Antibiotic-Resistance Profiles and Genetic Diversity of Shigella Isolates in China: Implications for Control Strategies.

The urgent need for comprehensive and systematic analyses of Shigella as the key pathogen led us to meticulously explore the epidemiology and molecular attributes of Shigella isolates. Accordingly, we procured 24 isolates (10 from Xinjiang and 14 from Wuhan, China) and performed serotype identification and antimicrobial susceptibility testing. Resistance gene detection and homology analysis by polymerase chain reaction and pulsed-field gel electrophoresis (PFGE), respectively, were performed for genetic diversity analysis. All isolates were identified as Shigella flexneri, with 70% (35.4-91.9%) and 30% (8.1-64.6%) of the Xinjiang isolates and 85.7% (56.2-97.5%) and 14.3% (2/14, 2.5-43.9%) of the Wuhan isolates belonging to serotype 2a and serotype 2b, respectively. All isolates displayed resistance to at least two antibiotics and complete resistance to ampicillin. Multidrug resistance (MDR) was recorded in 70.8% (48.8-86.6%) of isolates, with Xinjiang isolates exhibiting relatively higher resistance to ampicillin-sulbactam, piperacillin, ceftriaxone, and aztreonam. Conversely, Wuhan isolates displayed higher MDR and resistance to tetracycline, ciprofloxacin, levofloxacin, and cefepime relative to Xinjiang isolates. Molecular scrutiny of antibiotic-resistance determinants revealed that blaTEM was the main mechanism of ampicillin resistance, blaCTX-M was the main gene for resistance to third- and fourth-generation cephalosporins, and tetB was the predominant gene associated with tetracycline resistance. Four Xinjiang and seven Wuhan isolates shared T1-clone types (>85%), and two Xinjiang and one Wuhan isolates were derived from the T6 clone with a high similarity of 87%. Six PFGE patterns (T1, T2, T5, T6-3, T8, and T10) of S. flexneri were associated with MDR. Thus, there is a critical need for robust surveillance and control strategies in managing Shigella infections, along with the development of targeted interventions and antimicrobial stewardship programs tailored to the distinct characteristics of Shigella isolates in different regions of China.

Nurses' preferences for interventions to improve infection prevention and control behaviors based on systems engineering initiative to patient safety model: a discrete choice experiment.

BACKGROUND: The evidence of preferences for infection prevention and control (IPC) intervention from system perspective was lacked. This study aimed to elicit nurses' preferences for the intervention designed to improve IPC behaviors based on the Systems Engineering Initiative to Patient Safety (SEIPS) model using Discrete Choice Experiment (DCE). METHODS: A DCE was conducted among nurses who were on active duty and willing to participate from July 5th to 10th, 2021 in a tertiary hospital in Ganzhou City, Jiangxi Province, using convenience sampling. A self-administered questionnaire included scenarios formed by six attributes with varying levels based on SEIPS model: person, organization, tools and technology, tasks, internal environment and external environment. A conditional logit and latent class logit model were performed to analyze the data. RESULTS: A total of 257 valid questionnaires were analyzed among nurses. The results from the latent class logit model show that nurses' preferences can be divided into three classes. For nurses in multifaceted-aspect-preferred class (41.9%), positive coefficients were obtained in those six attributes. For person-preferred class (19.7%), only person was positively significant. For environment-preferred class (36.4%), the most important attribute were tasks, tools and technology, internal environment and external environment. CONCLUSIONS: This finding suggest that nurses have three latent-class preferences for interventions. Multifaceted interventions to improve IPC behaviors based on the SEIPS model are preferred by most nurses. Moreover, relevant measured should be performed targeted the latent class of person-preferred and external-environment-preferred nurses.

A Novel Platinum Resistance-Related Immune Gene Signature for Overall Survival Prediction in Patients with Ovarian Cancer.

