Alterations of human CSF and serum-based mitophagy biomarkers in the continuum of Alzheimer disease.

Defective mitophagy is consistently found in postmortem brain and iPSC-derived neurons from Alzheimer disease (AD) patients. However, there is a lack of extensive examination of mitophagy status in serum or cerebrospinal fluid (CSF), and the clinical potential of mitophagy biomarkers has not been tested. We quantified biomarkers of mitophagy/autophagy and lysosomal degradation (PINK1, BNIP3L and TFEB) in CSF and serum from 246 individuals, covering mild cognitive impairment due to AD (MCI-AD, n = 100), dementia due to AD (AD-dementia, n = 100), and cognitively unimpaired individuals (CU, n = 46), recruited from the Czech Brain Aging Study. Cognitive function and brain atrophy were also assessed. Our data show that serum and CSF PINK1 and serum BNIP3L were higher, and serum TFEB was lower in individuals with AD than in corresponding CU individuals. Additionally, the magnitude of mitophagy impairment correlated with the severity of clinical indicators in AD patients. Specifically, levels of PINK1 positively correlated with phosphorylated (p)-MAPT/tau (181), total (t)-MAPT/tau, NEFL (neurofilament light chain), and NRGN (neurogranin) levels in CSF and negatively with memory, executive function, and language domain. Serum TFEB levels negatively correlated with NEFL and positively with executive function and language. This study reveals mitophagy impairment reflected in biofluid biomarkers of individuals with AD and associated with more advanced AD pathology.Abbreviation: Aß: amyloid beta; AD: Alzheimer disease; AVs: autophagic vacuoles; BNIP3L: BCL2 interacting protein 3 like; CU: cognitively unimpaired; CSF: cerebrospinal fluid; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCI: mild cognitive impairment; NRGN: neurogranin; NEFL: neurofilament light chain; p-MAPT/tau: phosphorylated microtubule associated protein tau; PINK1: PTEN induced kinase 1; t-MAPT/tau: total microtubule associated protein tau; TFEB: transcription factor EB; TMT: Trail Making Test.

Clinical effect of double plasma molecular adsorption system in treatment of patients with chronic liver failure in high-altitude areas / 临床肝胆病杂志

ObjectiveTo investigate the differences in clinical features and mortality rate between native patients with chronic liver failure （CHF） and migrated patients with CHF after treatment with double plasma molecular adsorption system （DPMAS） in high-altitude areas. MethodsA total of 63 patients with CHF who received DPMAS treatment in the intensive care unit of General Hospital of Tibet Military Command from January 2016 to December 2021 were enrolled， and according to their history of residence in high-altitude areas， they were divided into native group with 29 patients and migrated group with 34 patients. The two groups were compared in terms of baseline data and clinical features before and after DPMAS treatment. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the paired t-test was used for comparison before and after treatment within each group； the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups， and the Wilcoxon signed rank sum test was used for comparison before and after treatment within each group； the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves， and the Log-rank test was used for comparison of the risk of death. ResultsCompared with the native group， the migrated group had a significantly higher proportion of Chinese Han patients （χ2=41.729， P<0.001）， and compared with the migrated group， the native group had a significantly longer duration of the most recent continuous residence in high-altitude areas （Z=3.364， P<0.001）. Compared with the native group， the migrated group had significantly higher MELD score and incidence rates of hepatic encephalopathy， hepatorenal syndrome， and gastrointestinal bleeding （Z=2.318， χ2=6.903， 5.154， and 6.262， all P<0.05）. Both groups had significant changes in platelet count （PLT）， hemoglobin count （HGB）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， albumin， total bilirubin （TBil）， direct bilirubin （DBil）， lactate dehydrogenase （LDH）， creatinine （Cr）， and international normalized ratio （INR） after DPMAS treatment （all P<0.05）. Before DPMAS treatment， compared with the native group， the migrated group had significantly higher levels of ALT， AST， TBil， DBil， LDH， Cr， BUN， and INR （all P<0.05） and a significantly lower level of HGB （P<0.05）； after DPMAS treatment， compared with the native group， the migrated group had significantly greater reductions in PLT and HGB （both P<0.05） and still significantly higher levels of ALT， AST， TBil， DBil， LDH， BUN， and INR （all P<0.05）. The 60-day mortality rate of patients after DPMAS treatment was 52.5% （95% confidence interval ［CI］： 41.7 — 63.8） in the native group and 81.3% （95%CI： 77.9 — 85.6） in the migrated group. Compared with the native group （hazard ratio ［HR］=0.47， 95%CI： 0.23 — 0.95）， the migrated group had a significant increase in the risk of death on day 60 （HR=2.14， 95%CI： 1.06 — 4.32， P=0.039）. ConclusionCompared with the native patients with CHF in high-altitude areas， migrated patients have a higher degree of liver impairment， a lower degree of improvement in liver function after DPMAS treatment， and a higher mortality rate. Clinical medical staff need to pay more attention to migrated patients with CHF， so as to improve their survival rates.

