BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a severe congenital disorder characterized by vaginal hypoplasia caused by dysplasia of the Müllerian duct. Patients with MRKH syndrome often require nonsurgical or surgical treatment to achieve satisfactory vaginal length and sexual outcomes. The extracellular matrix has been successfully used for vaginal reconstruction. METHODS: In this study, we developed a new biological material derived from porcine vagina (acellular vaginal matrix, AVM) to reconstruct the vagina in Bama miniature pigs. The histological characteristics and efficacy of acellularization of AVM were evaluated, and AVM was subsequently transplanted into Bama miniature pigs to reconstruct the vaginas. RESULTS: Macroscopic analysis showed that the neovaginas functioned well in all Bama miniature pigs with AVM implants. Histological analysis and electrophysiological evidence indicated that morphological and functional recovery was restored in normal vaginal tissues. Scanning electron microscopy showed that the neovaginas had mucosal folds characteristics of normal vagina. No significant differences were observed in the expression of CK14, HSP47, and a-actin between the neovaginas and normal vaginal tissues. However, the expression of estrogen receptor (ER) was significantly lower in the neovaginas than in normal vaginal tissues. In addition, AVM promoted the expression of b-catenin, c-Myc, and cyclin D1. These results suggest that AVM might promotes vaginal regeneration by activating the b-catenin/cMyc/cyclin D1 pathway. CONCLUSION This study reveals that porcine-derived AVM has potential application for vaginal regeneration.

Cancer is a major threat to human health and causes death worldwide. Research on the role of radiotherapy (RT) in the treatment of cancer is progressing; however, RT not only causes fatal DNA damage to tumor cells, but also affects the interactions between tumor cells and different components of the tumor microenvironment (TME), including immune cells, fibroblasts, macrophages, extracellular matrix, and some soluble products. Some cancer cells can survive radiation and have shown strong resistance to radiation through interaction with the TME. Currently, the complex relationships between the tumor cells and cellular components that play major roles in various TMEs are poorly understood. This review explores the relationship between RT and cell-cell communication in the TME from the perspective of immunity and hypoxia and aims to identify new RT biomarkers and treatment methods in lung cancer to improve the current status of unstable RT effect and provide a theoretical basis for further lung cancer RT sensitization research in the future.
Humans ; Neoplasms/pathology* ; Lung Neoplasms/complications* ; Fibroblasts/pathology* ; Biomarkers ; Macrophages/pathology* ; Hypoxia ; Tumor Microenvironment

This study explores the application effect of the case-based teaching method based on Xuexitong learning platform in the online teaching of Digestive System, and analyzes the learner's emotional experience, learning behavior, and learning effect in the case-based online teaching. The results of the study show that the case-based online teaching model based on Xuexitong learning platform improves students' online learning interest, and the students have good emotional experience, high learning enthusiasm, good classroom interaction, enhanced self-learning ability before and after class, and good learning effect. In addition, precise teaching can be used for individual students who are not enthusiastic about online learning.

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma (NSCLC), we performed a two-cohort of genome-wide association studies (GWAS), including 34 for WES-based and 433 for microarray-based analyses, as well as two independent validation cohorts. After integrating the results of two studies, the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples, and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments. We found that a total of 68 variations were significant at P < 1 × 10^-3 in cohort 1 discovery stage, of which 3 SNPs were verified in 262 independent samples. A total of 541 SNPs were significant at P < 1 × 10^-4 in cohort 2 discovery stage, of which 8 SNPs were verified in 347 independent samples. Comparing the validated SNPs in two GWAS, ADCY1 gene was verified in both independent studies. The results of fine-mapping showed that the G allele carriers of ADCY1 rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy. In conclusion, our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

Objective:To study the clinical features of children with pertussis and the risk factors of severe pertussis.Methods:A retrospective analysis was performed based on clinical data and laboratory examination results of hospitalized children with pertussis who admitted to the intensive care unit, respiratory department, and emergency general department at Hunan Children′s Hospital from January 2019 to March 2020.According to the age, the patients were divided into age ≤3 months group( n=58)and age >3 months group( n=64). According to sputum culture, 63 cases were divided into negative sputum culture group and 59 cases were positive sputum culture group.The patients were also divided into vaccinated group( n=19)and unvaccinated group( n=103). Severe disease was seen in 28 cases, and the other 94 cases had the modest disease.The clinical characteristics between two groups were compared, and the risk factors of severe pertussis pneumonia were analyzed. Results:The hospitalization days in age ≤3 months group was higher than that in age >3 months group.It was also found that shortness of breath, apnea, cyanosis after coughing, heart rate decline were more common in age ≤3 months group than those in age >3 months group( P<0.05). The incidences of respiratory failure and heart failure in positive sputum culture group were higher than those in negative sputum culture group.Clinical characteristics such as hospitalization days, hospitalization expenses, peak white blood cell count, peak lymphocyte count, and incidence of bacterial infection were higher in severe pertussis group than those in non-severe pertussis group( P<0.05). Four patients were treated with exchange blood transfusion, and one patient died.Logistic regression analysis revealed that fever, wheezing, cyanosis after coughing and white blood cell count>20×10 9/L were risk factors for severe pertussis.White blood cell count of 20×10 9/L and lymphocyte count of 14×10 9/L had the highest sensitivity and specificity in predicting severe pertussis(0.71, 0.78; 0.54, 0.79). Conclusion:The younger the children are, the more likely they have shortness of breath, apnea, cyanosis, heart rate falls, and the longer the hospital stay.Bacterial infection will aggravate pertussis.Patients with fever, wheezing, cyanosis after coughing, and white blood cell count>20×10 9/L are more likely to develop severe pertussis.The white blood cell count >20×10 9/L and the lymphocyte count >14×10 9/L are associated with severe pertussis.

