Sex Differences in Outcomes of Late-Window Endovascular Stroke Therapy.

BACKGROUND: The association between sex and outcome after endovascular thrombectomy of acute ischemic stroke is unclear. The aim of this study was to compare the clinical and safety outcomes between men and women treated with endovascular thrombectomy in the late 6-to-24-hour window period. METHODS: This multicenter, retrospective observational cohort study included consecutive patients who underwent endovascular thrombectomy of anterior circulation stroke in the late window from 66 clinical sites in 10 countries from January 2014 to May 2022. The primary outcome was the 90-day ordinal modified Rankin Scale score. Secondary outcomes included 90-day functional independence (FI), return of Rankin (RoR) to prestroke baseline, FI or RoR, symptomatic intracranial hemorrhage, and mortality. Multivariable and inverse probability of treatment weighting methods were used. We explored the interaction of sex with baseline characteristics on the outcomes ordinal modified Rankin Scale and FI or RoR. RESULTS: Of 1932 patients, 1055 were women and 877 were men. Women were older (77 versus 69 years), had higher rates of atrial fibrillation, hypertension, and greater prestroke disability, but there was no difference in baseline National Institutes of Health Stroke Scale score. Inverse probability of treatment weighting analysis showed no difference between women and men in ordinal modified Rankin Scale (odds ratio, 0.98 [95% CI, 0.79-1.21]), FI or RoR (odds ratio, 0.98 [95% CI, 0.78-1.22]), severe disability or mortality (odds ratio, 0.99 [95% CI, 0.80-1.23]). The multivariable analysis of the above end points was concordant. There were no interactions between baseline characteristics and sex on the outcomes of ordinal modified Rankin Scale and FI or RoR. CONCLUSIONS: In late presenting patients with anterior circulation stroke treated with endovascular thrombectomy in the 6 to 24-hour window, there was no difference in clinical or safety outcomes between men and women.

Magnetic PiezoBOTs: a microrobotic approach for targeted amyloid protein dissociation.

Piezoelectric nanomaterials have become increasingly popular in the field of biomedical applications due to their high biocompatibility and ultrasound-mediated piezocatalytic properties. In addition, the ability of these nanomaterials to disaggregate amyloid proteins, which are responsible for a range of diseases resulting from the accumulation of these proteins in body tissues and organs, has recently gained considerable attention. However, the use of nanoparticles in biomedicine poses significant challenges, including targeting and uncontrolled aggregation. To address these limitations, our study proposes to load these functional nanomaterials on a multifunctional mobile microrobot (PiezoBOT). This microrobot is designed by coating magnetic and piezoelectric barium titanate nanoparticles on helical biotemplates, allowing for the combination of magnetic navigation and ultrasound-mediated piezoelectric effects to target amyloid disaggregation. Our findings demonstrate that acoustically actuated PiezoBOTs can effectively reduce the size of aggregated amyloid proteins by over 80% in less than 10 minutes by shortening and dissociating constituent amyloid fibrils. Moreover, the PiezoBOTs can be easily magnetically manipulated to actuate the piezocatalytic nanoparticles to specific amyloidosis-affected tissues or organs, minimizing side effects. These biocompatible PiezoBOTs offer a promising non-invasive therapeutic approach for amyloidosis diseases by targeting and breaking down protein aggregates at specific organ or tissue sites.

Robotic Interventional Neuroradiology: Progress, Challenges, and Future Prospects.

Advances in robotic technology have improved standard techniques in numerous surgical and endovascular specialties, offering more precision, control, and better patient outcomes. Robotic-assisted interventional neuroradiology is an emerging field at the intersection of interventional neuroradiology and biomedical robotics. Endovascular robotics can automate maneuvers to reduce procedure times and increase its safety, reduce occupational hazards associated with ionizing radiations, and expand networks of care to reduce gaps in geographic access to neurointerventions. To date, many robotic neurointerventional procedures have been successfully performed, including cerebral angiography, intracranial aneurysm embolization, carotid stenting, and epistaxis embolization. This review aims to provide a survey of the state of the art in robotic-assisted interventional neuroradiology, consider their technical and adoption limitations, and explore future developments critical for the widespread adoption of robotic-assisted neurointerventions.

