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Hainan Province is in a tropical area of China and previously experienced serious P. falciparum and P. vivax malaria epidemics. After nearly 70 consecutive years of malaria prevention and control, malaria in Hainan has gradually been eliminated. To achieve the elimination of malaria, Hainan enacted six stages: investigative research and pilot prevention and control, large-scale antimalaria measures, adjustment of strategies for prevention and control, joint prevention and control measures, global funding of routine malaria control, and malaria elimination. Different strategies for malaria control were adopted at different stages. Malaria was most prevalent in the mountainous areas of central and southern Hainan, which contain a high-risk population (the forest goers) and two highly effective malaria vectors (An. dirus and An. minimus). Forest goers have been a high-risk population for malaria in Hainan since their identification in the 1990s. This paper summarizes malaria monitoring in forest goers and the response of forest goers to malaria control and elimination, distilling specific malaria control and elimination measures via case studies in Hainan Province. Two case studies in the malaria control stage demonstrated different measures for outbreaks and sporadic cases in forest goers. In view of the malaria outbreak in Sanya during the elimination stage, three-layered strategies (TLSs) were implemented to control outbreaks and improve control measures. Moreover, this paper also illustrates specific management measures to prevent malaria retransmission from sporadic imported malaria cases during the elimination phase. Hainan finally eliminated malaria in 2020. However, the risk of malaria retransmission is still high due to the prevalence of effective malaria vectors in Hainan, and forest goers are still a high-risk population for malaria retransmission.

Background Caloric restriction (CR) has become increasingly attractive in the treatment of type 2 diabetes mellitus (T2DM) because of the increasingly common high-calorie diet and sedentary lifestyle. This study aimed to evaluate the role of CR in T2DM treatment and further explore its potential molecular mechanisms. Methods Sixty male Sprague–Dawley rats were used in this study. The diabetes model was induced by 8 weeks of high-fat diet (HFD) followed by a single dose of streptozotocin injection (30 mg/kg). Subsequently, the diabetic rats were fed HFD at 28 g/day (diabetic control) or 20 g/day (30% CR regimen) for 20 weeks. Meanwhile, normal rats fed a free standard chow diet served as the vehicle control. Body mass, plasma glucose levels, and lipid profiles were monitored. After diabetes-related functional tests were performed, the rats were sacrificed at 10 and 20 weeks, and glucose uptake in fresh muscle was determined. In addition, western blotting and immunofluorescence were used to detect alterations in AKT/AS160/GLUT4 signaling. Results We found that 30% CR significantly attenuated hyperglycemia and dyslipidemia, leading to alleviation of glucolipotoxicity and thus protection of islet function. Insulin resistance was also markedly ameliorated, as indicated by notably improved insulin tolerance and homeostatic model assessment for insulin resistance (HOMA-IR). However, the improvement in glucose uptake in skeletal muscle was not significant. The upregulation of AKT/AS160/GLUT4 signaling in muscle induced by 30% CR also attenuated gradually over time. Interestingly, the consecutive decrease in AKT/AS160/GLUT4 signaling in white adipose tissue was significantly reversed by 30% CR. Conclusion CR (30%) could protect islet function from hyperglycemia and dyslipidemia, and improve insulin resistance. The mechanism by which these effects occurred is likely related to the upregulation of AKT/AS160/GLUT4 signaling.

