Acute hyperextension spinal cord injury in children: A retrospective study / 中华骨科杂志

Objective:To summarize the clinical characteristics and prognosis of acute hyperextension spinal cord injury (SCI) in children, and to provide some recommendations for the treatment and prevention of this disease.Methods:Reviewed the data of children of SCI after sustained or repeated hyperextension of the spine at Wuhan Union Hospital and Wuhan Children's Hospital from September 2010 to September 2020. According to the American Spinal Injury Association impairment scale (AIS grade), the patients were divided into complete SCI group and incomplete SCI group. The age, symptoms and evolution after injury, neurological level of injury, imaging data, laboratory examination data, prognosis and complications of the two groups were analyzed. Retrospectively summarize the characteristics of this type of injury.Results:Forty-four cases of acute hyperextension SCI in children were included. Their age ranged from 3 to 10 years old, 95% of them were under 8 years old and 95% of them were female. There was no significant difference in age at injury and time of dance training between children with complete SCI and incomplete SCI. Back and leg pain, lower limb weakness or paresthesia, and rapidly progress to complete or incomplete SCI in a short period were typical symptoms. All blood test results anddiagnostic analysis of cerebrospinal fluid were unremarkable or negative. There was no fracture or dislocation in the whole spine. Magnetic resonance imaging showed a longitudinally extended intramedullary high-intensity signal in the thoracolumbar spinal cord. Complete SCI accounted for 60% of all cases, and the prognosis was poor with spinal cord atrophy and various complications.Conclusion:Children younger than 10 years old after sustained or repeated hyperextension of the spine may suffer acute hyperextension SCI. Children with complete SCI have poor prognosis and serious complications. Therefore, prevention of this type of injury is the best strategy.

Clinical phenotype and genotype analysis in 9 children with nephronophthisis / 中华肾脏病杂志

Objective:To investigate and analyze the clinical phenotypes and genotypes in children diagnosed with nephronophthisis (NPHP), and to provide references for clinical diagnosis.Methods:Clinical data of 9 children with NPHP diagnosed by genetic testing in the Department of Nephrology, Wuhan Children′s Hospital from April 2017 to January 2022 were retrospectively collected. The clinical characteristics and genetic test results were analyzed.Results:The median onset age was 11.2(3.4, 14.2) years old in 9 patients, including 5 females and 4 males. There were 8 cases of glomerular proteinuria, 8 cases of renal tubular proteinuria, and 7 cases of reduced urinary gravity in 9 patients. All the children had varying degrees of impaired renal function at the time of diagnosis. Seven cases entered chronic kidney disease (CKD) stage 5, 1 case entered CKD stage 3, and 1 case entered CKD stage 4 at the time of diagnosis. All the children had renal ultrasound abnormalities of varying degrees: size change (3/9), echo enhancement (8/9) and cysts (3/9). Extrarenal phenotypes were present in 3 children. Genetic test showed that 6 patients had mutation of NPHP1 gene, 1 patient had mutation of WDR19 gene, 1 patient had mutation of NPHP3 gene and 1 patient had mutation of NPHP5 gene. Conclusions:Deletion mutation of NPHP1 gene is the most common, while NPHP3, NPHP5 and extremely rare WDR19 mutations have also been found in NPHP patients. The clinical manifestations of NPHP are not typical, so it is necessary to find a specific diagnosis method in the early.

Analysis of the clinical characteristics and risk factors of postoperative atrial fibrillation in patients with critical burns / 中华烧伤杂志

