A multicenter, randomized, open-label, phase 2 clinical study of telitacicept in adult patients with generalized myasthenia gravis.

BACKGROUND AND PURPOSE: This study aimed to investigate the clinical efficacy and safety of telitacicept in patients with generalized myasthenia gravis (gMG) who tested positive for acetylcholine receptor antibodies or muscle-specific kinase antibodies and were receiving standard-of-care therapy. METHODS: Patients meeting the eligibility criteria were randomly assigned to receive telitacicept subcutaneously once a week for 24 weeks in addition to standard-of-care treatment. The primary efficacy endpoint was the mean change in the quantitative myasthenia gravis (QMG) score from baseline to week 24. Secondary efficacy endpoints included mean change in QMG score from baseline to week 12 and gMG clinical absolute score from baseline to week 24. Additionally, safety, tolerability and pharmacodynamics were assessed. RESULTS: Twenty-nine of the 41 patients screened were randomly selected and enrolled. The mean (± standard deviation [SD]) reduction in QMG score from baseline to week 24 was 7.7 (± 5.34) and 9.6 (± 4.29) in the 160 mg and 240 mg groups, respectively. At week 12, mean reductions in QMG scores for these two groups were 5.8 (± 5.85) and 9.5 (± 5.03), respectively, indicating rapid clinical improvement. Safety analysis revealed no adverse events leading to discontinuation or mortalities. All patients showed consistent reductions in serum immunoglobulin (Ig) A, IgG and IgM levels throughout the study. CONCLUSION: Telitacicept demonstrated safety, good tolerability and reduced clinical severity throughout the study period. Further validation of the clinical efficacy of telitacicept in gMG will be conducted in an upcoming phase 3 clinical trial.

MIST: multiple instance learning network based on Swin Transformer for whole slide image classification of colorectal adenomas.

Colorectal adenoma is a recognized precancerous lesion of colorectal cancer (CRC), and at least 80% of colorectal cancers are malignantly transformed from it. Therefore, it is essential to distinguish benign from malignant adenomas in the early screening of colorectal cancer. Many deep learning computational pathology studies based on whole slide images (WSIs) have been proposed. Most approaches require manual annotation of lesion regions on WSIs, which is time-consuming and labor-intensive. This study proposes a new approach, MIST - Multiple Instance learning network based on the Swin Transformer, which can accurately classify colorectal adenoma WSIs only with slide-level labels. MIST uses the Swin Transformer as the backbone to extract features of images through self-supervised contrastive learning and uses a dual-stream multiple instance learning network to predict the class of slides. We trained and validated MIST on 666 WSIs collected from 480 colorectal adenoma patients in the Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School. These slides contained six common types of colorectal adenomas. The accuracy of external validation on 273 newly collected WSIs from Nanjing First Hospital was 0.784, which was superior to the existing methods and reached a level comparable to that of the local pathologist's accuracy of 0.806. Finally, we analyzed the interpretability of MIST and observed that the lesion areas of interest in MIST were generally consistent with those of interest to local pathologists. In conclusion, MIST is a low-burden, interpretable, and effective approach that can be used in colorectal cancer screening and may lead to a potential reduction in the mortality of CRC patients by assisting clinicians in the decision-making process. © 2022 The Pathological Society of Great Britain and Ireland.

Ultrasound-guided pacemaker implantation at the bedside: A lifesaving technique for cardiac emergencies.

