Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

Objective:To analyze and predict the future trend of the premature mortality of major chronic and non-communicable diseases in Anhui Province, evaluate the implementation of the "Healthy China 2030" Plan, and explore its influencing factors.Methods:Using data from death-cause surveillance and statistical yearbooks in Anhui, the trend prediction and analysis on influencing factors were conducted by using methods such as time series accumulation and logarithmic linear Joinpoint regression, principal component regression.Results:In Anhui, 28.10% of the deaths were premature ones, of which 84.40% were attributed to chronic and non-communicable diseases. In premature deaths attributed to chronic and non-communicable diseases, the deaths caused by malignant tumor and cardiovascular disease accounted for 45.88% and 41.65% respectively. The prediction results showed that the premature mortality of major chronic and non-communicable diseases would decrease in Anhui in the future, and by 2030, the goal in the "Healthy China 2030" Plan would be reached only in rural area. To reduce premature death, it is necessary to pay attention to the prevention and control of malignant tumor and cardiovascular disease. Men in urban area are the key population. Factors that reflect urban infrastructure had a significant impact on premature mortality of major chronic non-communicable diseases, such as garden and green space area per capita. Factors such as concentration of PM 2.5 had a negative impact on premature mortality of chronic non-communicable diseases, while factors such as garden and green space area per capita had a positive impact. Conclusions:Disease burden caused by chronic and non-communicable diseases, such as malignant tumor, exits in Anhui. Men in urban area are key population in the prevention and control of chronic and non-communicable diseases in the future.

Cultivating salt-alkali tolerant rice varieties is one of the important ways to meet the increasing food demand of growing global population. In this study, twenty-one rice germplasms with different salt-alkali tolerance were treated with six salt-alkali concentrations at germination and seedling stages. The germination potential, germination rate, shoot length, root length, root number, fresh weight of shoot and seedlings were measured. The average value of salt damage rate was used to evaluate the salt-alkali tolerance. As the salt-alkali concentration increases, the inhibition on seed germination and growth became more obvious. Upon treatment with 1% NaCl plus 0.25% NaHCO₃, the salt damage rate of germination rate has the largest variation, ranging from 0% to 89.80%. The salt damage rate of each trait shows a similar trend at all concentrations. Four germplasm resources with strong salt-alkali tolerance (Dajiugu, Nippobare, Mowanggu and 02428) and 7 sensitive germplasms were screened. The salt-tolerant gene sequence of 4 salt-alkali tolerant varieties and 3 sensitive germplasms were analyzed. OSHAL3 and OsRR22 were identical among the 7 germplasms, but SKC1 and DST showed clear variations between the salt-alkali tolerant and sensitive germplasms. Besides the salt-alkali tolerant germplasm resources, this study can also serve as a reference for mining of genes involved in salt-alkali tolerance and breeding of salt-alkali tolerant rice varieties.
Alkalies ; Germination ; Oryza/genetics* ; Plant Breeding ; Seedlings/genetics*

Tumor metastasis is responsible for most mortality in cancer patients, and remains a challenge in clinical cancer treatment. Platelets can be recruited and activated by tumor cells, then adhere to circulating tumor cells (CTCs) and assist tumor cells extravasate in distant organs. Therefore, nanoparticles specially hitchhiking on activated platelets are considered to have excellent targeting ability for primary tumor, CTCs and metastasis in distant organs. However, the activated tumor-homing platelets will release transforming growth factor-β (TGF-β), which promotes tumor metastasis and forms immunosuppressive microenvironment. Therefore, a multitalent strategy is needed to balance the accurate tumor tracking and alleviate the immunosuppressive signals. In this study, a fucoidan-functionalized micelle (FD/DOX) was constructed, which could efficiently adhere to activated platelets through P-selectin. Compared with the micelle without P-selectin targeting effect, FD/DOX had increased distribution in both tumor tissue and metastasis niche, and exhibited excellent anti-tumor and anti-metastasis efficacy on 4T1 spontaneous metastasis model. In addition, due to the contribution of fucoidan, FD/DOX treatment was confirmed to inhibit the expression of TGF-β, thereby stimulating anti-tumor immune response and reversing the immunosuppressive microenvironment. The fucoidan-functionalized activated platelets-hitchhiking micelle was promising for the metastatic cancer treatment.

