Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

Objective: To investigate the functional changes of key gut microbiota (GM) that produce lipopolysaccharide (LPS) in atrial fibrillation (AF) patients and to explore their potential role in the pathogenesis of AF. Methods: This was a prospective cross-sectional study. Patients with AF admitted to Beijing Chaoyang Hospital of Capital Medical University were enrolled from March 2016 to December 2018. Subjects with matched genetic backgrounds undergoing physical examination during the same period were selected as controls. Clinical baseline data and fecal samples were collected. Bacterial DNA was extracted and metagenomic sequencing was performed by using Illumina Novaseq. Based on metagenomic data, the relative abundances of KEGG Orthology (KO), enzymatic genes and species that harbored enzymatic genes were acquired. The key features were selected via the least absolute shrinkage and selection operator (LASSO) analysis. The role of GM-derived LPS biosynthetic feature in the development of AF was assessed by receiver operating characteristic (ROC) curve, partial least squares structural equation modeling (PLS-SEM) and logistic regression analysis. Results: Fifty nonvalvular AF patients (mean age: 66.0 (57.0, 71.3), 32 males(64%)) were enrolled as AF group. Fifty individuals (mean age 55.0 (50.5, 57.5), 41 males(82%)) were recruited as controls. Compared with the controls, AF patients showed a marked difference in the GM genes underlying LPS-biosynthesis, including 20 potential LPS-synthesis KO, 7 LPS-biosynthesis enzymatic genes and 89 species that were assigned as taxa harbored nine LPS-enzymatic genes. LASSO regression analysis showed that 5 KO, 3 enzymatic genes and 9 species could be selected to construct the KO, enzyme and species scoring system. Genes enriched in AF group included 2 KO (K02851 and K00972), 3 enzymatic genes (LpxH, LpxC and LpxK) and 7 species (Intestinibacter bartlettii、Ruminococcus sp. JC304、Coprococcus catus、uncultured Eubacterium sp.、Eubacterium sp. CAG:251、Anaerostipes hadrus、Dorea longicatena). ROC curve analysis revealed the predictive capacity of differential GM-derived LPS signatures to distinguish AF patients in terms of above KO, enzymatic and species scores: area under curve (AUC)=0.957, 95%CI: 0.918-0.995, AUC=0.940, 95%CI 0.889-0.991, AUC=0.972, 95%CI 0.948-0.997. PLS-SEM showed that changes in lipopolysaccharide-producing bacteria could be involved in the pathogenesis of AF. The key KO mediated 35.17% of the total effect of key bacteria on AF. After incorporating the clinical factors of AF, the KO score was positively associated with the significantly increased risk of AF (OR<0.001, 95%CI:<0.001-0.021, P<0.001). Conclusion: Microbes involved in LPS synthesis are enriched in the gut of AF patients, accompanied with up-regulated LPS synthesis function by encoding the LPS-enzymatic biosynthesis gene.
Aged ; Atrial Fibrillation/complications* ; Cross-Sectional Studies ; Gastrointestinal Microbiome ; Humans ; Lipopolysaccharides ; Male ; Middle Aged ; Prospective Studies

Objective: To analyze the genetic landscape of 52 fusion genes in patients with de novo acute lymphoblastic leukemia (ALL) and to investigate the characteristics of other laboratory results. Methods: The fusion gene expression was retrospectively analyzed in the 1 994 patients with de novo ALL diagnosed from September 2016 to December 2020. In addition, their mutational, immunophenotypical and karyotypical profiles were investigated. Results: In the 1 994 patients with ALL, the median age was 12 years (from 15 days to 89 years). In the panel of targeted genes, 15 different types of fusion genes were detected in 884 patients (44.33%) and demonstrated a Power law distribution. The frequency of detectable fusion genes in B-cell ALL was significantly higher than that in T-cell ALL (48.48% vs 18.71%), and fusion genes were almost exclusively expressed in B-cell ALL or T-cell ALL. The number of fusion genes showed peaks at<1 year, 3-5 years and 35-44 years, respectively. More fusion genes were identified in children than in adults. MLL-FG was most frequently seen in infants and TEL-AML1 was most commonly seen in children, while BCR-ABL1 was dominant in adults. The majority of fusion gene mutations involved signaling pathway and the most frequent mutations were observed in NRAS and KRAS genes. The expression of early-stage B-cell antigens varied in B-cell ALL patients. The complex karyotypes were more common in BCR-ABL1 positive patients than others. Conclusion: The distribution of fusion genes in ALL patients differs by ages and cell lineages. It also corresponds to various gene mutations, immunophenotypes, and karyotypes.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Gene Expression ; Genes, ras ; Humans ; Infant ; Infant, Newborn ; Middle Aged ; Oncogene Fusion ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism* ; Retrospective Studies ; Young Adult

