Intranasal delivery of small extracellular vesicles from specific subpopulation of mesenchymal stem cells mitigates traumatic spinal cord injury.

Vascular injury following spinal cord injury (SCI) can significantly exacerbate secondary SCI and result in neurological dysfunction. Strategies targeting angiogenesis have demonstrated potential in enhancing functional recovery post-SCI. In the context of angiogenesis, the CD146+ and CD271+ subpopulations of mesenchymal stem cells (MSCs) have been recognized for their angiogenic capabilities in tissue repair. Small extracellular vesicles (sEVs) derived from MSCs are nanoscale vesicles containing rich bioactive components that play a crucial role in tissue regeneration. However, the precise role of sEVs derived from CD146+CD271+ UCMSCs (CD146+CD271+ UCMSC-sEVs) in SCI remain unclear. In this study, CD146+CD271+ UCMSC-sEVs were non-invasively administered via intranasal delivery, demonstrating a significant capacity to stimulate angiogenesis and improve functional recovery in mice following SCI. Furthermore, in vitro assessments revealed the effective enhancement of migration and tube formation capabilities of the murine brain microvascular endothelial cell line (bEnd.3) by CD146+CD271+UCMSC-sEVs. MicroRNA array analysis confirmed significant enrichment of multiple microRNAs within CD146+CD271+ UCMSC-sEVs. Subsequent in vivo and in vitro experiments demonstrated that CD146+CD271+ UCMSC-sEVs promote enhanced angiogenesis and improved functional recovery mediated by miR-27a-3p. Further mechanistic studies revealed that miR-27a-3p sourced from CD146+CD271+ UCMSC-sEVs enhances migration and tube formation of bEnd.3 cells in vitro by suppressing the expression of Delta Like Canonical Notch Ligand 4 (DLL4), thereby promoting angiogenesis in vivo. Collectively, our results demonstrate that a crucial role of CD146+CD271+ UCMSC-sEVs in inhibiting DLL4 through the transfer of miR-27a-3p, which leads to the promotion of angiogenesis and improved functional recovery after SCI.

Exosomes derived from CD271+CD56+ bone marrow mesenchymal stem cell subpopoulation identified by single-cell RNA sequencing promote axon regeneration after spinal cord injury.

Rationale: Spinal cord injury (SCI) results in neural tissue damage. However, the limited regenerative capacity of adult mammals' axons upon SCI leads to persistent neurological dysfunction. Thus, exploring the pathways that can enhance axon regeneration in injured spinal cord is of great significance. Methods: Through the utilization of single-cell RNA sequencing in this research, a distinct subpopulation of bone marrow mesenchymal stem cells (BMSCs) that exhibits the capacity to facilitate axon regeneration has been discovered. Subsequently, the CD271+CD56+ BMSCs subpopulation was isolated using flow cytometry, and the exosomes derived from this subpopulation (CD271+CD56+ BMSC-Exos) were extracted and incorporated into a hydrogel to create a sustained release system. The aim was to investigate the therapeutic effects of CD271+CD56+ BMSC-Exos and elucidate the underlying mechanisms involved in promoting axon regeneration and neural function recovery. Results: The findings indicate that CD271+CD56+ BMSC-Exos share similar physical and chemical properties with conventional exosomes. Importantly, in an SCI model, in situ implantation of CD271+CD56+ BMSC-Exos hydrogel resulted in increased expression of NF and synaptophysin, markers associated with axon regeneration and synapse formation, respectively. This intervention also contributed to improved neural function recovery. In vitro experiments demonstrated that CD271+CD56+ BMSC-Exos treatment significantly enhanced axon extension distance and increased the number of branches in dorsal root ganglion axons. Moreover, further investigation into the molecular mechanisms underlying CD271+CD56+ BMSC-Exos-mediated axon regeneration revealed the crucial involvement of the miR-431-3p/RGMA axis. Conclusion: In summary, the implantation of CD271+CD56+ BMSC-Exos hydrogel presents a promising and effective therapeutic approach for SCI.

Clinical Features, Diagnosis, and Treatment of Congenital and Neonatal Tuberculosis: A Retrospective Study.