Objective: To investigate the clinical characteristics and risk factors of postoperative atrial fibrillation (POAF) in patients with critical burns. Methods: A retrospective case series study was conducted. From January 2017 to December 2021, two hundred and twenty-seven critically burned aldult patients who met the inclusion criteria were admitted to Guangzhou Red Cross Hospital of Jinan University, including 173 males and 54 females, aged 19-83 (43±14) years. The admission years of patients were collected, and the percentage of patients complicated with POAF in each year was calculated. According to whether the patients were complicated with POAF or not, they were divided into POAF group (n=17) and non-POAF group (n=210). Following data were collected in patients in POAF group, including operation methods, duration of operation, intraoperative blood loss before occurrence of POAF each time, occurrence time and times of POAF, postoperative body temperature, blood pressure, hemoglobin, blood glucose, blood lactate, sepsis, and electrolyte, and type, duration, and treatment of POAF. General data of patients in the two groups including age, gender, burn reason, total burn area, full-thickness burn area, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sepsis-related organ failure evaluation (SOFA) scores on admission, combined with underlying diseases (hypertension, diabetes, and other types of arrhythmias), and sepsis were collected and analyzed. The mortality and factors influencing the prognosis of patients in the two groups such as mechanical ventilation time, operations times, and burn intensive care unit (BICU) length of stay were also collected and analyzed. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, chi-square test or Kruskal-Wallis H test. The multivariate logistic regression analysis was performed on the general data with statistically significant differences between the two groups, and the independent risk factors influencing the onset of POAF in 227 patients with critical burns were screened. Results: From 2017 to 2021, the percentage of critically burned patients complicated with POAF increased year by year. In POAF group, eschar debridement in limbs was the main surgical procedure prior to POAF complication, with the operation time of (3.5±1.2) h and the intraoperative blood loss volume of (365±148) mL.The POAF occurred 25 times in total in patients of POAF group, mostly within one week after the injury and within 6 hours after the operation with most of these patients having POAF only once. When POAF happened, the patients were often complicated with hypothermia, anemia, hyperglycemia, high blood lactate, sepsis, and electrolyte disturbance, and few patients had complications of hypotension. The POAF lasted (5±3) h, with all being paroxysmal atrial fibrillation, and most of POAF patients were reverted to sinus rhythm after amiodarone intervention. Most patients in the two groups suffered from flame burn, and the gender, age, and SOFA score on admission of patients in the two groups were similar (P>0.05); the APACHEⅡ score on admission, total burn area, full-thickness burn area, incidence proportion of sepsis, combined with diabetes and hypertension and other types of arrhythmias of patients in POAF group were significantly higher or larger than those in non-POAF group (t=3.47, with χ2 values of 7.44, 10.86, 12.63, 14.65, 6.49, and 7.52, respectively, P<0.05 or P<0.01). The full-thickness burn area, combined with other types of arrhythmias, and sepsis were the independent risk factors for POAF in 227 critically burned patients (with odds ratios of 4.45, 0.04, and 3.06, respectively, with 95% confidence intervals of 2.23-8.87, 0.01-0.22, and 1.77-5.30, respectively, P<0.01). Compared with those in non-POAF group, the mechanical ventilation time, BICU length of stay, number of operations, and mortality rate of patients in POAF group were significantly increased (Z=3.89, Z=2.57, t=3.41, χ2=3.72, P<0.05 or P<0.01). Conclusions: POAF is a common postoperative complication in critically burned patients, and the incidence is increasing year by year, which seriously affects the prognosis of patients. The full-thickness burn area together with other types of arrhythmias and sepsis are the high-risk factors for POAF complication in patients with critical burns.

Clinical efficacy of ultrasound-guided closed reduction for pediatric distal radius fracture / 中华实用儿科临床杂志

