Optimization design of support structure based on 3D printing technology.

Parts are often warped and deformed when they are molded using selective laser melting (SLM) technology. Thus, it is necessary to study the addition support modes of parts molded using SLM. Consequently, we designed dendritic, E-stage and conical supports, having different structural parameters and different partitions using Magics, and then, we analyzed their performances using the finite element software Abaqus. The structural parameters of the supports were optimized and finally tested using SLM molding technology. The maximum stress concentration was found for dendritic supports, followed by E-stage supports, and then conical supports. The stress concentration and deformation level of Scheme 2 were less than those of Scheme 1. The stress intensity and deformation levels for two partitions were less than those for three partitions. For parts molded by SLM, the deformation was maximum for conical supports, followed by dendritic supports, and then E-stage supports. When gradient supports of similar volumes were added, additional partitions did not effectively improve the molding quality. When supports of similar volumes were added, adding gradient supports did not effectively improve the molding quality. The results provide a basis for the application of SLM in molding high-precision parts.

Effect of cardiac rehabilitation program on rapid recovery of patients undergoing minimally invasive incision coronary artery bypass grafting: A propensity score-matching study / 中国胸心血管外科临床杂志

@#Objective To investigate the role of cardiac rehabilitation program in the early recovery after minimally invasive incision coronary artery bypass grafting with general anesthesia. Methods A retrospective study was performed on the patients who underwent minimally invasive incision coronary artery bypass grafting from January 2015 to January 2020 with general anesthesia in our hospital. The patients were divided into a cardiac rehabilitation group and a control group. The clinical data of the patients were collected in 6 months and 12 months after the beginning of cardiac rehabilitation program and were analyzed by propensity score-matching analysis with a ratio of 1∶1. The main outcomes were the peak oxygen uptake (VO2 peak) of cardiopulmonary function test and the number of patients attending cardiovascular specialties in tertiary hospitals during the follow-up period (20 months). Results A total of 600 patients were enrolled, including 200 patients in the cardiac rehabilitation group [137 males and 63 females, aged 61.00 (56.00, 65.00) years] and 400 patients in the control group [285 males and 115 females, aged 60.00 (56.00, 65.00) years]. After matching, 176 patients were included in each group, and the basical clinical data of the pateints were comparable (P>0.05). The VO2 peak of the cardiac rehabilitation group after 6 months and 12 months of cardiac rehabilitation was significantly different from that of the control group [6 months: 1.96 (1.59, 2.38) L/min vs. 1.72 (1.38, 2.12) L/min, P<0.001; 12 months: 2.40 (2.21, 2.63) L/min vs. 2.12 (1.83, 2.45) L/min, P<0.001]. During the follow-up period, there was a statistical difference in the cardiovascular specialist visits in tertiary hospitals (P=0.004). Conclusion Cardiac rehabilitation program has a positive effect on the recovery of minimally invasive incision coronary artery bypass grafting with general anesthesia, and can improve the exercise ability of patients.

The design and processing of a 3D-printed high-performance biological fixation plate.

In order to generate a high-performance personalized biological fixation plate with matching mechanical properties and biocompatibility, reverse reconstruction and fracture reduction of a femur were performed by combining reverse and forward approaches, and the surface was extracted according to the installation position of the plate to complete plate modeling by shifting, thickening, and performing other operations. Subsequently, topology optimization and three-dimensional (3D) printing were performed, and the properties of the manufactured plate were probed. The results showed that the maximum displacement of the plate was 4.13 mm near the femoral head, the maximum stress was 5.15e2 MPa on both sides of the plate across its entire length, and the stress concentration decreased following topology optimization. The plate with optimized topology and filled with porous structure has a good filling effect. The final mass of the H-shaped plate was 12.05 g, while that of the B-shaped plate was 11.05 g, which dropped by 20.93% and 27.49%, respectively, compared with the original plate. The surface of the 3D-printed plate was bright and new, with a clear pore structure and good lap joint. The B-shaped and H-shaped plates were closely dovetailed with the host bone, which met the assembly requirements. This lays a foundation for the direct application of a high-performance personalized biological fixation plate.

Advances in brain-computer interface based on high-frequency steady-state visual evoked potential / 生物医学工程学杂志

Steady-state visual evoked potential (SSVEP) has been widely used in the research of brain-computer interface (BCI) system in recent years. The advantages of SSVEP-BCI system include high classification accuracy, fast information transform rate and strong anti-interference ability. Most of the traditional researches induce SSVEP responses in low and middle frequency bands as control signals. However, SSVEP in this frequency band may cause visual fatigue and even induce epilepsy in subjects. In contrast, high-frequency SSVEP-BCI provides a more comfortable and natural interaction despite its lower amplitude and weaker response. Therefore, it has been widely concerned by researchers in recent years. This paper summarized and analyzed the related research of high-frequency SSVEP-BCI in the past ten years from the aspects of paradigm and algorithm. Finally, the application prospect and development direction of high-frequency SSVEP were discussed and prospected.

