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OBJECTIVE: The outbreak of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), has resulted in the death of up to 5 million people worldwide, with a mortality rate of approximately 2%. Wearing masks, maintaining social distance, tracking, and isolating close contacts are not sufficient to control the epidemic. The effectiveness of vaccines is affected by the willingness of people to be vaccinated. Therefore, in this review, we aimed to examine the efficacy of different types of vaccines in reducing hospitalization rates, disease severity, and mortality. MATERIALS AND METHODS: We searched five databases (Embase, PubMed, Cochrane, EBSCO, and CEPS) for related research on September 3, 2021. We used a random-effects model for analysis. RESULTS: Seven studies were identified, involving 1,366,700 participants (689,967 participants in the vaccinated group and 676,733 participants in the non-vaccinated group). There were 292 significant incidents (56 in the vaccinated group and 236 in the non-vaccinated group) with a risk ratio of 0.12 and a 95% confidence interval of 0.040-0.363. Compared with no vaccine, all types of vaccines can effectively prevent the rate of severe illness. CONCLUSIONS: We evaluated whether different brands of vaccines or types of COVID-19 vaccines could prevent the risk of severe illness after diagnosis. The analysis showed that all types of vaccines can effectively prevent severe disease. Implementing epidemic prevention guidelines and obtaining vaccines in different countries can improve vaccine protection and reduce COVID-19-related deaths worldwide. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Mechanical-stress has been reported to trigger cartilage fibrosis, in which transforming growth factor (TGF)-β and connective tissue growth factor (CCN2) are involved. However, the function of integrin-a5β1, a cytomembrane receptor, on mechanical-stress related fibrosis has not yet been elucidated. This study aims to reveal the interaction of TGF-β1/CCN2/integrin-α5β1 in the mechanical-stress induced chondrocyte (CH) fibrosis. PATIENTS AND METHODS: We used different levels (5% and 10%) of cyclic tension simulation (CTS) to stretch CHs and observed the gene expression of TGF-β1/CCN2/integrin-α5β1 as well as the fibrous related genes containing collagen I/II/III, Runx2, MMP13, and ADAMTS-5 by real-time polymerase chain reaction (RT-PCR) or immunofluorescence. We used the siRNA or the corresponding antagonist of TGF-β1, CCN2, integrin-α5β1 during the CTS to clear the effect of them in the fibrosis progress. In addition, to verify the crosstalk between TGF-β1, CCN2, and integrin-α5β1, we used the recombinant human (rh)-TGF-β1 and CCN2 to culture CHs without CST. RESULTS: 24 hours-10% CTS was sufficient to induce a decrease of collagen II and increase the collagen I/III, Runx2, MMP13, and ADAMTS-5 gene expression. Under CTS, TGF-β1 silencing resulted in a decline of CCN2, integrin-α5β1, and alleviated the CHs fibrosis. Apart from this, blocking CCN2 or integrin-α5β1 expression also contributed to the suppression of 10% CTS induced CHs fibrosis. Meanwhile, the exogenic protein supplement raised the cellular TGF-β1 or CCN2 expression and increased the integrin-α5β1 mRNA level. However, the downregulation of TGF-β1 or CCN2 did not affect integrin-α5β1 expression, whether the CTS exited or not. CONCLUSIONS: High mechanical-stress induces CHs fibrosis via the activation of TGF-β1/CCN2/integrin-α5β1 signaling, and interrupting the TGF-β1, CCN2, or integrin-α5β1 expression can alleviate the fibrous process. