ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

Background: Diabetes-induced cardiac fibrosis is one of the main mechanisms of diabetic cardiomyopathy. As a common histone methyltransferase, enhancer of zeste homolog 2 (EZH2) has been implicated in fibrosis progression in multiple organs. However, the mechanism of EZH2 in diabetic myocardial fibrosis has not been clarified. Methods: In the current study, rat and mouse diabetic model were established, the left ventricular function of rat and mouse were evaluated by echocardiography and the fibrosis of rat ventricle was evaluated by Masson staining. Primary rat ventricular fibroblasts were cultured and stimulated with high glucose (HG) in vitro. The expression of histone H3 lysine 27 (H3K27) trimethylation, EZH2, and myocardial fibrosis proteins were assayed. Results: In STZ-induced diabetic ventricular tissues and HG-induced primary ventricular fibroblasts in vitro, H3K27 trimethylation was increased and the phosphorylation of EZH2 was reduced. Inhibition of EZH2 with GSK126 suppressed the activation, differentiation, and migration of cardiac fibroblasts as well as the overexpression of the fibrotic proteins induced by HG. Mechanical study demonstrated that HG reduced phosphorylation of EZH2 on Thr311 by inactivating AMP-activated protein kinase (AMPK), which transcriptionally inhibited peroxisome proliferator-activated receptor γ (PPAR-γ) expression to promote the fibroblasts activation and differentiation. Conclusion Our data revealed an AMPK/EZH2/PPAR-γ signal pathway is involved in HG-induced cardiac fibrosis.

The relationship between gut microbiota and disease has become one of the hotspots in recent years. The gut-brain axis may be involved in the pathogenesis of metabolic diseases such as obesity， diabetes and polycystic ovary syndrome （PCOS）， yet the mechanism of gut-brain axis in neuroencrine regulation is still unclear and the gut microbiota as a target to influence hypothalamic-pituitary-ovarian （HPO） axis remains uncertain. Recent reports indicate that enteroendocrine hormones may play a role. Incretins， including glucagon like peptide-1 （GLP-1） and glucose-dependent insulinotropic peptide （GIP）， could promote insulin release and reduce serum glucose level. While the research on incretins and HPO axis is still in its infancy， and the effects of incretins on PCOS has not yet been clarified. This review focuses on the possible role and mechanism of incretins in the pathogenesis of PCOS.

To construct a non-communicable disease system recommended by WHO, develop the key techniques and promote their applications, obtain the main health indicators and understand the prevalence of chronic diseases, and provide support for the prevention, control and research of chronic diseases. Based on factor analysis, K-means clustering and multi-cluster random sampling, 30 typical sampling areas at provincial level were designed and constructed; By referring to WHO's Non-communicable Disease Surveillance Framework and the American behavioral risk factor sampling and questionnaire and combined with China's actual needs, a comprehensive surveillance system for chronic diseases, covering morbidity and mortality, risk factor exposure and community management and control of chronic diseases, was established, a "5+12+1" quality control system for surveillance data collection, management, analysis and feedback was formed and a three-level surveillance information management platform and information technology construction standards in the province were established, resulting the integration of life registration, chronic disease case reporting and community chronic disease management. Using these key techniques, we have obtained high-quality surveillance data of the whole province, produced the main health indicators, carried out research of chronic diseases, and analyze the prevalence and changing trend of the main chronic diseases and related risk factors to boost the government's practical projects for the reform of the people's livelihood and facilitate the construction of "Healthy Zhejiang". The successful experiences and key techniques have been applied in the construction of chronic disease surveillance system in some provinces in China.
China/epidemiology* ; Chronic Disease ; Chronic Disease Indicators ; Humans ; Noncommunicable Diseases ; Prevalence

Objective: To evaluate the accuracy of automated classification of ICD-O-3 morphology code from pathology reports by text-mining and support vector machine ( SVM ) , in order to provide basis for automated tumor coding in Chinese. Methods: The tumor report cards of Zhejiang residents from 2017 to 2019 were collected from Chronic Disease Surveillance Information Management System of Zhejiang Province. According to ICD-O-3, the keywords of the pathology reports were extracted, and SVM was used for automatic classification. The classification results were compared with those of 16 professionals with more than two years of experience in tumor coding, and the accuracy rate, recall rate and F-score were calculated for effect evaluation. Results: Totally 83 082 cases from 2017 to 2019 were included and were categorized into 17 morphological classifications, with 52 877 ( 63.65% ) cases of adenocarcinoma, squamous carcinoma and transitional cell carcinoma. A total of 1 090 keywords were enrolled into main corpus. The total F-score, accuracy rate and recall rate are 85.69, 77.20% and 96.27%, respectively. Conclusion Text-mining combined with SVM can improve the efficiency of ICD-O-3 morphology coding; however, the accuracy needs to be further improved.