OBJECTIVE: To investigate the safety and effectiveness of implanting temporary pacemakers using ultrasound-guidance at the bedside for rescuing patients in case of cardiac emergencies. METHODS: We enrolled 194 patients with cardiac emergencies requiring temporary pacemakers in this study, and randomly assigned them to either a bedside ultrasound-guided installation group or an electrocardiogram-guided installation group. There were 105 cases in the bedside ultrasound-guided installation group, aged approximately 66.3 ± 10.2 years, and 89 cases in the electrocardiogram-guided installation group, aged approximately 65.8 ± 9.5 years old, and disease composition was similar between the two groups. We then compared the duration of the procedure, success rates, and occurrence of adverse events between the two groups. RESULTS: The two groups showed similar clinical characteristics. The success rates of venipuncture and temporary pacemaker electrode placement were both 100% in the bedside ultrasound-guided installation group, compared to 87.8% and 96.7% respectively, in the electrocardiogram-guided installation group, with a statistically significant difference between the two groups. The duration of puncture was significantly shorter in the bedside ultrasound-guided installation group than in the electrocardiogram-guided installation group, with statistically significant differences. Moreover, no adverse events such as hematoma, pneumothorax and electrode dislodgement occurred in the bedside ultrasound-guided installation group, while 13 cases in the electrocardiogram-guided installation group experienced adverse events, and the difference was statistically significant. CONCLUSIONS: The bedside installation of temporary pacemakers using ultrasound guidance is a simple, safe, effective, and cost-efficient procedure that boasts a high success rate, does not involve radiation, and enables accurate placement of the electrode catheter.

Sleep disorders in the acute phase of coronavirus disease 2019: an overview and risk factor study.

BACKGROUND: Sleep disorders are common during the outbreak of pandemic diseases, and similar disorders are noted in hospitalized COVID-19 patients. It is valuable to explore the clinical manifestations and risk factors for sleep disorders in COVID-19 patients. METHODS: Inpatients with COVID-19 were enrolled. Detailed clinical information was collected, and sleep quality was assessed by PSQI. Patients were divided into a sleep disorder group and a normal group based on a PSQI ≥ 7, and the clinical features were compared between the groups. RESULTS: Fifty-three patients were enrolled, and 47.2% presented sleep disorders. Sleep disorders were associated with older age (> 50), anemia and carbon dioxide retention. Furthermore, factors associated with abnormal component scores of the PSQI were: (1) patients with older age were more likely to have decreased sleep quality, prolonged sleep latency, decreased sleep efficiency, sleep disturbances, and daytime dysfunction; (2) decreased sleep quality and prolonged sleep latency were associated with dyspnea, whereas carbon dioxide retention and more lobes involved in chest CT were associated with prolonged sleep latency; (3) decreased sleep efficiency was more prevalent in patients with anemia. CONCLUSIONS: Sleep disorders were prevalent in patients during the acute phase of COVID-19, and many risk factors (older age, anemia, carbon dioxide retention, the number of lobes involved in chest CT, and dyspnea) were identified. It is important to assess the presence of sleep disorders in patients to provide early intervention.

Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19.

RATIONALE: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. OBJECTIVE: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. METHODS AND RESULTS: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension. CONCLUSIONS: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.

What Is Different about Teratoma-Associated Anti-LGI1 Encephalitis? A Long-Term Clinical and Neuroimaging Case Series.

INTRODUCTION: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is clinically heterogeneous, especially at presentation, and though it is sometimes found in association with tumor, this is by no means the rule. METHODS: Clinical data for 10 patients with anti-LGI1 encephalitis were collected including one case with teratoma and nine cases without and compared for clinical characteristics. Microscopic pathological examination and immunohistochemical assay of the LGI1 antibody were performed on teratoma tissue obtained by laparoscopic oophorocystectomy. RESULTS: In our teratoma-associated anti-LGI1 encephalitis case, teratoma pathology was characterized by mostly thyroid tissue and immunohistochemical assay confirmed positive nuclear staining of LGI1 in some tumor cells. The anti-LGl1 patient with teratoma was similar to the non-teratoma cases in many ways: age at onset (average 47.3 in non-teratoma cases); percent presenting with rapidly progressive dementia (67% of non-teratoma cases) and psychiatric symptoms (33%); hyponatremia (78%); normal cerebrospinal fluid results except for positive LGI1 antibody (78%); bilateral hippocampal hyperintensity on magnetic resonance imaging (44%); diffuse slow waves on electroencephalography (33%); good response to immunotherapy (67%); and mild residual cognitive deficit (22%). Her chronic anxiety and presentation with status epilepticus were the biggest differences compared with the non-teratoma cases. CONCLUSION: In our series, anti-LGI1 encephalitis included common clinical features in our series: rapidly progressive dementia, faciobrachial dystonic seizures, behavioral disorders, hyponatremia, hippocampal hyperintensity on magnetic resonance imaging, and residual cognitive deficit. We observed some differences (chronic anxiety and status epilepticus) in our case with teratoma, but a larger accumulation of cases is needed to improve our knowledge base.