Risk factors analysis for tibial fracture in patients with congenital anterolateral bowing of the tibia / 中华骨科杂志

Objective:To explore the risk factors associated with tibia fractures in children with congenital anterolateral bowing of the tibia (ALBT).Methods:A retrospective analysis was conducted on data from 87 children diagnosed with ALBT at the Children's Hospital of Hunan Province from January 2012 to January 2020. The collected data included age at initial diagnosis, affected limb side, whether there was a concomitant type I neurofibromatosis, whether there was a concomitant fibular pseudoarthrosis, whether there was concomitant ankle joint deformity, whether there was bone cystic change in the region of tibial bowing deformity, location of the apex of the bowing deformity, diameter of the tibial bowing deformity on the affected side, diameter on the healthy side in the same plane as the tibial bowing deformity, angle of lateral bending deformity of the tibia, angle of anterior bending deformity of the tibia, occurrence of tibia fracture, history of trauma before fracture, location of fracture, and age at the time of fracture. The follow-up endpoint was January 2023. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff values for the angles of lateral and anterior bending deformity of the tibia and the ratio of cross-sectional areas. The correlation between the above factors and tibial fractures in children was analyzed by single factor survival analysis, and the indicators with statistical significance were included in multivariate Cox proportional risk regression analysis to determine the risk factors for tibial fractures in children with ALBT.Results:Of the 87 children diagnosed with ALBT, the median age at initial diagnosis was 14.0 months (range, 1-93 months), with 42 males and 45 females, 44 left-sided and 43 right-sided cases. The median follow-up time for non-fracture cases was 42.0 months (range, 1-124 months). At the last follow-up, 43 children had experienced fractures, while 44 had not. The average time to fracture-free survival was 70.3 months, the median fracture-free survival time was 55.0 months, and the median survival time without fractures was 42.0 months. The ROC curve results indicated a cutoff value of 25.55° for the lateral bending angle of the tibia and 32.63° for the anterior bending angle of the tibia, with no statistically significant significance for the cross-sectional area ratio [AUC=0.54, 95% CI (0.42, 0.66), P=0.530]. Single-factor analysis of fracture-free survival suggested that there were statistically significant differences in the intergroup fracture-free survival rates of four factors: lateral bending angle of the tibia (χ 2=7.06, P=0.008), anterior bending angle of the tibia (χ 2=8.96, P=0.003), history of trauma (χ 2=18.26, P<0.001), and tibial bone cystic change (χ 2=4.30, P=0.038). The results of the multivariate Cox proportional hazards regression analysis showed that a lateral bending angle of the tibia≥25.55° ( HR=2.73, P=0.007), tibial bone cystic change ( HR=2.35, P=0.018), and history of trauma ( HR=2.65, P=0.004) were all positively correlated with fractures. Conclusion:The main risk factors for tibia fractures in children with ALBT include trauma, tibial bowing deformity with concomitant bone cystic change, and lateral bending angle of the tibia≥25.55°.

A scope review of self-management intervention research in patients with hematopoietic stem cell transplantation / 中华护理杂志

Objective To review the research of self-management intervention in patients with hematopoietic stem cell transplantation,clarify the intervention elements,so as to provide references for clinical practice and future related research.Methods According to the scoping review framework,a literature search was performed in the PubMed,Embase,CINAHL,Web of Science,Cochrane Library,CNKI,Wan fang Database,VIP,CBMdisc for all the studies on self-management intervention of patients with hematopoietic stem cell transplantation.The retrieval time was from the establishment of the database to December,2022.There were 2 researchers who extracted and analyzed the data of the included literature.Results A total of 12 articles were included,including 3 randomized controlled trials,8 quasi-experimental studies,and 1 mixed study.6 studies were conducted with interventions based on the theoretical basis or nursing model such as self-management oriented 5A nursing model,continuous nursing model,problem-based learning theory.The intervention methods of 12 studies included nurse-led self-management guidance,mobile applications,multidisciplinary collaboration,and graphic cards.The intervention time was mostly 1～3 months.The outcome indicators included feasibility evaluation indicators such as operability,ease of use,and user satisfaction of the application,and effect evaluation indicators such as self-management ability,quality of life,and medication compliance of patients.The results showed that self-management interventions could improve patient self-management ability,quality of life,medication compliance,and improve their psychological and nutritional status.Conclusion The research on self-management intervention in patients with hematopoietic stem cell transplantation is still in the development stage,and its positive effect has been preliminarily verified.Medical staff should strengthen the self-management evaluation of patients with hematopoietic stem cell transplantation,play the role of multidisciplinary team,use electronic health intervention methods,and formulate multi-level,scientific and effective self-management intervention programs.

