China is a country with a high incidence of esophageal cancer.The pathological type is mainly squamous cell carcinoma.Squamous intraepithelial neoplasia is the most recognized precancerous lesion of esopha-geal squamous cell carcinoma,and its monitoring and intervention is an effective method to reduce the incidence of esophageal squamous cell carcinoma and improve the quality of life of patients.Understanding the etiology,clinical features,diagnosis and treatment of esophageal squamous cell carcinoma plays a crucial role in the prevention and early diagnosis and treatment of esophageal squamous cell carcinoma.At present,the clinical research related to esophageal squamous intraepithelial neoplasia is still insufficient,and there are some differences in clinical treat-ment.This review summarizes the risk factors,clinical features,diagnosis,prognosis and treatment of esophageal squamous intraepithelial neoplasia,hoping to provide ideas for the clinical management of esophageal squamous intraepithelial neoplasia.

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes,leading to facial bone destruction and a high recurrence rate.However,the mechanisms governing tumor initiation and recurrence are poorly understood.Here,we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution.Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response(IR),bone remodeling(BR),tooth development(TD),epithelial development(ED),and cell cycle(CC)signatures.Of note,we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence,which was dominated by the EZH2-mediated program.Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids.These data described the tumor subpopulation and clarified the identity,function,and regulatory mechanism of CC ameloblastoma cells,providing a potential therapeutic target for ameloblastoma.

Pleomorphic adenoma (PA) is the most common benign tumour in the salivary gland and has high morphological complexity. However, the origin and intratumoral heterogeneity of PA are largely unknown. Here, we constructed a comprehensive atlas of PA at single-cell resolution and showed that PA exhibited five tumour subpopulations, three recapitulating the epithelial states of the normal parotid gland, and two PA-specific epithelial cell (PASE) populations unique to tumours. Then, six subgroups of PASE cells were identified, which varied in epithelium, bone, immune, metabolism, stemness and cell cycle signatures. Moreover, we revealed that CD36⁺ myoepithelial cells were the tumour-initiating cells (TICs) in PA, and were dominated by the PI3K-AKT pathway. Targeting the PI3K-AKT pathway significantly inhibited CD36⁺ myoepithelial cell-derived tumour spheres and the growth of PA organoids. Our results provide new insights into the diversity and origin of PA, offering an important clinical implication for targeting the PI3K-AKT signalling pathway in PA treatment.
Humans ; Adenoma, Pleomorphic/genetics* ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins c-akt ; Transcriptome ; Myoepithelioma

Objective:To investigate risk factors of arrhythmia in elderly patients with early lung cancer after thoracoscopic pulmonary resection to construct a prediction model.Methods:Two hundreds and twenty elderly patients with early lung cancer after thoracoscopic pulmonary resection were retrospectively chosen in the period from January 2017 to January 2023 in Guang'an People's Hospital of Sichuan Province. The occurrence of arrhythmia was calculated, and the clinical data of patients with arrhythmia and those without arrhythmia were compared. Logistic regression was employeed to analyze the independent influencing factors of arrhythmia in elderly patients with early lung cancer after thoracoscopic pneumonectomy. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of regression model on arrhythmia after thoracoscopic pneumonectomy in elderly patients with early lung cancer.Results:Forty-one of 220 (18.64%) elderly patients with early lung cancer treated by thoracoscopic pneumonectomy had arrhythmia. There were statistically significant differences between patients with arrhythmia and patients without arrhythmia in age ( χ2=17.76, P<0.001), combined with essential hypertension ( χ2=21.06, P<0.001), forced expiratory volume in one second as a percentage of predicted value (FEV 1%) ( χ2=17.88, P<0.001), left atrium anterior-and-posterior diameter ( χ2=37.82, P<0.001), operation type ( χ2=27.09, P<0.001) and postoperative constipation ( χ2=18.25, P<0.001). The results of multivariate analysis showed that age>75 years old ( OR=22.17, 95% CI: 3.78-130.11, P=0.001), combined with essential hypertension ( OR=26.55, 95% CI: 3.99-176.95, P=0.001), FEV 1%≤70% ( OR=6.20, 95% CI: 1.37-28.11, P=0.018), left atrium anterior-and-posterior diameter>40 mm ( OR=10.84, 95% CI: 2.24-52.45, P=0.003), thoracoscopic lobectomy ( OR=7.07, 95% CI: 1.62-30.80, P=0.009), and postoperative constipation ( OR=79.97, 95% CI: 11.87-538.83, P<0.001) were all independent risk factors for arrhythmia after thoracoscopic pulmonary resection in elderly patients with early lung cancer. A prediction model was established for statistically significant indicators in multivariate analysis, ln ( P/1- P) =-7.89+3.10×age+3.28×combined with essential hypertension+1.82×FEV 1%+2.38×left atrium anterior-and-posterior diameter+1.96×operation type+4.38×postoperative constipation ( P was the prediction probability of P value in regression model). ROC curve analysis showed that the area under the curve (AUC) of predict arrhythmia after thoracoscopic pulmonary resection in elderly patients with early lung cancer were 0.64, 0.71, 0.68, 0.74, 0.76, 0.87 and 0.98, respectively. The Yoden index was 27.29%, 42.28%, 34.92%, 47.42%, 73.63%, 50.97% and 91.97%, respectively. Conclusion:Age>75 years old, combined with essential hypertension, FEV 1%≤70%, left atrium anterior-and-posterior diameter>40 mm, thoracoscopic lobectomy and postoperative constipation are all independent risk factors for arrhythmia after thoracoscopic pulmonary resection in elderly patients with early lung cancer. Nomogram model based on the above risk factors has high efficacy in predicting arrhythmia occurance after thoracoscopic pulmonary resection.