N-salicyloyl tryptamine derivatives as potential therapeutic agents for Alzheimer's disease with neuroprotective effects.

Alzheimer's disease (AD) has become a serious threat to the developed nations with burgeoning patients and annual costs on health care system in modern society. Neuroinflammation, as one of the specific biochemical factors in the progress of neurodegeneration diseases, performs a crucial role in the pathogenesis and development of AD. Therefore, it is of great significance to develop effective anti-neuroinflammatory strategies for the treatment of AD. N-salicyloyl tryptamine derivatives were previously reported and demonstrated that possessed great potential anti-neuroinflammatory effects and favorable blood-brain barrier (BBB) permeation. Herein, a series of novel N-salicyloyl tryptamine derivatives were synthesized and their anti-AD potential was evaluated both in vitro and in vivo. Among them, L7 performed well anti-neuroinflammatory effects and excellent neuroprotective effects, as well as little toxicity. To lucubrate its potential for the treatment of AD, behavior tests including morris water maze (MWM), eight-arm radial maze, open field test and novel object recognition (NOR) test were carried out and the results showed that L7 could remarkably improve Aß-induced cognitive impairment. Moreover, the mechanism of action of L7 on improving Aß-induced AD was preliminarily investigated, and the results uncovered that the neuroprotective effects of L7 was might exerte via intervening Aß-induced pyroptosis through NLRP3-caspase-1-GSDMD axis and ameliorating neuronal apoptosis by mitochondrial apoptosis pathway. Besides, the distribution of Aß plaques in brain tissues were detected by immunohistochemical (IHC) assay and the results indicated that L7 could significantly attenuate the deposition of Aß plaques in the brain.

IRF-5 accelerates leukocyte adhesion to endothelial cells in ischemia-reperfusion injury through regulating the transcription of VCAM-1.

Ischemia-reperfusion injury (IRI) has been implicated in many pathological conditions, including cardiovascular diseases. Adhesion of leukocytes to the surface of endothelial cells has been considered as one of the principle steps in the pathological cascade of inflammatory tissue damage during IRI. The role of the transcriptional factor interferon regulatory factor-5 (IRF-5) in endothelial physiology remains unknown. Here, we report that IRF-5 is expressed in human umbilical vein endothelial cells (HUVECs) and is rapidly upregulated in response to IRI, mediated by the JAK2/STAT3 pathway. Importantly, IRF-5 is involved in IRI-induced attachment of THP-1 leukocytes to HUVECs. Mechanistically, it was found that IRF-5 targeted the expression of vascular cell adhesion molecule 1 (VCAM-1) at the transcriptional level by binding to its promoter. In conclusion, we identify IRF-5 as a new regulator and thus a therapeutic target in IRI-driven cardiovascular pathologies.

The Efficacy and Safety of Granulocyte Colony-Stimulating Factor for Patients with Stroke.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) has been shown to reduce lesion volume and improve functional outcome in experimental stroke models. However, whether G-CSF plays a role currently in patients with stroke remains uncertain. Our study aimed at examining the efficacy and safety of G-CSF in patients with acute ischemic stroke. METHODS: A comprehensive search was conducted in 5 online databases up to April 2014, and 10 studies with 711 patients met the criteria. RESULTS: The results showed that G-CSF was beneficial in improving the National Institutes of Health Stroke Scale (standardized mean difference [SMD], .43; 95% confidence interval [CI], .03-.82; P = .04) and modified Rankin Scale (mRS) scores (SMD, .72; 95% CI, .51-.93; P = .01), and elevating CD34(+) count (P < .001). No treatment effects were found in Barthel Index scores (SMD, -.13; 95% CI, -.61 to .35; P = .59), serious adverse events (relative ratio [RR], 1.12; 95% CI, .91-1.38; P = .28), or the death of serious adverse events (RR, 1.25; 95% CI, .82-1.91; P = .30) between groups at day 90. Adverse effect on vascular complications was not detected to be increased although G-CSF produced a marked elevation in the total leukocyte count (SMD, 3.52; 95% CI, 2.54-4.49; P < .001). CONCLUSIONS: In conclusion, G-CSF is effective at mobilizing bone marrow-derived CD34(+) stem cells to the peripheral blood. It also seems to improve the National Institutes of Health Stroke Scale and mRS scores. The administration of G-CSF appears to be safe and well tolerated. Further studies need to be done on a large sample to verify or fully characterize the results.