BackgroundForest-goers have been the most severely infected by malaria in Hainan since the 1990s. In 2015, there were successively 6 cases of P. malariae infection as an outbreak by forest-goers in Sanya city, Hainan Province. According to the 1-3-7 approach, active case detection(ACD) was performed with guidance from information from Case 1. Cases 2-4 had the same epidemiological history as Case 1 and were similarly confirmed to be infected with P. malariae. However, the clues from Case1 came to an end and it was uncertain whether there were other potential infection sources or whether transmission was established in local villages. MethodsThere was no detailed strategy for the outbreak until 2015, although the 1-3-7 approach was certified to be effective for sporadic case. A retrospective study was conducted on this epidemic of P. malariae transmission among forest-goers in Hainan, 2015. A three-layer strategy (TLS) that integrated malaria joint prevention and control strategies(JPCS) and the 1-3-7 approach was first generated and applied to the disposal of the outbreak in Sanya in 2015, and its was also applied to strengthen epidemic measures to prevent emergence by residual foci from 2016 to 2018. The data were entered by Microsoft Office Excel 2007 for collection and statistic analysis by SPSS.ResultsWith guideline of TLS, three villages in Gaofeng town, Sanya city and Seven villages in Xinzheng Town, Baoting County, were selected as the first layer with design of TLS. In the first layer, 1,823 blood slides and PCR screening from villages in Baoting and Sanya were conducted on all residents by active case detection (ACD) and four cases were identified. In the second layers, passive case detection (PCD) and ACD for forest-goers were conducted and 7,831 blood slides were screened on all forest-goers. In the third layer, PCD was conducted for forest-goers, and 95,350 blood slides were screened on all forest-goers. Meanwhile, vector surveillance and control were also conducted to support foci disposals and to minimize the possibility of transmission. From 2016 to 2018, TLS was also applied to strengthen epidemic measures to prevent emergence by residual foci. In the first layer, chemoprophylaxis and ACD were conducted on residents in the villages of the foci and the surrounding villages, and 89.5% residents accepted chemoprophylaxis. Chemoprophylaxis and ACD were conducted and 79.1% received chemoprophylaxis while seeking forest-goers in the second layer. In the third layer, 89.6% received chemoprophylaxis while seeking forest-goers. ConclusionsThe innovative strategy of TLS not only was successfully applied in an epidemic response strategy in Sanya in 2015 but also was implemented in a strengthened intervention on forest-goers from 2016 to 2018 and finally achieved the goal of eliminating malaria in 2020 as scheduled. TLS is suitable for outbreak by indigenous case of unknown causes or for sporadic cases with defects in epidemic information, while 1-3-7 approach is suitable for sporadic cases which have clearly epidemic clues. Furthermore, TLS could be one of the major achievements after 1-3-7 approach, targeting outbreak in elimination malaria.

l -carnitine infusion has been proven to reduce fasting-induced fatigue and hunger in patients with metabolic syndrome in our former study. However, the association between l -carnitine and clinical outcomes of fasting therapy is yet to be investigated. In this study, data from 192 patients who finished fasting therapy from September 2008 to July 2018 were reviewed, among which 142 patients received l -carnitine infusion in fasting regimen. Propensity matching was used to overcome retrospective bias. Patients’ anthropometric measurements and metabolic markers were evaluated. After propensity matching, 40 patients were included in each group. Weight (-4.05 ± 1.65 kg vs -3.25 ± 1.68 kg, P = 0.031) and BMI (-1.51±0.61 kg/m2 vs -1.20 ± 0.62 kg/m2, P = 0.036) decreased in both groups, but significantly more in l -carnitine group, while diastolic blood pressure (-1.67±9.82 mmHg vs -6.21±8.83 mmHg, P = 0.043) and triglycerides (-0.18±0.63 mmol/L vs -1.05±1.70 mmol/L, P = 0.007) decreased significantly more in non- l -carnitine group compared between groups, blood glucose did not differ significantly between groups. l -carnitine can boost the positive effects of fasting therapy on weight loss and maintain the stability of blood pressure.

Background There are conflicting reports on the outcomes of patients with metabolic liver disease after liver transplantation. We aimed to compare the outcomes of living donor liver transplantation (LDLT) for metabolic disease vs orthotopic liver transplantation (OLT) from deceased donation. Methods Clinical data of 89 patients undergoing liver transplantation for the treatment of metabolic disorders were reviewed. Pre- and peri-transplant demographics, survival rate, complications and laboratory test data were collected and analyzed. Results For the 89 patients, only 2 died by the end of the last follow-up. The post-transplant EAD rate and severe complications were higher for OLT than LDLT. No significant difference was found between LDLT and OLT for the incidence of EBV and CMV infections. In terms of laboratory indexes, the recovery time of PLT, AKP and AST levels were significantly longer for OLT than LDLT. Among different types of metabolic disease, no significant difference was found in viral infection, EAD, laboratory indexes, severe complications or duration of hospital stay. Conclusions LDLT shows a lower incidence rate of EAD and complications, while it also shows a 1-year survival rate and incidence of viral infections compared similar to that of OLT. LDLT is the better treatment option of pediatric liver transplantation for metabolic liver disease compared with OLT.