Objective:To compare the clinical efficacy of ultrasound-guided closed reduction and bare-handed reduction on pediatric distal radius fractures.Methods:Clinical data of 118 consecutive pediatric patients with distal radius fracture treated in the Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science & Technology from April 2018 to August 2019 were retrospectively analyzed.Patients treated with bare-handed reduction and ultrasound-guided closed reduction were respectively classified into group Ⅰ (58 cases) and group Ⅱ (60 cases). Baseline characteristics, treatment duration, out-patient treatment cost, postoperative pain and the modified Mayo wrist function score during the follow-up visits between groups were compared by the t test.The success rate of initial reduction, reduction times, hospitalization rate and complication between 2 groups were compared by the Chi- square test.The number of postoperative imaging scans between 2 groups was compared by the Mann- Whitney U test. Results:There were no significant differences in out-patient treatment cost and hospitalization rate between 2 groups (all P>0.05). There were significant differences in the length of stay [ (166.2±54.8) min vs.(142.6±49.2) min], success rate of initial reductions [72.4%(42/58 cases ) vs.88.3%(53/60 cases)], incidence of repeated reductions (27.6% vs.1.7%) and the incidence of postoperative repeated imaging scans (20.7% vs.1.7%) between groupⅠ and group Ⅱ (all P<0.05). A total of 104 patients (88.1%) were successfully treated with closed reduction and followed up, with a rate of success reductions.Among them, success rate of closed reduction in group Ⅰ and Ⅱ were 86.2% and 90.0%, respectively.The mean time of fracture healing was 43 (34-56) days.There were no significant differences in fracture healing time and pain score between 2 groups(all P>0.05). The modified Mayo wrist score was significantly lower in group Ⅰ than that of group Ⅱ[(97.3±4.1) points vs.(98.8±2.9) points, P<0.05]. Seven patients in group Ⅰ suffered fracture re-displacement, including 6 cases within 1 case week and 1 within 2 weeks, and 4 cases admitted to the surgical ward for further management.Five patients in group Ⅱ had re-displacement within 1 week of plaster fixation, of which 2 cases admitted to the surgical ward for further management, which was comparable between groups( P>0.05). Conclusions:Both ultrasound-guided closed reduction and bare-handed reduction are effective on the treatment of pediatric distal radius fractures, showing low incidence of complications and satisfactory functional results.Owing to its higher success rate of initial reduction, lower frequency of postoperative ra-diography and shorter length of stay, ultrasound-guided closed reduction should be recommended.

Four-Octyl itaconate ameliorates periodontal destruction via Nrf2-dependent antioxidant system / 国际口腔科学杂志·英文版

Periodontitis is a widespread oral disease characterized by continuous inflammation of the periodontal tissue and an irreversible alveolar bone loss, which eventually leads to tooth loss. Four-octyl itaconate (4-OI) is a cell-permeable itaconate derivative and has been recognized as a promising therapeutic target for the treatment of inflammatory diseases. Here, we explored, for the first time, the protective effect of 4-OI on inhibiting periodontal destruction, ameliorating local inflammation, and the underlying mechanism in periodontitis. Here we showed that 4-OI treatment ameliorates inflammation induced by lipopolysaccharide in the periodontal microenvironment. 4-OI can also significantly alleviate inflammation and alveolar bone loss via Nrf2 activation as observed on samples from experimental periodontitis in the C57BL/6 mice. This was further confirmed as silencing Nrf2 blocked the antioxidant effect of 4-OI by downregulating the expression of downstream antioxidant enzymes. Additionally, molecular docking simulation indicated the possible mechanism under Nrf2 activation. Also, in Nrf2-/- mice, 4-OI treatment did not protect against alveolar bone dysfunction due to induced periodontitis, which underlined the importance of the Nrf2 in 4-OI mediated periodontitis treatment. Our results indicated that 4-OI attenuates inflammation and oxidative stress via disassociation of KEAP1-Nrf2 and activation of Nrf2 signaling cascade. Taken together, local administration of 4-OI offers clinical potential to inhibit periodontal destruction, ameliorate local inflammation for more predictable periodontitis.

Aging weakens Th17 cell pathogenicity and ameliorates experimental autoimmune uveitis in mice

Aging-induced changes in the immune system are associated with a higher incidence of infection and vaccination failure. Lymph nodes, which filter the lymph to identify and fight infections, play a central role in this process. However, careful characterization of the impact of aging on lymph nodes and associated autoimmune diseases is lacking. We combined single-cell RNA sequencing (scRNA-seq) with flow cytometry to delineate the immune cell atlas of cervical draining lymph nodes (CDLNs) of both young and old mice with or without experimental autoimmune uveitis (EAU). We found extensive and complicated changes in the cellular constituents of CDLNs during aging. When confronted with autoimmune challenges, old mice developed milder EAU compared to young mice. Within this EAU process, we highlighted that the pathogenicity of T helper 17 cells (Th17) was dampened, as shown by reduced GM-CSF secretion in old mice. The mitigated secretion of GM-CSF contributed to alleviation of IL-23 secretion by antigen-presenting cells (APCs) and may, in turn, weaken APCs' effects on facilitating the pathogenicity of Th17 cells. Meanwhile, our study further unveiled that aging downregulated GM-CSF secretion through reducing both the transcript and protein levels of IL-23R in Th17 cells from CDLNs. Overall, aging altered immune cell responses, especially through toning down Th17 cells, counteracting EAU challenge in old mice.