Ovarian cancer (OV) is a highly heterogeneous gynecological tumor that makes the prognostic prediction challenging. Resistance to platinum-based chemotherapy is associated with a poor prognosis in OV. There seems to be an overlap between molecular mechanisms responsible for platinum resistance and immunogenicity in OV. However, the predictive role of platinum resistance-related immune genes for OV prognosis needs to be further explored. In our study, the mRNA expression data of OV patients with corresponding clinical information were collected from The Cancer Genome Atlas (TCGA) cohort and International Cancer Genome Consortium (ICGC) cohort. A multigene signature was constructed for OV patients in the TCGA cohort using the least absolute shrinkage and selection operator (LASSO) Cox regression model according to the optimal value of λ and was validated in the ICGC cohort. Furthermore, we performed functional analysis to explore the immune status between low- and high-risk groups based on the median value of the risk score for the multigene signature. Our data showed that there were 41.1% of the platinum resistance-related genes which differentially expressed between immune score low- and high-OV patients in the TCGA cohort. Univariate Cox regression analysis identified 30 differentially expressed genes (DEGs) associated with overall survival (OS) (P < 0.05). 14 genes were identified to construct a novel platinum resistance-related immune model for classifying OV patients into the low- and high- risk groups. Patients in the low-risk group showed significantly higher OS than those in the high-risk group (P < 0.0001 in the both TCGA and ICGC cohort), which was associated with different immune status for the two risk groups. A novel platinum resistance-related immune model can be used for prognostic prediction in OV. Targeting tumor immunity may be a therapeutic alternative for OV with platinum resistance.

Diagnosis, treatment, and prevention of monkeypox in children: an experts' consensus statement.

Monkeypox is a zoonotic disease. Since the first human monkeypox case was detected in 1970, it has been prevalent in some countries in central and western Africa. Since May 2022, monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide. As of September 14, 2022, there have been more than 58,200 human monkeypox cases, and there is community transmission. The cessation of smallpox vaccination in 1980, which had some cross-protection with monkeypox, resulted in a general lack of immunity to monkeypox, which caused global concern and vigilance. As of September 14, 2022, there are four monkeypox cases in China, including three in Taiwan province and one in Hong Kong city. Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications. In order to improve pediatricians' understanding of monkeypox and achieve early detection, early diagnosis, early treatment,  and early disposal, we have organized national authoritative experts in pediatric infection, respiratory, dermatology, critical care medicine, infectious diseases, and public health and others to formulate this expert consensus, on the basis of the latest "Clinical management and infection prevention and control for monkeypox" released by The World Health Organization, the "guidelines for diagnosis and treatment of monkeypox (version 2022)" issued by National Health Commission of the People's Republic of China and other relevant documents. During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis, differential diagnosis, treatment, discharge criteria, prevention, disposal process, and key points of prevention and control of suspected and confirmed cases.

Post-operative uric acid: a predictor for 30-days mortality of acute type A aortic dissection repair.

BACKGROUND: Hyperuricemia is associated with aortic dissection and cardiovascular diseases. The implication of high serum uric acid (UA) level after acute aortic dissection repair remains unknown. The aim of this study is to explore the role of peri-operative serum UA level in predicting 30-days mortality with acute type A aortic dissection (AAAD) patients, who underwent surgery. METHODS: This study retrospectively enrolled 209 consecutive patients with AAAD, who underwent surgery in Xiangya Hospital from 2017 to 2020. Post-operative laboratory examinations were measured within 24 h after surgery. Univariate analysis and logistic regression analysis were used for predictor finding. RESULTS: 209 consecutive AAAD patients were included, 14.3% (n = 30) were dead within 30 days after surgery. By univariate analysis, we found AAAD repair patients with 30-days mortality had a higher prevalence of cerebral malperfusion, lower pre-operative fibrinogen, longer cardiopulmonary bypass and aortic crossclamp time, and higher post-operative day 1 (POD1) creatinine and urea levels. Both pre-operative (433.80 ± 152.59 vs. 373.46 ± 108.31 mmol/L, p = 0.038) and POD1 (559.78 ± 162.23 vs. 391.29 ± 145.19 mmol/L, p < 0.001) UA level were higher in mortality group than in survival group. In regression model, only cerebral malperfusion (OR, 7.938, 95% CI 1.252-50.323; p = 0.028) and POD1 UA level (OR, 2.562; 95% CI 1.635-4.014; p < 0.001) were independent predictors of 30-days mortality in AAAD repair patients. According to the ROC curve, the POD1 UA level provided positive value for 30-days mortality in AAAD repair patients with 0.799 areas under the curve. The optimum cutoff value selected by ROC curve was 500.15 mmol/L, with a sensitivity of 65% and a specificity of 86%. CONCLUSION: Pre- and post-operative hyperuricemia are potentially associated with worsened outcomes in AAAD surgery patients. The POD1 UA level has a predictive role in 30-days mortality in AAAD repair patients.