Objective:To analyze the metabolic status of forest encephalitis patients, research the effect of forest encephalitis on lipid metabolism, and clarify the possible pathogenesis.Methods:Based on liquid chromatography-mass spectrometry (LC-MS), lipidomics analysis was performed in 50 patients with tick-borne encephalitis and 39 healthy samples from Hulunbuir region. The patients′ serum samples were analyzed by utilizing the multivariate statistical analysis method such as principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA).Results:A total of 465 peaks were detected in the samples, and metabolites such as phospholipids and glycerides were identified. To identify the significant differential metabolites ( P<0.01, VIP>1, FC>2), a total of 26 biomarkers were screened, which phospholipids tend to be upregulated[log 2(Fold change)>0], such as phosphatidylcholine (PC) and phosphatidylethanolamine (PE); while glycerides tend to be decreased[log 2(Fold change)<0], such as diacylglycerol (DAG) and triacylglycerol (TAG), and those metabolites were closely related to anti-inflammatory and other metabolic pathways. The AUC value of potential biomarkers obtained was 0.999, which could be used for diagnosis of disease group and healthy group. Conclusions:The study showed that phospholipid metabolism and glyceride metabolism pathways would have some change after human infected by virus, and the differential metabolites could be used as potential markers for the diagnosis of tick-borne encephalitis, which provide a theoretical basis for disease research.

Objective:To differentiate hyperintense hepatocellular carcinoma (HCC) with focal nodular hyperplasia (FNH) in the hepatobiliary phase by MRI multimodal parameters.Methods:A retrospective cross-sectional study method was adopted. Clinical data on 15 cases with hyperintense HCC and 15 cases with FNH in the hepatobiliary phase admitted to the First Affiliated Hospital of the Army Medical University from January 2012 to December 2019 were collected. All patients with solitary lesions who underwent Gd-EOB-DTPA-enhanced MRI examinations were included. Surgically resected specimens were verified by pathological and immunohistochemical examination. HCC and FNH imaging features were analyzed by two radiologists.Results:(1) HCC and FNH apparent diffusion coefficient (ADC) values were 1 205.07±239.65×10 -3 mm 2/s and 1 434.73±217.6×10 -3 mm 2/s, respectively, and the SI ADC difference was statistically significant ( P<0.05) between the two groups. (2) In the dynamic contrast-enhanced MRI sequence, 15 cases of HCC were significantly enhanced in the arterial phase, of which 13 cases were characterized by continuous enhancement, and 2 cases were characterized by wash-in and wash-out enhancement. There was no statistically significant difference ( P>0.05) between the two groups. SI enhancement rate between HCC and FNH (1.39±0.60 vs. 1.33±0.50, P>0.05) had no significant difference. (3) HCC and FNH morphological features in the hepatobiliary phase included: annular hypointensity: HCC (8 cases) vs. FNH (0 cases); contrast filling defects: HCC (8 cases) vs. FNH (0 cases); linear hyposignal separation: HCC (10 cases) vs. FNH (0 cases); and stellate scars: HCC (0) vs. FNH (5 cases), and there were statistically significant differences ( P<0.05) between the two groups . Conclusion:Multimodal MRI have significant value for differentiating hyperintense HCC and FNH in the hepatobiliary phase.

Objective:To retrospectively analyze the clinical application of extracorporeal membrane oxygenation (ECMO) in severe adenovirus pneumonia, and to evaluate the application value of ECMO in children with severe adenovirus pneumonia.Methods:Children diagnosed with severe adenovirus pneumonia and intervened with ECMO in the Hunan Children′s Hospital from January 1, 2018 to December 31, 2019 were recruited in this study for analyzing.The gender, age, clinical manifestations, mechanical ventilation duration, ECMO duration, the length of hospital stay, complications and prognosis were collected and analyzed.Results:A total of 4 children were included in the study, involving 2 cases were successfully evacuated from ECMO.Finally, 3 children died, and 1 case survived.Three death cases had a longer than 18 days of duration from the onset to the start with ECMO.Their ventilator assist time before star-ting ECMO was 3-5 days, and ECMO intervention time was longer, with the maximum of 27.5 days.The survived case had an 11-day duration from the onset to the start with ECMO, and the ventilator assisted time and ECMO intervention time were 5 days, and less than 10 days, respectively.Conclusions:ECMO treatment for children with severe adenovirus pneumonia has a low success rate, but it is still the most important way to save children.Early application of ECMO can improve the prognosis of children with severe adenovirus pneumonia.

