Objective To investigate the role of triggering receptor expressed on myeloid cells-1(TREM-1)in ath-erosclerosis induced by chronic intermittent hypoxia(CIH).Methods ApoE-/-mice were randomly divided into blank group,model group and experimental group.The mice in the model group and the experimental group were kept in a hypoxic environment and fed with a high-fat diet.After 4 weeks of high-fat feeding,mice in the experi-mental group were intraperitoneally injected with TREM-1 inhibitor LR12(5 mg/kg)for 8 weeks.After 12 weeks of feeding,the level of serum total cholesterol(TC),low density lipoprotein(LDL),triglyceride(TG),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-10(IL-10)were detected.Histological analysis of aortic TREM-1 expression,plaque area and macrophage level were examined.Results Compared with blank group,the expression of TREM-1 in the aorta of the model group significantly increased(P＜0.05).Com-pared with model group,the aortic plaque,the level of lipids in serum(TC,LDL,TG)and inflammatory factors(TNF-α,IL-1β,IL-10),aortic plaque,the expression of TREM-1 and infiltrating macrophages in aortic plaque of the experimental group were all significantly reduced(P＜0.05).Conclusions TREM-1 is involved in the develop-ment of CIH-induced AS.Inhibition of TREM-1 can alleviate CIH-induced AS and its mechanism is related to the inhibition of macrophage activation.

Objective:There is a lack of scientifically validated tools to measure the knowledge attitude and practice(KAP)of informal caregivers for patients with pressure injury(PI).This study aims to develop a KAP Scale for Informal Caregivers of PI Patients and to evaluate its reliability and validity. Methods:Based on the KAP theory framework and relevant literature,an initial pool of items was created through expert brainstorming sessions.The initial scale was formed after a Delphi expert consultation and a preliminary survey.From April to October 2023,a convenient sample of informal caregivers for PI patients was recruited from an inpatient department of the Third Xiangya Hospital of Central South University,as well as its associated community and nursing homes.The first round included 186 participants,and the second round included 213 participants,who were used for item analysis and reliability and validity testing.After a 3-week interval,20 participants from the initial group were randomly selected for a retest to assess the test-retest reliability of the scale. Results:The KAP Scale for informal caregivers of PI patients consists of 3 dimensions with 19 items.The overall internal consistency(Cronbach's α)of the scale was 0.916.The item-level content validity index(I-CVI)ranged from 0.826 to 1.000,and the scale level-content validity index/average(S-CVI/Ave)was 0.94.Exploratory factor analysis extracted 3 common factors,accounting for 64.643％of the total variance.Confirmatory factor analysis showed that the model fit the data well,with x2/df=2.54,root mean square error of approximation(RMSEA)=0.085,comparative fit index(CFI)=0.920,and standardized root mean square residual(SRMR)=0.059. Conclusion:The KAP scale for informal caregivers of PI patients demonstrates good reliability and validity and can be used to assess the KAP levels of informal caregivers regarding PI.

Objective:To investigate the current situation and characteristics of post-intensive care syndrome in elderly patients during the transitional period, and explore its influencing factors.Methods:From December 2022 to September 2023, convenience sampling was used to select 119 elderly patients in the Intensive Care Unit of China-Japan Friendship Hospital as the research subject. The General Information Questionnaire, Short Physical Performance Battery, Fatigue Scale-14, Barthel Index, Hospital Anxiety and Depression Scale, and Mini-mental State Examination were used to evaluate patients for post-intensive care syndrome from cognitive, psychological, and physiological aspects 7 days after their transfer from the Intensive Care Unit. Binomial Logistic regression was used to analyze the influencing factors of post-intensive care syndrome in elderly patients.Results:Among 119 elderly patients, 84 developed post-intensive care syndrome, with an incidence of 70.6%. The binomial Logistic regression showed that women and high nutritional risk were risk factors for the occurrence of post-intensive care syndrome in elderly patients ( P<0.05) . Conclusions:The incidence of post-intensive care syndrome is high in elderly patients during the transition period, with females and patients with high nutritional risk being prone to developing post-intensive care syndrome. Medical and nursing staff should pay attention to identifying gender differences, focus on high-risk populations, and dynamically evaluate different symptoms early on to provide precise interventions for elderly patients.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