Clinical analysis of 8 cases of refractory upper gastrointestinal fistula treated with endoscopic injection of autologous platelet rich plasma / 中华消化杂志

Objective:To evaluate the safety and efficacy of endoscopic injection of autologous platelet rich plasma(PRP)in the treatment of refractory upper gastrointestinal fistula(RUGF).Methods:From June 1, 2022 to March 1, 2023, at the Department of Gastroenterology of the First Affiliated Hospital of Nanjing Medical University, 8 RUGF patients who received PRP treatment were enrolled. The baseline data such as gender, age, course of disease, and body mass index, etc. as well as the PRP treatment-related data such as the time of first treatment, length of hospital stay after the first treatment, and adverse events were recorded. The postoperative follow-up lasted till 6 months after the first treatment to assess fistula healing, and to record body mass index and health survey short form. Paired t-test and non-parametric test were used for statistical analysis. Results:Among the 8 RUGF patients, there were 7 males and 1 female. The median age was 58.5 years old (ranged from 27.0 to 75.0 years old), and the median duration of the disease was 14 months (ranged from 4 to 120 months). The maximum diameter of the fistula was(4.50±2.62) mm, the concentration multiple of PRP was (4.02±0.48) times. The operation time of the first endoscopic PRP treatment was (21.88±4.52) min; the median length of the first postoperative hospital stay was 2 days (ranged from 1 to 2 days), and the median total number of treatment was 4 (ranged from 1 to 5). The healing time was (2.57±1.72) months, 7 RUGF patients healed within 6 months after the first treatment, and the fistula was narrowed in 1 patient. There were no adverse events during or after the operation. After 6 months of treatment, the body mass index and the scores of 8 dimensions of the health survey short form which included physical functioning, physical role functioning, body pain, general health, vitality, social functioning, emotional role functioning and mental health were all higher than those before treatment ((20.91±2.15) kg/m 2 vs. (18.67±3.21) kg/m 2, 86.88±13.35 vs. 58.13±20.34, 100 (0 to 100) vs. 0(0 to 100), 83.06±11.74 vs. 56.94±28.86, 67.88±26.77 vs. 31.88±13.08, 81.88±13.87 vs. 46.25±24.02, 76.56±22.60 vs. 37.50±26.73, 100 (0 to 100) vs. 0 (0 to 100), 78.00±17.37 vs. 51.50±22.77), and the differences were statistically significant ( t=-3.40 and -3.87, Z=2.06, t=-3.03, -4.26, -4.73 and -6.06, Z=-2.06, t=-4.32; P=0.012, 0.006, 0.039, 0.019, 0.004, 0.002, 0.001, 0.039 and 0.003). Conclusion:Endoscopic injection of autologous PRP for the treatment of RUGF is safe and effective, and has a significant promotion effect on the healing of small (maximum diameter ≤ 6 mm) fistula.

Cardiac rehabilitation program for patients undergoing small incision aortic valve replacement / 中华胸心血管外科杂志

Objective:To study the effect of cardiac rehabilitation program on recovery of patients after small incision aortic valve replacement.Methods:600 patients who underwent small incision aortic valve replacement in our hospital from January 2015 to January 2020 were retrospectively collected and divided into Cardiac rehabilitation group(CR) and control group by propensity matching analysis. Clinical data of CR group and control group were collected 6 months and 12 months after the beginning of Cardiac rehabilitation program. The primary outcome measures were the peak oxygen uptake(VO 2 Peak) of cardiopulmonary function test and the number of patients attending cardiovascular specialty in tertiary hospitals after the rehabilitation program began. The secondary outcome measures were 6-minute Walk test(6-MWT), psychological evaluation, and assessment of cardiovascular disease risk factors. Results:After 6 months and 12 months of cardiac rehabilitation program, the VO2 peak in CR group was statistically significant compared with the control group, and the 6-MWT index after 12 months was statistically significant.The cardiovascular specialist visits in tertiary hospitals in the two groups were statistically significant. The comparison of psychological self-rating scale and cardiovascular disease risk factors between the two groups was statistically significant after propensity matching analysis.Conclusion:Cardiac rehabilitation has a positive effect on postoperative recovery after small incision aortic valve replacement, and can improve patients’ motor ability.