Single-nucleus transcriptomic landscape of primate hippocampal aging

The hippocampus plays a crucial role in learning and memory, and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases. Yet a systematic profiling of the aging effects on various hippocampal cell types in primates is still missing. Here, we reported a variety of new aging-associated phenotypic changes of the primate hippocampus. These include, in particular, increased DNA damage and heterochromatin erosion with time, alongside loss of proteostasis and elevated inflammation. To understand their cellular and molecular causes, we established the first single-nucleus transcriptomic atlas of primate hippocampal aging. Among the 12 identified cell types, neural transiently amplifying progenitor cell (TAPC) and microglia were most affected by aging. In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory; additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte, as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis. This rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases.

Application of bilingual mixed grouping in ward round teaching for overseas students in cardiology department / 中华医学教育探索杂志

Due to the problems of language barriers and cultural differences existing in the current clinical practice teaching activities of overseas students, this study proposes to divide the oversea students and Chinese students into bilingual mixed groups in the ward rounds teaching. Through the selection of typical cases and the application of flipped classroom, the Chinese and English versions of learning materials related to disease are provided to the interns for learning in advance, and the oversea students and Chinese students are requested to complete the history and auxiliary examination data collection in Chinese and English in cooperation, and then the teacher leads the group to carry out ward rounds teaching, including bedside English history report, physical examination, case analysis, discussion and summary, so as to improve the participation enthusiasm of overseas students and also improve the teaching effects.

Association between school bullying and mental health of adolescent students in low-income and middle-income countries / 中国学校卫生

Objective@#To understand the incidence of school bullying and its influencing factors among adolescents in low-income and middle-income countries, and to explore the association between school bullying and mental health of adolescent students, so as to provide reference for prevention and control of school bullying and mental health intervention.@*Methods@#Data was obtained from the 2009-2015 Global School Student Health Survey from 19 low-income and middle-income countries (n=22 963). Binary Logistic regression was used to analyze the influencing factors of school bullying, and multiple linear regression was used to analyze the relationship between school bullying and mental health.@*Results@#The average score of students mental health was(5.75±2.09), and approximately 35.1% of adolescent students reported suffering from school bullying. The rates of school bullying among students in low-income and middle-income countries were 39.4% amd 34.3%, respectively. Students with lower grades, overweight, poor family economic status, low family learning and psychological support, poor perceived family relationship, more truancy, and poor relationship with classmates were more likely to suffer from school bullying(P<0.05). Exposure to school bullying was positively associated with adverse mental health outcomes for women(B=1.27, P<0.01).@*Conclusion@#Not only were school bullying more common in low-income countries, but also school bullying had a greater negative impact on the mental health of girls. We need to pay more attention to school bullying among adolescent students, especially in low-income countries and girls, with cost-effective interventions to reduce or mitigate the consequences of bullying.

Intraoperative arthrography monitoring assisted closed reduction and internal fixation for intercondylar fracture of humerus in children / 中国骨伤