Association between the MMP-9-1562 C>T polymorphism and the risk of stroke: a meta-analysis.

Matrix metalloproteinase (MMP)-9 so far is identified as extremely large and complicated MMP family member. Recently, dozens of studies have explored the association between a promoter polymorphism (-1562 C>T) in MMP-9 and stroke susceptibility. However, the conclusions of these studies still remain equivocal. Therefore, our current meta-analysis was conducted to investigate whether or not the MMP-9 promoter polymorphism is related to the risk of stroke. Electronic databases (PubMed, EMBASE, Web of Science, Cochrane Library and the Chinese Biomedical Literature Database) were searched to obtain all the available studies investigating this polymorphism and stroke from inception to October 2013. Overall and subgroup analyses were rigorously conducted after data extraction. Pooled odds ratio (OR) corresponding to 95 % confidence interval (CI) were estimated. The statistical analysis was performed using Review Manager 5.2. Totally, seven studies involving 1,624 cases and 1,525 controls were identified. The overall results suggested that there was no association of the C-1562T variant on stroke risk under the T allele versus C allele [OR T vs. C 0.98, 95 % CI (0.84, 1.15), P = 0.84], the dominant model [OR TT+TC vs. CC 0.95, 95 % CI (0.81, 1.13), P = 0.59], the recessive model [OR TT vs. TC+CC 1.55, 95 % CI (0.86, 2.81), P = 0.15], the homozygote comparison [OR TT vs. CC 1.48, 95 % CI (0.82, 2.68), P = 0.20] and the heterozygote comparison [OR TC vs. CC 0.93, 95 % CI (0.78, 1.10), P = 0.38]. In the subgroup analyses by ethnicity, age, stroke type and source of controls, no significant relations were observed in any genetic models. Our results indicated that MMP-9-1562 C>T polymorphism was not a risk factor for stroke. Further studies should focus on gene-gene and gene-environment interactions, and provide a more convincing explanation for this association.

China's Land Market Auctions: Evidence of Corruption?

This paper studies the urban land market in China in 2003-2007. In China, all urban land is owned by the state. Leasehold use rights for land for (re)development are sold by city governments and are a key source of city revenue. Leasehold sales are viewed as a major venue for corruption, prompting a number of reforms over the years. Reforms now require all leasehold rights be sold at public auction. There are two main types of auction: regular English auction and an unusual type which we call a "two stage auction". The latter type of auction seems more subject to corruption, and to side deals between potential bidders and the auctioneer. Absent corruption, theory suggests that two stage auctions would most likely maximize sales revenue for properties which are likely to have relatively few bidders, or are "cold", which would suggest negative selection on property unobservables into such auctions. However, if such auctions are more corruptible, that could involve positive selection as city officials divert hotter properties to a more corruptible auction form. The paper finds that, overall, sales prices are lower for two stage auctions, and there is strong evidence of positive selection. The price difference is explained primarily by the fact that two stage auctions typically have just one bidder, or no competition despite the vibrant land market in Chinese cities.

[Pathogenic factors and prognosis of non cardiac inpatients with acute myocardial infarction].