Visible-light-driven photocatalyst-free deoxygenative alkylation of imines with alcohols.

In this report, we developed a photocatalyst-free visible-light-promoted deoxygenative alkylation of imines with alcohols assisted by carbon disulfide and tricyclohexylphosphine. The key to success of this method is the activation of alcohols upon the formation and direct photoexcitation of xanthate anions. This one-pot protocol enables the selective C-O bond homolysis of diverse primary, secondary and tertiary alcohols to react with a variety of N-sulfonyl and N-aryl imines, providing a general and efficient platform for α-branched amine synthesis from alcohols.

MoSBOTs: Magnetically Driven Biotemplated MoS2 -Based Microrobots for Biomedical Applications.

2D layered molybdenum disulfide (MoS2 ) nanomaterials are a promising platform for biomedical applications, particularly due to its high biocompatibility characteristics, mechanical and electrical properties, and flexible functionalization. Additionally, the bandgap of MoS2 can be engineered to absorb light over a wide range of wavelengths, which can then be transformed into local heat for applications in photothermal tissue ablation and regeneration. However, limitations such as poor stability of aqueous dispersions and low accumulation in affected tissues impair the full realization of MoS2 for biomedical applications. To overcome such challenges, herein, multifunctional MoS2 -based magnetic helical microrobots (MoSBOTs) using cyanobacterium Spirulina platensis are proposed as biotemplate for therapeutic and biorecognition applications. The cytocompatible microrobots combine remote magnetic navigation with MoS2 photothermal activity under near-infrared irradiation. The resulting photoabsorbent features of the MoSBOTs are exploited for targeted photothermal ablation of cancer cells and on-the-fly biorecognition in minimally invasive oncotherapy applications. The proposed multi-therapeutic MoSBOTs hold considerable potential for a myriad of cancer treatment and diagnostic-related applications, circumventing current challenges of ablative procedures.

Neurotechnological Approaches to the Diagnosis and Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, clinically defined by progressive cognitive decline and pathologically, by brain atrophy, neuroinflammation, and accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles. Neurotechnological approaches, including optogenetics and deep brain stimulation, have exploded as new tools for not only the study of the brain but also for application in the treatment of neurological diseases. Here, we review the current state of AD therapeutics and recent advancements in both invasive and non-invasive neurotechnologies that can be used to ameliorate AD pathology, including neurostimulation via optogenetics, photobiomodulation, electrical stimulation, ultrasound stimulation, and magnetic neurostimulation, as well as nanotechnologies employing nanovectors, magnetic nanoparticles, and quantum dots. We also discuss the current challenges in developing these neurotechnological tools and the prospects for implementing them in the treatment of AD and other neurodegenerative diseases.

Feasibility and reliability of the Brockport physical fitness test among visually impaired adolescents in China / 中国学校卫生

Objective@#To investigate the feasibility and reliability of the Brockport physical fitness test in visually impaired adolescents in China to determine its applicability in clinical practice and research.@*Methods@#A total of 41 visually impaired adolescents 10-17 years of age were included. Body mass index (BMI), dominant grip strength, modified curl up, trunk lift, shoulder stretch, back saver sit and reach and PACER were tested twice with a 1 week interval by the same tester using the same instrument.@*Results@#Each item in the Brockport physical fitness test was completed. The intraclass correlation coefficients for height, weight, BMI, dominant grip strength, modified curl up, trunk lift, back saver sit and reach (left/right leg straight), and PACER in all subjects were 1.00, 1.00, 1.00, 0.94, 0.75, 0.78, 0.90, 0.87, 0.89, respectively. In blind subjects, the corresponding values were 1.00, 1.00, 1.00, 0.97, 0.80, 0.92, 0.89, 0.87, 0.87, respectively. In low vision subjects, the corresponding values were 1.00 , 1.00, 1.00, 0.90, 0.71, 0.40, 0.89, 0.85, 0.85, respectively. The Cohen kappa values for shoulder stretch (left/right hand on top) were 0.79 and 0.78 in all subjects, 0.72 and 0.64 in blind subjects, and 0.87 and 1.00 in low vision subjects.@*Conclusion@#The Brockport physical fitness test is a feasible and reliable physical fitness test for visually impaired adolescents in China, however, trunk lift is not recommended for adolescents with low vision.