INTRODUCTION: Limited studies have explored the clinical features, treatment, and prognosis of neonatal tuberculosis (TB). Here, we attempted to delineate the clinical characteristics of neonatal TB, which may help clinicians further understand this disease. METHODS: A retrospective analysis of neonates diagnosed with congenital and/or neonatal TB disease from January 2010 to December 2020 was performed. Information on the demographic and epidemiological features, clinical symptoms, laboratory and imaging examinations, therapeutic regimens, and outcomes was collected. Kaplan-Meier analysis was used to present the time to disease onset, time to diagnosis, etc. Results: Forty-eight cases of neonatal TB were classified into congenital (n = 33) and postnatal (n = 15). The median time to disease onset in postnatal group was significantly longer than that in congenital group. Positive results for gastric fluid acid-fast bacilli, TB culture, Xpert MTB/RIF, interferon-γ release assay (IGRA), and tuberculin skin test were detected in 26/48 (54.2%), 14/34 (41.2%), 11/18 (61.1%), 19/29 (65.5%), and 8/24 (33.3%) patients, respectively. For lymphadenopathy, computed tomography (CT) scans showed a higher detection rate than did X-ray (80.0% vs. 0). Of the 48 infants, 44/48 (91.7%) received anti-TB therapy, and 33/44 (75%) were clinically improved or cured after 22.1 months (interquartile range: 12.4-27.7) of follow-up. Drug-induced liver injury occurred in 14/44 (31.8%) patients. DISCUSSION/CONCLUSION: IGRA and Xpert MTB/RIF showed good positive rate in neonatal TB infection/disease. In cases where TB is presumed but etiological evidence is lacking, low-dose CT could be considered. Prompt treatment under careful surveillance is important for preventing mortality and avoiding severe adverse effects.

Targeted Delivery of RGD-CD146+CD271+ Human Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Promotes Blood-Spinal Cord Barrier Repair after Spinal Cord Injury.

Spinal cord injury (SCI) disrupts the blood-spinal cord barrier (BSCB), potentially exacerbating nerve damage and emphasizing the criticality of preserving the BSCB integrity during SCI treatment. This study explores an alternative therapeutic approach for SCI by identifying a subpopulation of exosomes with stable BSCB function and achieving a specific targeted delivery. Specific subpopulations of CD146+CD271+ umbilical cord mesenchymal stem cells (UCMSCs) were isolated, from which engineered exosomes (RGD-CD146+CD271+ UCMSC-Exos) with targeted neovascularization function were obtained through gene transfection. In vivo and in vitro experiments were performed to explore the targeting and therapeutic effects of RGD-CD146+CD271+ UCMSC-Exos and the potential mechanisms underlying BSCB stabilization and neural function recovery. The results demonstrated that RGD-CD146+CD271+ UCMSC-Exos exhibited physical and chemical properties similar to those of regular exosomes. Notably, following intranasal administration, RGD-CD146+CD271+ UCMSC-Exos exhibited enhanced aggregation at the SCI center and demonstrated the specific targeting of neovascular endothelial cells. In the SCI model, intranasal administration of RGD-CD146+CD271+ UCMSC-Exos reduced Evans blue dye leakage, increased tight junction protein expression, and improved neurological function recovery. In vitro testing revealed that RGD-CD146+CD271+ UCMSC-Exos treatment significantly reduced the permeability of bEnd.3 cells subjected to oxygen-glucose deprivation, thereby restoring the integrity of tight junctions. Moreover, further exploration of the molecular mechanism underlying BSCB stabilization by CD146+CD271+ UCMSC-Exos identified the crucial role of the miR-501-5p/MLCK axis in this process. In conclusion, targeted delivery of RGD-CD146+CD271+ UCMSC-Exos presents a promising and effective treatment option for SCI.

Growth and anemia among children with tuberculosis infection at different sites in Southwest China.