Research progress in artificial intelligence assisted diabetic retinopathy diagnosis.

Diabetic retinopathy (DR) is one of the most common retinal vascular diseases and one of the main causes of blindness worldwide. Early detection and treatment can effectively delay vision decline and even blindness in patients with DR. In recent years, artificial intelligence (AI) models constructed by machine learning and deep learning (DL) algorithms have been widely used in ophthalmology research, especially in diagnosing and treating ophthalmic diseases, particularly DR. Regarding DR, AI has mainly been used in its diagnosis, grading, and lesion recognition and segmentation, and good research and application results have been achieved. This study summarizes the research progress in AI models based on machine learning and DL algorithms for DR diagnosis and discusses some limitations and challenges in AI research.

Gorham-Stout disease affecting the spine with cerebrospinal fluid leakage and Chiari-like tonsillar herniation: a rare case report and review of literature.

BACKGROUND: Gorham-Stout disease (GSD) is a very rare disorder characterized by massive osteolysis of poorly understood aetiology. The association between GSD involving the skull base and cerebrospinal fluid (CSF) leakage has been reported in the literature. However, few cases of CSF leakage and Chiari-like tonsillar herniation in GSD involving the spine have been reported. CASE PRESENTATION: We present the case of a 20-year-old man with GSD involving the thoracic and lumbar spine, which caused CSF leakage and Chiari-like tonsillar herniation. The patient underwent four spinal surgeries for osteolytic lesions of the spine over a 10-year period. Here, we discuss the possible aetiology of the development of CSF leakage. Epidural blood patch (EBP) was performed at the T11-T12 level to repair the CSF leakage. After EBP treatment, rebound intracranial hypertension (RIH) developed, and tonsillar herniation disappeared 2 months later. CONCLUSIONS: GSD involving the spine with CSF leakage and Chiari-like tonsillar herniation is relatively rare. For patients who have undergone multiple spinal surgeries, minimally invasive treatment is an alternative treatment for CSF leakage. EBP can repair CSF leakage secondary to GSD and improve chronic brain sagging, with reversibility of Chiari-like malformations.

Integration of RRBS and RNA-seq unravels the regulatory role of DNMT3A in porcine Sertoli cell proliferation.

DNMT3A participates in de novo methylation, yet its impact on the proliferation of testicular Sertoli cells remains unclear. Development-specific methylation has been proven to be associated with cellular development. Therefore, in this study, we simulated DNMT3A expression pattern during testicular development by DNMT3A interference. Then, RRBS and RNA-seq were used to decipher DNMT3A regulatory mechanisms on Sertoli cell proliferation. Immunofluorescence staining revealed the expression of DNMT3A in the Sertoli cells of the prepubertal testis. DNMT3A was demonstrated to inhibit the cell cycle and proliferation of Sertoli cells, while promoting cell apoptosis. After transfected with DNMT3A interference, a total of 560 DEGs and 2,091 DMGs produced by DNMT3A interference were identified between two treated groups, respectively. Integrating the results from RRBS and RNA-seq, the overlapping genes between DMGs and DEGs were found to be enriched in the Gene Ontology (GO) terms related to cellular development and the Apelin signaling pathway. The present study demonstrated the impact of DNMT3A on the proliferation of porcine testicular Sertoli cells, suggesting that DNMT3A primarily acts through the Apelin signaling pathway. These findings provide valuable insights into how DNMT3A influences testicular development and health, offering new perspectives.