ARHGEF37 overexpression promotes extravasation and metastasis of hepatocellular carcinoma via directly activating Cdc42.

BACKGROUND: The extravasation capability of hepatocellular carcinoma (HCC) cells plays a vital role in distant metastasis. However, the underlying mechanism of extravasation in HCC lung metastasis remains largely unclear. METHODS: The expression of ARHGEF37 in human HCC specimens and HCC cell lines was examined by quantitative RT-PCR, western blot, and immunohistochemistry (IHC) analyses. The biological roles and mechanisms of ARHGEF37/Cdc42 in promoting lung metastasis were investigated in vitro and in vivo using cell lines, patient samples, xenograft models. RESULTS: In the current study, we found that Rho guanine nucleotide exchange factor 37 (ARHGEF37) was upregulated in human HCC samples and was associated with tumor invasiveness, pulmonary metastasis and poor prognosis. Overexpressing ARHGEF37 significantly enhanced the extravasation and metastatic capability of HCC cells via facilitating tumor cell adhesion to endothelial cells and trans-endothelial migration. Mechanistically, ARHGEF37 directly interacted with and activated Cdc42 to promote the invadopodia formation in HCC cells, which consequently disrupted the interaction between endothelial cells and pericytes. Importantly, treatment with ZCL278, a specific inhibitor of Cdc42, dramatically inhibited the attachment of ARHGEF37-overexpressing HCC cells to endothelial cells, and the adherence and extravasation in the lung alveoli, resulting in suppression of lung metastasis in mice. CONCLUSION: Our findings provide a new insight into the underlying mechanisms on the ARHGEF37 overexpression-mediated extravasation and pulmonary metastasis of HCC cells, and provided a potential therapeutic target for the prevention and treatment of HCC pulmonary metastasis.

Effect of rock salt aerosol therapy on quality of life of patients with pneumoconiosis: A multicenter, randomized, double-blind clinical trial.

This study aimed to explore the impact of rock salt aerosol therapy on the quality of life in pneumoconiosis patients. It may provide new treatment method for the comprehensive control of pneumoconiosis. A total of 452 subjects from 6 hospitals were divided based on the multi-level hierarchical random design. The patients in the treatment group received conventional comprehensive treatment + rock salt aerosol therapy. The baseline data were collected, including gender, age, age of dust exposure, stage and COPD combination. Cough, expectoration and dyspnea levels were valuated. Both of the two methods exhibited good curative effect following time extension. Rock salt aerosol therapy showed more significant effect compared with routine method. The clinical symptom tends to be stable after two weeks treatment of rock salt aerosol therapy. The curative effect increases with the extension of treatment time. 2-4 weeks for one course of treatment can improve the curative effect. Rock salt aerosol therapy can effectively improve the quality of life of pneumoconiosis patients. It is a good treatment and rehabilitation method for the prevention and treatment of pneumoconiosis, thus is worthy of clinical application.

Specific Regulation of m6A by SRSF7 Promotes the Progression of Glioblastoma.

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N6-methyladenosine (m6A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m6A methylation. We then indicate that SRSF7 is a novel m6A regulator, which specifically facilitates the m6A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m6A methyltransferase. The two m6A sites on PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m6A and validates the presence and functional importance of temporal- and spatial-specific regulation of m6A mediated by RNA-binding proteins (RBPs).

Association of Apoptosis-Mediated CD4+ T Lymphopenia With Poor Outcome After Type A Aortic Dissection Surgery.