Objectives: To explore the effects of tuberculosis (TB) infection at different sites on anthropometric indicators, malnutrition and anemia incidence in children in Southwest China. Methods: From January 2012 to December 2021, a total of 368 children aged 1 month to 16 years were enrolled. According to the sites of TB infection, they were divided into three groups: tuberculous meningitis (T group), tuberculous meningitis complicated withpulmonary tuberculosis (TP group), and tuberculous meningitis complicated with pulmonary tuberculosis and abdominal tuberculosis (TPA group). Data on weight, height, nutritional risk, blood biochemical indicators and basic descriptions were collected within 48 h after admission. Results: The body mass index-for-age z score (BAZ), height-for-age z score (HAZ), and concentrations of hemoglobin (Hb) and albumin (ALB) decreased in the following order: T group, TP group, and TPA group. The prevalence of malnutrition was the highest in the TPA group (69.5%, 82/118) and 10-to 16-year-old group (72.4%, 63/87). Children aged 0.5-2 years exhibited the highest anemia prevalence of 70.6% (48/68) among the four age groups.The TPA group had the highest incidence of anemia (70.5%, 67/95) compared to T group and TP group.Compared with the treatment group, the abandonment group had a lower BAZ, HAZ and levels of HB and ALB, a higher rate of severe malnutrition, and higher nutritional risk scores. Children who had a low BAZ [odds ratio (OR) = 1.98], nutritional risk (OR = 0.56) and anemia (OR = 1.02) were less likely to obtain treatment with their guardians' support. Conclusions: Children with tuberculous meningitis were at risk for growth disorders and anemia, especially when complicated with pulmonary tuberculosis and abdominal tuberculosis. The prevalence of anemia and malnutrition was the highest among patients aged 1 month to 2 years and 10-16 years, respectively. Nutritional status was one of the causes of abandoning treatment.

Atrial cardiomyopathy markers predict ischemic cerebrovascular events independent of atrial fibrillation in patients with acute myocardial infarction.

Background: Contemporary data on atrial cardiomyopathy (ACM) markers and ischemic cerebrovascular events (ICVE) in patients with acute myocardial infarction (AMI) is lacking. We aimed to examine whether ACM markers predict ICVE among AMI patients. Materials and methods: A total of 4,206 AMI cases diagnosed in clinical examinations between January 2016 and June 2021 were assessed for markers of ACM including B-type natriuretic peptide (BNP), P-wave terminal force in ECG lead V1 (PTFV1), and left atrium diameter (LAD). Left atrial enlargement (LAE) and abnormal PTFV1 were defined by previously published cut-off points. The primary outcome was incident ICVE composed of ischemic stroke (IS) and transient ischemic attack (TIA). Receiver operating curve analyses were used to compare the predictive performance of the CHA2DS2-VASc score combined with ACM markers to the CHA2DS2-VASc score alone. Results: During a median follow-up of 44.0 months, 229 (5.44%) ICVE occurred. Of these, 156 individuals developed IS and the remaining 73 cases were diagnosed with TIAs. The ICVE group showed larger PTFV1 and increased LAD as well as elevated BNP levels at baseline. In the multivariate analysis, we found significant associations with ICVE for PTFV1 (HR per 1,000 µV*ms, 1.143; 95% CI, 1.093-1.196), LAD (HR per millimeter, 1.148; 95% CI, 1.107-1.190), but not BNP after adjusting for known ICVE risk factors and interim atrial fibrillation (AF). The addition of abnormal PTFV1 and LAE improved the predictive accuracy of the CHA2DS2-VASc score with C-statistic increasing from 0.708 to 0.761 (p < 0.001). Conclusion: Atrial cardiomyopathy markers including PTFV1 and LAD were associated with incident ICVE independent of well-established risk factors and AF occurrence. The addition of ACM markers with CHA2DS2-VASc score may well discriminate individuals at high risk of ICVE in AMI patients.

Development and Validation of a Nomogram for Estimation of Left Atrial Thrombus or Spontaneous Echo Contrast Risk in Non-Valvular Atrial Fibrillation Patients with Low to Borderline CHA2DS2-VASc Score.