Case report: Epidural blood patches are effective in treating intracranial hypotension due to a subarachnoid-pleural fistula.

Background: Intracranial hypotension (IH) is usually associated with cerebrospinal fluid (CSF) leakage and/or CSF hypotension, and epidural blood patch (EBP) therapy has been proven to be effective for treating spontaneous IH and post-dural puncture headaches. Tarlov cysts (TCs) are common lesions of the sacral spine. They have rarely been reported in thoracic locations and are even less common in the posterior mediastinum, which can lead to their misdiagnosis as neurogenic tumors. Case presentation: Here, we report the case of a 60-year-old woman who developed an orthostatic headache after the thoracoscopic resection of a TC in the posterior mediastinum that was presumed to be a schwannoma preoperatively. The patient was finally diagnosed with IH caused by a subarachnoid-pleural fistula (SPF) and was cured by targeted EBP treatment. Conclusion: This is a case to show that a single targeted EBP treatment is effective for a patient with IH caused by an SPF after thoracoscopic resection of a TC. This case reminds us to be vigilant that a TC may be masquerading as a posterior mediastinal neurogenic tumor, and a detailed examination should be performed to identify it before deciding on a surgical procedure. In addition, postural headache after thoracoscopic spinal surgery should be alert to the possibility of IH induced by an SPF. Once it occurs, early treatment is necessary, and targeted EBP treatment can serve as a safe and effective alternative when conservative treatment fails.

Systematic Bibliometric and Visualized Analysis of Research Hotspots and Trends on Autism Spectrum Disorder Neuroimaging.

Background: Autism spectrum disorder (ASD) is a chronic developmental disability caused by differences in the brain. The gold standard for the diagnosis of this condition is based on behavioral science, but research on the application of neurological detection to diagnose the atypical nervous system of ASD is ongoing. ASD neuroimaging research involves the examination of the brain's structure, functional connections, and neurometabolic. However, limited medical resource and the unique heterogeneity of ASD have resulted in many challenges when neuroimaging is utilized. Objective: This bibliometric study is aimed at summarizing themes and trends in research on autism spectrum disorder neuroimaging and at proposing potential directions for future inquiry. Methods: Citations were downloaded from the Web of Science Core Collection database on neuroimaging published from January 1, 2012, to December 31, 2021. The retrieved information was analyzed using Bibliometric.com, CiteSpace.5.8. R3, and VOS viewer. Results: A total of 1,363 papers were published across 58 regions. The United States was the leading source of publications. The League of European Research Universities published the largest number of articles (171). Burst keywords from 2018 to 2021 include identification and network. The clusters of references that continued into 2020 included graph theory, functional connectivity, and classification, which represent key research topics. Conclusions: Imaging data is being used to identify neuro-network models with higher accuracy for ASD discrimination. Functional near-infrared imaging is advantageous compared to other neuroimaging. In the future, research on systematic and accurate computer-aided diagnosis technology should be encouraged. Moreover, the study of neuroimaging of ASD in different psychological and behavioral states can inspire new ideas about the diagnosis and intervention training of ASD and should be explored.

Regulation of WOX11 Expression Represents the Difference Between Direct and Indirect Shoot Regeneration.