OBJECTIVE@#To investigate clinical effects of intraoperative arthrography monitoring assisted closed reduction and internal fixation for intercondylar fracture of humerus in children.@*METHODS@#From January 2013 to July 2018, 18 children with intercondylar fracture of humerus were treated by operation, including 13 males and 5 females aged from 3 to 12 years old with an average age of (8.50±2.57) years old. According to Toniolo & Wilkinson classification, 8 children were typeⅠand 10 children were typeⅡ. During the operation, closed reduction and internal fixation were performed under the monitoring of intraoperative radiography, open reduction and internal fixation were performed in necessity. Mayo score of elbow joint was used to evaluate clinical effect at 6 months after operation.@*RESULTS@#All children were underwent arthrography monitoring during operation, 5 children were treated with closed reduction and internal fixation for intraoperative arthrography found no fracture of articular cartilage, 11 children by closed reduction and internal fixation because of fracture of articular cartilage involving the joint space with displacement less than 2 mm, and 2 children by closed or open reduction and internal fixation for fracture of articular cartilage surface with displacement above 2 mm, which 1 child with smooth of joint surface was performed closed reduction and internal fixation, 1 child without smooth of joint surface and displacement above 2 mm was performed open reduction and internal fixation. All children were followed up from 8 to 26 months with an average of (20.28±4.40) months. All factures were healed from 6 to 9 weeks with an average of (7.33±0.77) weeks. Postoperative Mayo score of elbowjoint at 6 months was (89.44±11.36), and 12 patients got excellent results, 5 good and 1 poor. One patient occurred partial limitation of flexion or extension of elbow joint. No elbow deformity and other complications occurred.@*CONCLUSION@#The treatment of intercondylar fracture of humerus in children under monitoring of intraoperative radiography could reduce opertaion injuries and complications, confirm the reduction effect of articular surface of cartilage in time and clearly, and promote recovery of elbow joint function.

Analysis of the effect of surgical treatment of periprosthetic femoral fractures after hip replacement / 中国骨伤

OBJECTIVE@#To analyze and compare the clinical efficacy of different types of surgical treatment of periprosthetic femoral fracture(PFF) after hip arthroplasty (HA).@*METHODS@#From September 2010 to September 2016, 47 patients (47 hips) with periprosthetic fractures after total hip arthroplasty were retrospectively analyzed, including 13 males and 34 females. According to Vancouver classification, there were 2 patients with type AG, 17 patients with type B1, 19 patients with type B2, 7 patients with type B3 and 2 patients with type C. The age of patients ranged from 56 to 94 (71.5±8.3) years. After admission, nutritional risk screening (NRS2002) was used to assess the nutritionalstatus of the patients. Eighteen patients (38%) had malnutrition risk (NRS>3 points). After admission, the patients were given corresponding surgical treatment according to different types. Intraoperative blood loss was recorded. Harris score was used to evaluate the hip function. VAS pain score was performed on admission and after operation.@*RESULTS@#All the 47 patients were followed up for 19 to 62 (34±11) months. The Harris scores were (41.8±12.1) and (89.0±2.6) respectively before and 1 year after operation, and the difference was statistically significant (@*CONCLUSION@#The treatment of hip periprosthetic fracture patients should be based on the general situation of patients, imaging data, intraoperative correction classification, etc. to develop individualized treatment plan in line with patients. For patients with preoperative malnutrition risk, preoperative nutritional intervention may reduce intraoperative bleeding.

Detection Method and Degradation Dynamics of Chlorfenapyr in Honeysuckle Under Field Conditions / 中国药学杂志

OBJECTIVE: To develop a gas chromatography (GC) method for determination of chlorfenapyr in flower buds of Lonicera japonica Thunb, and study the degradation dynamics of chlorfenapyr in honeysuckle collected through field experiment, thus providing theoretical references for the application of chlorfenapyr in practical production of honeysuckle. METHODS: Honeysuckle samples were extracted with acetone using a vortex mixer and then cleaned up by passing through a neutral alumina chromatography column, followed by detection by gas chromatography with electronic capture detector (GC-ECD). External standard method was used for quantification. RESULTS: At fortified levels of 0.02-0.5 mg•kg-1, the average recoveries of chlorfenapyr in honeysuckle were from 83.9% to 97.6%, with RSDs of 0.6%-9.2%. The limit of detection was estimated to be 7.3 μg•kg-1. The degradation dynamics of chlorfenapyr in honeysuckle conformed to first-order dynamic equation. The degradation half-life of chlorfenapyr was 2.3 d. CONCLUSION: The method developed in this experiment is simple, rapid, reliable and in line with the requirements of pesticide residue analysis. The degradation rate of chlorfenapyr in honeysuckle is relatively rapid. Chlorfenapyr belongs to pesticides which are liable to degradation.

SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer

SIRT7, a sirtuin family member implicated in aging and disease, is a regulator of metabolism and stress responses. It remains elusive how human somatic stem cell populations might be impacted by SIRT7. Here, we found that SIRT7 expression declines during human mesenchymal stem cell (hMSC) aging and that SIRT7 deficiency accelerates senescence. Mechanistically, SIRT7 forms a complex with nuclear lamina proteins and heterochromatin proteins, thus maintaining the repressive state of heterochromatin at nuclear periphery. Accordingly, deficiency of SIRT7 results in loss of heterochromatin, de-repression of the LINE1 retrotransposon (LINE1), and activation of innate immune signaling via the cGAS-STING pathway. These aging-associated cellular defects were reversed by overexpression of heterochromatin proteins or treatment with a LINE1 targeted reverse-transcriptase inhibitor. Together, these findings highlight how SIRT7 safeguards chromatin architecture to control innate immune regulation and ensure geroprotection during stem cell aging.

A human circulating immune cell landscape in aging and COVID-19

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.

SIRT7 antagonizes human stem cell aging as a heterochromatin stabilizer

SIRT7, a sirtuin family member implicated in aging and disease, is a regulator of metabolism and stress responses. It remains elusive how human somatic stem cell populations might be impacted by SIRT7. Here, we found that SIRT7 expression declines during human mesenchymal stem cell (hMSC) aging and that SIRT7 deficiency accelerates senescence. Mechanistically, SIRT7 forms a complex with nuclear lamina proteins and heterochromatin proteins, thus maintaining the repressive state of heterochromatin at nuclear periphery. Accordingly, deficiency of SIRT7 results in loss of heterochromatin, de-repression of the LINE1 retrotransposon (LINE1), and activation of innate immune signaling via the cGAS-STING pathway. These aging-associated cellular defects were reversed by overexpression of heterochromatin proteins or treatment with a LINE1 targeted reverse-transcriptase inhibitor. Together, these findings highlight how SIRT7 safeguards chromatin architecture to control innate immune regulation and ensure geroprotection during stem cell aging.

A human circulating immune cell landscape in aging and COVID-19

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.

A human circulating immune cell landscape in aging and COVID-19

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.

Molluscicidal activity of 25% wettable powder of pyriclobenzuron sulphate against Oncomelania hupensis robertsoni / 中国血吸虫病防治杂志

Objective To evaluate the molluscicidal activity of a novel molluscicide pyriclobenzuron against Oncomelania hupensis robertsoni in the mountain regions of Yunan Province, and test its toxicity to fish, so as to provide scientific evidence for the extensive application of this molluscicide in schistosomiasis-endemic foci of Yunan Province. Methods In the laboratory and snail-breeding field of Dali Prefecture, Yunnan Province, the molluscicidal activity of 5% wettable powder of pyriclobenzuron sulphate (25% PBU) against O. hupensis robertsoni was assessed by using the immersion and spraying method, and the acute toxicity of 25% PBU to carp fries was tested, while 25% wettable powder of niclosamide ethanolamine salt (50% WPNES) served as a control. Results The 1-, 2- and 3-day 25% PBU LC50 and LC90 values were 0.47, 0.25 and 0.23 mg/L, and 1.54, 0.61 and 0.49 mg / L for O. h. robertsoni by using the immersion method in laboratory, and immersion with 25% PBU at 1.0 mg / L for 1 day achieved a comparable molluscicidal efficacy in relative to 50% WPNES at 1.0 mg/L. Spraying with 25% PBU at 4.0 g/m2 achieved 1-, 3- and 7-day snail mortalities of 64.23%, 96.67% and 100.00% in laboratory, respectively, which were not significantly different from those caused by treatment with 50% WPNES at 1.0 g/m2 (all P values > 0.05). One-day field immersion with 25% PBU at doses of 1, 2 and 4 g/m3 resulted in snail mortalities of 90.00%, 93.33% and 100.00%, respectively, which were not significantly different from those caused by treatment with 50% WPNES at 1.0 g/m3 (all P values > 0.05), and 3-day field spraying with 25% PBU at doses of 2.0 and 4.0 g/m2 caused snail mortalities of 86.36% and 87.72%, respectively, which were not significantly different from those caused by 50% WPNES treatment (both P values > 0.05). The 24-, 48- and 72-hour LC50 values of 25% PBU to carp fries were 29.38, 24.62 and 23.38 mg/L, respectively, and no fish death was observed within 72 hours of exposure to 25% PBU at a concentration of 17.5 mg/L and lower. Conclusion 25% PBU is a novel, highly potent and environment-friendly molluscicide that is feasible in fish ponds, and the recommended dose is 1 g/m3 for field immersion and 2 g/m2 for field spraying in schistosomiasis-endemic areas of Yunnan Province.