OBJECTIVE: To collect the clinical data of non-cardiac inpatients with coronary heart disease risk factors and analyze the pathogenic factors and prognosis features of these inpatients with acute myocardial infarction. METHODS: Retrospective analyses were performed for 650 cases of consecutive non-cardiac inpatients with coronary heart disease risk factors at Tianjin Union Medical Center between January 2009 and January 2012.They were divided into non myocardial infarction (UnAMI, n = 551) and myocardial infarction groups (AMI, n = 99). Firstly the method of single factor analysis was employed to screen some significant influencing factors of acute myocardial infarction.Secondly multivariate Logistic regression analysis was performed to analyze the risk factors associated with the onset of AMI. Also the cardiovascular death event rates during hospitalization were compared between two groups. Cox regression analysis was performed to analyze independent risk factors for cardiovascular death of two group during hospitalization. RESULTS: (1) The significant influencing factors of AMI included total cholesterol (TC), low-density lipoprotein (LDL), advanced age, discontinuation of antiplatelet drug, recent episodes of angina above II grade, arrhythmia, 5 years of PCI or CABG history, blood glucose control or not, cardiac dysfunction (NYHA II-IV), dehydration, severe inflammatory response, infection, peroperative period, emergency operation and without cardiological consultation. (2) Multivariate Logistic regression analysis showed that LDL (OR (odds ratio): 2.047, 95% CI (confidence interval): 1.066-3.930, P = 0.031), discontinuation of antiplatelet drug therapy (OR:15.213, 95% CI: 5.746-40.281, P = 0.000), recent episodes of angina above II grade (OR: 1.990, 95%CI: 1.155-3.430, P = 0.013), glucose non-control (OR: 2.991, 95% CI:1.485-6.026, P = 0.002), advanced age (OR: 2.499, 95% CI: 1.299-4.808, P = 0.006), severe inflammation (OR:4.425, 95% CI: 2.984-6.561, P = 0.000), infection (OR:2.405, 95% CI: 1.058-5.464, P = 0.036), emergency operation (OR:4.365, 95% CI: 1.580-12.060, P = 0.004) were all AMI-related occurring factors. And cardiologic consultation (OR: 0.011, 95% CI:0.003-0.040, P = 0.000) was a favorable factors to reduce AMI; (3) AMI group during hospitalization for cardiovascular death event rate was higher than the UnAMI group; (4) Advanced age (ß = 0.776, OR = 0.460, 95% CI: 0.217-0.974, P = 0.042) and without consultation of cardiology department (ß = 1.366, OR = 3.918, 95% CI: 1.549-9.912, P = 0.004) were cardiovascular death independent risk factors. CONCLUSION: (1) Non cardiac inpatients during hospitalization LDL, discontinuation antiplatelet drug therapy, recent episodes of angina above II grade, blood sugar non-control, advanced age, severe inflammatory response, infection and without cardiologic consultations were significant risk factors for AMI. (2) The treatment of Department of Cardiology specialist for non cardiac inpatients with coronary heart disease risk factors to improve the prognosis of them.

A Nomogram for Predicting the Recurrence of Acute Non-Cardioembolic Ischemic Stroke: A Retrospective Hospital-Based Cohort Analysis.

Non-cardioembolic ischemic stroke (IS) is the predominant subtype of IS. This study aimed to construct a nomogram for recurrence risks in patients with non-cardioembolic IS in order to maximize clinical benefits. From April 2015 to December 2019, data from consecutive patients who were diagnosed with non-cardioembolic IS were collected from Lanzhou University Second Hospital. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to optimize variable selection. Multivariable Cox regression analyses were used to identify the independent risk factors. A nomogram model was constructed using the "rms" package in R software via multifactor Cox regression. The accuracy of the model was evaluated using the receiver operating characteristic (ROC), calibration curve, and decision curve analyses (DCA). A total of 729 non-cardioembolic IS patients were enrolled, including 498 (68.3%) male patients and 231 (31.7%) female patients. Among them, there were 137 patients (18.8%) with recurrence. The patients were randomly divided into training and testing sets. The Kaplan-Meier survival analysis of the training and testing sets consistently revealed that the recurrence rates in the high-risk group were significantly higher than those in the low-risk group (p < 0.01). Moreover, the receiver operating characteristic curve analysis of the risk score demonstrated that the area under the curve was 0.778 and 0.760 in the training and testing sets, respectively. The nomogram comprised independent risk factors, including age, diabetes, platelet-lymphocyte ratio, leukoencephalopathy, neutrophil, monocytes, total protein, platelet, albumin, indirect bilirubin, and high-density lipoprotein. The C-index of the nomogram was 0.752 (95% CI: 0.705~0.799) in the training set and 0.749 (95% CI: 0.663~0.835) in the testing set. The nomogram model can be used as an effective tool for carrying out individualized recurrence predictions for non-cardioembolic IS.