Somatic cells of higher plants possess the remarkable ability to regenerate new individuals via reestablishing apical meristems. Reconstitution of shoot meristem is the vital process and is required for application of plant biotechnology. Under in vitro culture condition, shoot meristem can be formed directly or indirectly, depending on the absence or presence of callus as the intermediate status. However, the difference of regulatory mechanisms between the two regeneration types remains unknown. In this study, we established a bi-directional system in which shoots regenerated directly from lateral root primordia (LRP) and indirectly from hypocotyl-derived callus simultaneously. The results based on this system revealed that regulation of WOX11 expression represents the difference between the two regeneration types in two aspects. Firstly, number of founder cells expressing WOX11 is tightly associated with regeneration types. Relatively more founder cells gave rise to callus and produce larger meristem, whereas less founder cells produce LRP that regenerate smaller meristem. Secondly, non-CG DNA methylation specifically regulated WOX11 transcription in LRP and promoted direct shoot regeneration, but had no influence on indirect regeneration. The results provide new insights for understanding the regulatory mechanisms of cell fate transition during de novo organogenesis.

Preliminary evaluation on the efficacy of emergency transcatheter aortic valve replacement: a multicenter study / 中华心血管病杂志

Objectives: To explore the efficacy and safety of emergency transcatheter aortic valve replacement (TAVR). Methods: Data of patients who underwent emergency TAVR in eight centers, namely Fuwai Hospital, Wuhan Asia Heart Hospital, Xijing Hospital, Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Guangdong Provincial People's Hospital, Zhongshan Hospital Affiliated to Fudan University, the First Affiliated Hospital of Zhengzhou University, the Second Xiangya Hospital of Central South University, between May 2017 and December 2020 were retrospectively analyzed. The use of mechanical circulatory support system (MCS) and the results of laboratory tests (N-terminal B-type natriuretic peptide (NT-proBNP)) and echocardiography (mean aortic valve cross valve pressure difference and left ventricular ejection fraction) before and after operation were collected. The primary endpoint was all-cause death, and the secondary endpoints were stroke, major bleeding, major vascular complications, myocardial infarction, permanent pacemaker implantation, and acute renal injury. Device success was caculated, which refered to absence of procedural mortality and correct positioning of a single prosthetic heart valve into the proper anatomical location and intended performance of the prosthetic heart valve (mean aortic valve gradient<20 mmHg(1 mmHg=0.133 kPa) or peak velocity<3 m/s, with no moderate or severe prosthetic valve regurgitation). Kaplan-Meier survival curve was used to estimate the survival rate of patients during follow-up. Results: This study included 48 patients. The age was (72.5±8.1) years, and 34 patients were males (70.8%). Device success rate was 91.7% (44/48). The mean aortic valve transvalvular pressure was significantly decreased after operation ((12.3±6.4)mmHg vs. (60.2±23.8)mmHg, P<0.000 1). Left ventricular ejection fraction was significantly increased ((41.5±11.7)% vs. (31.0±11.3)%, P<0.000 1). NT-proBNP significantly decreased (3 492.0 (1 638.8, 7 165.5) ng/L vs. 12 418.5 (6 693.8, 35 000.0) ng/L, P<0.000 1). In-hospital all-cause mortality was 8.3% (4/48). During hospitalization, the rate of stroke was 2.1% (1/48), major bleeding was 6.3% (3/48), major vascular complications was 10.4% (5/48), myocardial infarction was 4.2% (2/48), permanent pacemaker implantation was 6.3% (3/48), and the rate of acute renal injury was 12.5% (6/48). MCS was used in 20 patients (41.7%). The median follow-up time was 196 days. During the follow-up, one patient died (due to systemic metastasis of pancreatic cancer), two cases suffered new myocardial infarction and one case received permanent pacemaker implantation. The survival rate of 30 days, 1 year and 2 years after the operation were 91.7% (44/48), 89.6% (43/48), 89.6% (43/48), respectively. Conclusion: Emergency TAVR may be a safe and effective treatment for patients with severe decompensated aortic valve stenosis.

Targeted Epidural Blood Patch Treatment for Refractory Spontaneous Intracranial Hypotension: A Case Report.