Application of traditional teaching combined with PBL in the teaching of transfusion medicine——taking Clinical Blood Transfusion Testing Technique as an example / 中国输血杂志

【Objective】 To explore the application effect of traditional teaching combined with problem based learning (PBL) in the teaching of transfusion medicine taking the chapter of Human Leukocyte Antigen System and Testing in Clinical Blood Transfusion Testing Technique as an example. 【Methods】 Firstly, practical problems in chapter Human Leukocyte Antigen System and Testing were analyzed. Then, in response to the key and difficult points in the teaching of this chapter, examples were given to illustrate the practical application of traditional teaching combined with PBL in the teaching of Clinical Blood Transfusion Testing Technique from the aspects of teaching objectives, teaching processes, course implementation and implementation effects. The teaching effectiveness was evaluated through a questionnaire. 【Results】 Traditional teaching combined with PBL helped students grasp important knowledge and techniques, break down thinking barriers, grasp internal connections and characteristics, simplify the learning process, stimulate interest in learning and enhance team collaboration. Meanwhile, students' exploration and innovation abilities could be further cultivated through extracurricular expansion by teachers, thus achieving ideal teaching effect. The questionnaire showed that over 90% of the students consider that combining traditional teaching with PBL was beneficial for improving teaching effect. 【Conclusion】 In the teaching of transfusion medicine, adopting traditional teaching combined with PBL according to the textbook content can improve the teaching effect, which is beneficial for the cultivation of comprehensive talents.

Preliminary exploration on operation process for autologous ozonized blood transfusion / 中国输血杂志

Autologous ozonized blood transfusion(AOBT) is a therapy of re-transfusion of 100-200 mL of autologous blood after shaking and agitation with appropriate amount of oxygen-ozone in vitro. The oxidation of blood through the strong oxidation of ozone can enhance the non-specific immune response of the body, regulate the internal environment and promote health. This therapy has been increasingly applied in clinical practice, while no unified standard for the operation process in terms of ozone concentration, treatment frequency and treatment course had been established. This operation process of AOBT is primarily explored in order to standardize the operation process and ensure its safety and efficacy.

Phosphorylated PKM2 regulates endothelium-dependent vasodilation in diabetes / 中南大学学报(医学版)

OBJECTIVES@#Endothelium-dependent vasodilation dysfunction is the pathological basis of diabetic macroangiopathy. The utilization and adaptation of endothelial cells to high glucose determine the functional status of endothelial cells. Glycolysis pathway is the major energy source for endothelial cells. Abnormal glycolysis plays an important role in endothelium-dependent vasodilation dysfunction induced by high glucose. Pyruvate kinase isozyme type M2 (PKM2) is one of key enzymes in glycolysis pathway, phosphorylation of PKM2 can reduce the activity of pyruvate kinase and affect the glycolysis process of glucose. TEPP-46 can stabilize PKM2 in its tetramer form, reducing its dimer formation and phosphorylation. Using TEPP-46 as a tool drug to inhibit PKM2 phosphorylation, this study aims to explore the impact and potential mechanism of phosphorylated PKM2 (p-PKM2) on endothelial dependent vasodilation function in high glucose, and to provide a theoretical basis for finding new intervention targets for diabetic macroangiopathy.@*METHODS@#The mice were divided into 3 groups: a wild-type (WT) group (a control group, C57BL/6 mice) and a db/db group (a diabetic group, db/db mice), which were treated with the sodium carboxymethyl cellulose solution (solvent) by gavage once a day, and a TEPP-46 group (a treatment group, db/db mice+TEPP-46), which was gavaged with TEPP-46 (30 mg/kg) and sodium carboxymethyl cellulose solution once a day. After 12 weeks of treatment, the levels of p-PKM2 and PKM2 protein in thoracic aortas, plasma nitric oxide (NO) level and endothelium-dependent vasodilation function of thoracic aortas were detected. High glucose (30 mmol/L) with or without TEPP-46 (10 μmol/L), mannitol incubating human umbilical vein endothelial cells (HUVECs) for 72 hours, respectively. The level of NO in supernatant, the content of NO in cells, and the levels of p-PKM2 and PKM2 protein were detected. Finally, the effect of TEPP-46 on endothelial nitric oxide synthase (eNOS) phosphorylation was detected at the cellular and animal levels.@*RESULTS@#Compared with the control group, the levels of p-PKM2 in thoracic aortas of the diabetic group increased (P<0.05). The responsiveness of thoracic aortas in the diabetic group to acetylcholine (ACh) was 47% lower than that in the control group (P<0.05), and that in TEPP-46 treatment group was 28% higher than that in the diabetic group (P<0.05), while there was no statistically significant difference in the responsiveness of thoracic aortas to sodium nitroprusside (SNP). Compared with the control group, the plasma NO level of mice decreased in the diabetic group, while compared with the diabetic group, the phosphorylation of PKM2 in thoracic aortas decreased and the plasma NO level increased in the TEPP-46 group (both P<0.05). High glucose instead of mannitol induced the increase of PKM2 phosphorylation in HUVECs and reduced the level of NO in supernatant (both P<0.05). HUVECs incubated with TEPP-46 and high glucose reversed the reduction of NO production and secretion induced by high glucose while inhibiting PKM2 phosphorylation (both P<0.05). At the cellular and animal levels, TEPP-46 reversed the decrease of eNOS (ser1177) phosphorylation induced by high glucose (both P<0.05).@*CONCLUSIONS@#p-PKM2 may be involved in the process of endothelium-dependent vasodilation dysfunction in Type 2 diabetes by inhibiting p-eNOS (ser1177)/NO pathway.