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to detect the expression of RBM5-AS1 during fracture healing, and to explore its possible mechanism. MATERIALS AND METHODS: A mice tibia fracture model was constructed in this study. Mice in the control group and experimental group were sham-operated on the left tibia and were operated in the right tibia, respectively. The tibia bones of both groups were obtained at 4 d, 8 d, 12 d, 16 d, 20 d, and 24 d after the operation. Quantitative polymerase chain reaction (qPCR) was used to detect the expression of RBM5-AS1 in tibiae. After interfering with the expression of RBM5-AS1 in bone cells, Cell Counting Kit- 8 (CCK-8) was used to detect cell proliferation ability, and flow cytometry was applied to detect apoptosis. Western blot was used to measure the protein expression of b-catenin and RBM5 after down-regulating RBM5-AS1. Finally, b-catenin was interfered in osteoblasts to explore the relationship between RBM5-AS1 and b-catenin. RESULTS: Compared with the control group, the expression of RBM5-AS1 in the experimental group was significantly increased on the 4 d, 8 d, 12 d, and 16 d after fracture surgery. However, no statistical difference was observed on the 20 d and 24 d between the two groups. After interfering with RBM5-AS1, the apoptosis of chondrocytes and osteoblasts was significantly increased in both mouse and human cells, while the expression of b-catenin was strikingly decreased. Further up-regulation of b-catenin could reduce the apoptosis of bone cells. The expression of RBM5, which was a natural antisense transcript of RBM5-AS1, was increased after down-regulating RBM5-AS1. CONCLUSIONS: RBM5-AS1 can inhibit the apoptosis of bone cells by promoting the expression of b-catenin and can be used as a biomarker for fracture healing. [ABSTRACT FROM AUTHOR]

Load distribution factor (LDF) is an important index for evaluating the performance of existing bridges. However, few researchers have studied the change of transverse load distribution coefficients of beams before and after the widening and reinforcement of existing bridges. To work out such problem, a reinforcement method for widening longitudinal and cross beam was proposed. A Finite element (FE) model was built to simulate the widening reinforcement of existing bridge, Load distribution factor for all girders were analyzed in the cases of different position, quantity and stiffness of cross beam, different added width of girder, different existing bridge stiffness and different connection system. Results show that the LDF of side beams decreases by 63.92% to the highest extent after bridge reinforcement, which significantly improves load-carrying condition of girder. However, the LDF at fulcrum increases by 30% after reinforcement. Therefore, some strengthening measures are necessary in these positions. The quantity, position and dimension of cross beam have not much influence on the LDF of each girder. The LDF of beams are smaller when the widened girders are connected rigidly to the old girders than that hinge connected to. The LDF of each girder shows not much difference when the main beams are connected to widened girders with rigid or hinged connection, respectively. This study is meaningful for the development of widening and reinforcement design of existing bridges. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of DNA methylation of laminin α3 (LAMA3) on the prognosis of platinum-resistant epithelial ovarian cancer (EOC) and its possible mechanism. Methods: (1) The relationship between DNA methylation of LAMA3 and platinum resistance in EOC was evaluated by bioinformatics. (2) A total of 67 EOC patients treated at Guangxi Medical University Cancer Hospital from January 2000 to December 2012 were selected to detect the levels of LAMA3 DNA methylation in EOC tissues using pyrophosphate sequencing technology to explore its diagnostic efficacy for platinum resistance and prognosis in EOC patients. Furthermore, its impact on chemotherapy efficacy and prognosis of platinum resistant EOC patients were also analyzed. Results: (1) Ten proteins highly interacting with LAMA3 were screened from the Gene Interaction Retrieval Platform (STRING) database, including laminin β (LAMB) 3, laminin γ (LAMC) 3, integrin α (ITGA) 6, intestine protein β4 (ITGB4), ITGA3, LAMC1,LAMB2, dystrophin associated glycoprotein 1 (DAG1), LAMB1 and cytochrome P450c17α (COL17A1) protein; kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis showed that LAMA3 and its related interacting proteins participate in the regulation of malignant tumor occurrence and development through signaling pathways such as apoptosis, cell cycle, DNA damage response, epithelial mesenchymal transition (EMT), androgen receptor (AR), estrogen receptor (ER), phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt), RAS/mitogen activated protein kinase (MAPK), receptor tyrosine kinase (RTK), tuberous sclerosis protein complex (TSC)/mammalian target of rapamycin (mTOR), and their expression levels were related to the sensitivity of chemotherapy drugs such as cisplatin in EOC. (2) Our clinical data analysis found that the LAMA3 DNA methylation level in EOC tissue of the platinum-sensitive group (35 cases) was 71% (25/35), which was higher than 69% (22/32) in the platinum-resistant group (32 cases), with statistically insignificant difference ( χ 2 =0.057, P =0.811). The area under the curve (AUC) of LAMA3 DNA methylation level for assessing platinum resistance in EOC was 0.601, and the AUC for predicting EOC patient prognosis was 0.686. The chemotherapy efficacy of EOC patients with high methylation of LAMA3 DNA was worse than that of patients with low methylation, 50% (12/24) vs 15/15, with statistically significant difference ( χ 2 =10.833, P =0.001). The level of LAMA3 DNA methylation had a significant impact on the progression free survival and overall survival of EOC patients (both P <0.05). Conclusion: The level of LAMA3 DNA methylation has certain diagnostic and predictive value for platinum resistance and prognosis in EOC patients, which may be closely related to the regulatory mechanism, platinum resistance and prognosis of EOC.

Objective: To reveal the similarities and differences in myocardial metabolic characteristics between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) mice using metabolomics. Methods: The experimental mice were divided into 4 groups, including control, HFpEF, sham and HFrEF groups (10 mice in each group). High fat diet and Nω-nitroarginine methyl ester hydrochloride (L-NAME) were applied to construct a"two-hit"HFpEF mouse model. Transverse aortic constriction (TAC) surgery was used to construct the HFrEF mouse model. The differential expression of metabolites in the myocardium of HFpEF and HFrEF mice was detected by untargeted metabolomics (UHPLC-QE-MS). Variable importance in projection>1 and P <0.05 were used as criteria to screen and classify the differentially expressed metabolites between the mice models. KEGG functional enrichment and pathway impact analysis demonstrated significantly altered metabolic pathways in both HFpEF and HFrEF mice. Results: One hundred and nine differentially expressed metabolites were detected in HFpEF mice, and 270 differentially expressed metabolites were detected in HFrEF mice. Compared with the control group, the most significantly changed metabolite in HFpEF mice was glycerophospholipids, while HFrEF mice presented with the largest proportion of carboxylic acids and their derivatives. KEGG enrichment and pathway impact analysis showed that the differentially expressed metabolites in HFpEF mice were mainly enriched in pathways such as biosynthesis of unsaturated fatty acids, ether lipid metabolism, amino sugar and nucleotide sugar metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and arginine and proline metabolism. The differentially expressed metabolites in HFrEF mice were mainly enriched in arginine and proline metabolism, glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and arachidonic acid metabolism, etc. Conclusions: HFpEF mice have a significantly different myocardial metabolite expression profile compared with HFrEF mice. In addition, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, glycerophospholipid metabolism and arginine and proline metabolism are significantly altered in both HFpEF and HFrEF mice, suggesting that these metabolic pathways may play an important role in disease progression in both types of heart failure.