Purpose of Review Spontaneous intracranial hypotension (SIH) is recognized far more commonly than before, and it is well known that SIH is sometimes complicated by chronic subdural hematoma (SDH). We reported a patient who was treated with epidural blood patch (EBP) five times for refractory SIH and SDH surgery. Recent Findings We experienced that targeted EBP was useful in refractory SIH, and also can be performed safely prior to drainage of the hematoma. Summary We report the case of SIH patient with a bilateral SDH who came to our hospital and was discharged 2 weeks later with no neurologic deficit after trephination and five times EBP treatment. It shows that targeted EBP was useful in refractory SIH, and also can be performed safely prior to drainage of the hematoma.

Retinal nerve fiber layer characteristics in patients with spontaneous intracranial hypotension: a retrospective case series.

OBJECTIVE: To evaluate changes in retinal nerve fiber layer (RNFL) and macular thicknesses, included ganglion cell-inner plexiform layer (GCIPL) thickness, in patients with spontaneous intracranial hypotension (SIH). METHODS: This was a retrospective, nonrandom, observational case series study. Comprehensive ophthalmic examinations and systemic examinations were performed. Spectral domain optical coherence tomography angiography scanning was used to measure peripapillary RNFL thickness and macular volume. RESULTS: In total, 108 eyes in 54 patients with SIH were evaluated; these were compared with 108 eyes in 54 healthy controls. The mean ages were 38.2 ± 9.4 years (patients with SIH) and 38.9 ± 9.4 years (healthy controls). In both groups, 33 patients were women (61.1%). The peripapillary RNFL and GCIPL were thinner in patients with SIH than in healthy controls (100.08 ± 9.94 µm vs 104.83 ± 8.35 µm and 81.46 ± 5.67 µm vs 85.67 ± 4.57 µm, respectively). Among patients with SIH, the GCIPL was thinner in patients with visual field defects (79.81 ± 5.62 µm vs 82.39 ± 5.12 µm). CONCLUSIONS: The RNFL and GCIPL were thinner in patients with SIH than in healthy controls. The GCIPL was thinner in eyes with visual field defects among patients with SIH.

Attitudes of medical workers in China toward artificial intelligence in ophthalmology: a comparative survey.

BACKGROUND: In the development of artificial intelligence in ophthalmology, the ophthalmic AI-related recognition issues are prominent, but there is a lack of research into people's familiarity with and their attitudes toward ophthalmic AI. This survey aims to assess medical workers' and other professional technicians' familiarity with, attitudes toward, and concerns about AI in ophthalmology. METHODS: This is a cross-sectional study design study. An electronic questionnaire was designed through the app Questionnaire Star, and was sent to respondents through WeChat, China's version of Facebook or WhatsApp. The participation was voluntary and anonymous. The questionnaire consisted of four parts, namely the respondents' background, their basic understanding of AI, their attitudes toward AI, and their concerns about AI. A total of 562 respondents were counted, with 562 valid questionnaires returned. The results of the questionnaires are displayed in an Excel 2003 form. RESULTS: There were 291 medical workers and 271 other professional technicians completed the questionnaire. About 1/3 of the respondents understood AI and ophthalmic AI. The percentages of people who understood ophthalmic AI among medical workers and other professional technicians were about 42.6 % and 15.6 %, respectively. About 66.0 % of the respondents thought that AI in ophthalmology would partly replace doctors, about 59.07 % having a relatively high acceptance level of ophthalmic AI. Meanwhile, among those with AI in ophthalmology application experiences (30.6 %), above 70 % of respondents held a full acceptance attitude toward AI in ophthalmology. The respondents expressed medical ethics concerns about AI in ophthalmology. And among the respondents who understood AI in ophthalmology, almost all the people said that there was a need to increase the study of medical ethics issues in the ophthalmic AI field. CONCLUSIONS: The survey results revealed that the medical workers had a higher understanding level of AI in ophthalmology than other professional technicians, making it necessary to popularize ophthalmic AI education among other professional technicians. Most of the respondents did not have any experience in ophthalmic AI but generally had a relatively high acceptance level of AI in ophthalmology, and there was a need to strengthen research into medical ethics issues.