Objective:To investigate the anti-anxious depression mechanism of Baihe Dihuangtang from the NOD-like receptor thermal protein domain 3 （NLRP3） inflammasome. Method:Fifty SD rats were randomly divided into normal group， model group， venlafaxine group （13.5 mg·kg^-1）， Baihe Dihuangtang high and low dose group （16，4 g·kg^-1）， with 10 rats in each group. Chronic restraint stress for 28 days （6 h） combined with subcutaneous injection of corticosterone （30 mg·kg^-1） was used to establish induce an anxious depression model. From the 8th day of modeling， the rats in the normal group and the model group received distilled water， and those in groups with drug intervention were treated with corresponding drugs by gavage for 21 days. Elevated plus maze and open field test were used to evaluate the behavioral changes of rats. Enzyme- linked immunosorbent assay （ELISA） was used to detect serum and hippocampal interleukin-1β （IL-1β）， interleukin-6 （IL-6） and interleukin-18 （IL-18） levels. Western blot were used to detect the relative expression of hippocampal NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， and Caspase-1. The pathological changes of the hippocampus were observed by hematoxylin-eosin（HE） staining， the average fluorescence intensity of NLRP3， ASC， and Caspase-1 was detected by immunofluorescence. The ultrastructure of neurons was observed under electron microscopy. Result:Compared with the normal group， the model group showed reduced total entries （TE）， the ratio of open-arm entries （OE%）， the ratio of open-arm times （OT%）， and the autonomous activity score （P<0.01）， significant anxiety and depression-like behaviors， increased levels of IL-1β， IL-6， and IL-18 in the serum and hippocampus （P<0.01）， elevated protein expression of NLRP3， ASC， and Caspase-1 （P<0.01）， activated NLRP3 inflammasomes， and injured hippocampal neurons. Compared with the model group， the high-dose Baihe Dihuangtang group showed improved anxiety and depression-like behaviors （P<0.01）， and decreased levels of IL-1β， IL-6， and IL-18 in the serum and hippocampus （P<0.05，P<0.01）， reduced protein expression of NLRP3， ASC， and Caspase-1 （P<0.01）， and alleviated hippocampal neuron damage. Conclusion:Baihe Dihuangtang can improve neuronal damage in anxious depression by inhibiting the excessive activation of NLRP3 inflammasomes.

Objective To investigate the epidemic character of injuries among rural left-behind children, so as to provide evidence for strategies and processes on preventing injuries. Methods Using stratified cluster sampling, a town was randomly selected from each of the two layers with different economic development levels in Qingxin district, Qingyuan city, Guangdong Province. The local left-behind children of 3-9 grades from 3 elementary schools and 3 middle schools were randomly selected from the local area. The student self-administered questionnaire was used to investigate the occurrence of injuries, personal circumstances, family environment and school situation in the past year. Data of injury situation, personal situation, family situation and school situation during last year were analysed by Chi-square and multiple logistic analysis. Results Injuries were reported to occur in 440 left-behind children, with an injury rate of 17.5%. Significant difference of injury rate was observed between groups divided by grades, being only-child in family, health conditions, anxiety, getting along with other students, teacher’s attitude to students, emphasizing security by teachers, knowledge level about injury, and injury-relative behaviors (all P<0.05). Multivariate logistic regression model results suggested that middle school, physical health, behavioral level, and relationship with classmates are protective factors, anxiety is a risk factor (OR=1.262,95%CI:1.009~1.577,P=0.041). Conclusions We have to take some comprehensive methods to prevent injuries that are influenced by all kinds of factors. While constructing an advantage circumstance to left-behind children, their awareness of security should also be improved to reduce the occurrence of injuries.

