteristics should be systematically studied so as to provide data for vaccine research and development and the designation of immunization strategies.

Inhaled heparin polysaccharide nanodecoy against SARS-CoV-2 and variants

The heparin polysaccharide nanoparticles block the interaction between heparan sulfate/S protein and inhibit the infection of both wild-type SARS-CoV-2 pseudovirus and the mutated strains through pulmonary delivery.Image 1.

A subset of Memory B-derived antibody repertoire from 3-dose vaccinees is ultrapotent against diverse and highly transmissible SARS-CoV-2 variants, including Omicron

Omicron, the most heavily mutated SARS-CoV-2 variant so far, is highly resistant to neutralizing antibodies, raising unprecedented concerns about the effectiveness of antibody therapies and vaccines. We examined whether sera from individuals who received two or three doses of inactivated vaccine, could neutralize authentic Omicron. The seroconversion rates of neutralizing antibodies were 3.3% (2/60) and 95% (57/60) for 2- and 3-dose vaccinees, respectively. For three-dose recipients, the geometric mean neutralization antibody titer (GMT) of Omicron was 15, 16.5-fold lower than that of the ancestral virus (254). We isolated 323 human monoclonal antibodies derived from memory B cells in 3-dose vaccinees, half of which recognize the receptor binding domain (RBD) and show that a subset of them (24/163) neutralize all SARS-CoV-2 variants of concern (VOCs), including Omicron, potently. Therapeutic treatments with representative broadly neutralizing mAbs individually or antibody cocktails were highly protective against SARS-CoV-2 Beta infection in mice. Atomic structures of the Omicron S in complex with three types of all five VOC-reactive antibodies defined the binding and neutralizing determinants and revealed a key antibody escape site, G446S, that confers greater resistance to one major class of antibodies bound at the right shoulder of RBD through altering local conformation at the binding interface. Our results rationalize the use of 3-dose immunization regimens and suggest that the fundamental epitopes revealed by these broadly ultrapotent antibodies are a rational target for a universal sarbecovirus vaccine. One sentence summaryA sub-set of antibodies derived from memory B cells of volunteers vaccinated with 3 doses of an inactivated SARS-CoV-2 vaccine work individually as well as synergistically to keep variants, including Omicron, at bay.

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.

Effectiveness and safety of mesenchymal stem cells versus hyaluronic acid for treating knee osteoarthritis: a Meta-analysis / 中华风湿病学杂志

Objective:To systematically evaluate the effectiveness and safety of intra-articular in-jection of mesenchymal stem cells (MSCs) and hyaluronic acid (HA) in the treatment of knee osteoarthritis.Methods:The relevant literatures published in both English and Chinese were systematically searched in PubMed, Embase, Wanfang database, China Knowledge Network (CNKI), SinoMed database and other data-bases from inception to May 2020. Two researchers independently extracted data and evaluated the included literature. Risk assessment of literature bias was carried out. RevMan 5.3 software was used for Meta analysis, and the combined sensitivity were calculated.Results:Finally, 13 references were included, including a total of 726 patients with knee osteoarthritis. Meta-analysis results showed that compared with the HA group, the Western Ontario and McMaster University Osteopathic Index Total Score (WOMAC) [ MD=-10.92, 95% CI (-16.87, -4.96), P<0.01], the visual analogue scale (VAS) score [ MD=-1.70, 95% CI(-2.44, -0.95), P<0.01], and the knee joint Lequesne index score of MSCs group all decreased significantly [ MD=-13.78, 95% CI (-15.03,-12.52), P<0.01]. Furthermore, there was no significant difference in the incidence of adverse events (AEs) between the two groups [ RR=1.11, 95% CI(0.90, 1.37), P=0.33]. However, American Knee Association Score (AKS score) [ MD=-10.15, 95% CI(-22.33, 2.03), P=0.10] and whole-organ magnetic resonance imaging score (WORMS) [ MD=-3.93, 95% CI(-11.60, 3.75), P=0.32] were not statistically significant ( P>0.05). Conclusion:Compared with intra-articular injection of HA, intra-articular injection of MSCs can significantly improve the symptoms and dysfunction, and has favorable clinical tolerability and safety, suggesting that MSCs is expected to bea new treatment for knee osteoarthritis.