Management of an intracranial hypotension patient with diplopia as the primary symptom: A case report.

BACKGROUND: Intracranial hypotension (IH) is a disorder involving cerebrospinal fluid (CSF) hypovolemia due to spontaneous or traumatic spinal CSF leakage and is easily being misdiagnosed or missed, especially in these patients without the prototypical manifestation of an orthostatic headache. At present, the management of IH with both cranial nerve VI palsy and bilateral subdural hematomas (SDHs) is still unclear. CASE SUMMARY: A 67-year-old male Chinese patient complained of diplopia on the left side for one and a half mo. Computed tomography revealed bilateral SDHs and a midline shift. However, neurotrophic drugs were not effective, and 3 d after admission, he developed a non-orthostatic headache and neck stiffness. Enhanced magnetic resonance imaging revealed dural enhancement as an additional feature, and IH was suspected. Magnetic resonance myelography was then adopted and showed CSF leakage at multiple sites in the spine, confirming the diagnosis of having IH. The patient fully recovered following multiple targeted epidural blood patch (EBP) procedures. CONCLUSION: IH is a rare disease, and to the best of our knowledge, IH with diplopia as its initial and primary symptom has never been reported. In this study, we also elucidated that it could be safe and effective to treat IH patients with associated cranial nerve VI palsy and bilateral SDHs using repeated EBP therapy.

The role of gut microbiota in tumorigenesis and treatment.

A large number of microbial communities exist in normal human intestinal tracts, which maintain a relatively stable dynamic balance under certain conditions. Gut microbiota are closely connected with human health and the occurrence of tumors. The colonization of certain intestinal bacteria on specific sites, gut microbiota disturbance and intestinal immune disorders can induce the occurrence of tumors. Meanwhile, gut microbiota can also play a role in tumor therapy by participating in immune regulation, influencing the efficacy of anti-tumor drugs, targeted therapy of engineered probiotics and fecal microbiota transplantation. This article reviews the role of gut microbiota in the occurrence, development, diagnosis and treatment of tumors. A better understanding of how gut microbiota affect tumors will help us find more therapies to treat the disease.

Trends in prevalence of gestational diabetes mellitus in Zhejiang Province, China, 2016-2018.

BACKGROUND: Limited population-based studies have investigated the secular trend of prevalence of gestational diabetes mellitus (GDM) in mainland China. Therefore, this study aimed to estimate the prevalence of GDM and time trends in Chinese female population. METHODS: Based on Diabetes Surveillance System of Zhejiang Province, 97,063 diagnosed GDM cases aged 20-50 years were identified from January 1, 2016 to December 31, 2018. Annual prevalence, prevalence rate ratios (PRRs) and average annual percentage change with their 95% confidence intervals (CIs) were reported. RESULTS: The age-standardized overall prevalence of GDM was reported to be 7.30% (95% CI 7.27-7.33%); 9.13% (95% CI 9.07-9.19%) in urban areas and 6.24% (95% CI 6.21-6.27%) in rural areas. Compared with 20-24 years age group, women in advanced age groups (25-50 years) were at higher risk for GDM (PRRs ranged from 1.37 to 8.95 and the 95% CIs did not include the null). Compared with rural areas, the risk for GDM was higher in urban areas (PRR: 1.69, 95% CI 1.67-1.72). The standardized annual prevalence increased from 6.02% in 2016 to 7.94% in 2018, with an average annual increase of 5.48%, and grew more rapidly in rural than urban areas (11.28% vs. 0.00%). CONCLUSIONS: This study suggested a significant increase in the prevalence of GDM among Chinese female population in Zhejiang province during 2016-2018, especially in women characterized by advanced age and rural areas.