Feasibility and reliability of the Brockport physical fitness test among visually impaired adolescents in China / 中国学校卫生

Objective@#To investigate the feasibility and reliability of the Brockport physical fitness test in visually impaired adolescents in China to determine its applicability in clinical practice and research.@*Methods@#A total of 41 visually impaired adolescents 10-17 years of age were included. Body mass index (BMI), dominant grip strength, modified curl up, trunk lift, shoulder stretch, back saver sit and reach and PACER were tested twice with a 1 week interval by the same tester using the same instrument.@*Results@#Each item in the Brockport physical fitness test was completed. The intraclass correlation coefficients for height, weight, BMI, dominant grip strength, modified curl up, trunk lift, back saver sit and reach (left/right leg straight), and PACER in all subjects were 1.00, 1.00, 1.00, 0.94, 0.75, 0.78, 0.90, 0.87, 0.89, respectively. In blind subjects, the corresponding values were 1.00, 1.00, 1.00, 0.97, 0.80, 0.92, 0.89, 0.87, 0.87, respectively. In low vision subjects, the corresponding values were 1.00 , 1.00, 1.00, 0.90, 0.71, 0.40, 0.89, 0.85, 0.85, respectively. The Cohen kappa values for shoulder stretch (left/right hand on top) were 0.79 and 0.78 in all subjects, 0.72 and 0.64 in blind subjects, and 0.87 and 1.00 in low vision subjects.@*Conclusion@#The Brockport physical fitness test is a feasible and reliable physical fitness test for visually impaired adolescents in China, however, trunk lift is not recommended for adolescents with low vision.

Effect of noninvasive positive pressure ventilation and high-flow nasal cannula oxygen therapy on the clinical efficacy of coronavirus disease 2019 patients with acute respiratory distress syndrome / 中华危重病急救医学

Objective:To observe the effect of noninvasive positive pressure ventilation (NIPPV) and high-flow nasal cannula oxygen therapy (HFNC) on the prognosis of patients with coronavirus disease 2019 (COVID-19) accompanied with acute respiratory distress syndrome (ARDS).Methods:A retrospective study was conducted in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology when authors worked as medical team members for treating COVID-19. COVID-19 patients with pulse oxygen saturation/fraction of inspiration oxygen (SpO 2/FiO 2, S/F) ratio < 235, managed by medical teams [using S/F ratio instead of oxygenation index (PaO 2/FiO 2) to diagnose ARDS] from February to April 2020 were included. The patients were divided into NIPPV group and HFNC group according to their oxygen therapy modes. Clinical data of patients were collected, including general characteristics, respiratory rate (RR), fraction of FiO 2, SpO 2, heart rate (HR), mean arterial pressure (MAP), S/F ratio in the first 72 hours, lymphocyte count (LYM), percentage of lymphocyte (LYM%) and white blood cell count (WBC) at admission and discharge or death, the duration of dyspnea before NIPPV and HFNC, and the length from onset to admission. The differences of intubation rate, all-cause mortality, S/F ratio and RR were analyzed, and single factor analysis and generalized estimation equation (GEE) were used to analyze the risk factors affecting S/F ratio. Results:Among the 41 patients, the proportion of males was high (68.3%, 28 cases), the median age was 68 (58-74) years old, 28 cases had complications (68.3%), and 34 cases had multiple organ dysfunction syndrome (MODS, 82.9%). Compared with HFNC group, the proportion of complications in NIPPV group was higher [87.5% (21/24) vs. 41.2% (7/17), P < 0.05], and the value of LYM% was lower [5.3% (3.4%-7.8%) vs. 10.0% (3.9%-19.7%), P < 0.05], the need of blood purification was also significantly lower [0% (0/24) vs. 29.4% (5/17), P < 0.05]. The S/F ratio of NIPPV group gradually increased after 2 hours treatment and RR gradually decreased with over time, S/F ratio decreased and RR increased in HFNC group compared with baseline, but there was no significant difference in S/F ratio between the two groups at each time point. RR in NIPPV group was significantly higher than that in HFNC group after 2 hours treatment [time/min: 30 (27-33) vs. 24 (21-27), P < 0.05]. There was no significant difference in rate need intubation and hospital mortality between NIPPV group and HFNC group [66.7% (16/24) vs. 70.6% (12/17), 58.3% (14/24) vs. 52.9% (9/17), both P > 0.05]. Analysis of the factors affecting the S/Fratio in the course of oxygen therapy showed that the oxygen therapy mode and the course of illness at admission were the factors affecting the S/F ratio of patients [ β values were -15.827, 1.202, 95% confidence interval (95% CI) were -29.102 to -2.552 and 0.247-2.156, P values were 0.019 and 0.014, respectively]. Conclusion:Compared with HFNC, NIPPV doesn't significantly reduce the intubation rate and mortality of patients with COVID-19 accompanied with ARDS, but it significantly increases the S/F ratio of those patients.

