The extraordinary advantages associated with mRNA vaccines, including their high efficiency, relatively low severity of side effects, and ease of manufacture, have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers. Nevertheless, most mRNA delivery carriers have many disadvantages, such as high toxicity, poor biocompatibility, and low efficiency in vivo, which have hindered the widespread use of mRNA vaccines. To further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier, a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate (SA). Intriguingly, the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA, which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@DOTAP-mRNA. In addition, we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen targeting. Finally, we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E. G7-OVA tumor-bearing mice, dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor effect. Therefore, we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects.

Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.
Humans ; Mesothelioma, Malignant ; Prognosis ; Nomograms ; Retrospective Studies ; Proportional Hazards Models

Objective: To analyze the dynamic changes and influencing factors of HIV-1 DNA load in HIV-1 infected individuals under antiretroviral therapy (ART) in Dehong Dai and Jingpo autonomous prefecture, Yunnan province, and provide information support for the clinical use of HIV-1 DNA quantitative detection. Methods: The HIV infection cases in recent infection cohort from Dehong Center for Disease Control and Prevention during 2009-2018 were selected as study subjects. The dynamic curve of HIV-1 DNA load varrying with time was generated and logistic regression analysis was conducted to identify the risk factors for HIV-1 load in the recent follow up after ART and statistical analysis was performed by using SPSS 17.0. Results: Among the 113 HIV infection cases detected from the recent infection cohort, the recent HIV infection rate were 49.6%(56/113) males, sexual transmission cases and drug injection transmission cases accounted for 53.1% (60/113), 80.5% (91/113) and 19.5% (22/113), respectively. The dynamic changes curve showed that HIV-1 DNA load was relatively high (>800 copies /10⁶ PBMCs) before ART, and droped rapidly (<400 copies /10⁶ PBMCs) after ART for 1 year. However, HIV-1 DNA load decreased insignificantly from the second year of ART, and remained to be 269 copies/10⁶ PBMCs after ART for 6 years. Univariable logistic regression analysis indicated that OR (95%CI) of CD8, CD4/CD8 and HIV-1 DNA load were 1.00 (1.00-1.00), 0.30 (0.09-1.05) and 1.01 (1.00-1.01), respectively. Multivariable logistic regression analysis showed that OR value of HIV-1 DNA load base was 1.00 (1.00-1.01). Conclusions: HIV-1 DNA load decreased significantly in the first year of ART, then remained stable for years. HIV-1 DNA load base was the key factor associated with the decrease of HIV-1 DNA load, the lower the HIV-1 DNA load base, the lower HIV-1 DNA load. Therefore, earlier ART can contribute to the decrease of HIV-1 DNA load.
China/epidemiology* ; DNA/therapeutic use* ; HIV Infections/drug therapy* ; HIV Seropositivity ; HIV-1/genetics* ; Humans ; Male ; Viral Load

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

Objective To observe the role of working memory in the process of language, and provide an objective evaluation for Chinese language rehabilitation.Methods From December, 2017 to June, 2018, 20 healthy subjects accepted word-picture matching tasks as the word and picture showed on the different (task 1) or same (task 2) screens, and their event-related potential of N400 were compared in matched and mismatched conditions.Results Forteen subjects were included finally. Task 1 induced N400 appeared earlier with higher amplitude and more activation in central parietal occipital region, followed larger N170 and P1 wave. There were significant differences in most cerebral regions between the two tasks in N400 amplitude difference of matched and mismatched conditions (t＞ 2.319, P ＜ 0.05).Conclusion Word-picture matching tasks may involve more language-related brain regions with the intervention of working memory, that might work better in process of vocabulary. The tasks simulating the scene of Chinese language rehabilitation can be used as an objective evaluation for clinical activities.

Objective: To explore the prevalence and characteristics of traditional bullying and cyberbullying behavior among primary and middle school students and to provide evidence for the comprehensive intervention. Methods: An anonymous self-administrated questionnaire survey was conducted among 12 417 students (grade 5 to 12) selected with multi-stage cluster random sampling in 16 districts in Beijing between Sept. and Oct. 2017. Descriptive statistics and chi square test were used for statistical analysis. Results: In the past 6 months, 2.6% of students were reported to be involved in traditional bullying,10.6% were reported of being bullied. 1.0% of students were reported to be involved in cyberbullying, and 2.8% reported of being bullied. Boys reported significantly higher rates of traditional bullying and cyberbullying behavior. The reporting rate of traditional bullying and cyberbullying gradually increased with grade. The reporting rate of traditional bullying was highest in junior high school, while cyberbullying was common in both junior and senior high school. Students with low academic performance were more likely to involve in bully as perpetrators in both types(P<0.05). The higher maternal education background was, the higher their children involved in bullying perpetrators(P=0.03). The proportion of students who reported bullied at school was higher than cyberbullying(χ2=15.25, P<0.01). Cyberbullying were more likely to take place outside school compared with traditional bullying(χ2=3.98, 9.76, P<0.05). Compared with traditional bullying, cyberbullying has a higher proportion of various types of bullying or being bullied. Conclusion Bullying is still prevalent among primary and middle school students in Beijing, and cyberbullying is becoming more widespread. Schools, family and the community-based comprehensive prevention strategies should be developed for a safe campus and network environment to prevent traditional and cyberbullying.