Background: Many patients with type A aortic dissection (AAD) show low lymphocyte counts pre-operatively. The present study investigated the prognostic values of lymphopenia and lymphocyte subsets for the postoperative major adverse events (MAEs) in AAD patients undergoing surgery, and explore mechanisms of lymphopenia. Methods: We retrospectively analyzed pre-operative lymphocyte counts in 295 AAD patients treated at two hospitals, and evaluated their correlation with MAEs. We prospectively recruited 40 AAD patients and 20 sex- and age-matched healthy donors (HDs), and evaluated lymphocyte subsets, apoptosis, and pyroptosis by flow cytometry. Results: Multivariable regression analysis of the retrospective cohort revealed pre-operative lymphopenia as a strong predictor of MAEs (odds ratio, 4.152; 95% CI, 2.434-7.081; p < 0.001). In the prospective cohort, lymphocyte depletion in the AAD group was mainly due to loss of CD4+ and CD8+ T cells as compared with HDs (CD4+ T cells: 346.7 ± 183.6 vs. 659.0 ± 214.6 cells/µl, p < 0.0001; CD8+ T cells: 219.5 ± 178.4 vs. 354.4 ± 121.8 cells/µl, p = 0.0036). The apoptosis rates of CD4+ and CD8+ T cells were significantly higher in AAD patients relative to HDs (both p < 0.0001). Furthermore, the pre-operative CD4+ T cells count at a cut-off value of 357.96 cells/µl was an effective and reliable predictor of MAEs (area under ROC curve = 0.817; 95% CI, 0.684-0.950; sensitivity, 74%; specificity, 81%; p < 0.005). Pre-operative lymphopenia, mainly due to CD4+ T cells exhaustion by apoptosis, correlates with poor prognosis in AAD patients undergoing surgery. Conclusion: Pre-operative lymphopenia in particular CD4+ T lymphopenia via apoptosis correlates with poor prognosis in AAD patients undergoing surgery.

Admission Systolic Blood Pressure Predicts Post-Operative Delirium of Acute Aortic Dissection Patients in the Intensive Care Unit.

PURPOSE: Post-operative delirium (POD) is a common complication after aortic surgery with poor outcomes. Blood pressure may play a role in the occurrence of POD. The study aimed to identify whether admission systolic blood pressure (SBP) level in the intensive care unit (ICU) is correlated with POD in acute Stanford type A aortic dissection (AAAD) patients undergoing aortic surgery. PATIENTS AND METHODS: We conducted a single-center retrospective cohort study enrolling consecutive 205 patients with acute type A aortic dissection undergoing aortic surgery. Patients were divided into 3 groups: low, normal, and high SBP level group. Outcomes of interest were POD, 30-day mortality and other complications including acute kidney injury, cardiac complications, spinal cord ischemia, stroke, and pneumonia. Confusion Assessment Method for Intensive Care Unit (CAM-ICU) method was used to assess POD. Univariate and multivariate logistic regression, Cox regression, and subgroup analysis were performed to uncover the association between SBP and POD. RESULTS: The mean age of these patients was 51±16 years old. Thirty-six patients (17.6%) developed POD. Patients with high admission SBP were more likely to develop POD (P < 0.01). Univariate analysis showed that high admission SBP was associated with a higher risk of POD among AAAD patients (OR, 3.514; 95% CI, 1.478-8.537, P < 0.01). Multivariate logistic regression model confirmed that high SBP was an independent predictor of POD. Subgroup analysis indicated that patients with anemia and high admission SBP were at higher risk of POD. CONCLUSION: High admission SBP was positively associated with the incidence of POD in AAAD patients who underwent surgical repair in ICU.