Optimized design and key performance factors of a gas circulation filtration system in a metal 3D printer.

To further improve the quality of parts in metal 3D printers, it is necessary to optimize the structure and study the performance of their gas circulation filtration systems. First, we used the parametric modeling method to complete the formed cavity modeling. We then optimized the design of the air inlet structure of the formed cavity using the moldflow simulation method, and finally, we evaluated the optimized design results through assembly experiments and measurements of the molded parts' components. The combination of parametric modeling and moldflow simulation methods produced a high modeling efficiency and had a good effect on the optimized design of the gas circulation filtration systems. After optimizing the design, the turbulence intensities and distribution areas of the formed cavities were reduced. During the 3D printing of the curved guide plate, the plane of the guide plate holder was inclined 55° relative to the machining datum plane, which improved the form quality. The 3D printed curved guide plate closely matched the inlet end of the printer's air duct, and the upper guide plate was fixed at a suitable position using screws. The niobium contents of the parts formed by the guide plate in Design 2 were low, which lays a foundation for the 3D printing of high-performance metal parts.

Epidemiological characteristics and transmission dynamics of the outbreak caused by the SARS-CoV-2 Omicron variant in Shanghai, China: a descriptive study

BackgroundIn early March 2022, a major outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant spread rapidly throughout Shanghai, China. Here we aimed to provide a description of the epidemiological characteristics and spatiotemporal transmission dynamics of the Omicron outbreak under the population-based screening and lockdown policies implemented in Shanghai. MethodsWe extracted individual information on SARS-CoV-2 infections reported between January 1 and May 31, 2022, and on the timeline of the adopted non-pharmacological interventions. The epidemic was divided into three phases: i) sporadic infections (January 1-February 28), ii) local transmission (March 1-March 31), and iii) city-wide lockdown (April 1 to May 31). We described the epidemic spread during these three phases and the subdistrict-level spatiotemporal distribution of the infections. To evaluate the impact on the transmission of SARS-CoV-2 of the adopted targeted interventions in Phase 2 and city-wide lockdown in Phase 3, we estimated the dynamics of the net reproduction number (Rt). FindingsA surge in imported infections in Phase 1 triggered cryptic local transmission of the Omicron variant in early March, resulting in the largest coronavirus disease 2019 (COVID-19) outbreak in mainland China since the original wave. A total of 626,000 SARS-CoV-2 infections were reported in 99.5% (215/216) of the subdistricts of Shanghai. The spatial distribution of the infections was highly heterogeneous, with 40% of the subdistricts accounting for 80% of all infections. A clear trend from the city center towards adjacent suburban and rural areas was observed, with a progressive slowdown of the epidemic spread (from 544 to 325 meters/day) prior to the citywide lockdown. During Phase 2, Rt remained well above 1 despite the implementation of multiple targeted interventions. The citywide lockdown imposed on April 1 led to a marked decrease in transmission, bringing Rt below the epidemic threshold in the entire city on April 14 and ultimately leading to containment of the outbreak. InterpretationOur results highlight the risk of widespread outbreaks in mainland China, particularly under the heightened pressure of imported infections. The targeted interventions adopted in March 2022 were not capable of halting transmission, and the implementation of a strict, prolonged city-wide lockdown was needed to successfully contain the outbreak, highlighting the challenges for successfully containing Omicron outbreaks. FundingKey Program of the National Natural Science Foundation of China (82130093). Research in contextO_ST_ABSEvidence before this studyC_ST_ABSOn May 24, 2022, we searched PubMed and Europe PMC for papers published or posted on preprint servers after January 1, 2022, using the following query: ("SARS-CoV-2" OR "Omicron" OR "BA.2") AND ("epidemiology" OR "epidemiological" OR "transmission dynamics") AND ("Shanghai"). A total of 26 studies were identified; among them, two aimed to describe or project the spread of the 2022 Omicron outbreak in Shanghai. One preprint described the epidemiological and clinical characteristics of 376 pediatric SARS-CoV-2 infections in March 2022, and the other preprint projected the epidemic progress in Shanghai, without providing an analysis of field data. In sum, none of these studies provided a comprehensive description of the epidemiological characteristics and spatiotemporal transmission dynamics of the outbreak. Added value of this studyWe collected individual information on SARS-CoV-2 infection and the timeline of the public health response. Population-based screenings were repeatedly implemented during the outbreak, which allowed us to investigate the spatiotemporal spread of the Omicron BA.2 variant as well as the impact of the implemented interventions, all without enduring significant amounts of underreporting from surveillance systems, as experienced in other areas. This study provides the first comprehensive assessment of the Omicron outbreak in Shanghai, China. Implications of all the available evidenceThis descriptive study provides a comprehensive understanding of the epidemiological features and transmission dynamics of the Omicron outbreak in Shanghai, China. The empirical evidence from Shanghai, which was ultimately able to curtail the outbreak, provides invaluable information to policymakers on the impact of the containment strategies adopted by the Shanghai public health officials to prepare for potential outbreaks caused by Omicron or novel variants.