To evaluate the effectiveness and safety of Xin Huang Pian skin patches for patients with acute gouty arthritis.In China, patients with acute gouty arthritis benefit from skin patcheses with herbal medicines. But the clinical effects of skin patches with Xin Huang Pian are rarely reported.A Randomized, Double-Blind, Active-Controlled Trial.The trial was performed from January 2015-December 2018 at the First Affiliated Hospital of Sun Yat-sen University in China. It was conducted with one intervention group (skin patches of Xin Huang Pian, N = 30) and one active control group (skin patches of Diclofenac Diethylamine Emulgel, N = 31). Participants and study investigators were both blinded to the treatment assignments. The primary outcomes were the improvement of joints' symptoms. The secondary outcomes were changes in white blood cells, erythrocyte sedimentation rate and C-reactive protein.Skin patches of Xin Huang Pian showed quick effect on decreasing joint pain at 3rd day of treatment. Wherever only at 7th day, Diclofenac Diethylamine Emulgel markedly lowered joint pain. Xin Huang Pian also showed superior effect than Diclofenac Diethylamine Emulgel on improving joint swelling and range of motion and decreasing the levels of C-reactive protein and erythrocyte sedimentation rate. No adverse reactions were observed in skin patches of Xin Huang Pian treatment.Skin patches of Xin Huang Pian appeared to be safe and efficacious for relieving joint symptoms in patients with acute gouty arthritis. The mechanism might be associated with the decreased levels of C-reactive protein and erythrocyte sedimentation rate.Skin-patcheses with Xin Huang Pian are more effective than Diclofenac Diethylamine Emulgel on improving joint pain, swelling and range of motion. Xin Huang Pian treatment showed superior effects compared with Diclofenac Diethylamine Emulgel on decreasing levels of C-reactive protein and erythrocyte sedimentation rate. Patients with acute gouty arthritis may benefit from skin patches of Xin Huang Pian for effective relief from joint pain and swelling. Chinese Clinical Trial Registration: ChiCTR-TRC-1300 4122.目的: 评估新癀片贴剂治疗急性痛风性关节炎的有效性和安全性。 背景: 在中国,患有急性痛风性关节炎的患者可使用草药药贴。但关于新癀片贴剂临床疗效的报道较少。 设计: 随机、双盲、阳性对照试验。 方法: 于2015年1月至2018年12月在中国中山大学附属第一医院开展此项试验。该试验分为干预组1例(新癀片贴剂,N=30)和阳性对照组1例(双氯芬酸二乙胺乳胶剂贴剂,N=31)。在治疗任务中,随机分配受试者和研究人员。主要研究结果是发现关节症状得到改善,其次是白细胞、红细胞沉降率和C反应蛋白的变化。 结果: 治疗第3天,新癀片贴剂对缓解关节疼痛有明显疗效。而双氯芬酸二乙胺乳胶剂贴剂仅在治疗第7天发现对缓解关节疼痛有明显疗效。在改善关节肿胀和活动度以及降低C反应蛋白水平和红细胞沉降率方面,新癀片疗效优于双氯芬酸二乙胺乳胶剂。使用新癀片贴剂未见不良反应。 结论: 新癀片贴剂在治疗急性痛风性关节炎方面安全有效,其作用机制可能与C反应蛋白水平和红细胞沉降率降低有关。 影响: 在改善关节疼痛、肿胀和活动度方面,新癀片疗效优于双氯芬酸二乙胺乳胶剂。与双氯芬酸二乙胺乳胶剂相比,新癀片在降低C反应蛋白水平和红细胞沉降率方面的作用更为明显。急性痛风性关节炎患者可使用新癀片贴剂有效缓解关节疼痛和肿胀。 中国临床试验注册中心: ChiCTR-TRC-1300 4122.

Hyperuricemia (HUA) is the most common disease associated with cardiovascular disease, metabolic syndrome, hypertension, and kidney disease. The objective of the current study was to evaluate the preliminary efficacy, mechanism, and safety of acupuncture on serum uric acid in patients with asymptomatic HUA.A randomized, placebo-controlled trial among 123 patients with asymptomatic HUA was conducted. The acupoints used in the acupuncture group were bilateral Five Shu in Spleen Meridian. Each participant received the intervention once daily for 10 consecutive days. The sham group received the same treatment duration on the same acupoints by the Park Sham Device. All patients underwent measurements of serum or urine creatinine, uric acid, serum lipid profiles, fasting plasma glucose, HbA1c, xanthine oxidase (XOD) and urate-anion exchanger (URAT-1).At the end of the intervention, the individuals in the acupuncture group were found to have significantly less levels of serum uric acid than those in the sham group [(453±65 vs. 528±81) μmol/L, p0.01]. Acupuncture was effective on increasing the urine uric acid level, urine pH value and 24-hour urine volume than the sham treatment (p0.05 for all). Interestingly, acupuncture significantly decreased the level of URAT-1 (p0.01) but not XOD than that of the sham intervention. The adverse events were that 3 patients experienced severe pain.Acupuncture on Five Shu in Spleen Meridian appeared to be safe and efficacious for decreasing serum uric acid in a Chinese HUA patient population. The mechanism might be associated with the decrease level of enzyme URAT-1.ChiCTR-TRC-13004122.