RNA viruses are critically dependent upon virally encoded proteases to cleave the viral polyproteins into functional proteins. Many of these proteases exhibit a similar fold and contain an essential catalytic cysteine, offering the opportunity to inhibit these enzymes with electrophilic small molecules. Here we describe the successful application of quantitative irreversible tethering (qIT) to identify acrylamide fragments that target the active site cysteine of the 3C protease (3C^pro) of Enterovirus 71, the causative agent of hand, foot and mouth disease in humans, altering the substrate binding region. Further, we re-purpose these hits towards the main protease (M^pro) of SARS-CoV-2 which shares the 3C-like fold and a similar active site. The hit fragments covalently link to the catalytic cysteine of M^pro to inhibit its activity. We demonstrate that targeting the active site cysteine of M^pro can have profound allosteric effects, distorting secondary structures to disrupt the active dimeric unit.

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

Objective:To investigate the feasibility of reducing the radiation dose on coronary artery calcium score (CS) of virtual non-contrast (VNC) scanning in dual-layer spectral coronary CT angiography(CCTA).Methods:One hundred and twenty-two patients were examined on a dual-layer spectral detector CT scanner from March 2019 to August 2020. Volume CT dose index (CTDI vol), dose length product (DLP), effective dose ( E) were all evaluated for each patient. CS was calculated from both true non-contrast (TNC) and VNC images for left anterior descending (LAD), left circumflex (LCx), right coronary artery (RCA), and the total coronary artery (Total) by two radiologists independently. Pearson′s correlation coefficient was calculated for measuring the association between variables. The correction coefficients of each branch (λ LAD, λ LCx, and λ RCA) and the average correction coefficient (λ AVG) of the total coronary artery were obtained. The calibrated calcium score (CCS_VNC) was equal to λ multiplied by CS_VNC. The CS_TNC and CCS_VNC were compared using repeated oneway analysis of variance test. Correlation analyses for CS_TNC and CCS_VNC and agreement evaluation with Bland-Altman-Plots were performed. Results:The average effective doses in TNC, CCTA and total group were 0.69, 6.47 and 7.16 mSv, respectively. The effective dose was reduced by 10.6% and the scan time was reduced by 39% while using VNC images. There were significant differences among the CS_TNC and CS_VNC of LAD, LCx, RCA and Total ( t=6.75, 5.33, 4.99, 6.60, P< 0.05). Excellent correlations were observed between CS_VNC and CS_TNC ( R2 values were 0.929, 0.896, 0.958, and 0.918; λ values were 2.18, 1.18, 2.15, and 2.07, respectively). There were no significant statistically difference among the CS_TNC, CCS_VNC AVG, and CCS_VNC LAD/RCA of the LAD and RCA (all P> 0.05). The difference was statistically significant among the CS_TNC, CCS_VNC AVG, and CCS_VNC LCx of the LCx ( F=10.94, P<0.05). The paired comparison were performed in groups and the differences were statistically significant between the CS_TNC versus CCS_VNC AVGand CCS_VNC AVG versus CCS_VNC LCx ( t=3.31, 3.43, all P<0.05). There was no significant statistically difference between the CCS_VNC LCx and CCS_VNC AVG( P>0.05). Conclusions:It was feasible to accurately evaluate the CS_VNC from spectral data in comparison to TNC imaging, and to reduce the patient radiation dose and acquisition time.