Simultaneous and sequential multi-species coronavirus vaccination

Although successful COVID-19 vaccines have been developed, multiple pathogenic coronavirus species exist, urging for development of multi-species coronavirus vaccines. Here we developed prototype LNP-mRNA vaccine candidates against SARS-CoV-2 (Delta variant), SARS-CoV and MERS-CoV, and test how multiplexing of these LNP-mRNAs can induce effective immune responses in animal models. A triplex scheme of LNP-mRNA vaccination induced antigen-specific antibody responses against SARS-CoV-2, SARS-CoV and MERS-CoV, with a relatively weaker MERS-CoV response in this setting. Single cell RNA-seq profiled the global systemic immune repertoires and the respective transcriptome signatures of multiplexed vaccinated animals, which revealed a systemic increase in activated B cells, as well as differential gene expression signatures across major adaptive immune cells. Sequential vaccination showed potent antibody responses against all three species, significantly stronger than simultaneous vaccination in mixture. These data demonstrated the feasibility, antibody responses and single cell immune profiles of multi-species coronavirus vaccination. The direct comparison between simultaneous and sequential vaccination offers insights on optimization of vaccination schedules to provide broad and potent antibody immunity against three major pathogenic coronavirus species. One sentence summaryMultiplexed mRNA vaccination in simultaneous and sequential modes provide broad and potent immunity against pathogenic coronavirus species.

Heterotypic vaccination responses against SARS-CoV-2 Omicron BA.2

The Omicron sub-lineage BA.2 of SARS-CoV-2 has recently become dominant across many areas in the world in the on-going waves of COVID-19. Compared to the ancestral/wild-type (WT) virus, Omicron lineage variants, both BA.1 and BA.2, contain high number of mutations, especially in the spike protein, causing significant immune escape that leads to substantial reduction of vaccine and antibody efficacy. Because of this antigenic drift, BA.2 exhibited differential resistance profile to monoclonal antibodies than BA.1. Thus, it is important to understand whether the immunity elicited by currently available vaccines are effective against the BA.2 subvariant. We directly tested the heterotypic vaccination responses against Omicron BA.2, using vaccinated serum from animals receiving WT- and variant-specific mRNA vaccine in lipid nanoparticle (LNP) formulations. Omicron BA.1 and BA.2 antigen showed similar reactivity to serum antibodies elicited by two doses of WT, B.1.351 and B.1.617 LNP-mRNAs. Neutralizing antibody titers of B.1.351 and B.1.617 LNP-mRNA were ~2-fold higher than that of WT LNP-mRNA. Both homologous boosting with WT LNP-mRNA and heterologous boosting with BA.1 LNP-mRNA substantially increased waning immunity of WT vaccinated mice against both BA.1 and BA.2 subvariants. The BA.1 LNP-mRNA booster was ~3-fold more efficient than WT LNP-mRNA at elevating neutralizing antibody titers of BA.2. Together, these data provided a direct preclinical evaluation of WT and variant-specific LNP-mRNAs in standard two-dose and as boosters against BA.1 and BA.2 subvariants.