Activation of mitogen-activated protein kinases (MAPKs) in neurons may underlie the pathogenesis of Alzheimer's disease (AD). Acrolein, a ubiquitous pollutant, has been reported to implicate in the etiology of AD. Our previous data showed that acrolein changed the levels of key AD-associated proteins, including advanced glycation end products (RAGE), A-disintegrin and metalloprotease (ADAM-10), and beta-site amyloid-beta peptide cleaving enzyme 1 (BACE-1). In this study, we investigated whether acrolein-induced alterations of AD-associated proteins are relevant to MAPKs activation, and strategies to inhibit MAPKs activation yield benefits to acrolein-induced neurotoxicity in HT22 mouse hippocampal cells. We found that acrolein activated MAPKs signaling pathways to mediate cells apoptosis, and then altered the levels of AD-associated proteins ADAM-10, BACE-1 and RAGE. Inhibitors of MAPKs signaling pathways attenuated the cells death and restored the proteins levels of ADAM-10, BACE-1 and RAGE in varying degrees induced by acrolein. Taken together, activated MAPKs signaling pathways should be underlying the pathology of acrolein-induced neuronal disorders. Inhibitors of MAPKs pathways might be promising agents for acrolein-related diseases, such as AD.

This paper reports a novel and remarkably facile approach towards vertically aligned nanosheets on three-dimensional (3D) Ni foams. Conducting polypyrrole (PPy) sheets were grown on Ni foam through the volatilization of the environmentally friendly solvent from an ethanol-water solution of pyrrole (Py), followed by the polymerization of the coated Py in ammonium persulfate (APS) solution. The PPy-decorated Ni foams and commercial activated carbon (AC) modified Ni foams were employed as the two electrodes for the assembly of flexible all-solid-state asymmetric supercapacitors. The sheet-like structure of PPy and the macroporous feature of the Ni foam, which render large electrode-electrolyte interfaces, resulted in good capacitive performance of the supercapacitors. Moreover, a high energy density of ca. 14 Wh kg(-1) and a high power density of 6.2 kW kg(-1) were achieved for the all-solid-state asymmetric supercapacitors due to the wide cell voltage window.

Objective Acrolein, a highly reactive unsaturated aldehyde, is a ubiquitous environmental pollutant and oxidative damage induced by acrolein is hypothesized to involve in the etiology of Alzheimer’s disease (AD). Calorie restriction (CR) is the only non-genetic intervention that has consistently been verified to retard aging by ameliorating oxidative stress. Therefore, we investigated the effects of CR on acrolein-induced neurotoxicity in Sprague-Dawley (SD) rats. Methods A total of 45 weaned and specific-pathogen-free SD rats (male, weighing 180–220 g) were gavage-fed with acrolein (2.5 mg/kg/day) and fed ab libitum of 10 g/day or 7 g/day (representing 30% CR regimen), or gavage-fed with same volume of tap water and fed al libitum as vehicle control for 12 weeks. After behavioral test conducted by Morris Water Maze, SD rats were sacrificed and brain tissues were prepared for histochemical evaluation and Western blotting to detect alterations in oxidative stress, BDNF/TrkB pathway and key enzymes involved in amyloid precursor protein (APP) metabolism. Results Treatment with 30% CR in SD rats significantly attenuated acrolein-induced cognitive impairment. Oxidative damage including deletion of glutathione and superoxide dismutase and sharp rise in malondialdehyde were notably improved by 30% CR. Further study suggested that 30% CR showed protective effects against acrolein by modulating BDNF/TrkB signaling pathways. Moreover, 30% CR restored acrolein-induced changes of APP, β-secretase, α-secretase and receptor for advanced glycation end products. Conclusion These findings suggest that CR may provide a promising approach for the treatment of AD, targeting acrolein.

Crystallization behaviors and kinetics of iPP in an in-situ prepared isotactic polypropylene/graphene (iPP/G) composites were studied in this paper. In samples used in this study, the graphene fillers were well dispersed, and the interfacial adhesion exhibited enhanced features between graphene and iPP components. The thermal stability of the composites was improved by about 100 °C compared to the pristine iPP. It was found that the crystallization morphology, crystallization rate and kinetics of the iPP/G composites were significantly influenced by the presence of graphene. The nucleation and epitaxial growth of iPP on the graphene surface were observed and studied in detail. It was observed that the nucleation of iPP favored to occur at the wrinkles and edges due to the good match of the lattice parameters and the weak spatial hindrance compared to the smooth surface. Numerous nuclei epitaxially formed and the size of the crystals was very small. The schematic diagram was also proposed for the nucleation and growth process of iPP on the graphene surface in the iPP/G composites. Meanwhile, the overall crystallization kinetics and crystals growth were analyzed through Avrami equation. The obtained Avrami index n decreased with the graphene loadings and was close to 2 for the iPP/G composites, which implied that the growth of iPP in the composites was in two-dimension. And this was caused by the structure of graphene and the spatial confinement effect of graphene platelets in the iPP/G composites.