Optical coherence tomography observation of retinal paravascular abnormalities in young myopic population / 中华眼底病杂志

Objective:To observe the abnormal clinical manifestations of retinal blood vessels and the characteristic image characteristics of optical coherence tomography (OCT) in young myopia.Methods:A case observation study. From July to December 2020, 523 young patients with different myopia refractive powers who were treated in Department of Ophthalmology of The Second Hospital of Hebei Medical University were included in the study. Among them, 277 were males and 246 were females; the median age was 19.0 (5.0) years. All the affected eyes underwent best corrected visual acuity (BCVA), frequency domain OCT (SD-OCT) examination and axial length (AL) measurement. The BCVA examination was performed using the Snellen eye chart. The median myopia refractive power of the affected eye was 5.00 (3.25) D. Among them, low myopia, moderate myopia, and high myopia were 227, 405, and 414 eyes, respectively. The average AL of the affected eye was 25.6±2.8 mm. The frequency domain OCT instrument was used to scan the temporal side of the retina, the upper and lower nasal vascular arches and the macular fovea radially. The images of retinal vascular cysts, microfolds, and lamellar hole were acquired and stored. The prevalence, composition ratio, distribution rule and OCT imaging characteristics of retinal paravascular abnormalities were observed and analyzed. The distribution of paravascular abnormalities in the retina was compared by the χ2 test; the age, refractive power, and AL of different paravascular abnormalities were compared by the K-W rank sum test. Results:Of the 1046 different diopters of myopic eyes, there were 227 eyes in mild myopia, 405 eyes in moderate myopia and 414 eyes in high myopia. Retinal paravascular abnormalities were detected by SD-OCT in 40 eyes (3.8%,40/1046). The prevalence of retinal paravascular abnormalities in moderate myopia was 0.7% (3/405) and high myopia was 8.9% (37/414). No retinal paravascular abnormalities were observed in mild myopia.Retinal paravascular cysts in 40 eyes (3.8%, 40/1046), retinal paravascular microfolds in 28 eyes (2.7%, 28/1046) and retinal paravascular lamellar holes in 13 eyes (1.2%, 13/1046). Of 40 eyes with retinal paravascular abnormalities, retinal paravascular cysts in all 40 eyes (100.0%, 40/40), retinal paravascular microfolds in 28 eyes (70.0%, 28/40) and retinal paravascular lamellar holes in 13 eyes (32.5%, 13/40). Twelve eyes with simple cyst cavity (30.0%, 12/40); 15 eyes were with cyst cavity with micro-wrinkles (37.5%, 15/40); 13 eyes were with cyst cavity, micro-wrinkles and lamellar holes (32.5%, 13/40). The temporal vascular arch retinal paravascular cysts ( χ2=25.664), microfolds ( χ2=14.973), and lamellar holes ( χ2=13.499) were significantly more than those on the nasal side, and the difference was statistically significant ( P <0.001). Conclusions:The total prevalence of retinal paravascular abnormalities in young myopia is 3.8%; it can occur in both moderate and high myopia. The paravascular cyst may be the earliest pathology of paravascular abnormalities in the retina. The three paravascular abnormalities are mostly distributed along the temporal arch of the retina.