Comparison of different neonatal illness severity scores in predicting mortality risk of extremely low birth weight infants / 浙江大学学报·医学版

To compare different illness severity scores in predicting mortality risk of extremely low birth weight infants (ELBWI). From January 1st, 2019 to January 1st, 2020, all ELBWI admitted in the Children's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital and the First Affiliated Hospital of Nanjing Medical University were included in the study. ELBWI with admission age ≥1 h, gestational age ≥37 weeks and incomplete data required for scoring were excluded. The clinical data were collected, neonatal critical illness score (NCIS), score for neonatal acute physiology version Ⅱ (SNAP-Ⅱ), simplified version of the score for neonatal acute physiology perinatal extension (SNAPPE-Ⅱ), clinical risk index for babies (CRIB) and CRIB-Ⅱ were calculated. The scores of the fatal group and the survival group were compared, and the receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the above illness severity scores for the mortality risk of ELBWI. Pearson correlation analysis was used to analyze the correlation between illness scores and birth weight, illness scores and gestational age. A total of 192 ELBWI were finally included, of whom 114 cases survived (survival group) and 78 cases died (fatal group). There were significant differences in birth weight, gestational age and Apgar scores between fatal group and survival group (all <0.01). There were significant differences in NCIS, SNAP-Ⅱ, SNAPPE-Ⅱ, CRIB and CRIB-Ⅱ between fatal group and survival group (all <0.01). The CRIB had a relatively higher predictive value for the mortality risk. Its area under the ROC curve (AUC) was 0.787, the sensitivity was 0.678, the specificity was 0.804, and the Youden index was 0.482. The scores of NCIS, SNAP-Ⅱ, SNAPPE-Ⅱ, CRIB and CRIB-Ⅱ were significantly correlated with birth weight and gestational age (all <0.05). The correlation coefficients of CRIB-Ⅱ and CRIB with birth weight and gestational age were relatively large, and the correlations coefficients of NCIS with birth weight and gestational age were the smallest (0.191 and 0.244, respectively). Among these five illness severity scores, CRIB has better predictive value for the mortality risk in ELBWI. NCIS, which is widely used in China, has relatively lower sensitivity and specificity, and needs to be further revised.

Progress in Clinical Research on Chronic Pancreatitis During Pregnancy / 胃肠病学

Chronic pancreatitis (CP) during pregnancy is rare but complicated in clinic, and its pathophysiology, clinical manifestations, diagnosis and treatment are special, which may seriously harm the health of mother and fetus if not properly treated. During pregnancy, physiological changes such as insulin resistance, mechanical pressure caused by the enlarged uterus and increased secretion of estrogen and progesterone will affect patients with CP. CP may increase the risk of pregnancy⁃related complications and adverse perinatal outcomes. The management of pregnant patients with CP mainly includes the improvement of lifestyle, symptomatic treatment and obstetric management. This article mainly reviewed the pancreatic physiology, clinical manifestations and management of pregnant patients with CP.

Systems immune profiling of variant-specific vaccination against SARS-CoV-2

Lipid-nanoparticle(LNP)-mRNA vaccines offer protection against COVID-19. However, multiple variant lineages caused widespread breakthrough infections. There is no report on variant-specific vaccines to date. Here, we generated LNP-mRNAs specifically encoding wildtype, B.1.351 and B.1.617 SARS-CoV-2 spikes, and systematically studied their immune responses in animal models. All three LNP-mRNAs induced potent antibody responses in mice. However, WT-LNP-mRNA vaccination showed reduced neutralization against B.1.351 and B.1.617; and B.1.617-specific vaccination showed differential neutralization. All three vaccine candidates elicited antigen-specific CD8 and CD4 T cell responses. Single cell transcriptomics of B.1.351-LNP-mRNA and B.1.617-LNP-mRNA vaccinated animals revealed a systematic landscape of immune cell populations and global gene expression. Variant-specific vaccination induced a systemic increase in reactive CD8 T cell population, with a strong signature of transcriptional and translational machineries in lymphocytes. BCR-seq and TCR-seq unveiled repertoire diversity and clonal expansions in vaccinated animals. These data provide direct systems immune profiling of variant-specific LNP-mRNA vaccination in vivo.