CD8+ T cell epitope variations suggest a potential antigen presentation deficiency for spike protein of SARS-CoV-2

COVID-19 is caused by a newly identified coronavirus, SARS-CoV-2, and has become a pandemic around the world. The illustration of the immune responses against SARS-CoV-2 is urgently needed for understanding the pathogenesis of the disease and its vaccine development. CD8+ T cells are critical for virus clearance and induce long lasting protection in the host. Here we identified specific HLA-A2 restricted T cell epitopes in the spike protein of SARS-CoV-2. Seven epitope peptides (n-Sp1, 2, 6, 7, 11, 13, 14) were confirmed to bind with HLA-A2 and potentially be presented by antigen presenting cells to induce host immune responses. Tetramers containing these peptides could interact with specific CD8+ T cells from convalescent COVID-19 patients, and one dominant epitope (n-Sp1) was defined. In addition, these epitopes could activate and generate epitope-specific T cells in vitro, and those activated T cells showed cytotoxicity to target cells. Meanwhile, all these epitopes exhibited high frequency of variations. Among them, n-Sp1 epitope variation 5L>F significantly decreased the proportion of specific T cell activation; n-Sp1 epitope 8L>V variant showed significantly reduced binding to HLA-A2 and decreased the proportion of n-Sp1-specific CD8+ T cell, which potentially contributes to the immune escape of SAR-CoV-2.

Gene editing the BmNPV inhibitor of apoptosis protein 2 (iap2) as an antiviral strategy in transgenic silkworm.

Apoptosis is a cellular defense mechanism used for the elimination of host cells infected by viruses. Viruses have evolved corresponding inhibitors of apoptosis genes to promote their replication. Anti-apoptosis-related genes, involved in baculovirus proliferation, have been proposed but it is unclear whether these genes can be manipulated in gene therapy. We constructed a transgenic silkworm, using the CRISPR/Cas9 system to knock out the BmNPV inhibitor of apoptosis 2 (iap2). The sequencing results showed that all the sequences could edit the target site of BmNPV iap2 gene. There were no differences in economic traits and growth tests between the BmNPV iap2 knockout strain transgenic silkworm lines and the control groups. However, the mortality rate was significantly reduced, the median lethal dose (LD50) was about 100 times higher than the control group, and the onset time was prolonged by 1-2 days after knocking out BmNPV iap2. In addition, the expression levels of apoptotic-related genes Bmiap2, BmICE and BmDreed were significantly affected and the activity of caspase 9 was increased after BmNPV iap2 being edited in transgenic silkworm. These results demonstrated that gene editing BmNPV iap2 could significantly inhibit BmNPV replication and proliferation. This approach provides a new strategy for antiviral research.

Investigation and analysis of work stress of medical staff in Shanghai during the period of normalized epidemic prevention and control / 中华医院管理杂志

Objective:To analyze the work stress of medical staff at different medical institutions in Shanghai under the background of normalized prevention and control of 2019 novel coronavirus diseases(COVID-19), for evidence of relieving the work stress of medical staff.Methods:From September to November 2020, two community health service centers, one secondary hospital and one tertiary hospital were selected from each district of Jing′an District, Jiading District and Pudong New Area of Shanghai, totaling 12 medical institutions. The medical staff were selected by stratified random sampling. A self-designed questionnaire was used to conduct an online questionnaire survey on the work stress of medical staff. The survey data were analysied by descriptive analysis, and different groups were compared with chi square test.Results:1 422 valid questionnaires were obtained. There was a significant difference in self-rated routine work stress of medical staff between community health service centers and secondary/tertiary hospitals( P<0.001). The proportions of medical staff whose self-rated routine work stress was " quite stressed" or " very stressed" at community health service centers and secondary/tertiary hospitals were 39.77%(317)and 55.36%(346)respectively. There was a significant difference in self-rated COVID-19 prevention stress of medical staff between community health service centers and secondary/tertiary hospitals( P<0.001), the proportions of medical staff who considered the COVID-19 prevention was " quite stressed" or " very stressed" were 86.45%(689)and 76.48%(478)respectively. Conclusions:The overall work stress of medical staff at medical institutions in Shanghai was high.The prevention and control of COVID-19 increased the pressure of medical staff at all levels of medical institutions.