Objective:To investigate the current status and temporal trend of probability of premature death, caused by four major non-communicable diseases (NCDs) in Anhui province, from 2014 to 2018, and to explore the possibility of achieving the goal of "Healthy China 2030".Methods:Data of death were collected from the "Information System for Death Cause Register and Management". The mortality, standardized mortality, premature mortality rate and annual percentage change (APC) were calculated. Based on the reduction target of "Healthy China 2030"(-30%) and "Healthy Anhui 2030"(-25%) for premature death probability of four major NCDs, the possibility of achieving the target was evaluated.Results:From 2014 to 2018, the proportion of four major NCDs deaths to total deaths increased from 82.76% to 84.77%, showing an upward trend(APC=0.50%). The standardized mortality rate of four major NCDs in the population aged 30-69 years was decreasing annually (APC=-1.78%). The premature death probability of four major NCDs decreased from 15.53% to 14.43% with a downward trend. The decline rate of men (APC=-1.80%) was slightly lower than that of women (APC =-2.00%). The decline rate of urban (APC=-1.57%) and rural (APC=-1.99%), Northern Anhui (APC=-2.32%) and Central Anhui (APC=-1.81%) areas were all showed a downward trend. The premature death probability in the same year was higher in men, rural areas and northern Anhui areas. The decrease of chronic respiratory diseases was the greatest (APC=-9.19%), followed by cancer (APC=-1.77%), but increased in diabetes for men (APC=-2.90%). According to the average growth rate of premature death probability from 2014 to 2018, it was predicted that the goal of healthy Anhui would be achieved by 2030. However, to achieve the goal of healthy China, the rate of decline needs to be increased by 26.40% on the existing basis. Comparing to the proportion, the descent speed needs to be increased between different genders, urban and rural areas and regions. Conclusions:The premature death probability of four major NCDs in Anhui province has a continuous downward trend. Men, rural residents and residents in northern Anhui province are the key population. We should carry out intervention against the main risk factors of NCDs, reduce the premature mortality rate of NCDs, and strive to achieve the goal of "Healthy China 2030".

Objective:Based on the data of the baseline survey of hypertension and sodium intake monitoring in Anhui province in 2019, the salt intake in adult residents was estimated.Methods:Multi-stage stratified cluster random sampling was used to select participants aged 18-69 years, questionnaire survey and related measurements were conducted. Salt intake in participants with different characteristics were estimated with complex sample and linearization of Taylor series based on design and the correlation between salt intake and blood pressure, waist circumference and BMI were tested by linear regression.Results:A total of 1 500 participants were included. The overall salt intake was 9.14 g/d, which was 9.84 g/d in men and 8.47 g/d in women ( P<0.05). The differences in salt intake across different subgroups were significant ( P<0.05). Univariate linear regression analysis showed that salt intake was positively correlated with SBP, DBP, waist circumference and BMI ( P<0.05), while multivariate linear regression analysis (adjusted for other factors) only showed a positive correlation between salt intake and BMI ( β=0.053,95% CI: 0.028-0.078, P<0.05). Conclusion:The dietary salt intake in adult residents in Anhui was higher than WHO recommendation, suggesting that public health education need to be taken to reduce salt intake.