Objective: Currently, the Overlap anastomosis is one of the most favored reconstruction methods of intracorporeal esophagojejunostomy (EJS). Despite many advantages of the method, it remains some shortcomings to be improved when it comes to the retraction of the esophagus stump, the insertion of the anvil fork of the linear stapler into a "pseudo" lumen, and the closure of the common entry hole. This study aims to investigate the safety and feasibility of a multi-mode modified Overlap anastomosis. Methods: A descriptive case series study was conducted. Medical records of 152 consecutive patients who underwent totally laparoscopic total gastrectomy (TLTG) with our multi-mode modified Overlap EJS method by the same surgical team at our department from February 2017 to June 2020 were retrospectively analyzed. The multi-mode modified Overlap method mainly included (1) After ensuring the safety of tumor resection margin (proximal margin was at least 3 cm from the tumor), the esophagus was partially transected from left to right (with 5-8 mm width esophagus continuation). The specimen was then placed in a plastic bag which was tied up at the mouth using strings with a part of the esophageal wall poking through. Then the plastic bag containing the specimen was transferred to the right lumbar region, while the patient's body position was adjusted so that the abdominal esophagus could be pulled by the gravity of the specimen. (2) Using the "three-direction traction" method. The esophageal lumen was properly exposed, then guided by the gastric tube, the anvil fork was accurately placed into the esophageal lumen for completing the side-to-side EJS. (3) The 3-0 barbed suture was used in the closure of the common entry hole of the stapler from dorsally to ventrally with simple one-layer continuous suture (the stitch going from inside to inside) followed by continuous Lembert's suture (the stitch going from outside to outside). Combined with clinicopathological characteristics, the perioperative outcomes and postoperative complications of the whole group were analyzed and evaluated. Results: The study cohort included 129 men and 23 women, with a mean age of (60.2±9.1) years and a mean body mass index (BMI) of (23.2±3.1) kg/m(2). Of the 152 patients, 23 patients (15.1%) had a history of previous abdominal surgery; dentate line was invaded by tumor in 21 patients (13.8%). The mean length of the proximal resection margin was (3.3±0.3) cm and the postoperative pathological examination indicated negative resection margin tumor. The mean operative time and anastomotic time were (302.1±39.9) minutes and (29.8±5.4) minutes, respectively. The mean estimated blood loss was (87.9±46.4) ml. The mean length of postoperative hospital stay was (12.3±7.3) days. The overall severe postoperative complications (Clavien-Dindo ≥ II) occurred in 22 patients (14.5%). Six cases of pancreatic leakage were successfully recovered by adequate drainage, inhibition of pancreatic exocrine secretion and nutritional support. Ten cases of pneumonia and three cases of abdominal infection were cured with anti-infection and physical therapy. Two patients developed anastomotic leakage postoperatively. One case was caused by excessive tension of the Roux loop of the jejunum and excessive opening on the side of the jejunum after side-to-side anastomosis, and the other case was caused by an accidental intraoperative occurrence of "nasogastric tube stapled to the side-to-side anastomosis". Both of them recovered after conservative treatment including adequate drainage, anti-infection, and adequate nutritional support. One patient underwent immediate open surgery because of Peterson's hernia 7 days after TLTG, and the patient died due to extensive small bowel necrosis. Conclusions: Multi-mode modified overlap method simplifies the operation and reduces the difficulty of EJS. It is a safe and feasible method for EJS.
Aged ; Anastomosis, Surgical/methods* ; Feasibility Studies ; Female ; Gastrectomy/methods* ; Humans ; Laparoscopy/methods* ; Male ; Margins of Excision ; Middle Aged ; Plastics ; Postoperative Complications/etiology* ; Retrospective Studies ; Stomach Neoplasms/pathology*