Molluscicidal activity of 25% wettable powder of pyriclobenzuron sulphate against Oncomelania hupensis robertsoni / 中国血吸虫病防治杂志

Objective To evaluate the molluscicidal activity of a novel molluscicide pyriclobenzuron against Oncomelania hupensis robertsoni in the mountain regions of Yunan Province, and test its toxicity to fish, so as to provide scientific evidence for the extensive application of this molluscicide in schistosomiasis-endemic foci of Yunan Province. Methods In the laboratory and snail-breeding field of Dali Prefecture, Yunnan Province, the molluscicidal activity of 5% wettable powder of pyriclobenzuron sulphate (25% PBU) against O. hupensis robertsoni was assessed by using the immersion and spraying method, and the acute toxicity of 25% PBU to carp fries was tested, while 25% wettable powder of niclosamide ethanolamine salt (50% WPNES) served as a control. Results The 1-, 2- and 3-day 25% PBU LC50 and LC90 values were 0.47, 0.25 and 0.23 mg/L, and 1.54, 0.61 and 0.49 mg / L for O. h. robertsoni by using the immersion method in laboratory, and immersion with 25% PBU at 1.0 mg / L for 1 day achieved a comparable molluscicidal efficacy in relative to 50% WPNES at 1.0 mg/L. Spraying with 25% PBU at 4.0 g/m2 achieved 1-, 3- and 7-day snail mortalities of 64.23%, 96.67% and 100.00% in laboratory, respectively, which were not significantly different from those caused by treatment with 50% WPNES at 1.0 g/m2 (all P values > 0.05). One-day field immersion with 25% PBU at doses of 1, 2 and 4 g/m3 resulted in snail mortalities of 90.00%, 93.33% and 100.00%, respectively, which were not significantly different from those caused by treatment with 50% WPNES at 1.0 g/m3 (all P values > 0.05), and 3-day field spraying with 25% PBU at doses of 2.0 and 4.0 g/m2 caused snail mortalities of 86.36% and 87.72%, respectively, which were not significantly different from those caused by 50% WPNES treatment (both P values > 0.05). The 24-, 48- and 72-hour LC50 values of 25% PBU to carp fries were 29.38, 24.62 and 23.38 mg/L, respectively, and no fish death was observed within 72 hours of exposure to 25% PBU at a concentration of 17.5 mg/L and lower. Conclusion 25% PBU is a novel, highly potent and environment-friendly molluscicide that is feasible in fish ponds, and the recommended dose is 1 g/m3 for field immersion and 2 g/m2 for field spraying in schistosomiasis-endemic areas of Yunnan Province.

Modeling CADASIL vascular pathologies with patient-derived induced pluripotent stem cells

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary cerebrovascular disease caused by a NOTCH3 mutation. However, the underlying cellular and molecular mechanisms remain unidentified. Here, we generated non-integrative induced pluripotent stem cells (iPSCs) from fibroblasts of a CADASIL patient harboring a heterozygous NOTCH3 mutation (c.3226C>T, p.R1076C). Vascular smooth muscle cells (VSMCs) differentiated from CADASIL-specific iPSCs showed gene expression changes associated with disease phenotypes, including activation of the NOTCH and NF-κB signaling pathway, cytoskeleton disorganization, and excessive cell proliferation. In comparison, these abnormalities were not observed in vascular endothelial cells (VECs) derived from the patient's iPSCs. Importantly, the abnormal upregulation of NF-κB target genes in CADASIL VSMCs was diminished by a NOTCH pathway inhibitor, providing a potential therapeutic strategy for CADASIL. Overall, using this iPSC-based disease model, our study identified clues for studying the pathogenic mechanisms of CADASIL and developing treatment strategies for this disease.