Purpose: Left atrial thrombus (LAT)/left atrial spontaneous echo contrast (LASEC) still exists in CHA2DS2-VASc score-defined low/borderline risk population. The purpose of this study is to explore the risk factors that associate with LAT/SEC and to create a nomogram to predict LAT/SEC risk in NVAF patients with low/borderline CHA2DS2-VASc scores. Patients and Methods: A total of 834 NVAF patients with complete data on transesophageal echocardiography (TEE) were included in this study. Univariate and multivariate logistic regression analyses were performed to identify the risk factors that associate with LAT/SEC, and a nomogram was established based on the results. Receiver operating characteristic curve (ROC), calibration curve and decision curve analysis were performed to verify the predictive power of nomogram. Results: The rates for LAT/SEC for the training and validation cohorts were 84 (14.7%) and 30 (11.4%), respectively. Independent factors including age, left ventricular ejection fraction (LVEF), left atrial diameter (LAD), smoke, non-paroxysmal AF (NPAF), and E/e' were considered to construct the nomogram for LAT/SEC. The AUC for nomogram was 0.839 and 0.811 in the training and validation cohorts, respectively. The calibration and decision curve analysis showed that the nomogram had a good prediction capacity and would be clinically useful. Conclusion: Age, LVEF, LAD, smoke, NPAF, and E/e' are independently associated with LAT/SEC in NVAF patients with low/borderline CHA2DS2-VASc scores. The nomogram that incorporates these six variables effectively predict LAT/SEC risk in NVAF patients with low/borderline CHA2DS2-VASc scores.

Atrial cardiomyopathy markers and new-onset atrial fibrillation risk in patients with acute myocardial infarction.

BACKGROUND: New-onset atrial fibrillation (NOAF) after acute myocardial infarction (AMI) is common and independently correlated with poor prognosis. The purpose of this study is to explore whether atrial cardiomyopathy (ACM) markers improve NOAF risk assessment and contribute to therapy decision-making to improve prognosis. METHODS: We retrospectively analyzed 4713 patients with AMI without a documented history of atrial fibrillation (AF). We measured markers of ACM including P-wave terminal force in ECG lead V1 (PTFV1), Left atrial dimension (LAD), and B-type natriuretic peptide (BNP). Patients were stratified into tertiles of PTFV1, LAD, and BNP levels. Associations between markers and NOAF were evaluated using logistic regression analysis. RESULTS: Overall, 222 (4.71%) patients had NOAF out of 4713 patients. The prevalence of NOAF increased gradually with PTFV1, LAD, and BNP tertiles. On multivariable regression analysis with potential confounders, elevated PTFV1, LAD, and BNP markers were significantly associated with an increased risk of NOAF. The addition of PTFV1, LAD, and BNP to the AF risk factors recommended by the 2020 ESC Guidelines significantly improved risk discrimination for NOAF. CONCLUSION: Atrial cardiomyopathy markers including PTFV1, LAD, and BNP were strongly associated with NOAF after AMI. The prediction performance of the clinical model for NOAF was increased by the addition of these markers.

Clinical features of Chinese children with COVID-19 and other viral respiratory infections.

OBJECTIVE: Few studies have explored the clinical features in children infected with SARS-CoV-2 and other common respiratory viruses, including respiratory syncytial virus (RSV), Influenza virus (IV), and adenovirus (ADV). Herein, we reported the clinical characteristics and cytokine profiling in children with COVID-19 or other acute respiratory tract infections (ARTI). METHODS: We enrolled 20 hospitalized children confirmed as COVID-19 positive, 58 patients with ARTI, and 20 age and sex-matched healthy children. The clinical information and blood test results were collected. A total of 27 cytokines and chemokines were measured and analyzed. RESULTS: The median age in the COVID-19 positive group was 14.5 years, which was higher than that of the ARTI groups. Around one-third of patients in the COVID-19 group experienced moderate fever, with a peak temperature of 38.27°C. None of the patients displayed wheezing or dyspnea. In addition, patients in the COVID-19 group had lower white blood cells, platelet counts as well as a neutrophil-lymphocyte ratio. Lower serum concentrations of 14 out of 27 cytokines were observed in the COVID-19 group than in healthy individuals. Seven cytokines (IL-1Ra, IL-1ß, IL-9, IL-10, TNF-α, MIP-1α, and VEGF) changed serum concentration in COVID-19 compared with other ARTI groups. CONCLUSION: Patients with COVID-19 were older and showed milder symptoms and a favorable prognosis than ARTI caused by RSV, IV, and ADV. There was a low grade or constrained innate immune reaction in children with mild COVID-19.

Nomogram to Predict Left Atrial Thrombus or Spontaneous Echo Contrast in Patients With Non-valvular Atrial Fibrillation.