The safety and feasibility of the screening for retinopathy of prematurity assisted by telemedicine network during COVID-19 pandemic in Wuhan, China.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) epidemic, due to the traffic blockade and the shortage of medical resources, more and more premature infants could not receive timely and effective ROP screening, which delayed treatment and even caused children blindness. Therefore, how to carry out ROP screening safely and effectively during the epidemic was very important and urgent. This study aimed to evaluate the safety and feasibility of ROP screening assisted by telemedicine network during COVID-19 outbreak. METHODS: This retrospective study was conducted at Wuhan Children's hospital in Wuhan, China, from January to October, 2020. The measures which were performed to make the ROP screening more safe and effective were summarized and the comparison between ROP screening assisted by telemedicine network in 2020 and usual screening in 2019 were analyzed. RESULTS: A total of 267 outpatient infants completed ROP screening. The median gestational age was 32 weeks (30w to 34w) and the median birth weight was 1780 g (1460 g to 2100 g). Meanwhile, 149 (55.8%) out of 267 infants were males. During January to May in 2020, 86 screening appointments were received, among which 67 (77.9%) were from telemedicine platform online. The completing percentage of total online ROP appointments was higher than that of total face-to-face appointments (58.1% VS 22. 1%, P = 0.018). As for the number of infants screened between 2020 and 2019 from Februaryto October, 54 infants completed ROP screening in 2020, which was higher than that (51participants) in 2019 on September. Furthermore, compared with the usual screening in 2019, ROP screening assisted by telemedicine network in 2020 had smaller gestational age (32w VS 33w, p<0.001) and lower birth weight (1780 g VS 1900 g, p = 0.001). However, of the 267 infants screened, 18(6.7%) had ROP while the percentage of ROP screened in 2019 was the same (44[6.7%]). During follow-up, none of medical staffs was infected and no adverse reaction was reported. CONCLUSIONS: The screening for retinopathy of prematurity assisted by telemedicine network was safe and feasible during the COVID-19 pandemic. Preventive measures before and after screening were very necessary, which could effectively avoid cross infection.

Treatment of thoracoabdominal aortic aneurysm by prosthetic vessel replacement under left heart bypass. / å·¦å¿ƒè½¬æµä¸‹äººå·¥è¡€ç®¡ç½®æ¢æœ¯æ²»ç–—èƒ¸è ¹ä¸»åŠ¨è„‰ç˜¤.

OBJECTIVES: Thoracoabdominal aortic aneurysm (TAAA) prosthetic vessel replacement is one of the most complex operations in the field of cardiovascular surgery. The key to success of this operation is to prevent and avoid ischemia of important organs while repairing TAAA. This study aims to summarize and analyze the effect of prosthetic vessel replacement under left heart bypass in the treatment of TAAA. METHODS: Data of 15 patients with TAAA who underwent prosthetic vessel replacement under left heart bypass in Xiangya Hospital of Central South University were retrospectively analyzed. According to Crawford classification, there were 2 cases of type I, 8 cases of type II, 3 cases of type III, and 2 cases of type V. There were 14 cases of selective operation and 1 case of emergency operation. All operations were performed under left heart bypass, and cerebrospinal fluid drainage was performed before operation. Left heart bypass was established by intubation of left inferior pulmonary vein and distal abdominal aorta or left femoral artery. The thoracoabdominal aorta was replaced segment by segment. After aortic dissection, the kidneys were perfused with cold crystalloid renal protective solution, and the celiac trunk and superior mesenteric artery were perfused with warm blood. RESULTS: One patient with TAAA after aortic dissection of type A died. During the operation, straight blood vessels were used to repair TAAA, and the celiac artery branches were trimmed into island shape and anastomosed with prosthetic vessels. After the operation, massive bleeding occurred at the anastomotic stoma, then anaphylactic reaction occurred during massive blood transfusion, resulting in death. One patient suffered from paraplegia due to ischemic injury of spinal cord. The other patients recovered well and were discharged. The postoperative ventilation time was (16.5±13.8) h and the postoperative hospital stay was (10±4) d. The amount of red blood cell transfusion was (13±9) U. The patients were followed up for 2 months to 2 years, and the recovery was satisfactory. CONCLUSIONS: The effect of prosthetic vessel replacement under left heart bypass in the treatment of TAAA is good, which is worthy of clinical promotion.

Clinical features and follow-up of pediatric patients hospitalized for COVID-19.