【Objective】 To explore the effect of B lymphocytes on cardiac structure and function and myocardial immune cells during heart development. 【Methods】 Echocardiography, immunofluorescence staining and flow cytometry were used to evaluate the composition of immune cells of the heart and the cardiac structure and function in wild-type (WT) mice and B-lymphocyte-deficient (μMT) mice, respectively. 【Results】 Compared with those of μMT mice, the ratio of heart weight to mouse weight (P<0.05), left ventricular mass (P<0.05) and the cross-sectional area of myocardial cells WT mice were significantly increased, while the ventricular ejection fraction was significantly decreased (P<0.05). The results of mRNA sequencing showed that WT mice and μMT mice differentially expressed genes were mainly enriched in the signal pathway of heart development and hypertrophic cardiomyopathy. The results of flow cytometry showed that WT mice had more Ly6g⁺ neutrophils, CD4⁺ positive T cells (P<0.001) and CD8⁺T cells (P<0.05) compared with μMT mice. 【Conclusion】 B-lymphocyte depletion alters the composition of cardiomyocyte immune cells, reduces left ventricular mass, and increases myocardial contractility.

Protein aggregation is a critical issue in the production of biopharmaceuticals. During protein production, transport and storage, various factors can lead to protein aggregation. With the in-depth study, different ways of protein aggregation and various influencing factors were identified. This includes physical and chemical factors, translation modifications and protein structure. Since protein aggregation exerts major impact on the activity and homogeneity of proteins, it is of great importance to study the ways of protein aggregation and how to control it to obtain high-quality proteins. The review focuses on three ways of protein aggregation, namely 3D domain swapping, salt bridge formation, and oxidative stress, as well as methods to control protein aggregation during protein production, transport and storage. This may facilitate reducing the loss caused by the formation of protein aggregation and improving the purity and homogeneity of protein in research and commercial production.
Protein Aggregates ; Proteins/chemistry* ; Oxidative Stress

【Objective】 To explore B lymphocytes’ role and mechanisms in angiotensinⅡ/phenylephrine (AngⅡ/PE) induced cardiomyopathy so as to understand the role of inflammatory cells in myocardial injury. 【Methods】 AngⅡ/PE was administered to wild-type (WT) and B cells deficiency (μMT) mice for 14 days or 28 days. The mice were analyzed by blood pressure measurement, echocardiography imaging, flow cytometry, and histology. Cardiac fibrosis was evaluated by Masson staining. 【Results】 Compared with the control group, the left ventricular mass (P<0.01), heart mass/tibia length ratio (P<0.01) and cross-sectional area of cardiomyocytes in AngⅡ/PE group were significantly increased (P<0.01). After 2 weeks of AngⅡ/PE treatment, B lymphocytes (P<0.05), CD45⁺ leukocytes (P<0.05), CD64^-Ly6C⁺ monocytes (P<0.05), CD64⁺Ly6C^-macrophages (P<0.05) and Ly6g⁺ neutrophils (P<0.05) were recruited in myocardial tissue. Compared with WT_AngⅡ/PE group, the heart weight/tibia length ratio (P<0.05), left ventricular weight (P<0.05) and myocardial cell cross-sectional area (P<0.05) of μMT_AngⅡ/PE mice were significantly improved. CD45⁺Ly6C⁺CD64^- monocytes (P<0.05) and CD45⁺Ly6C^-CD64⁺ macrophages (P<0.05) were significantly decreased. 【Conclusion】 B lymphocytes deficiency improves AngⅡ/PE induced cardiac hypertrophy by reducing the infiltration of CD45⁺Ly6C⁺CD64^- monocytes and CD45⁺Ly6C^- CD64⁺ macrophages.