Progress on surgical treatment for hemophiliac arthropathy / 中国骨伤

Surgical treatment is the main treatment for hemophilia arthritis, including synoviectomy, joint replacement and joint fusion. Synoviectomy is suitable for early hemophilia synovitis, and is divided into radiation, chemical, arthroscopy, and open operation. Radionuclides were recommended as the first choice due to its positive efficacy and less side effects, but exsit some problems such as scarcity of nuclides. Chemical synoviectomy is cheap and easy to operate, which is suitable for developing countriesm, while mutiple doses and pain after injection are main fault. Synoviectomy under arthroscope has a significant effect on the advanced lesion, but has a higher surgical risk. Open surgery with severe trauma and postoperative joint stiffness, is rarely performed. Joint replacement could effectively improve range of motion in advanced patients and is suitable for joints with high range of motion. Arthrodesis are effective in improving symptoms but lead to loss of range of motion and are suitable for joints with low range of motion. Operation for hemophilia arthritis has some problems, such as single operation, untimely diagnosis and treatment in early stage, and unsatisfactory curative effect in late stage. In addition, the treatment of hemophilia arthritis should focus on the early treatment, the formation of the whole process, the system of individual treatment concept.

Spontaneous remission of follicular bronchiolitis with nonspecific interstitial pneumonia: A case report and literature review / 北京大学学报(医学版)

A 41-year-old female patient was admitted in Department of Respiratory and Critical Care Medicine, Peking University Third Hospital because of having cough for a year. Multiple subpleural ground grass and solid nodules could be seen on her CT scan. Four months before admission, she began to experience dry mouth and eyes, blurred vision, finger joints pain, muscle pain and weakness in both lower limbs and weight loss. At the time of admission, the patient's vital signs were normal, no skin rash was seen, breath sounds in both lungs were clear, no rales or wheeze, no deformities in her hands, no redness, swelling, or tenderness in the joints. There was no edema in both lower limbs. Some lab examinations were performed. Tumor markers including squamous cell carcinoma (SCC) antigen, neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), Cyfra21-1, pro-gastrin-releasing peptide (proGRP), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) were all normal. The antinuclear antibody, rheumatoid factor, antineutrophil cytoplasmic antibody, anti-dsDNA antibody, anti-Sm antibody, anti-SSA/SSB antibody, anti-ribonucleoprotein (RNP) antibody, anti-Jo-1 antibody, anti-SCL-70 antibody and anti-ribosomal antibody were all negative. The blood IgG level was normal. The blood fungal β-1.3-D glucose, aspergillus galactomannan antigen, sputum bacterial and fungal culture, and sputum smear test for acid-fast staining were all negative. Lung function was normal. Bronchoscopy showed the airways and mucosa were normal. To clarify the diagnosis, she underwent thoracoscopic lung biopsy, the histopathology revealed follicular bronchiolitis (FB) with nonspecific interstitial pneumonia (NSIP). She did not receive any treatment and after 7 months, the lung opacities were spontaneously resolved. After 7 years of follow-up, the opacities in her lung did not relapse. To improve the understanding of FB, a literature research was performed with "follicular bronchiolitis" as the key word in Wanfang, PubMed and Ovid Database. The time interval was from January 2000 to December 2018. Relative articles were retrieved and clinical treatments and prognosis of FB were analyzed. Eighteen articles concerning FB with complete records were included in the literature review. A total of 51 adult patients with FB were reported, including 18 primary FB and 33 secondary FB, and autoimmune disease was the most common underlying cause. Forty-one (80.4%) patients were prescribed with corticosteroids and/or immunosuppressive agents, 6 (11.8%) patients were treated with anti-infective, 5 (9.8%) patients did not receive any treatment. The longest follow-up period was 107 months. Among the 5 patients without any treatment, 1 patients died of metastatic melanoma, the lung opacities were unchanged in 1 patient and getting severe in 3 patients. In conclusion, FB is a rare disease, the treatment and prognosis are controversial. Corticosteroid and immunosuppressive agents could be effective. This case report suggests the possibility of spontaneous remission of FB.