OBJECTIVE: This report summarizes the clinical features and 1-month follow-up observations for pediatric patients who were hospitalized with coronavirus disease 2019 (COVID-19) in Wuhan Women and Children's Hospital. METHODS: The 1-month follow-up data included clinical manifestations and results from serum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG and IgM tests, reverse-transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2, lung computed tomography (CT) scans, and laboratory tests. RESULTS: Between January 20 and March 15, 2020, 127 patients aged 0-15 years were hospitalized for COVID-19 treatment, including 3 severe cases and 124 mild or moderate cases. The main therapies included inhalation of aerosolized interferon-α (122/127) and additional antiviral drugs (28/127). Among the 81 patients who had pneumonia at admission, 35 with right lobe pneumonia had the longest hospital stay (mean 14.5 ± 7 days); 17 with left lobe pneumonia had the highest creatine kinase (154 ± 106 U/L) and creatine kinase myocardial band  (CK-MB, 43 ± 48 U/L) levels; and 29 with bilateral pneumonia had the highest white blood cell counts (8.3 ± 4 × 109 /L). Among the 46 patients who were successfully followed up 1 month after discharge, two notable findings were right lobe pneumonia in 22% (95% confidence interval [CI]: 11%-37%) of patients and persistently elevated serum creatine kinase and CK-MB levels. The median duration of elevated CK-MB was 45 days. The mean concentrations of serum SARS-CoV-2 IgG and IgM in 41 patients were 8.0 ± 7.5 and 98 ± 40 ng/ml, respectively. At follow-up, four patients retested positive for SARS-CoV-2. CONCLUSIONS: The involvement of different lung lobes in patients with COVID-19 was associated with variations in the persistence of pneumonia and elevation of CK-MB levels and body temperature.

Be aware of acute kidney injury in critically ill children with COVID-19.

BACKGROUND: Acute kidney injury (AKI) is a common complication of critically ill adult patients with COVID-19. However, currently, no studies investigate kidney impairment in children with COVID-19. We investigated incidence and treatment of AKI in pediatric patients with COVID-19 in Wuhan Children's Hospital during the early stages of the COVID-19 pandemic and discuss possible mechanisms of AKI related to SARS-CoV-2 infection. METHODS: By extracting data from electronic medical records, we conducted a retrospective observational study of kidney involvement in confirmed pediatric COVID-19 cases in Wuhan Children's Hospital during the coronavirus outbreak, from January 24 to March 20, 2020. Clinical presentations, clinical courses, laboratory findings, and medical interventions are described below. RESULTS: Among 238 confirmed COVID-19 cases, only three were critically ill and needed intensive care unit (ICU) admission. All three developed AKI, but AKI was not detected in any non-critically ill patients outside the ICU. Two of the three patients with AKI had prodromal gastrointestinal symptoms. Significantly elevated interleukin-6 (IL-6) levels and complement activation were observed in these patients with AKI. The three patients with AKI were treated with plasma exchange (PE) and continuous kidney replacement therapy (CKRT), resulting in one complete recovery, one partial recovery, and one mortality due to critical illness. CONCLUSIONS: Critically ill children with COVID-19 may develop AKI, especially following prodromal gastrointestinal symptoms. An inflammatory storm and complement-mediated injury may underlie AKI development in children with COVID-19. Our study supports implantation of PE and CKRT in management of critically ill patients with AKI.

Updated diagnosis, treatment and prevention of COVID-19 in children: experts' consensus statement (condensed version of the second edition).

In the early February, 2020, we called up an experts' committee with more than 30 Chinese experts from 11 national medical academic organizations to formulate the first edition of consensus statement on diagnosis, treatment and prevention of coronavirus disease 2019 (COVID-19) in children, which has been published in this journal. With accumulated experiences in the diagnosis and treatment of COVID-19 in children, we have updated the consensus statement and released the second edition recently. The current version in English is a condensed version of the second edition of consensus statement on diagnosis, treatment and prevention of COVID-19 in children. In the current version, diagnosis and treatement criteria have been optimized, and early identification of severe and critical cases is highlighted. The early warning indicators for severe pediatric cases have been summarized which is utmost important for clinical practice. This version of experts consensus will be valuable for better prevention, diagnosis and treatment of COVID-19 in children worldwide.