Objective:To discuss the value of real-time three-dimensional speckle tracking imaging(RT3D-STI) in the evaluation of the left atrial (LA) volume and function in end-stage renal disease (ESRD) patients with different dialysis methods.Methods:Eighty-three ESRD patients who were treated in the Affiliated Hospital of Qingdao University from February to August 2019 were enrolled and divided into non-dialysis group ( n=25), hemodialysis group (HD group, n=31) and peritoneal dialysis group (PD group, n=27). And 30 healthy volunteers were enrolled as control group. Subsequently, the LA volume indexs including LA maximal volume index (LAVImax), LA minimal volume index (LAVImin) and LA presystolic volume index (LAVIpre), the LA function parameters including LA ejection fraction (LAEF), LA passive ejection fraction(LApEF) and LA active ejection fraction (LAaEF) and the LA global strain parameters including global longitudinal strain(GLS), global radial strain(GRS) and global circumferential strain(GCS) were obtained by RT3D-STI. The differences of the parameters among these groups were compared and the correlations between the myocardial strain parameters and dialysis time were analyzed. Results:①The LAVImax, LAVImin and LAVIpre of the non-dialysis group, PD group and HD group were higher than those in the control group, while the LAEF, LApEF, GLS, GRS and GCS were lower than those in the control group(all P<0.05); the LAVImin of the PD group as well as the LAVImin, LAVIpre and LAVImax of HD group were higher than those of non-dialysis group, while the LAEF, LApEF, GLS, GCS of the PD group and the LAEF, LApEF, GLS, GRS, GCS of HD group were lower than those of non-dialysis group (all P<0.05). The LAVImax, LAVImin, LAVIpre of HD group were higher than those of PD group, while the LAEF, LApEF, GLS, GRS and GCS of HD group were lower than those of PD group (all P<0.05). ②The GLS and GCS in PD group were negatively correlated with the dialysis time( r=-0.670, -0.596, all P<0.05), and the GLS, GCS and GRS in HD group were negatively correlated with the dialysis time( r=-0.624, -0.631, -0.551, all P<0.05). Conclusions:RT3D-STI can assess the LA volume and function of ESRD patients with different dialysis methods effectively and can further evaluate the prognosis of patients and guide timely clinical intervention.

Objective:To analyze the long-term efficacy and safety of thalidomide on refractory Crohn′s disease (CD).Methods:A total of 79 patients with refractory CD in the First Affiliated Hospital of Sun Yat-sen University treated with thalidomide were enrolled in this retrospective study from September 2005 to July 2018. Clinical effects and adverse drug reactions were recorded and assessed.Results:In this cohort,69 patients were treated with thalidomide for ≥6 months. Sixty-eight patients among the 69 patients achieved complete clinical remission and were followed up for a median 33.5 months (range, 7-110 months). Seventeen cases relapsed during follow-up. The cumulative probabilities of remaining in remission at 12, 24, 60 months were 88.6% (95% CI 80.6%-96.6%), 80.7% (95% CI 70.3%-91.1%), 53.7% (95% CI 32.1%-75.3%) respectively. Disease activity was the only variable associated with relapse risk, with a hazard ratio ( HR) of 3.559 for Crohn′s disease activity index (CDAI) ≥220(95% CI 1.213-10.449, P<0.05). Adverse reactions were recorded in 42 (53.2%) patients including12 (15.2%) leading to discontinuation of thalidomide. No serious side effects were observed in all subjects. Conclusions:This study suggests a long-term benefit of maintenance treatment with thalidomide in refractory CD.Moderate to severe patients have an increased risk of relapse. The high incidence of drug adverse reactions may restrain the clinical application of thalidomide.

Objective Based on the data of chronic diseases and nutrition surveillance among Chinese adults in 2015,dyslipidemia and related factors were analyzed.Methods Multi-stage stratified cluster random sampling was used to select participants who were aged 18 and over,with questionnaire survey and related measurements conducted.Prevalence rates of dyslipidemia among participants by different characteristics and influencing factors were analyzed,using the method of complex weighting and post-weighted stratification.Results In all,7 404 participants were included.The overall prevalence of dyslipidemia was 30.5％ among the adults.The overall prevalence of dyslipidemia were 36.5％ in males and 24.4％ in females (P＜0.05).The prevalence rates of hypercholesterolemia,hypertriglyceridemia,high LDL-C,and low HDL-C were 3.7％,12.2％,5.3％,and 19.4％,respectively.Results from the multivariate logistic regression model analysis showed that age (OR=1.009,95％CI:1.000-1.018),female (OR=0.501,95％CI:0.397-0.632),College degree or above (OR=1.728,95％CI:1.257-2.374),alcohol consumption 3 (OR=0.711,95％CI:0.536-0.943),central obesity (OR=1.868,95％CI:1.547-2.257),BMI (OR=1.141,95％CI:1.098-1.186),hypertension (OR=1.259,95％CI:1.077-1.473) and diabetes (OR=2.025,95％CI:1.446-2.835) were influencing factors on dyslipidemia.Conclusions The prevalence of dyslipidemia seemed high among adults in Anhui.Risk factors should be closely monitored and under control,including those people with unhealthy lifestyles or being overweight,obesity,hypertensive and diabetic.