Objective To evaluate risk and the direct economic burden of malignant tumor due to type 2 diabetes mellitus. Methods Combing the data of chronic disease surveillance, follow-up and the fifth health service investigation, we calculated the population attributable risk and the direct economic burden for malignant tumor due to type 2 diabetes mellitus in order to estimate the direct economic burden for tumor caused by type 2 diabetes mellitus. Results The relative risk was 1.68 (95%CI: 1.68-1.70) for people with type 2 diabetes mellitus to develop the malignant tumor than the people without type 2 diabetes mellitus. The proportions of attributable risk (AR%) and population attributable risk (PAR%) were 40.57% and 2.05%, respectively. Moreover, the annual average hospitalization costs for malignant tumor reached 11 billion CNY, which took part 6.48% of total health service costs. And the direct economic burden for malignant tumor due to type 2 diabetes mellitus was 0.228 billion CNY. In addition, the top two highest population attributable risks were colorectal cancer and liver cancer, while the top three greatest direct economic burdens for malignant tumor or malignant tumor due to type 2 diabetes mellitus were lung cancer, colorectal cancer and stomach cancer. Conclusion From this study, we found that type 2 diabetes mellitus increased the risks of tumor and therefore lead to sharply increasing in medical costs of malignant tumor. In order to decrease the risk of malignant tumor and medical costs, we should pay more attention to the prevention of type 2 diabetes mellitus and the screening of malignant tumor due to type 2 diabetes mellitus.

Objective To analyze the health life expectancy (HALE) of the residents aged 15 years and above in Zhejiang Province and to evaluate the health level among adults. Methods The study was based the mortality data collected from Zhejiang Chronic Disease Surveillance Information and Management System, and the mortality rates were from the Under-Reporting Survey and the sample data in Zhejiang from the 5th National Health Service Survey in 2013. A Sullivan' s method was used to calculate the HALE. Results The life expectancy and self-evaluated HALE were 63.62 years, 55.80 years, respectively, and the difference was 7.82 years (61.49 years VS 55.13 years in males and 66.10 years VS 56.57 years in females) . The self-evaluated HALE 55.89 years in urban and 55.54 years in rural residents aged 15 years and above. The proportion of self-evaluated HALE in the total life expectancy was 87.70%, and it decreased with age, and the proportion has dropped to 67.31% in ≥65 age group. Life expectancy without chronic morbidity was 46.68 years (46.35 years in males and 47.01 years in females; 44.03 years in urban and 47.15 years in rural areas) among residents aged 15 years and above, and the proportion of self-evaluated HALE without chronic morbidity in the total life expectancy without chronic morbidity was 73.37%. Conclusion In general the proportion of self-evaluated HALE in the total life expectancy was small , and males had a greater proportion than female, and adults in rural areas had a greater proportion than that in urban areas. We should consider NCDS management for the elderly residents and to improve the life quality among the elderly residents.

OBJECTIVETo establish the patent ductus arteriosus model in preterm rats using the improved natural development method.

METHODSIn the light of the flaws of the natural development method in establishing the patent ductus arteriosus model, the experimental technology was modified to avoid the influence of fixation, dehydration, and section method on blood vessel diameter. Cesarean section was performed for a Wistar rat pregnant for 19 days, and 8 neonatal rats were obtained. After they were sacrificed by dislocation, they were embedded as a whole to avoid dehydration, and the microsection and horizontal section were made. After hematoxylin and eosin staining, a microscope was used to measure the inner diameters of the ductus arteriosus, the main pulmonary artery, and the descending aorta.

RESULTSAfter the cesarean section for the rat pregnant for 19 days, patent ductus arteriosus occurred in all the 8 neonatal rats. The measurements of the inner diameters of blood vessels were as follows: the long diameter and short diameter of the descending aorta were 354±106 and 182±140 μm, respectively; the short diameter of the ductus arteriosus was 155±122 μm, and its area was 36,847±42,582 μm(2); the long axis and short axis of the main pulmonary artery were 589±150 and 174±170 μm, respectively.

CONCLUSIONSThe improved natural development method can help to successfully establish the patent ductus arteriosus model in preterm rats.