Although transition metal selenides are considered to be extremely promising anode materials for lithium-ion batteries (LIBs), severe volume changes and low electronic conductivity are their huge and unavoidable challenges. To solve these problems, CoSe nanoparticles in-situ grown on the inner surface of every macropore of 3D honeycomb C is successfully synthesized by three simple steps: dense assembling of polystyrene spheres, calcination and gaseous selenylation. The sizes of CoSe and honeycomb pores are 10-15 nm and 190 nm, respectively. The content of CoSe is 72 wt%. This unique architecture guarantees high electrochemical activity, rapid reaction kinetics and excellent structural stability of CoSe, as identified by cycling and rate performance measurements, various electrochemical kinetics analyses and ex-situ characterization of the cycled electrode material. As a result, the CoSe@honeycomb C anode exhibits extraordinary cycling performance (823.5 mAh g -1 after 200 cycles at 0.5 A g -1 , 610.1 mAh g -1 after 250 cycles at 2 A g -1 , 247 mAh g -1 after 1500 cycles at 5 A g -1 ) and exceptional rate capability (261.9 mAh g -1 at 10 A g -1 , 1491.4 mAh g -1 at 0.1 A g -1 ), demonstrating that it is a potential anode material for high-performance LIBs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To investigate the relationship between the levels of exosomes in bronchoalveolar lavage fluid (BALF) and plasma and the severity of lung injury and its outcome in patients with acute respiratory distress syndrome (ARDS). Methods: Patients who were admitted to the Department of Critical Care Medicine, Zhongda Hospital Affiliated to Southeast University and received invasive mechanical ventilation were selected from August 2020 to April 2021, and they were divided into ARDS group and non-ARDS group. Finally, 33 ARDS patients were included, including 18 males and 15 females, aged (65.5±15.5) years; 10 non-ARDS patients, 8 males and 2 females, aged (57.2±15.3) years. The BALF and plasma of the two groups of patients were collected within 24 hours after enrollment, and the total exosomes of the samples were collected by ultracentrifugation. Nanoparticle tracking analysis (NTA) was used to detect and compare the differences in exosome content between the two groups. Correlation of content with the severity and prognosis of lung injury in ARDS patients. Results: There was no significant difference in gender and age between ARDS group and non-ARDS group (both P >0.05). The exosome in plasma of ARDS group was significantly higher than that of non-ARDS group [(25.3±1.2)/ml vs (24.2±1.6)/ml, P =0.031], while the exosomes in BALF of ARDS group was also higher than that of non-ARDS group [(26.5±1.6)/ml vs (24.6±1.1)/ml, P =0.001]. The exosomes in BALF of patients with ARDS caused by intrapulmonary causes was higher than that in ARDS group caused by extrapulmonary causes [(26.9±1.5)/ml vs (25.2±0.9)/ml, P =0.01], and the infection caused by bacterial shows that the highest exosome level in BALF. The exosomes in the BALF of the mild ARDS group was significantly lower than that of the severe ARDS group [(25.7±1.3)/ml vs (27.2±1.5)/ml, P =0.038]; the exosomes in BALF of ARDS patients was negatively correlated with P/F ratio ( r =-0.38, P =0.03); and it was positively correlated with Murray lung injury score ( r =0.47, P =0.01). However, the static compliance levels, length of hospital stay, duration of mechanical ventilation, and 28-day outcome were not associated with the exosomes in BALF. Conclusion: Compared with non-ARDS patients, ARDS patients have significantly higher levels of exosomes in BALF and plasma, there is a certain correlation between exosomes derived from BALF and the severity of lung injury in ARDS.

Objective: To develop an area under curve (AUC)-based nomogram to predict vancomycin-associated nephrotoxicity in critically ill patients. Methods: This retrospective cohort study included adult patients treated with vancomycin in the intensive care unit at a tertiary teaching hospital from January 2015 to December 2017. Baseline clinical characteristics before vancomycin treatment and pharmacokinetic parameters were collected to establish a prediction model of nephrotoxicity. Univariate analysis was used to screen variables, and multivariate logistic regression analysis was used to establish the prediction model and nomogram. Results: A total of 159 patients met the inclusion criteria, sixty-four were included in the final analysis. Sixteen patients (25%, 16/64) developed vancomycin-associated nephrotoxicity. The following variables were incorporated into the prediction model: vancomycin AUC, estimated glomerular filtration rate (GFR), and combined nephrotoxic drugs. The following equation was established to calculate the probability of nephrotoxicity: logit (P)=-4.83+0.009×AUC-2.87×1 (if GFR>60 ml/min)+2.53×1 (if number of combined nephrotoxic drugs≥2). A nomogram was generated based on the equation. The receiver-operating characteristic curve demonstrated that the AUC of the prediction model was 0.927 (95% CI 0.851-1.000). The cut-off value of the probability of nephrotoxicity was 26.48%. The sensitivity and specificity were 87.5% and 87.5% respectively. Conclusion: The incidence of vancomycin-associated nephrotoxicity is high. The AUC-based nomogram can effectively predict vancomycin-associated nephrotoxicity in critically ill patients.