Paraneoplastic neurological syndrome with positive anti-Hu and anti-Yo antibodies: A case report.

BACKGROUND: Paraneoplastic neurological syndrome (PNS) is a rare complication in patients with cancer. PNS can affect the central, peripheral, autonomic nervous system, neuromuscular junction, or muscles and cause various neurological symptoms. Anti-Yo antibody-positive neurological paraneoplasms and anti-Hu antibody-positive neurological paraneoplasms are common, but coexistence of both types has not been described in the literature. CASE SUMMARY: Here we present a rare case of paraneoplastic neuropathy occurring in both breast and lung cancers. A 55-year-old woman was admitted to our hospital with unsteadiness while walking. The patient had a history of breast cancer two years previously. Chest computed tomography revealed a 4.6 cm × 3.6 cm mass in the right lung, which was diagnosed as small-cell lung cancer (SCLC). Blood test was positive for anti-Yo antibodies, and the cerebrospinal fluid was positive for both anti-Yo and anti-Hu antibodies, and the neurological symptoms were considered to be related to the paraneoplasm. The patient was treated with a course of intravenous immunoglobulin, without noticeable improvement. After being discharged from hospital, the patient underwent regular chemotherapy for SCLC and periodic reviews. The patient's neurological symptoms continued to deteriorate at the follow-up visit in April 2021. CONCLUSION: This case suggests the possibility of two types of tumors appearing simultaneously with two paraneoplastic antibodies. The clinical appearance of two or more paraneoplastic tumors requires additional attention.

Correlation between serum renin-angiotensin system (RAS) level and depression and anxiety symptoms in patients with Parkinson's disease.

To investigate the correlation between serum renin-angiotensin system (RAS) level and Symptoms of anxiety and depression in Parkinson disease patients (PD). A number of 90 PD patients (47 males and 43 females) were collected on an empty stomach 12 h after stopping taking anti-PD medicines. ELISA has been found in Serum RAS ((Ang) I, Ang II, Ang (1-7), Angiotensin converting enzyme (ACE), ACE2). Depression scale (HAMD) and Anxiety scale (HAMA) in Hamilton are used for the assessment of signs of depression and anxiety. The 90 patients were diagnosed with moderate depression (HAMD score 8 ~ 19); in 32 of those (35.56 percent), and 12 (13.33%) were diagnosed as moderate and severe depression (HAMD score ≥ 20). 20 cases (22.22%) were diagnosed as possible anxiety disorder (HAMA score 7 ~ 13) and 16 cases (17.78%) as definite anxiety disorder (HAMA score ≥ 14). The association of serum Ang I, Ang II and Ang (1-7) with HAMD (r= - 0.820, P < 0.001; r = -0.846, P < 0.001) showed negative linkage with HAMD (r = -0.887, P < 0.003; P < 0.001; Negative correlation of the settings with HAMA (r = -0.850, P < 0.001; r = -0.887, P < 0.001; r = 0.003; r = 0.001, P < 0.001, Fig. 2, Fig. 3); The HAMD score and the HAMA score (all P > 0.05) were not associated to the serum ACE and ACE2. The serum Ang I, Ang II, and Ang (1-7) were found to be adversely associated with HAMD score (r = 0.826, P < 0,001; r = -0.818, p> >0,001; r = -0.876, P < 0,001; P = 0,001) P < 0,001; And have been negatively correlated (r = 0.870, Fig. 1, Fig. 2, Fig. 3) with AMA-scores (r = -0.876, P < 0.001, Table 1, Fig. 3), R = -0.862, P > 0.001; The HAMD score and the HAMA score (all P > 0.05) were not correlated to the serum ACE and ACE2. Finally, in PD patients, non-engine signs, including depression and anxiety, are normal. Thus, Serum levels Ang I, Ang II and Ang (1-7) were substantially decreased in female and male patients and associated with symptoms of depression and anxiety, ACE and ACE2 levels have not been attributed to signs of depression and anxiety. Serum Ang I, Ang II, and Ang (1-7) are important markers of depression and anxiety prevention and diagnosis in patients with DP.