Objective : To investigate the expression and clinical significance of erbb2 interacting protein (ERBIN) and PDZ domain containing 2 protein (PDZD2) in colorectal cancer tissues，as well as the effects of ERBIN and PDZD2 on the progression of colorectal cancer and the corresponding mechanisms． Methods : Western blot was used to detect the expression of ERBIN and PDZD2 proteins in tumor tissues and corresponding adjacent tissues from 86 colorectal cancer patients，as well as normal human colon fibroblasts ( CCD-18Co) and human colorectal cancer cell lines ( SW480 ，HCT116 ，SW620 and HT29 ) ; SW620 and HCT116 cells were transfected with ERBIN or PDZD2 overexpression vector，and then cell proliferation，cell invasion and apoptosis were detected．The expres- sion of ERBIN or PDZD2 protein in SW620 cell was observed by immunofluorescence chemistry．Co-immunoprecip- itation assay was used to detect the interaction between ERBIN and PDZD2 proteins. Results : The expression levels of ERBIN and PDZD2 proteins in colorectal cancer tissues were lower than those in adjacent tissues (P＜0．01) ， and the expression levels of ERBIN and PDZD2 in colorectal cancer cells were lower than those in CCD-18Co cells (P＜0. 01) ．The expression levels of ERBIN and PDZD2 proteins were correlated with the depth of invasion，dif- ferentiation，TNM staging and lymph node metastasis of colorectal cancer (P＜0. 001) ; ERBIN or PDZD2 overex- pression reduced the proliferation and invasion of SW620 and HCT116 cells (P＜0. 01) ，increased cell apoptosis (P ＜0. 01 ) ; ERBIN directly bound to PDZD2 ，and overexpression of ERBIN increased the expression level of PDZD2 protein． Conclusion ERBIN can inhibit the proliferation and invasion of colorectal cancer cells and pro- mote apoptosis by promoting the expression of PDZD2 protein.

Objective:To evaluate the efficacy of SVF-gel and Coleman fat in facial volume filling.Methods:This investigation presents a retrospective study of facial fat transplantation in 186 patients (114 cases of SVF-gel transplantation and 72 cases of Coleman fat transplantation) from December 2018 to September 2020 in Shanghai Basilica Clinic. Patient satisfaction was evaluated with the satisfaction questionnaire and secondary operation rates were tallied.Results:Facial augmentation and contour were improved in all patients. The satisfaction rate among the patients in the SVF-gel group was 93.0%, while that among the patients in the Coleman fat transplantation group was only 56.9% (χ 2=8.694, P<0.05). Patients in the SVF-gel group experienced less swelling and there was a lower secondary operation rate in the SVF-gel group than those in the Coleman fat transplantation group (1.75% vs 18.1%) (χ 2=13.467, P<0.001). Conclusions:SVF-gel has obvious advantages over traditional fat transplantation in facial volume filling and rejuvenation.

BACKGROUND: Ambient temperature may contribute to seasonality of mortality; in particular, a warming climate is likely to influence the seasonality of mortality. However, few studies have investigated seasonality of mortality under a warming climate. METHODS: Daily mean temperature, daily counts for all-cause, circulatory, and respiratory mortality, and annual data on prefecture-specific characteristics were collected for 47 prefectures in Japan between 1972 and 2015. A quasi-Poisson regression model was used to assess the seasonal variation of mortality with a focus on its amplitude, which was quantified as the ratio of mortality estimates between the peak and trough days (peak-to-trough ratio (PTR)). We quantified the contribution of temperature to seasonality by comparing PTR before and after temperature adjustment. Associations between annual mean temperature and annual estimates of the temperature-unadjusted PTR were examined using multilevel multivariate meta-regression models controlling for prefecture-specific characteristics. RESULTS: The temperature-unadjusted PTRs for all-cause, circulatory, and respiratory mortality were 1.28 (95% confidence interval (CI): 1.27-1.30), 1.53 (95% CI: 1.50-1.55), and 1.46 (95% CI: 1.44-1.48), respectively; adjusting for temperature reduced these PTRs to 1.08 (95% CI: 1.08-1.10), 1.10 (95% CI: 1.08-1.11), and 1.35 (95% CI: 1.32-1.39), respectively. During the period of rising temperature (1.3 °C on average), decreases in the temperature-unadjusted PTRs were observed for all mortality causes except circulatory mortality. For each 1 °C increase in annual mean temperature, the temperature-unadjusted PTR for all-cause, circulatory, and respiratory mortality decreased by 0.98% (95% CI: 0.54-1.42), 1.39% (95% CI: 0.82-1.97), and 0.13% (95% CI: - 1.24 to 1.48), respectively. CONCLUSION Seasonality of mortality is driven partly by temperature, and its amplitude may be decreasing under a warming climate.
Cardiovascular Diseases/mortality* ; Cause of Death ; Climate Change/mortality* ; Cold Temperature/adverse effects* ; Hot Temperature/adverse effects* ; Humans ; Japan/epidemiology* ; Mortality/trends* ; Regression Analysis ; Respiratory Tract Diseases/mortality* ; Seasons ; Time