To determine the physicians'compliance of hour-1 bundle for sepsis. A management system of hour-1 bundle for sepsis was established. The clinical data of 286 sepsis patients were collected, who were classified into 3 months before the bundle (control group), 9 months during process (observation group) and 3 months after bundle (study group). The compliance of hour-1 bundle implementation was compared in three groups. The results showed that with the application and implementation of the management system, the compliance of hour-1 bundle for sepsis in the control group, observation group and study group was 58.3%(28/48), 69.1%(105/152) and 88.4%(76/86) respectively (χ 2 =7.053, P =0.029). The 28 day mortality in sepsis patients was 41.7%(20/48), 34.9%(53/152) and 23.3%(20/86) respectively (χ 2 =5.576, P =0.062).The management system of hour-1 bundle for sepsis can effectively improve the physicians' compliance.

Objective: To develop a fast track transfer to intensive care unit (ICU) for the perioperative high-risk elderly patients after hip fracture surgery and analyze the preliminary clinical effect of the application. Methods: From January 2014 to December 2017, before the application of postoperative fast track transfer to ICU, the clinical data of 195 elderly patients with hip fracture were included in a retrospective analysis. Among 195 hip fracture patients, 18 were transferred to ICU post operation (non-fast track group). Multivariate logistic regression analysis was applied to investigate relevant risk factors for transferring to ICU after hip fracture surgery. Based on risk factors acquired from the analysis and clinical experience, the fast track transfer to ICU for the perioperative high-risk elderly patients after hip fracture surgery was constructed according to the preliminary and experiential criteria. From January 2018 to December 2019, the clinical data of 70 patients (fast track group) who were transferred to ICU after hip fracture surgery through the fast track were collected and compared with non-fast track group. Results: Multivariate regression analysis revealed that American Society of Anesthesiologists classification(≥Ⅲ) ( OR =4.260, 95% CI :1.157-15.683, P =0.029), pre-hospital stage (≥48 h) ( OR =4.301, 95% CI :1.212-15.266, P =0.024), hemoglobin concentration at admission(<90 g/L) ( OR =7.979, 95% CI :1.936-32.889, P =0.004), coronary heart disease as one comorbidity( OR =6.063, 95% CI :1.695-21.693, P =0.006) were independent risk factors for transferring to ICU after hip fracture surgery. There were no significant difference in gender, age, fracture type, hemoglobin concentration at admission and time of pre-hospital stage between the non-fast track group and fast track group(all P >0.05). However, the number of comorbidities in the fast track group was significantly higher than that in the non-fast track group ( Z =-1.995, P =0.046). The time to surgery, postoperative hospital stay, and length of hospital stay in fast track group were all significantly less than those in non-fast track group ( Z =-2.121, -2.726, -3.130, all P <0.05). Also, there were fewer medical consultations needed and fewer patients who stayed in ICU more than or equal to 2 nights in fast track group than that in non-fast track group(all P <0.05). There were no significant difference in the rate of patients who transferred from the general ward to ICU after transferring from ICU to the general ward, the proportion of patients who received more than or equal to 4 departments, operation time, hospitalization expense, mortality during hospitalization, 30-day mortality and 90-day mortality after operation between the two groups(all P >0.05). Conclusions: The fast track constructed in this study can reduce time to surgery, postoperative hospitalization stay and length of hospitalization stay for the perioperative high-risk elderly patients with hip fractures and is a specific clinical application of eras concept based on multidisciplinary team.