Global diversity of policy, coverage, and demand of COVID-19 vaccines: a descriptive study

BackgroundHundreds of millions of doses of COVID-19 vaccines have been administered globally, but progress in vaccination varies considerably between countries. We aim to provide an overall picture of COVID-19 vaccination campaigns, including policy, coverage, and demand of COVID-19 vaccines. MethodsWe conducted a descriptive study of vaccination policy and doses administered data obtained from multiple public sources as of 23 October 2021. We used these data to develop coverage indicators and explore associations of vaccine coverage with socioeconomic and healthcare-related factors. We estimated vaccine demand as numbers of doses required to complete vaccination of countries target populations according to their national immunization program policies. FindingsUse of both mRNA and adenovirus vectored vaccines was the most commonly used COVID-19 vaccines formulary in high-income countries, while adenovirus vectored vaccines were the most widely used vaccines worldwide (176 countries). Almost all countries (98.3%, 173/176) have authorized vaccines for the general public, with 53.4% (94/176) targeting individuals over 12 years and 33.0% (58/176) targeting those [≥]18 years. Forty-one and sixty-seven countries have started additional-dose and booster-dose vaccination programs, respectively. Globally, there have been 116.5 doses administered per 100 target population, although with marked inter-region and inter-country heterogeneity. Completed vaccination series coverage ranged from 0% to more than 95.0% of country target populations, and numbers of doses administered ranged from 0 to 239.6 per 100 target population. Doses administered per 100 total population correlated with healthcare access and quality index (R2 = 0.58), socio-demographic index (R2 = 0.56), and GDP per capita (R2 = 0.65). At least 5.54 billion doses will be required to complete interim vaccination programs - 4.65 billion for primary immunization and 0.89 billion for additional/booster programs. Globally, 0.84 and 0.96 dose per individual in the target population are needed for primary immunization and additional/booster programs, respectively. InterpretationThere is wide country-level disparity and inequity in COVID-19 vaccines rollout, suggesting large gaps in immunity, especially in low-income countries. FundingKey Program of the National Natural Science Foundation of China, the US National Institutes of Health. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for articles in any language published up to October 21, 2021, using the following search terms: ("COVID-19" OR "SARS-CoV-2") AND ("vaccination" OR "vaccine") AND ("inequalit*" OR "inequity" OR "disparit*" OR "heterogeneity"). We also searched for dashboards associated with vaccine rollout from public websites. We identified several studies on tracking global inequalities of vaccine access, one of which constructed a COVID-19 vaccine dashboard (Our World in Data), and another that explored disparities in COVID-19 vaccination among different-income countries. However, we found no studies that depict global COVID-19 vaccination policies country-by-country and estimate demand for vaccine necessary to completely vaccinate countries designated target populations. Added value of this studyTo our knowledge, our study provides the most recent picture of COVID-19 vaccination campaigns, focusing on global vaccination policy and target-population demand. We found a diverse portfolio of vaccines in five technical platforms being administered globally, with 173 countries having authorized administration of vaccines to the general public in various age groups. We observed inter-region and inter-country heterogeneity in one-or-more-dose and full-dose coverage; countries with higher socio-demographic or health resource-related levels had higher coverage. We estimated dose-level demand for completing primary immunization programs and additional/booster dose programs separately. Implications of all the available evidenceWorldwide disparity and inequity of vaccine rollout implies that susceptibility among unvaccinated populations in some countries may impede or reverse pandemic control, especially in face of the emergence of variants and the dilemma of waning antibodies. Our findings suggest that global-level responses to the pandemic - financially, politically, and technically - are needed to overcome complex challenges that lie ahead.

Are Founders More Socially Responsible? -An Empirical Research on Private Listed Companies in China.

Personal factors such as the founder's values and psychological characteristics will influence founder's vision, his perception and interpretation of the decision-making environment, and his strategic choice and decision-making. Based on the theory of entrepreneurial characteristics, combined with the founder's unique psychological characteristics, this paper takes Chinese private listed companies between 2010 and 2018 as a research sample to study the effect of the founder of private enterprises on corporate social responsibility. Furthermore, this study analyzes the impact of different management roles of the founder on corporate social responsibility. We demonstrate that the private enterprises have better social responsibility performance when there are founders; the founders have different management roles, and their corporate social responsibility performance has certain differences, and the higher the management level of the founders, the better the corporate social responsibility performance. This paper studies the issue of corporate social responsibility from the perspective of the characteristics of founders, which expands the current framework of corporate social responsibility research and provides an empirical basis for founders to effectively participate in corporate management in practice.