Background: The predictive power of the CHADS2 and CHA2DS2-VASc scores for the presence of Left atrial thrombus (LAT)/ spontaneous echo contrast (SEC) in non-valvular atrial fibrillation (NVAF) is modest. The aim of this analysis is to define clinical and ultrasonic variables associated with LAT/SEC and to propose nomograms for individual risk prediction. Methods: Data on 1,813 consecutive NVAF patients who underwent transesophageal echocardiography (TEE) from January 2016 to January 2021 were collected. The univariate and multivariate logistic regression analyses were used to construct a nomogram. We examined the predictive ability of the risk scores by calculating the area under the curve (AUC). Moreover, the performance of the nomogram was assessed with respect to calibration, discrimination, and clinical usefulness. Results: LAT/SEC was found in 260 (21.0%) and 124 (21.6%) patients in the training and validation cohorts, respectively. On multivariate analysis, independent factors for LAT/SEC were Age, left atrial diameter (LAD), left ventricular ejection fraction (LVEF), hypertension (HTN), previous stroke or transient ischemic attack, Non-paroxysmal AF and a nomogram was built based on these variables. The calibration curve for the probability of LAT/SEC showed good prediction agreement with actual observation. The nomogram achieved good concordance indexes of 0.836 and 0.794 in predicting LAT/SEC in the training and validation cohorts, respectively. Decision curve analysis demonstrated that the nomogram would be clinically useful. Conclusions: In this study, a nomogram was constructed that incorporated six characteristics of NVAF patients. The nomogram may be of great value for the prediction of LAT/SEC in NVAF patients.

Analysis of Factors Influencing Multidrug-Resistant Tuberculosis and Validation of Whole-Genome Sequencing in Children with Drug-Resistant Tuberculosis.

OBJECTIVE: Pediatric tuberculosis (TB) is one of the top ten causes of death in children. Our study was to analyze influencing factors of multidrug-resistant tuberculosis (MDR-TB) and validation of whole-genome sequencing (WGS) used in children with drug-resistant TB (DR-TB). METHODS: All Mycobacterium tuberculosis (Mtb) strains were isolated from patients aged below 18 years old of Children's Hospital of Chongqing Medical University, China. A total of 208 Mtb isolates were tested for eight anti-TB drugs with phenotypic drug susceptibility test (DST) and for genetic prediction of the susceptible profile with WGS. The patients corresponding to each strain were grouped according to drug resistance and genotype. Influencing factors of MDR-TB and DR-TB were analyzed. RESULTS: According to the phenotypic DST and WGS, 82.2% of Mtb strains were susceptible to all eight drugs, and 6.3% were MDR-TB. Using the phenotypic DSTs as the gold standard, the kappa value of WGS to predict isoniazid, rifampin, ethambutol, rifapentine, prothionamide, levofloxacin, moxifloxacin and amikacin was 0.84, 0.89, 0.59, 0.86, 0.89, 0.82, 0.88 and 1.00, respectively. There was significant difference in the distribution of severe TB, diagnosis, treatment and outcome between MDR and drug-susceptible group (P<0.05). The distribution of severe TB and treatment between DR and drug-susceptible group was statistically different (P<0.05). The results of binary logistic regression showed that Calmette-Guérin bacillus (BCG) vaccine is the protective factor for MDR-TB (OR=0.19), and MDR-TB is the risk factor for PTB and EPTB (OR=17.98). CONCLUSION: The BCG vaccine is a protective factor for MDR-TB, and MDR-TB might not be confined to pulmonary infection, spreading to extrapulmonary organs in children. MDR-TB had more severe cases and a lower recovery rate than drug-susceptible TB. WGS could provide an accurate prediction of drug susceptibility test results for anti-TB drugs, which are needed for the diagnosis and precise treatment of TB in children.

[Clinical features of children with immunodeficiency and Mycobacterium tuberculosis infection].