C allele of -786 T>C polymorphism in the promoter region of endothelial nitric oxide synthase is responsible for endothelial dysfunction in the patients with rheumatoid arthritis.

BACKGROUND: This study aimed to explore the roles of endothelial nitric oxide synthase (eNOS) in the control of metastasis of infection with endothelial dysfunction, as well as the roles of -786T>C polymorphism in eNOS promoter in the control of metastasis of endothelial function. METHOD: In-silicon analysis and luciferase assay were used to identify the location of -786>C on the promoter of eNOS. Subsequently, real-time PCR and Western-blot were used to determine the expression level of eNOS. Ultrasound examination was used to detect baseline brachial artery diameter and flow-mediated dilation of patients in different treat groups. RESULTS: -786T>C was located on the promoter of eNOS, and the luciferase activity of cells transfected with -786-C allele was much higher than empty vector, while even higher subsequent to transfection of -786-T allele. In addition, the result of ultrasound examination showed that the baseline brachial artery diameter was comparable between patients genotyped as TT, TC and CC, while the flow-mediated dilation of patients genotyped as TC was much higher compared with CC group, and the flow-mediated dilation of patients genotyped as TT even higher than TC group. We found eNOS messenger RNA and protein with TT genotype was significantly higher compared with other genotypes. And the production of NO was remarkably higher in TT groups compared with TC and CC, while the production of NO in TC and CC groups were similar. CONCLUSION: These findings indicated that down-expression of -786T>C located on the promoter of eNOS is associated with an increased risk of endothelial dysfunction.

Genomic analysis of lncRNA and mRNA profiles in circulating exosomes of patients with rheumatic heart disease.

Rheumatic heart disease (RHD) remains one of the most common cardiovascular conditions in developing countries. Accumulating evidence suggests that circulating exosomes and their cargoes, including mRNA and long noncoding RNA (lncRNA), play essential roles in many cardiovascular diseases. However, their specific roles in RHD remain unexplored. In the present study, we identified 231 lncRNAs and 179 mRNAs differentially expressed in the circulating exosomes harvested from RHD patients compared to healthy controls. We performed gene ontology (GO) and KEGG pathway analysis, and identified five pairs of lncRNAs and their flanking coding genes simultaneously dysregulated in the circulating exosomes. Collectively, we provide the first transcriptome analysis identifying differentially expressed lncRNAs and mRNAs in circulating exosomes of RHD patients, which may bring valuable insights for the discovery of potential biomarkers and therapeutic targets for RHD.

LncRNA-H19 acts as a ceRNA to regulate HE4 expression by sponging miR-140 in human umbilical vein endothelial cells under hyperglycemia with or without α-Mangostin.

α-Mangostin play crucial role in several cellular progress, including hyperglycemia-induced inhibition of cell growth and promotion of cell apoptosis. Increasing evidence displayed the important roles of lncRNAs and their potential as novel targets for drug development in human disease. However, there is rare study to comprehensively and systematically explore the role and underlying mechanism of lncRNAs in human umbilical vein endothelial cells (HUVECs) under hyperglycemia with or without α-Mangostin. In this study, we firstly found that α-Mangostin reduced the high glucose-induced inhibition of cell proliferation and migration potential of HUVECs. Then, we performed RNA-seq to dissect the expression profiles of lncRNAs in HUVECs treated with high glucose or high glucose supplemented with α-Mangostin. The results showed that the expression of H19 and HE4 was down-regulated by high glucose and further, α-Mangostin restored the high glucose-induced inhibition of H19 and HE4 expression. Further examination demonstrated that the modulation of the H19 and HE4 expression affected the function of α-Mangostin in hyperglycemia. In addition, H19 regulated HE4 expression via the modulation of the miR-140 expression. Finally, we showed that H19 exerted its function via the modulation of H19/miR-140/HE4 in hyperglycemia with α-Mangostin. In summary, this study is the first to comprehensively identify the lncRNAs/mRNAs network in hyperglycemia with or without α-Mangostin, highlighting a novel regulatory pathway in hyperglycemia with or without α-Mangostin and indicating the potential therapeutic role of α-Mangostin in diabetes mellitus.