Objective To evaluate the clinical efficacy of radical surgery combined with irradiation in the treatment of rectal cancer and its effect on the angiogenesis and survival rate.Methods A total of 200 colorectal cancer patients admitted to Zhengzhou Central Hospital from March,2014 to March,2015 were recruited and divided into the observation group (n=105) and control group (n=95) by using random number table method.In the control group,radical surgery was performed,and radical surgery combined with irradiation was conducted in the observation group.The clinical efficacy,the serum levels of vascular endothelial growth factor-C (VEGF-C) and prostaglandin E2(PGE2) were statistically compared between the control and observation groups.The changes of the microvascular morphology and microvessel density (MVD) in the rectal cancer tissues were observed and recorded.The 3-year survival rate was calculated during postoperative follow-up.Results After corresponding treatment,the clinical overall response rate was 86.67％ in the observation group,and 70.53％ in the control group (P＞0.05).The 2-year survival rate did not significantly differ between two groups (P＞0.05).The 3-year survival rate in the observation group was significantly higher than that in the control group (P＜0.05).After treatment,the serum levels of VEGF-C and PGE2 were significantly improved in two groups (both P＜0.05).In the observation group,the serum levels of VEGF-C and PGE2 were significantly lower compared with those in the control group (both P＜0.05).The microvessel morphology in the cancer tissues remarkably differed between two groups.The microvessel diameter did not significantly differ,whereas the lumen diameter in the observation group was significantly smaller than that in the control group.The MVD in the observation group was 12.25±3.35,significantly lower than 28.14± 17.26 in the control group (P＜0.05).Conclusion Radical surgery combined with irradiation is an efficacious treatment of rectal cancer,which can effectively improve the serum levels of VEGF-C and PGE2,decrease the MVD,reduce the lumen diameter in the cancer tissues,lower the angiogenesis in rectal cancer and enhance the survival rate,which deserves widespread application in clinical practice.

Objective To understand the prevalence and epidemiological characteristics of hepatitis C virus (HCV) co-infection among newly reported HIV-infected patients from 2016 to 2017 in Dehong Prefecture of Yunnan Province. Methods A cross-sectional survey was conducted to detect HCV antibodies in 2 196 newly reported HIV-infected persons in Dehong Prefecture, Yunnan Province, from 2016 to 2017. Results A total of 694 cases(31.6%) were detected antibodies against HCV during HIV-infected persents. The prevalence of HCV co-infection among newly reported HIV-infected patients in Chinese and Burmese was 14.4% (112/780) and 41.1% (582/1 416), respectively. Moreover, the prevalence of HCV co-infection was higher in male, ethnic minorities such as Dai and Jingpo minority, primary school and below and farmers in both Chinese and Burmese. Multivariate Logistic regression model showed that HCV infection was associated with male, Dai minority, HIV infection by injecting drug and famers among Chinese and Burmese reported HIV-infected patients. Conclusions The prevalence of HCV co-infection was high among newly reported in Dehong Prefecture of Yunnan Province. Meanwhile, the epidemiological characteristics of HIV/HCV co-infections in Chinese and Burmese are different, thus different prevention and control measures are needed for patients of different nationalities.

Electroencephalogram (EEG) contains abundant physiological and pathological information. With the development of analysis, EEG can measure the neurodynamics at the sub-second level during impaired speech processing, providing a new perspective for revealing the occurrence, development and recovery mechanism of post-stroke aphasia. EEG plays an important role in the goal setting of rehabilitation for post-stroke aphasia, and serves as an evaluation of the efficacy for clinical rehabilitation.

Objective To investigate the clinical features of patients with acute ST-segment elevation myocardial infarction (STEMI) comorbid with diabetes mellitus (DM) and to analyze the prognosis within 12 months after primary percutaneous coronary intervention (pre-PCI). Methods A total of 375 STEMI patients were divided into the diabetes group (n=140) and the normal blood glucose group(n=235) according to whether they met the diagnostic criteria of DH. The clinical data,characteristics of coronary artery lesions,type of stent implant,rate of coronary slow flow or no-reflow after pre-PCI, and the prognosis within 12 months after PCI of the two groups were investigated.Results Patient in the diabetes group presented with higher mean age ,higher comorbid rates of hypertension , hyperlipidemia and heart function of Killip class Ш and above than patients in the normal blood glucose group (all P<0.05). patients in the diabetes group had higher rates of slow reflow /no-reflow after PCI(12.9% vs.5.5%,P=0.013),higher percentages of 3-ressel disease(40.7% vs. 28.9%,P=0.019)and lef t main lesions(13.6% vs. 7.2%,P=0.044). The in-hospital mortality rates(6.4% vs.1.7%,P=0.020),revascularization rates within 12 months(7.9% vs.0.9%,P=0.001)and incidence of heart failure(7.9% vs. 2.6%,P=0.017)were all higher in the diabetes group. Conclusions STEMI patients comorbid with DM were relatively older, had higher comorbidities of hypertension,hyperlipidemia, three-vessel disease, left main coronary lesions and higher mortality during hospitalization. No significant increase in cardiac death and recurrent myocardial infarction were deserved during the follow-up period. These patients may benefit more from early intervention.