Outcomes and prognostic factors in 70 non-survivors and 595 survivors with COVID-19 in Wuhan, China.

Since the first outbreak of coronavirus disease 2019 (COVID-19) occurred in December 2019, more than 51 million cases had been reported globally. We aimed to identify the risk factors for in-hospital fatal outcome and severe pneumonia of this disease. This is a retrospective, multicentre study, which included all confirmed cases of COVID-19 with definite outcomes (died or discharged) hospitalized between 1 January and 4 March 2020 in Wuhan. Of all 665 patients included, 70 died and 595 discharged (including 333 mild and 262 severe cases). Underlying comorbidity was more commonly observed among deaths (72.9%) than mild (26.4%) and severe (61.5%) survivors, with hypertension, diabetes and cardiovascular as dominant diseases. Fever and cough were the primary clinical magnifications. Older age (≥65 years) (OR = 3.174, 95% CI = 1.356-7.755), diabetes (OR = 2.540, 95% CI = 0.995-6.377), dyspnoea (OR = 7.478, 95% CI = 3.031-19.528), respiratory failure (OR = 10.528, 95% CI = 4.484-25.829), acute cardiac injury (OR = 25.103, 95% CI = 9.057-76.590) and acute respiratory distress syndrome (OR = 7.308, 95% CI = 1.501-46.348) were associated with in-hospital fatal outcome. In addition, older age (OR = 2.149, 95% CI = 1.424-3.248), diabetes (OR = 3.951, 95% CI = 2.077-7.788), cardiovascular disease (OR = 3.414, 95% CI = 1.432-8.799), nervous system disease (OR = 4.125, 95% CI = 1.252-18.681), dyspnoea (OR = 31.944, 95% CI = 18.877-92.741), achieving highest in-hospital temperature of >39.0°C (OR = 37.450, 95% CI = 7.402-683.403) and longer onset of illness to diagnosis (≥9 days) were statistically associated with higher risk of developing severe COVID-19. In conclusion, the potential risk factors forolder age, diabetes, dyspnoea, respiratory failure, acute cardiac injury and acute respiratory distress syndrome could help clinicians to identify patients with poor prognosis at an early stage.

Acute psychological impact on COVID-19 patients in Hubei: a multicenter observational study.

We conducted a multicentre cross-sectional survey of COVID-19 patients to evaluate the acute psychological impact on the patients with coronavirus disease 2019 (COVID-19) during isolation treatment based on online questionnaires from 2 February to 5 March 2020. A total of 460 COVID-19 patients from 13 medical centers in Hubei province were investigated for their mental health status using online questionnaires (including Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Patient Health Questionnaire-15, and Insomnia Severity Index scales). Among all 460 COVID-19 patients, 187 (40.65%) of them were healthcare workers (HCWs). 297 (64.57%) of them were females. The most common psychological problems were somatization symptoms (66.09%, n = 304), followed by depression (53.48%, n = 246), anxiety (46.30%, n = 213), problems of insomnia (42.01%, n = 171), and then self-mutilating or suicidal thoughts (23.26%, n = 107). Of all the patients, 15.65% (n = 72) had severe somatization symptoms, and 2.83% (n = 13) had severe (almost every day) self-mutilating or suicidal thoughts. The most common psychological problems for HCWs were somatization symptoms (67.84%, n = 125), followed by depression (51.87%, n = 97), anxiety (44.92%, n = 84), problems of insomnia (36.18%, n = 55), and then self-mutilating or suicidal thoughts (20.86%, n = 39). Patients with lower education levels were found to be associated with higher incidence of self-mutilating or suicidal thoughts (odds ratio [OR], 2.68, 95% confidence interval [95% CI], 1.66-4.33 [P < 0.001]). Patients with abnormal body temperature were found to be associated with higher incidence of self-mutilating or suicidal thoughts (OR, 3.97, 95% CI, 2.07-7.63 [P < 0.001]), somatic symptoms (OR, 2.06, 95% CI, 1.20-3.55 [P = 0.009]) and insomnia (OR, 1.66, 95% CI, 1.04-2.65 [P = 0.033]). Those with suspected infected family members displayed a higher prevalence of anxiety than those without infected family members (OR, 1.61, 95% CI, 1.1-2.37 [P = 0.015]). Patients at the age of 18-44 years old had fewer somatic symptoms than those aged over 45 years old (OR, 1.91, 95% CI, 1.3-2.81 [P = 0.001]). In conclusion, COVID-19 patients tended to have a high prevalence of adverse psychological events. Early identification and intervention should be conducted to avoid extreme events such as self-mutilating or suicidal impulsivity for COVID-19 patients, especially for those with low education levels and females who have undergone divorce or bereavement.