OBJECTIVE: To study the clinical features of Mycobacterium tuberculosis infection in children with secondary immunodeficiency disease (SID) versus primary immunodeficiency disease (PID). METHODS: A retrospective analysis was performed on the medical data of children with immunodeficiency and Mycobacterium tuberculosis infection (36 children with SID and 52 with PID) and 108 children with Mycobacterium tuberculosis infection but without immunodeficiency (control group). RESULTS: The onset age in the PID group was significantly lower than those in the control and SID groups (P < 0.05), and the proportation of males in the PID group was significantly higher than those in the control and SID groups (P < 0.05). Compared with the control group, the SID and PID groups had significantly lower incidence rates of tuberculosis poisoning symptoms (night sweeting, weight loss, fatigue and loss of appetite) and positive rate of PPD test (P < 0.05), as well as a significantly higher incidence rate of the involvement of ≥ 3 pulmonary lobes (P < 0.05). The children with PID tended to have the involvement of multiple organs (P < 0.05). The SID group had a significantly higher incidence rate of miliary shadow on chest CT than the control and PID groups (P < 0.05). The PID group had a significantly lower positive rate of IFN-gamma release assay (IGRA) than the control and SID groups (P < 0.05). Mycobacterium tuberculosis infection manifested as latent tuberculosis infection (36.1%) and active tuberculosis (63.9%) in the SID group. The infection mainly manifested as bacille Calmette-Guérin disease in the PID group (90.4%), among whom 2 children (3.8%) also had tuberculosis. CONCLUSIONS: Children with immunodeficiency and Mycobacterium tuberculosis infection have atypical clinical symptoms, with a high incidence rate of disseminated infection and low positive rates of PPD and IGRA tests, which may lead to misdiagnosis and missed diagnosis. Children with immunodeficiency should undergo regular tuberculosis screening for early identification and intervention.

Diagnosis and treatment of herpangina: Chinese expert consensus.

BACKGROUND: Herpangina is a common infectious disease in childhood caused by an enterovirus. This consensus is aiming to standardize and improve herpangina prevention and clinical diagnosis. METHODS: The Subspecialty Group of Infectious Diseases, the Society of Pediatric, Chinese Medical Association and Nation Medical Quality Control Center for Infectious Diseases gathered 20 experts to develop the consensus, who are specialized in diagnosis and treatment of herpangina. RESULTS: The main pathogenic serotypes of herpangina include Coxsackievirus-A, Enterovirus-A and Echovirus. Its diagnosis can be rendered on the basis of history of epidemiology, typical symptoms, characteristic pharyngeal damage and virological tests. The treatment is mainly symptomatic, and incorporates topical oral spray with antiviral drugs. The course of herpangina generally lasts 4-6 days with a good prognosis. CONCLUSION: The consensus could provide advices and references for the diagnosis, treatment and management of herpangina in children.

Safety of longer linezolid regimen in children with drug-resistant tuberculosis and extensive tuberculosis in Southwest China.

OBJECTIVES: Linezolid (LNZ) has recently been listed by the World Health Organization (WHO) as a Group A agent for the treatment of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) in longer regimens (18-20 months). However, little is known about the safety of LNZ in longer TB treatment regimens in children. METHODS: Here we report 31 children who received LNZ treatment for drug-resistant tuberculosis (DR-TB) and extensive tuberculosis in the Children's Hospital of Chongqing Medical University, China, during September 2016 to March 2019. The mean duration of LNZ treatment was 8.56 months (range, 1-24 months). RESULTS: Of the 31 patients, 13 (42%) had suspected or confirmed adverse events (AEs) related to LNZ treatment, including digestive symptoms, haematological toxicity, neuropathy and lactic acidosis. Haematological toxicity was the most frequent AE, presenting as leukopenia (9/13) and anaemia (5/13). No hepatotoxicity or nephrotoxicity was observed. Two patients suffered from life-threatening lactic acidosis when the LNZ dose was increased to 1.2 g daily, however they recovered following LNZ withdrawal. CONCLUSION: A high rate of AEs of LNZ treatment was observed in children receiving a longer regimen, which might relate to the treatment course and dose. Haematological toxicity was the most frequent AE in children. It is necessary to regularly monitor the blood chemistry and lactic acid concentration during LNZ treatment.

Decellularized human liver scaffold-based three-dimensional culture system facilitate hepatitis B virus infection.