Objective:To summary the mixed infection as well as clinical characteristics and analyze the risk factors for mixed infection of severe adenovirus pneumonia(SAP) in children.Methods:The clinical data of 114 children with SAP were retrospectively analyzed.Multivariate Logistic regression analysis was performed to assess the risk factors for mixed infection.Results:The incidence age was from 6 months to 2 years(62.5%). High fever(94.7%), cough(98.2%), dyspnea(86.8%) and lethargy(95.6%) were the main symptoms.Laboratory examination showed that children with SAP were prone to increased white blood cell count, C-reactive protein, procalcitonin, aspartate aminotransferase, alanine aminotransferase and CK-MB, as well as decreased proportion of CD3 + , CD4 + , CD8 + , CD4 + /CD8 + and NK cells.The main complications intrapulmonary organ were respiratory failure(80.7%). The main complications extrapulmonary organ were circulatory complications (55.3%). SAP was easily combined with other pathogenic infections.Streptococcus pneumoniae(22.9%)was the most common bacterial pathogen.Respiratory syncytial virus(10.0%)were the most common virus, in addition, mycoplasma pneumoniae(17.1%) was also common.Multivariable Logistic regression analysis showed that the decreasing ratio of CD4 + /CD8 + and NK cells, congenital heart disease and congenital airway dysplasia were the independent risk factors for mixed infection of SAP in children( P<0.05). Conclusion:The SAP patients could easily suffer from mixed infection and high fatality rate.Immune dysregulation is the important risk factors for mixed infection of SAP in children.So immunoregulatory treatment is very important.

Objectives:To summarize the clinical and genetic characteristics of the patients with isolated methylmalonic acidemia and investigate the strategies for the diagnosis, treatment and prevention.Methods:Three hundred and fourteen patients (180 males, 134 females) with isolated methylmalonic acidemia were ascertained from 26 provinces or cities across the mainland of China during January 1998 to March 2020. Genetic analysis was performed by Sanger sequencing, gene panel sequencing, whole exome sequencing, multiplex ligation-dependent probe amplification or quantitative PCR. According to the age of onset, the patients were divided to early-onset group (≤12 months of age) and the late-onset group (>12 months of age). They were treated by cobalamin, L-carnitine and (or) special diet and symptomatic treatment. Statistical analysis was done using Chi-square test.Results:Fifty-eight of 314 (18.5%) patients were detected by Newborn screening using liquid chromatography tandem mass spectrometry. Five cases (1.6%) had a postmortem diagnosis. Two hundred and fifty-one patients (79.9%) were clinically diagnosed with an age of onset ranged from 3 hours after birth to 18 years. One hundred and fifty-nine patients (71.0%) belonged to early-onset groups, 65 patients (29.0%) belonged to the late-onset group. The most common symptoms were metabolic crises, psychomotor retardation, epilepsy, anemia and multiple organ damage. Metabolic acidosis and anemia were more common in early-onset patients than that in late-onset patients (20.8%(33/159) vs. 9.2% (6/65), 34.6% (55/159) vs. 16.9% (11/165), χ 2=4.261, 6.930, P=0.039, 0.008). Genetic tests were performed for 236 patients (75.2%), 96.2%(227/236) had molecular confirmation. One hundred and twenty-seven variants were identified in seven genes (MMUT, MMAA, MMAB, MMADHC, SUCLG1, SUCLA2, and MCEE), of which 49 were novel. The mut type, caused by the deficiency of methylmalonyl-CoA mutase, was the most common ( n=211, 93%) cause of this condition. c.729_730insTT, c.1106G>A and c.914T>C were the three most frequent mutations in MMUT gene. The frequency of c.914T>C in early-onset patients was significantly higher than that in late-onset patients (8.3% (18/216) vs. 1.6% (1/64), χ 2=3.859, P=0.037). Metabolic crisis was more frequent in mut type than the other types (72.6% (114/157) vs. 3/13, χ 2=13.729, P=0.001),developmental delay and hypotonia were less frequent in mut type (38.2% (60/157) vs. 9/13, 25.5% (40/157) vs. 8/13, χ 2=4.789, 7.705, P=0.030, 0.006). Of the 58 patients identified by newborn screening, 44 patients (75.9%) who were treated from asymptomatic phase developed normally whereas 14 patients (24.1%) who received treatment after developing symptoms exhibited varying degrees of psychomotor retardation. Conclusions:The characteristics of phenotypes and genotypes among Chinese patients with isolated methylmalonic acidemia were analyzed. Expanded the mutation spectrum of the associated genes. Because of the complex clinical manifestations and severe early onset of isolated methylmalonic acidemia, Newborn screening is crucial for early diagnosis and improvement of prognosis. MMUT gene is recommended for carrier screening as an effort to move the test earlier as a part of the primary prevention of birth defects.