Organ transplantation is the most effective treatment for end-stage diseases. Although transplant rejection is the major restriction in successful long-lasting graft survival, induction of sustainable immune tolerance against transplant is one of the major goals in transplantation to enable long-term graft survival. Although various mechanisms have been suggested that induce immune tolerance during transplantation, the roles of long noncoding RNAs (lncRNAs), which modulate gene expression and regulate innate and adaptive immune responses, are not clearly understood in transplantation. Here, we described the role of 2 essential lncRNAs, lncRNA-A930015D03Rik and mouselincRNA1055, in regulating T helper 1 (Th1) response in graft rejection.To understand the gene expression and lncRNA profile during transplantation, we performed microarray to profile lncRNA and messenger (m)RNA of the heart graft and graft-infiltrating lymphocytes (GILs) in allogeneic and syngeneic mouse heart transplantation model. We screened the differentially expressed lncRNAs and mRNAs, and generated the network of lncRNA-mRNA coexpression and computationally predicted their association in transplantation. We further validated the selected T cell related lncRNAs by qPCR, which we identified in gene set enrichment analysis. The functional validation of these lncRNAs in the regulation of Th1 response in transplantation was performed by short hairpin RNA-mediated inhibition.We established a profile of lncRNA and mRNA, which are differentially expressed during transplant rejection in mouse model of heart transplant. Consistent with the microarray results, we have confirmed and validated the expression of 7 lncRNA by qPCR. The lncRNA-A930015D03Rik and mouselincRNA1055 were highly expressed in allogeneic heart graft and GILs. We further identified that expression of IL-12Rβ1 is strongly correlated with lncRNA-A930015D03Rik and mouselincRNA1055 in GILs. Further analysis revealed the association of lncRNA-A930015D03Rik and mouselincRNA1055 with Th1 cells in graft rejection. The functions of lncRNA-A930015D03Rik and mouselincRNA1055 were validated in differentiation of Th1 cells by knocking down their expression. Inhibition of lncRNA-A930015D03Rik and mouselincRNA1055 substantially suppressed the expression of IL-12Rβ1 and IFN-γ induction in Th1 cells.Our results provide a detailed profile of lncRNAs that may regulate immune response and graft outcomes. Our data not only suggest the involvement of lncRNA-A930015D03Rik and mouselincRNA1055 in the regulation of Th1 cells response during graft rejection but also identify them as novel biomarkers for subclinical graft rejection.

Insulin resistance is associated with obesity and type 2 diabetes. The aim of this study was to explore the mechanism of how Astragalus Polysaccharides (APS) improves insulin resistance in 3T3-L1 adipocytes. A cell culture model of insulin resistance was established in mature 3T3-L1 adipocytes by treating them with TNF-α, high glucose and insulin. Glucose uptake levels were detected in each group. To determine the mechanism by which APS improves insulin resistance in 3T3-L1 adipocytes, qRT-PCR was used to detect the expression of miR-721, and Western blots were used to detect the expression or activity of PPAR-γ, PAKT, PI3K, AKT, and GLUT4. Immunostaining was used to detect the expression of GLUT4. We successfully madea model of insulin resistance in mature 3T3-L1 adipocytes. APS increased glucose uptake levels in insulin-resistant adipocytes in a dose- and time-dependent manner, and also increased insulin sensitivity. APS suppressed miR-721 with its target gene PPAR-γ in a dose-dependent manner. miR-721 or PPAR inhibitor T0070907 inhibited the expressions of PPAR-γ, pAKT, and GLUT4 and also reduced glucose accumulation. APS attenuated these miR-721- and PPAR-γ-induced changes. APS increased insulin sensitivity by attenuating the effects of miR-721. The PI3K inhibitor wortmannin reduced the APS-increased pAKT, glucose uptake, and GLUT4 levels, and also reduced those levels in the presence of insulin with or without APS. Taken together, our findings suggest that APS promotes glucose uptake and increases insulin sensitivity in 3T3-L1 adipocytes and may involve the miR-721-PPAR-γ-PI3K/AKT-GLUT4 signaling pathway. These might be new therapeutic targets for treating insulin resistance in obesity and diabetes.

Objective To observe the effect of alternate-day fasting (ADF) therapy combined with Linggui Zhugan Decoction (苓桂术甘汤, LZD) on hepatic oxidative stress and blood lipids in hyperlipidemic rats.