Hepatitis B virus (HBV) study is hampered by lacking of idea cell model which support effective HBV infection and meanwhile recapitulate hepatocyte biology function in vivo. In this study, we developed decellularized human liver scaffolds for cell culture and further applied for HBV infection. As a result, primary human hepatocytes (PHHs) engrafted into liver scaffolds and maintained differentiation with stable albumin secretion and liver-specific gene expression. Comparing to mono-layer cell culture, scaffold-based three-dimensional (3D) culture system significantly augment HBV DNA (including cccDNA), RNA level as well as HBsAg secretion. Moreover, HepG2-NTCP cells cultured on 3D system exhibited higher infection efficiency and longer infection period in vitro. In addition, HBV DNA level was suppressed when anti-HBV medicine Entecavir (ETV) introduced into HepG2-NTCP 3D system. Herein, we evaluated the potential of decellularized human liver scaffold-based in 3D cell culture and disclosed that scaffold-based 3D culture system can facilitate HBV infection in vitro. This 3D culture system could be further applied in HBV-related study. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1744-1753, 2019.

Natural killer/T-cell lymphoma with concomitant syndrome of inappropriate antidiuretic hormone secretion: A case report and review of literature.

We report a case of natural killer (NK)/T-cell lymphoma with concomitant syndrome of inappropriate antidiuretic hormone secretion (SIADH). The patient was a 64-year-old woman with a history of nasopharyngeal carcinoma of over 30 years. She was admitted with a chief complaint of intermittent fever for 2 mo. Palpation after admission indicated a swollen lymph node below the left jaw. Multiple imaging examinations on admission indicated multiple enlarged lymph nodes throughout the body. We performed a left submandibular lymph node biopsy, and the results revealed NK/T-cell lymphoma. A biochemical examination indicated Epstein-Barr virus positivity. At the same time, the patient developed hyponatremia. Based on her laboratory examination and clinical manifestation, decreased plasma osmolality, urine osmolality greater than plasma osmolality, lack of skin swelling, normal blood pressure, normal renal function, no adrenal function detected on serology, and no abnormalities in imaging examination of the adrenal glands, the likelihood of SIADH in the patient was high. After fluid restriction and administration of sodium chloride, the patient's blood sodium level gradually increased. Subsequently, the immune function of the patient declined, there were severe symptoms of infection, and she died of respiratory failure. NK/T-cell lymphoma associated with SIADH has not, to our knowledge, been previously reported in PubMed. This case emphasizes the importance of monitoring serum ion levels, especially serum sodium, in patients with NK/T-cell lymphoma.

FAM98A promotes proliferation of non-small cell lung cancer cells via the P38-ATF2 signaling pathway.

BACKGROUND: FAM98A, a novel protein, is expressed in ovarian and colorectal cancer tissues. However, the association between FAM98A expression and the clinicopathological characteristics of non-small cell lung cancer (NSCLC) remains undetermined. MATERIALS AND METHODS: The FAM98A expression pattern was determined in NSCLC samples and corresponding adjacent normal lung tissues using immunohistochemical staining and Western blotting. The association of FAM98A expression with clinicopathological characteristics was measured in 131 NSCLC samples. Finally, the overexpression and inhibition of FAM98A was performed in the A549 and SPC-A1 cell lines to explore its role in the development of lung cancer. RESULTS: Western blot analysis of 20 paired NSCLC samples showed that expression of FAM98A was higher in lung cancer tissues than in the corresponding adjacent normal lung tissues (p<0.05). Immunohistochemical staining of 128 NSCLC specimens showed that expression of FAM98A was significantly higher in lung cancer samples than in adjacent normal lung tissues (118/128 vs 10/128; p<0.001). Positive expression of FAM98A was significantly related to tumor TNM stage (p<0.05) and lymph node metastasis (p<0.001). Additionally, overexpression of FAM98A induced an increase in the expression of phosphorylated P38, phosphorylated ATF2, and cyclin D1, which promoted proliferation of lung cancer cells. Correspondingly, the effects of FAM98A overexpression were reversed by administration of a specific inhibitor of phosphorylated P38. CONCLUSION: FAM98A was overexpressed in the cytoplasm of NSCLC samples and correlated with advanced TNM staging and lymph node metastasis. Thus, FAM98A increases the expression of cyclin D1 by activating the P38-ATF2 signaling pathway and subsequently enhancing tumor cell proliferation; these results are promising and need further validation.