Establishment of a pediatric COVID-19 biorepository: unique considerations and opportunities for studying the impact of the COVID-19 pandemic on children.

BACKGROUND: COVID-19, the disease caused by the highly infectious and transmissible coronavirus SARS-CoV-2, has quickly become a morbid global pandemic. Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. This biorepository enables pediatric centers world-wide to collect samples uniformly to drive forward our understanding of COVID-19 by addressing specific pediatric and neonatal COVID-19-related questions. METHODS: A COVID-19 biospecimen collection study was implemented with strategic enrollment guidelines to include patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2 infected mothers, and asymptomatic children. The methodology described here, details the importance of establishing collaborations between the clinical and research teams to harmonize protocols for patient recruitment and sample collection, processing and storage. It also details modifications required for biobanking during a surge of the COVID-19 pandemic. RESULTS: Considerations and challenges facing enrollment of neonatal and pediatric cohorts are described. A roadmap is laid out for successful collection, processing, storage and database management of multiple pediatric samples such as blood, nasopharyngeal and oropharyngeal swabs, sputum, saliva, tracheal aspirates, stool, and urine. Using this methodology, we enrolled 327 participants, who provided a total of 972 biospecimens. CONCLUSIONS: Pediatric biospecimens will be key in answering questions relating to viral transmission by children, differences between pediatric and adult viral susceptibility and immune responses, the impact of maternal SARS-CoV-2 infection on fetal development, and factors driving the Multisystem Inflammatory Syndrome in Children. The specimens in this biorepository will allow necessary comparative studies between children and adults, help determine the accuracy of current pediatric viral testing techniques, in addition to, understanding neonatal exposure to SARS-CoV-2 infection and disease abnormalities. The successful establishment of a pediatric biorepository is critical to provide insight into disease pathogenesis, and subsequently, develop future treatment and vaccination strategies.

Establishment of a Pediatric COVID-19 Biorepository: Unique Considerations and Opportunities for Studying the Impact of the COVID-19 Pandemic on Children.

Background: COVID-19, the disease caused by the highly infectious and transmissible coronavirus SARS-CoV-2, has quickly become a morbid global pandemic. Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. This biorepository enables pediatric centers world-wide to collect samples uniformly to drive forward our understanding of COVID-19 by addressing specific pediatric and neonatal COVID-19-related questions. Methods: A COVID-19 biospecimen collection study was implemented with strategic enrollment guidelines to include patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2 infected mothers, and asymptomatic children. The methodology described here, details the importance of establishing collaborations between the clinical and research teams to harmonize protocols for patient recruitment and sample collection, processing and storage. It also details modifications required for biobanking during a surge of the COVID-19 pandemic. Results: Considerations and challenges facing enrollment of neonatal and pediatric cohorts are described. A roadmap is laid out for successful collection, processing, storage and database management of multiple pediatric samples such as blood, nasopharyngeal and oropharyngeal swabs, sputum, saliva, tracheal aspirates, stool, and urine. Using this methodology, we enrolled 327 participants, who provided a total of 972 biospecimens. Conclusions: Pediatric biospecimens will be key in answering questions relating to viral transmission by children, differences between pediatric and adult viral susceptibility and immune responses, the impact of maternal SARS-CoV-2 infection on fetal development, and factors driving the Multisystem Inflammatory Syndrome in Children. The specimens in this biorepository will allow necessary comparative studies between children and adults, help determine the accuracy of current pediatric viral testing techniques, in addition to, understanding neonatal exposure to SARS-CoV-2 infection and disease abnormalities. The successful establishment of a pediatric biorepository is critical to provide insight into disease pathogenesis, and subsequently, develop future treatment and vaccination strategies.