The Myh3 (myosin heavy chain 3) gene is a marker gene of muscle cell differentiation and regulates the utilization of energy in muscle cells, but whether it affects the glycolysis process of muscle cells in different states is rarely reported. In this paper, the expression patterns of Myh3 and glycolysis-related genes Pkm (M-type pyruvate kinse), Prkag3 (protein kinase adenosine monophosphate-activated γ3-subunit), and Gsk3β (glycogen synthase kinase-3β) were studied by the qRT-PCR (quantitative-Real-Time-PCR) method using C2C12 cells at different stages of myoblast and adipogenic differentiation as models. It was found that in the process of myoblast differentiation of C2C12 cells, the relative expression trends of Myh3 and glycolysis genes Prkag3 and Pkm were basically the same, and the relative expression levels first increased, reached the peak on the second day of differentiation, and then decreased; glycogen synthase the expression trend of the inhibitory gene Gsk3β was relatively stable. In the process of adipogenic differentiation of C2C12 cells, the relative expression trend of Myh3 and glycolysis genes Prkag3 and Pkm remained basically the same, and the relative expression gradually increased, reaching the highest value on the 8th day of differentiation; glycogen synthase inhibitory gene Gsk3β expression remained stable. In the myogenic differentiation state of C2C12 cells, qRT-PCR and Western blotting were used to detect the effects of interfering Myh3 on the mRNA and protein expressions of glycolysis-related genes Pkm, Prkag3, and Gsk3β. The results showed that after interfering with Myh3, the mRNA expressions of glycolysis genes Pkm and Prkag3 were significantly decreased (P<0.01), while the mRNA expression of glycogen synthase inhibitory gene Gsk3β had no significant change (P > 0.05). The protein levels of Myh3 and Pkm were significantly lower than those in the blank group and NC group. Under the adipogenic differentiation state of C2C12 cells, after interfering with Myh3, the mRNA levels of glycogen synthase inhibitor Gsk3β and glycolysis gene Prkag3 were significantly increased (P<0.01), and the mRNA level of glycolysis gene Pkm was decreased; the protein levels of Myh3 and Pkm in the Myh3 interference group were also lower than those in the blank group and NC group. Based on the above studies, there are significant differences in the levels of glycolysis in C2C12 cells in the myogenic and adipogenic states, and the expression patterns of Myh3 and glycolysis genes are similar. Further results showed that Myh3 suppression could inhibit the glycolysis of C2C12 cells in the myogenic state without affecting the glycogen synthesis. Unlike in the myogenic state, interfering expression of Myh3 in the adipogenic state of C2C12 cells inhibited both glycogen synthesis and glycolysis.

BACKGROUND: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults. METHODS: Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose. RESULTS: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses. CONCLUSIONS: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).
Adult ; COVID-19 ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; SARS-CoV-2 ; Vaccines, Inactivated/adverse effects*

Foreign Bodies/diagnostic imaging* ; Humans ; Maxillary Sinus/diagnostic imaging* ; Tomography, X-Ray Computed