Risk factors for death in children with critical and severe hand-foot-and-mouth disease in Chongqing, China: An observational study.

Hand-foot-and-mouth disease (HFMD) is a common childhood infection that may lead to serious complications and even death. Globally, epidemics of HFMD are increasing each year, especially in China. This study aimed to identify risk factors for death in children with critical and severe HFMD in Chongqing, China.We performed an observational study involving patients with critical and severe HFMD admitted to the Children's Hospital of Chongqing Medical University from January 2009 to December 2016. Overall, 179 patients aged 2 months to 16 years, were included; 127 died (non-survival group) and 52 survived (survival group); the case-fatality rate was 70.94%. Data comprising demographic characteristics, clinical symptoms and signs, and laboratory findings were collected. Non-conditional logistic regression analysis was performed to determine the risk factors for death.Univariate analysis showed that sex, coma, light-reflex insensitivity, pulmonary rales, pulmonary edema or hemorrhage, cold extremities, tachycardia, hypotension, white blood cell count, blood glucose concentration, serum lactate level, creatine kinase-MB isoenzyme level, and acidosis were associated with death (P < .05). Logistic regression analysis identified female sex (odds ratio [OR] 9.6, 95% confidence interval [CI] 3.0-30.2), light-reflex insensitivity (OR 4.4, 95% CI 1.4-13.1), tachycardia (OR 1.05, 95% CI 1.03-1.07), and higher serum lactate levels (OR 1.14, 95% CI 1.19-1.69) as independent risk factors; and longer onset-to-hospitalization time (OR 0.43, 95% CI 0.28-0.66) as an independent protective factor for death in children with critical and severe HFMD.Female sex, light-reflex insensitivity, tachycardia, and higher serum lactate level are potential independent risk factors; and longer onset-to-hospitalization time is possibly an independent protective factor for death in patients with critical and severe HFMD.

[Human EV71 invades human neuroblastoma SK-N-SH cells by clathrin-mediated endocytosis].

Objective To study the mechanism ofhuman enterovirus 71 (EV71) entering human neuroblastoma SK-N-SH cells. Methods After the SK-N-SH cells were pretreated with chlorpromazine (CPZ) or nystatin (NT), real-time quantitative PCR (qRT-PCR) was employed to measure EV71 mRNA level, and indirect immunofluorescence microscopy was used to detect the expression level of viral protein 1 (VP1) in the target cells. In order to reveal the colocalization of EV71 with clathrin, laser confocal microscopy was performed on the infected cells. Results CPZ could significantly inhibit EV71 mRNA level and the expression of VP1 in the target cells, while NT had no effect on EV71 infection. Confocal microscopy showed that EV71 was colocalize with clathrin. Conclusion EV71 infects human neuroblastoma SK-N-SH cells by the clathrin-mediated endocytosis.

Effect of vitamin A and Zn supplementation on indices of vitamin A status, haemoglobin level and defecation of children with persistent diarrhea.

To investigate the effect of vitamin A and Zn supplementation on vitamin A status, haemoglobin level and defecation of children with persistent diarrhea, a total of 160 paediatric patients were randomly assigned to one of four intervention groups: daily supplementation of 1,500 IU VA for 14 days; daily Zn supplementation for 14 days; daily supplementation with both VA and Zn for 14 days; no supplementation. One hundred twenty-seven children with persistent diarrhea finished intervention (33 were lost to follow-up). Among the 127 children, 41 (32.28%) had anaemia, 104 (81.89%) had a VA deficiency and 38 (29.92%) had an iron insufficiency. Supplementation with VA or VA + Zn enhanced the serum VA levels and ameliorated anaemia. Supplementation with Zn and VA + Zn for 5 days significantly improved defecation, where the VA + Zn treatment resulted in superior outcomes. After 14 days of intervention, the total effectiveness rates were 93.94%, 96.77% and 96.67% in the three groups, significantly greater than that of the non-supplementation group (72.73%). These results indicate that single VA or concurrent VA + Zn supplementation can improve vitamin A status, haemoglobin level and defecation. However, concurrent VA + Zn supplementation is the optimal option and can shorten the duration of persistent diarrhea and markedly improve nutritional status. (www.clinicaltrials.gov registration number: ChiCTR-IOR-14005498).