Amyloid-ß42/40 ratio drives tau pathology in 3D human neural cell culture models of Alzheimer's disease.

The relationship between amyloid-ß (Aß) species and tau pathology in Alzheimer's disease (AD) is not fully understood. Here, we provide direct evidence that Aß42/40 ratio, not total Aß level, plays a critical role in inducing neurofibrillary tangles (NTFs) in human neurons. Using 3D-differentiated clonal human neural progenitor cells (hNPCs) expressing varying levels of amyloid ß precursor protein (APP) and presenilin 1 (PS1) with AD mutations, we show that pathogenic tau accumulation and aggregation are tightly correlated with Aß42/40 ratio. Roles of Aß42/40 ratio on tau pathology are also confirmed with APP transmembrane domain (TMD) mutant hNPCs, which display differential Aß42/40 ratios without mutant PS1. Moreover, naïve hNPCs co-cultured with APP TMD I45F (high Aß42/40) cells, not with I47F cells (low Aß42/40), develop robust tau pathology in a 3D non-cell autonomous cell culture system. These results emphasize the importance of reducing the Aß42/40 ratio in AD therapy.

Ｒeview on the association of CAG short tandem repeats of androgen receptor gene with tumorigenesis and prognosis / 中华疾病控制杂志

@#Abnormal expression of androgen receptor ( AＲ) and AＲ-mediated signaling pathways are closely related to the occurrence，outcome，and prognosis of various human disease，and to some ex- tent，AＲ lead to gender differences in these diseases． However，the specific mechanism is still unclear． CAG short tandem repeat ( STＲ) sequence in exon 1 of AＲ gene negatively correlates with the transcriptional regulation activity，affects the synthesis and biological function of the target proteins，and plays an important role in the development and prognosis of various tumors，such as prostate cancer，breast cancer，bladder cancer，liver cancer，and endometrial cancer． In this review，we summarized the current studies on the association between AＲ gene CAG STＲ and the common tumors，in order to provide clues for further exploring the mechanism of AＲ-related tumors with high incidence and gender differences，and screening populations with high risk for the corresponding tumors．

Exploration and practice of clinical medical postgraduates management during the national prevention of COVID-19 spread / 中华医学科研管理杂志

Objective:To explore the difficulties and measures of clinical medical postgraduates management during the national prevention of COVID-19 pandemic.Methods:This study mainly used the document review, interview and questionnaire survey methodologies, to investigate the clinical medical postgraduates school situation, online teaching, training, scientific research, psychological state during prevention of COVID-19 emergency.Results:Up to February 14, 2020, the return rate of professional degree postgraduates was 92.8% (256/276). The average score of postgraduates participating in epidemic prevention and control training was 86.59. The effect of online learning was basically the same as that of face-to-face classroom teaching. Up to March 6, 2020, the in-hospital submission rate of postgraduates’ thesis was 50.0% (65/130). Facing the pressures of COVID-19 emergency, 62.6% professional degree postgraduates (124/198) and 35.4% (70/198) academic postgraduates suffered some anxiety or depression, the difference was statistically significant ( P<0.05). Conclusions:During the COVID-19 prevention and control period, it is important to innovate work style, found the linkage system of education department-clinical department-tutor-postgraduates, pay attention to physical and mental health of postgraduates, ensure the quality of teaching, adopt various measures to do well in the education and management of clinical medical postgraduates.