Analysis on the appeals for rights and interests of medical staff in medical institutions at all levels in Shanghai / 中华医院管理杂志

Objective:To understand the current situation of appeals for rights and interests of medical staff in community health institutions and secondary/tertiary hospitals in Shanghai, for the suggestions on improving the job satisfaction and enthusiasm of medical staff.Methods:From September to November 2020, two community health service centers(stations), one secondary hospital and one tertiary hospital were selected from Jiading District, Pudong New Area and Jing′an District of Shanghai respectively. An online questionnaire survey was conducted among medical staff in medical institutions selected by stratified random sampling. The survey covered the main demographic information as well as 12 rights and interests demands, namely " salary promotion" among other. Descriptive analysis was performed on the data, and chi square test was used for comparison between groups.Results:1 759 valid questionnaires were recovered in this survey, and 1 654 medical employees(94.03%)reported a high degree of appeal for " salary promotion" . Compared with the medical staff in community health service centers(stations), the medical staff in secondary/tertiary hospitals reported higher demands for " training and study" " title appointment" and " academic promotion" , presenting a difference statistically significant( P<0.05). There were significant differences between doctors and nurses in " routine expense reimbursement" " staff recruitment" " professional title appointment" " children′s education" " cultural and recreational activities" and " opinion feedback channels" ( P<0.05). Conclusions:Salary promotion was the common demand of medical staff at all levels of medical institutions. Medical staff at secondary/tertiary hospitals had higher demands for career development. There were some differences in appeals for rights and interests between doctors and nurses. Medical institutions at all levels should continue to promote the reform of salary system, pay attention to the respective rights and interests of doctors and nurses, and improve their job satisfaction and enthusiasm.

Characteristics and outcomes following transcatheter aortic valve replacement in China: a report from China aortic valve transcatheter replacement registry (CARRY) / 中华医学杂志(英文版)

BACKGROUND@#The past decade has witnessed an ever-increasing momentum of transcatheter aortic valve replacement (TAVR) and a subsequent paradigm shift in the contemporary management of severe aortic stenosis (AS). We conducted a multi-centric TAVR registry based on Chinese patients (the China Aortic valve tRanscatheter Replacement registrY [CARRY]) to delineate the clinical characteristics and outcomes of Chinese patients who underwent TAVR and compare the results between different valve types in different Chinese regions.@*METHODS@#CARRY is an all-comer registry of aortic valve disease patients undergoing TAVR across China and was designed as an observational study that retrospectively included all TAVR patients at each participating site. Seven hospitals in China participated in the CARRY, and 1204 patients from April 2012 to November 2020 were included. Categorical variables were compared using the chi-squared test, and continuous variables were analyzed using a t test or analysis of variance (ANOVA) test. The Kaplan-Meier curve was used to estimate the risk of adverse events during follow-up.@*RESULTS@#The mean age of the patients was 73.8 ± 6.5 years and 57.2% were male. The median Society of Thoracic Surgeon-Predicted Risk of Mortality score was 6.0 (3.7-8.9). Regarding the aortic valve, the proportion of bicuspid aortic valve (BAV) was 48.5%. During the hospital stay, the stroke rate was 0.7%, and the incidence of high-degree atrioventricular block indicating permanent pacemaker implantation was 11.0%. The in-hospital all-cause mortality rate was 2.2%. After 1 year, the overall mortality rate was 4.5%. Compared to patients with tricuspid aortic valve (TAV), those with BAV had similar in-hospital complication rates, but a lower incidence of in-hospital mortality (1.4% vs. 3.3%) and 1 year mortality (2.3% vs. 5.8%).@*CONCLUSIONS@#TAVR candidates in China were younger, higher proportion of BAV, and had lower rates of post-procedural complications and mortality than other international all-comer registries. Given the use of early generation valves in the majority of the population, patients with BAV had similar rates of complications, but lower mortality than those with TAV. These findings further propel the extension of TAVR in low-risk patients.@*TRIAL REGISTRATION@#https://www.chictr.org.cn/ (No. ChiCTR2000038526).