Objective: To investigate the immunomodulatory activity of polysaccharides from the roots of Brassica rapa. Methods: The crude polysaccharide from roots of B. rapa (BRP) was extracted and purified to further investigate the active fraction of BRT for inducing macrophage phagocytosis. Results: Effects on RAW264.7 cells demonstrated that BRP behaved better phagocytic capacity and had potent immunomodulatory activity, including increasing production of nitric oxide (NO), tumor necrosis factor α (TNFα) and upregulating mRNA levels of inducible NO synthase (iNOS) and TNFα. Furthermore, modulation of macrophage by BRP was indicated to be mediated via the activation of Akt and nuclear factor-kappa B (NF-κB). Conclusion: The beneficial effects of BRP could be used as an immunotherapeutic adjuvant in treatment of inflammatory diseases.

Objective:To understand the overall satisfaction rate with vaccination services in parents of children, and the impact of additional time consumed for vaccination service on overall satisfaction rate.Methods:From December 2019 to January 2020, a total of 3 178 parents of 0-3 years old children were investigated to collect the information about their basic characteristics, additional time spent for vaccination service and overall satisfaction through questionnaires. Binary logistic regression model and restricted cubic spline model were used to evaluate the impact of additional time spend on the overall satisfaction rate.Results:The overall satisfaction rate of parents with vaccination services was 92.32%. The median time for parents to move from home to vaccination clinic was 10.00 (10.00, 20.00) minutes, the median waiting time to make an appointment was 10.00 (5.00, 15.00) minutes, the median waiting time for vaccination was 5.00 (3.00, 10.00) minutes, and the median total additional time spent was 30.00 (20.00, 45.00) minutes. The binary logistic regression analysis showed that after adjusting the relevant factors, the main factors affecting the overall satisfaction rate were the waiting time for making an appointment (the 4- minutes group vs. 8- minutes group: OR=1.863, 95% CI: 1.307-2.657), waiting time for vaccination (the <4 minutes group vs. 8- minutes group: OR=1.529, 95% CI: 1.102-2.120; the 4- minutes group vs. 8- minutes group: OR=1.534, 95% CI: 1.104-2.130), total additional time spent (the 15- minutes group vs. 30- minutes group: OR=1.470, 95% CI: 1.094-1.976). Restricted cubic spline analysis showed that the waiting time for making an appointment (non-linear: χ2=13.18, P=0.001), the waiting time for vaccination (non-linear: χ2=13.50, P=0.001), and the total additional time consumed (non-linear: χ2=9.38, P=0.009) showed a non-linear inverted "V" dose response relationship to the overall satisfaction of vaccination services. Conclusions:The waiting time for parents to make an appointment, the waiting time for vaccination and the total additional time spent for receiving vaccination services affected the overall satisfaction rate of the vaccination services. And the waiting time for making an appointment was the most important factor, and it is necessary to shorten the waiting time for appointment. It is suggested that the vaccination clinic should make use of information technology (such as WeChat public account, APP) to make accurate appointments, make appointments to the time period to control the number of people within time period.

Objective:To understand the time for observation and related factors in the clinics after vaccination among children's parents.Methods:From December 2019 to January 2020, parents of children aged 0-3 years were recruited by multiple-stage sampling from 34 vaccination clinics in 12 districts and counties in 6 provinces (Shandong, Guangdong, Henan, Sichuan, Inner Mongolia, and Liaoning). A questionnaire survey on the time of observation after vaccination was conducted. A multivariate logistic regression model was used to analyze the related factors of parental observation time after vaccination.Results:A total of 3 292 parents of 0-3 year's old children were selected, and 3 178 parents were finally included in the analysis. 87.85%(2 792/3 178) of the parents reported that the observation time after vaccination at clinics was ≥30 minutes. Multivariate logistic regression analysis showed that, after adjusting for the regions, the main factors affecting the observation time at clinics after vaccination among parents appeared as observation time informed by physicians at the clinic appeared ≥30 minutes ( OR=31.622, 95% CI: 19.847-50.384), parents were medical personnel ( OR=2.779, 95% CI: 1.505-5.133), parents being volunteers working on vaccination-related publicity and education activities ( OR=1.986, 95% CI: 1.438-2.743), parents aged 35 years old or above ( OR=1.900, 95% CI: 1.215-2.971), being parents of the first child ( OR=1.663, 95% CI: 1.282-2.156), per capita annual income of the family as 8 000- Yuan ( OR=1.646, 95% CI: 1.168-2.319), children aged 0-12 months old ( OR=1.646, 95% CI: 1.203-2.252) or 13-24 months old ( OR=1.506, 95% CI: 1.064-2.133), obedient to physicians' advice at the clinic ( OR=1.481, 95% CI: 1.067-2.055). Conclusions:The proportions of parents observed for ≥30 minutes at the clinics of vaccination were high. When the information was from the physicians at the vaccination clinic, the observation time was the most critical factor for parents to observe at clinics as required.