Strategy and practice of standardized residency training management during the national outbreak of COVID-19 / 中华医学教育探索杂志

The national outbreak of coronavirus disease 2019 (COVID-19) has brought a severe challenge to the management of standardized residency training (SRT). To protect SRT residents from being infected by 2019 novel coronavirus (2019-nCoV), to guarantee the training program well carried out, and to prevent psychological health problems are conundrums to the management of SRT. In this article, the specific countermeasures are introduced from the following aspects: perfecting the management system, implementing quarantine and life support, conducting epidemic prevention and control training, turning training patterns suitable to epidemic prevention, and maintaining the psychological health of the residents. And we expect to provide references for SRT management under the public health emergency in the future.

Dose selection of chloroquine phosphate for treatment of COVID-19 based on a physiologically based pharmacokinetic model

Chloroquine (CQ) phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019 (COVID-19). To develop a physiologically-based pharmacokinetic (PBPK) model for predicting tissue distribution of CQ and apply it to optimize dosage regimens, a PBPK model, with parameterization of drug distribution extrapolated from animal data, was developed to predict human tissue distribution of CQ. The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism. Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships. The model was also validated by clinical data from Chinese patients with COVID-19. The novel PBPK model allows in-depth description of the pharmacokinetics of CQ in several key organs (lung, heart, liver, and kidney), and was applied to design dosing strategies in patients with acute COVID-19 (Day 1: 750 mg BID, Days 2-5: 500 mg BID, CQ phosphate), patients with moderate COVID-19 (Day 1: 750 mg and 500 mg, Days 2-3: 500 mg BID, Days 4-5: 250 mg BID, CQ phosphate), and other vulnerable populations (.., renal and hepatic impairment and elderly patients, Days 1-5: 250 mg BID, CQ phosphate). A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.

Performance and comparison of assessment models to predict 30-day mortality in patients with hospital-acquired pneumonia / 中华医学杂志(英文版)

BACKGROUND@#Hospital-acquired pneumonia (HAP) is the most common hospital-acquired infection in China with substantial morbidity and mortality. But no specific risk assessment model has been well validated in patients with HAP. The aim of this study was to investigate the published risk assessment models that could potentially be used to predict 30-day mortality in HAP patients in non-surgical departments.@*METHODS@#This study was a single-center, retrospective study. In total, 223 patients diagnosed with HAP from 2012 to 2017 were included in this study. Clinical and laboratory data during the initial 24 hours after HAP diagnosis were collected to calculate the pneumonia severity index (PSI); consciousness, urea nitrogen, respiratory rate, blood pressure, and age ≥65 years (CURB-65); Acute Physiology and Chronic Health Evaluation II (APACHE II); Sequential Organ Failure Assessment (SOFA); and Quick Sequential Organ Failure Assessment (qSOFA) scores. The discriminatory power was tested by constructing receiver operating characteristic (ROC) curves, and the areas under the curve (AUCs) were calculated.@*RESULTS@#The all-cause 30-day mortality rate was 18.4% (41/223). The PSI, CURB-65, SOFA, APACHE II, and qSOFA scores were significantly higher in non-survivors than in survivors (all P < 0.001). The discriminatory abilities of the APACHE II and SOFA scores were better than those of the CURB-65 and qSOFA scores (ROC AUC: APACHE II vs. CURB-65, 0.863 vs. 0.744, Z = 3.055, P = 0.002; APACHE II vs. qSOFA, 0.863 vs. 0.767, Z = 3.017, P = 0.003; SOFA vs. CURB-65, 0.856 vs. 0.744, Z = 2.589, P = 0.010; SOFA vs. qSOFA, 0.856 vs. 0.767, Z = 2.170, P = 0.030). The cut-off values we defined for the SOFA, APACHE II, and qSOFA scores were 4, 14, and 1.@*CONCLUSIONS@#These results suggest that the APACHE II and SOFA scores determined during the initial 24 h after HAP diagnosis may be useful for the prediction of 30-day mortality in HAP patients in non-surgical departments. The qSOFA score may be a simple tool that can be used to quickly identify severe infections.