Objective: To compare the value of 25-hydroxyvitamin D3 (25-(OH)D3) with other clinical parameters in the prediction and diagnosis of eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). Methods: Eligible chronic rhinosinusitis with nasal polyps (CRSwNP) patients and healthy subjects in the Affiliated Hospital of Guizhou Medical University from January to April of 2021 were included for this study. The age, gender, past history and other basic characteristics of all subjects were recorded. The CRSwNP patients were classified into ECRSwNP and non-eosinophilic chronic rhinosinusitis with nasal polyps (nECRSwNP) endotypes by the percentage of tissue eosinophils. Serum 25-(OH)D3 levels measurements were performed in all subjects. Paranasal sinus CT scans, blood eosinophil counts, and determination of total immunoglobulin E (total IgE), Th1/Th2 plasma cytokines and nasal nitric oxide (nNO) levels were performed before surgery. Logistic regression analysis was used to evaluate the related factors of ECRSwNP. Receiver operating characteristic (ROC) curves was used to evaluate the predictive potential of the clinical parameters. Results: One hundred and twenty-seven CRSwNP patients and 40 healthy subjects were recruited, including 74 males and 93 females of the patients, with the age of (38.73±13.05) years. In patients with ECRSwNP, serum 25-(OH)D3 levels were significantly lower than those in nECRSwNP patients ((26.14±4.58) ng/ml vs (35.71±7.86) ng/ml, t=-8.564, P<0.01). The prevalence of asthma, prevalence of allergic rhinitis, peripheral blood eosinophil counts, total IgE levels, nNO levels and CT scores ratio for ethmoid sinus and maxillary sinus (E/M ratio) of ECRSwNP patients were significantly higher than those in nECRSwNP patients (all P<0.05). However, there was no significant difference in Th1/Th2 cytokines levels between the histological types of CRSwNP (all P>0.05). Among the predictive indicators, 25-(OH)D3 had the highest predictive value, with ROC area under curve (AUC) value of 0.882. The best cut-off point of 28.5 ng/ml for 25-(OH)D3 demonstrated a sensitivity of 0.871 and a specificity of 0.762 for ECRSwNP. Conclusion: Measurement of serum 25-(OH)D3 level may be used as an effective method to distinguish between ECRSwNP and nECRSwNP.
Adult ; Calcifediol ; Chronic Disease ; Eosinophils ; Female ; Humans ; Male ; Maxillary Sinus ; Middle Aged ; Nasal Polyps/diagnosis* ; Rhinitis/diagnosis* ; Sinusitis/diagnosis*

Objective To investigate the prevalence of Spirometra mansoni infections in hosts in Jiangsu Province, so as to provide the scientific basis for the management of sparganosis mansoni. Methods From 2018 to 2019, nine counties (cities, districts) were randomly selected from Jiangsu Province as the survey sites, and 100 healthy individuals were randomly selected to perform the serological test of S. mansoni infections and the detection of S. mansoni eggs. The procercoids were detected in the intermediate host Cyclops, and the S. mansoni eggs were identified in the stool samples of the definitive hosts cats and dogs. Results The prevalence of S. mansoni human infections was 0 (0/900) in the 9 survey sites of Jiangsu Province, and the sero-prevalence of the specific IgG antibody against S. mansoni was 1.22% (11/900). The positive rate of procercoids was 0.33% (3/900) in Cyclops. In addition, the S. mansoni egg-positive rate was 1.48% (2/135) in cats and dogs. Conclusions Sparganosis mansoni is prevalent in Jiangsu Province. Health education pertaining to the damages of sparganosis mansoni and the route of S. mansoni infections should be improved.

Objective To investigate the clinical features, laboratory findings, chest CT findings and treatment of patients with COVID-19, and to analyze their relationship with prognosis. Methods From January to February 2020, the clinical data on the 42 patients with COVID-19 admitted to the Wenzhou Sixth People′s Hospital were analyzed retrospectively. Results The clinical symptoms of the 42 cases included fever (35 cases), cough (26 cases), fatigue (14 cases), aspiration (9 cases), sore throat (4 cases), muscle ache (5 cases), headache (2 cases), nausea (4 cases), diarrhea (6 cases) and abdominal pain (1 case).The absolute number of blood lymphocyte decreased to different degrees in 22 cases.Fourteen cases had lactate dehydrogenase obviously, with no obvious change in procalcitonin.The imaging manifestations were cloud-like and ground-glass-like high density shadows scattered outside the lungs, small flaky consolidation and bronchus inflating sign were seen locally.A few images showed diffuse high density, most of the lesions showed consolidation or striate change, and local fibrosis was formed in the lower lobes of both lungs. Conclusion Fever and cough are the first symptoms of COVID-19, and a few cases are associated with shortness of breath and diarrhea, accompanied by different degrees of systemic symptoms, but most of the patients improve their conditions after active antivirus, anti-infection, systematic symptoms improvement and supportive treatment.The disease is highly infectious and its condition changes rapidly.Therefore, early detection, early diagnosis and comprehensive treatment of the whole body as soon as possible are the keys to treatment.