[Development and application of the phased HIFU system software].

This paper introduces HIFU system software based on a phased-array HIFU device. Combined with the database and computer graphics technology, this HIFU system software can be used to develop the therapy planning semi-automatically, implement the pilot project efficiently and accelerate the clinical studies.

Diabetes-Induced H3K9 Hyperacetylation Promotes Development of Alzheimer's Disease Through CDK5.

The connection between diabetes and Alzheimer's disease (AD) is not fully determined. Hyperphosphorylation of tau protein is mediated by binding and stabilization of truncated p25 with cyclin-dependent kinase-5 (CDK5) in AD. We recently showed that diabetes-associated hyperglycemia increased the CDK5 levels to promote development of AD. Here, we examined the underlying mechanisms. Hyperglycemia and glucose intolerance were induced in rats that had received a low dose of streptozotocin (STZ) and a high fat diet (HFD). Compared to the control rats that received no STZ and normal diet-fed, the STZ + HFD rats exhibited poorer performance in the behavioral test and showed hyperacetylation of H3K9 histone on CDK5 promoter, likely resulting from upregulation of a histone acetyltransferase, GCN5. Inhibition of acetylation of H3K9 histone by a specific GCN5 inhibitor, MB3, attenuated activation of CDK5, resulting in decreased tau phosphorylation in rat brain and improved performance of the rats in the behavior test. Thus, these data suggest that diabetes may promote future development of AD through hyperacetylation of H3K9 histone on CDK5 promoter.

M2-Like Microglia Polarization Attenuates Neuropathic Pain Associated with Alzheimer's Disease.

Many Alzheimer's disease (AD) patients suffer from persistent neuropathic pain (NP), which is mediated, at least partially, but microglia. Nevertheless, the exact underlying mechanism is unknown. Moreover, a clinically translatable approach through modulating microglia for treating AD-associated NP is not available. Here, in a doxycycline-induced mouse model (rTg4510) for AD, we showed development of NP. We found that the total number of microglia in the CA3 region was not increased, but polarized to pro-inflammatory M1-like phenotype, with concomitant increases in production and secretion of pro-inflammatory cytokines. To examine whether this microglia polarization plays an essential role in the AD-associated NP, we generated an adeno-associated virus (AAV) serotype PHP.B (capable of crossing the blood-brain barrier) carrying shRNA for DNA methyltransferase 1 (DNMT1) under a microglia-specific TMEM119 promoter (AAV-pTMEM119-shDNMT1), which specifically targeted microglia and induced a M2-like polarization in vitro and in vivo in doxycycline-treated rTg4510 mice. Intravenous infusion of AAV-pTMEM119-shDNMT1 induced M2-polarization of microglia and attenuated both AD-associated behavior impairment but also NP in the doxycycline-treated rTg4510 mice. Thus, our data suggest that AD-associated NP may be treated through M2-polarization of microglia.